{ "Contributors": "BC4-chem", "Source": "BC4-chem", "URL": "https://github.com/cambridgeltl/MTL-Bioinformatics-2016/tree/master/data", "Categories": [ "Named Entity Recognition" ], "Definition": [ "Given a sentence, you need to reconize the name of the chemical. There might be several correct answers. If it does not exist, you need to output \"There is no related enetity.\"." ], "Reasoning": [], "Input_language": [ "English" ], "Output_language": [ "English" ], "Instruction_language": [ "English" ], "Domains": [ "Public Health", "Heathcare" ], "Positive Examples": [], "Negative Examples": [], "Instances": [ { "input": "Effects of docosahexaenoic acid and methylmercury on child ' s brain development due to consumption of fish by Finnish mother during pregnancy: a probabilistic modeling approach.", "output": "docosahexaenoic acid, methylmercury." }, { "input": "Fish contains both beneficial substances e. g. docosahexaenoic acids but also harmful compounds e. g. methylmercury.", "output": "docosahexaenoic acids, methylmercury." }, { "input": "Importantly, the health effects caused by these two substances can be evaluated in one common end point, intelligence quotient ( IQ ), providing a more transparent analysis.", "output": "There is no related enetity." }, { "input": "We estimated health effects of maternal fish consumption on child ' s central nervous system by creating a model with three alternative maternal fish consumption scenarios ( lean fish, fatty fish, and current fish consumption ).", "output": "There is no related enetity." }, { "input": "Additionally, we analyzed impacts of both regular fish consumption and extreme fish consumption habits.", "output": "There is no related enetity." }, { "input": "At the individual level, the simulated net effects were small, encompassing a range of one IQ point in all scenarios.", "output": "There is no related enetity." }, { "input": "Fatty fish consumption, however, clearly generated a beneficial net IQ effect, and lean fish consumption evoked an adverse net IQ effect.", "output": "There is no related enetity." }, { "input": "In view of the current fish consumption pattern of Finnish mothers the benefits and risks seem to more or less compensate each other.", "output": "There is no related enetity." }, { "input": "This study clearly shows the significance of which fish species are consumed during pregnancy and lactation, and the results can be generalized to apply to typical western population fish consumption habits.", "output": "There is no related enetity." }, { "input": "The mechanisms responsible for garlic - drug interactions and their in vivo relevance.", "output": "There is no related enetity." }, { "input": "Garlic phytochemicals and garlic supplements influence the pharmacokinetic and pharmacodynamic behavior of concomitantly ingested drugs.", "output": "There is no related enetity." }, { "input": "In this paper we have summarized the mechanisms responsible for first - pass intestinal pharmacokinetic interactions by investigating the intestinal permeability of some cardiovascular, antiviral drugs, their transport with hepatic transporters and CYP3A4 metabolism.", "output": "There is no related enetity." }, { "input": "Transporter - enzyme interplay was studied with several in vitro models of varying complexity: rat small intestine and Caco - 2 cell monolayers were used in studies of intestinal processes, and hepatic pharmacokinetics was monitored in HepG2 cells, isolated rat hepatocytes and rat liver slices.", "output": "There is no related enetity." }, { "input": "Garlic phytochemicals from aged garlic extract modified the activities of secretory and absorptive transporters in both intestine and liver and competitively inhibited CYP3A4 enzyme.", "output": "There is no related enetity." }, { "input": "The increased activities of the most important intestinal efflux ( P - glycoprotein - Pgp, Multidrug Resistance Associated Protein 2 - MRP - 2, Breast Cancer Resistance Protein - BCRP ) and uptake ( MonoCarboxylate Transporter 1 - MCT1, Organic Anion Transporting Polypeptide - OATP, Peptide transporter 1 - PepT1 ) transporters were caused by changes in electrophysiological membrane properties and by allosteric modifications.", "output": "MonoCarboxylate." }, { "input": "Because clinical studies investigating interactions between garlic and human immunodeficiency virus protease inhibitors saquinavir and ritonavir have already been performed, we used these in vivo data to evaluate the in vitro results and the reliability of the models employed as screening tools for forecasting the potential of first - pass intestinal metabolism changes.", "output": "saquinavir, ritonavir." }, { "input": "We also assessed the probability of pharmacokinetic interactions with garlic of the novel drug darunavir and other cardiovascular drugs.", "output": "darunavir." }, { "input": "Finally, selected garlic phytochemicals were tested for their ability to influence P - glycoprotein and CYP3A4 activities.", "output": "There is no related enetity." }, { "input": "Endothelial nitric oxide synthase genotypes and haplotypes modify the responses to sildenafil in patients with erectile dysfunction.", "output": "nitric oxide, sildenafil." }, { "input": "Erectile dysfunction ( ED ) is usually treated with sildenafil.", "output": "sildenafil." }, { "input": "Although genetic polymorphisms in the endothelial nitric oxide synthase ( eNOS ) gene may impair endogenous NO formation, there is little information about how eNOS polymorphisms and haplotypes affect the responses to sildenafil.", "output": "nitric oxide, NO, sildenafil." }, { "input": "We studied 118 patients; 63 patients had ED secondary to radical prostatectomy ( PED ) and 55 had organic, clinical ED.", "output": "There is no related enetity." }, { "input": "eNOS genotypes for three eNOS polymorphisms ( T ( - 786 ) C, rs2070744; a variable number of tandem repeats ( VNTR ) in intron 4; and Glu298Asp, rs1799983 ) were determined, and eNOS haplotypes were estimated using PHASE 2. 1.", "output": "There is no related enetity." }, { "input": "The clinical responses to sildenafil were evaluated and the patients were classified as good responders ( GR ) or poor responders ( PR ) when their changes in five - item version of International Index for Erectile Function questionnaire were above or below the median value.", "output": "sildenafil." }, { "input": "The TC / CC genotypes and the C allele for the T ( - 786 ) C polymorphism were more common in GR, compared with PR patients with PED.", "output": "There is no related enetity." }, { "input": "However, the 4b4a / 4a4a genotypes and the 4a allele for the VNTR polymorphism in intron 4 were more common in GR, compared with PR patients with clinical ED.", "output": "There is no related enetity." }, { "input": "The C - 4a - Glu haplotype was more common in GR than in PR patients with PED.", "output": "There is no related enetity." }, { "input": "Conversely, the T - 4b - Asp haplotype was less common in GR than in PR patients with PED.", "output": "There is no related enetity." }, { "input": "No other significant differences were found.", "output": "There is no related enetity." }, { "input": "Our findings show evidence that eNOS polymorphisms affect the responses of PED and clinical ED patients to sildenafil.", "output": "sildenafil." }, { "input": "On the benefit of magnetic magnesium nanocarrier in cardiovascular toxicity of aluminum phosphide.", "output": "magnesium, aluminum phosphide." }, { "input": "The present study was designed to determine the effect of a new ( 25 ) Mg ( 2 + ) - carrying nanoparticle ( ( 25 ) MgPMC16 ) on energy depletion, oxidative stress, and electrocardiographic ( ECG ) parameters on heart tissue of the rats poisoned by aluminum phosphide ( AlP ).", "output": "( 25 ) Mg ( 2 + ), ( 25 ) MgPMC16, aluminum phosphide, AlP." }, { "input": "( 25 ) MgPMC16 at doses of 0. 025, 0. 05, and 0. 1 median lethal dose ( LD50 = 896 mg / kg ) was administered intravenously ( iv ) 30 min after a single intragastric administration of AlP ( 0. 25 LD50 ).", "output": "( 25 ) MgPMC16, AlP." }, { "input": "Sodium bicarbonate ( Bicarb; 2 mEq / kg, iv ) was used as the standard therapy.", "output": "Sodium bicarbonate, Bicarb." }, { "input": "After anesthesia, the animals were rapidly connected to an electronic cardiovascular monitoring device for monitoring of ECG, blood pressure ( BP ), and heart rate ( HR ).", "output": "There is no related enetity." }, { "input": "Later lipid peroxidation, antioxidant power, ATP / ADP ratio, and Mg concentration in the heart were evaluated.", "output": "ATP, ADP, Mg." }, { "input": "Results indicated that after AlP administration, BP and HR decreased while R - R duration increased.", "output": "AlP." }, { "input": "( 25 ) MgPMC16 significantly increased the BP and HR at all doses used.", "output": "( 25 ) MgPMC16." }, { "input": "We found a considerable increase in antioxidant power, Mg level in the plasma and the heart and a reduction in lipid peroxidation and ADP / ATP ratio at various doses of ( 25 ) MgPMC16, but ( 25 ) MgPMC16 - 0. 025 + Bicarb was the most effective combination therapy.", "output": "Mg, ADP, ATP, ( 25 ) MgPMC16, ( 25 ) MgPMC16, Bicarb." }, { "input": "The results of this study support that ( 25 ) MgPMC16 can increase heart energy by active transport of Mg inside the cardiac cells. ( 25 ) MgPMC16 seems ameliorating AlP - induced toxicity and cardiac failure necessitating further studies.", "output": "( 25 ) MgPMC16, Mg, ( 25 ) MgPMC16, AlP." }, { "input": "Ventilatory functions in cotton textile workers and the role of some inflammatory cytokines.", "output": "There is no related enetity." }, { "input": "Exposure to cotton dust in industrial environments causes inflammation in the airways of the exposed workers.", "output": "There is no related enetity." }, { "input": "This may manifest as respiratory complaints and changes in the respiratory functions after work shift and in the baseline of their ventilatory functions.", "output": "There is no related enetity." }, { "input": "The study aimed to investigate the effect of occupational exposure to cotton dust on respiratory symptoms, ventilatory functions and pro - inflammatory cytokine levels ( tumor necrosis factor alpha, interleukin 6 and interleukin 1 beta ).", "output": "There is no related enetity." }, { "input": "The study was conducted on 63 textile workers and 65 nonexposed subjects.", "output": "There is no related enetity." }, { "input": "Both groups were matched for age, socioeconomic status and smoking habit.", "output": "There is no related enetity." }, { "input": "The respirable dust measured in the workplace did not exceed the permissible values of the Egyptian law 1994.", "output": "There is no related enetity." }, { "input": "The bacterial counts detected were within the occupational exposure limits of the industrial settings.", "output": "There is no related enetity." }, { "input": "The results revealed that the percentage of respiratory symptoms was higher in textile workers.", "output": "There is no related enetity." }, { "input": "Respiratory complaints were chronic cough ( 33. 2 % ), chronic bronchitis ( 39. 7 % ) and dyspnea ( 23. 8 % ) in textile workers compared to ( 6. 2 %, 6. 2 % and 1. 5 % ), respectively, in controls.", "output": "There is no related enetity." }, { "input": "There was a marked reduction in the ventilatory functions ( forced vital capacity and forced expiratory volume in 1 s ) in the textile workers compared to the controls.", "output": "There is no related enetity." }, { "input": "The additive effect of smoking on the ventilatory functions was not apparent.", "output": "There is no related enetity." }, { "input": "The ventilatory functions of the workers were significantly positively correlated with the duration of exposure.", "output": "There is no related enetity." }, { "input": "The cytokines were insignificantly higher in the textile workers compared to their controls.", "output": "There is no related enetity." }, { "input": "The textile workers with respiratory complaints showed significant decline in ventilatory functions and elevation in the cytokine levels compared to the nonsymtomatizing workers with significant difference in interleukin 1 beta and interleukin 6.", "output": "There is no related enetity." }, { "input": "In conclusion, the results supported the fact that exposure to cotton dust deteriorates ventilatory functions and elevates proinflammatory cytokine levels.", "output": "There is no related enetity." }, { "input": "Analysis of the release of cytokines can be used to evaluate the immune responses to organic dust - induced airway inflammation.", "output": "There is no related enetity." }, { "input": "Heat stress decreases testicular germ cell proliferation and increases apoptosis in short term: an immunohistochemical and ultrastructural study.", "output": "There is no related enetity." }, { "input": "Scrotal hyperthermia has been known as a cause of male infertility but the exact mechanism leading to impaired spermatogenesis is unknown.", "output": "There is no related enetity." }, { "input": "This work was aimed to investigate the role of scrotal hyperthermia on cell proliferation and apoptosis in testes.", "output": "There is no related enetity." }, { "input": "The rats were randomly allotted into one of the four experimental groups: A ( control ), B ( 1 day after scrotal hyperthermia ), C ( 14 days after scrotal hyperthermia ), and D ( 35 days after scrotal hyperthermia ); each group comprised 7 animals.", "output": "There is no related enetity." }, { "input": "Scrotal hyperthermia was carried out in a thermostatically controlled water bath at 43 degrees C for 30 min once daily for 6 consecutive days.", "output": "There is no related enetity." }, { "input": "Control rats were treated in the same way, except the testes were immersed in a water bath maintained at 22 degrees C.", "output": "There is no related enetity." }, { "input": "Hyperthermia - exposed rats were killed under 50 mg / kg ketamine anaesthesia and tissue samples were obtained for biochemical and histopathological investigations.", "output": "ketamine." }, { "input": "Hyperthermia treatment significantly decreased the testicular antioxidant system, including decreases in the glutathione level, superoxide dismutase, and glutathione peroxidase activities.", "output": "glutathione, superoxide, glutathione." }, { "input": "Moreover, exposure to hyperthermia resulted in lipid peroxidation increase in testes.", "output": "There is no related enetity." }, { "input": "Our data indicate a significant reduction in the expression of proliferating cell nuclear antigen and an enhancement in the activity of terminal deoxynucleotidyl transferase dUTP nick end labelling after scrotal hyperthermia.", "output": "dUTP." }, { "input": "In scrotal hyperthermia, the mitochondrial degeneration, dilatation of smooth endoplasmic reticulum, and enlarged intercellular spaces were observed in both Sertoli and spermatid cells.", "output": "There is no related enetity." }, { "input": "Scrotal hyperthermia is one of the major factors that impair spermatogenesis in testis.", "output": "There is no related enetity." }, { "input": "This heat stress is shown to be closely associated with oxidative stress, followed by apoptosis of germ cells.", "output": "There is no related enetity." }, { "input": "A genomic approach to predict synergistic combinations for breast cancer treatment.", "output": "There is no related enetity." }, { "input": "We leverage genomic and biochemical data to identify synergistic drug regimens for breast cancer.", "output": "There is no related enetity." }, { "input": "In order to study the mechanism of the histone deacetylase ( HDAC ) inhibitors valproic acid ( VPA ) and suberoylanilide hydroxamic acid ( SAHA ) in breast cancer, we generated and validated genomic profiles of drug response using a series of breast cancer cell lines sensitive to each drug.", "output": "valproic acid, VPA, suberoylanilide hydroxamic acid, SAHA." }, { "input": "These genomic profiles were then used to model drug response in human breast tumors and show significant correlation between VPA and SAHA response profiles in multiple breast tumor data sets, highlighting their similar mechanism of action.", "output": "VPA, SAHA." }, { "input": "The genes deregulated by VPA and SAHA converge on the cell cycle pathway ( Bayes factor 5. 21 and 5. 94, respectively; P - value 10 ( - 8. 6 ) and 10 ( - 9 ), respectively ).", "output": "VPA, SAHA." }, { "input": "In particular, VPA and SAHA upregulate key cyclin - dependent kinase ( CDK ) inhibitors.", "output": "VPA, SAHA." }, { "input": "In two independent datasets, cancer cells treated with CDK inhibitors have similar gene expression profile changes to the cellular response to HDAC inhibitors.", "output": "There is no related enetity." }, { "input": "Together, these results led us to hypothesize that VPA and SAHA may interact synergistically with CDK inhibitors such as PD - 033299.", "output": "VPA, SAHA, PD - 033299." }, { "input": "Experiments show that HDAC and CDK inhibitors have statistically significant synergy in both breast cancer cell lines and primary 3 - dimensional cultures of cells from pleural effusions of patients.", "output": "There is no related enetity." }, { "input": "Therefore, synergistic relationships between HDAC and CDK inhibitors may provide an effective combinatorial regimen for breast cancer.", "output": "There is no related enetity." }, { "input": "Importantly, these studies provide an example of how genomic analysis of drug - response profiles can be used to design rational drug combinations for cancer treatment.", "output": "There is no related enetity." }, { "input": "Chemical constituents and allelopathic and antioxidant activities of Alchorneopsis floribunda M u ll.", "output": "There is no related enetity." }, { "input": "Arg.", "output": "There is no related enetity." }, { "input": "( Euphorbiaceae ).", "output": "There is no related enetity." }, { "input": "Chemical investigation of extracts from the stems and leaves of Alchorneopsis floribunda M u ll.", "output": "There is no related enetity." }, { "input": "Arg., collected in the Amazon region, was performed.", "output": "There is no related enetity." }, { "input": "The main isolated compounds were triterpenes ( alpha - amyrin, beta - amyrin, lupeol, betulin, betulinic acid, uvaol, erythrodiol and oleanolic acid ) and phenolic acid derivatives from 4 - hydroxybenzoic acid ( gallic and protocatechuic acids and isocorilagin ).", "output": "triterpenes, alpha - amyrin, beta - amyrin, lupeol, betulin, betulinic acid, uvaol, erythrodiol, oleanolic acid, phenolic acid, 4 - hydroxybenzoic acid, gallic and protocatechuic acids, isocorilagin." }, { "input": "In the germination assays, high inhibitory allelopathic effects of the extracts and isocorilagin were observed and 2, 2 - diphenyl - 1 - picrylhydrazyl radical scavenging activity of isocorilagin was higher than those of the standards used ( Trolox and butylated hydroxyanisole ).", "output": "isocorilagin, 2 , 2 - diphenyl - 1 - picrylhydrazyl, isocorilagin, Trolox, butylated hydroxyanisole." }, { "input": "This is the first chemical study of the genus Alchorneopsis ( Euphorbiaceae ).", "output": "There is no related enetity." }, { "input": "Evaluation of total oxidative status and total antioxidant capacity in patients with endemic fluorosis.", "output": "There is no related enetity." }, { "input": "The objective of the present study was to determine the plasma total oxidative status ( TOS ) and total antioxidant capacity ( TAC ) in patients with endemic fluorosis.", "output": "There is no related enetity." }, { "input": "A total of 79 ( 35 males and 44 females; mean age 44. 0 +/- 11. 9 years ) patients with endemic fluorosis and 55 ( 23 males and 32 females; mean age 48. 3 +/- 8. 5 years ) age -, sex - and body mass index - matched healthy controls were included in this study.", "output": "There is no related enetity." }, { "input": "The urine fluoride levels and plasma TOS and TAC levels were measured.", "output": "fluoride." }, { "input": "The urine fluoride levels of fluorosis patients were significantly higher than control subjects as expected ( 1. 91 +/- 0. 15 vs. 0. 49 +/- 0. 13 mg / L, respectively; p < 0. 001 ).", "output": "fluoride." }, { "input": "TOS was significantly higher in fluorosis group than in control group ( 17. 55 +/- 3. 82 vs. 15. 06 +/- 4. 31 mu mol H ( 2 ) O ( 2 ) Eq / L, respectively; p = 0. 001 ).", "output": "There is no related enetity." }, { "input": "TAC was significantly lower in fluorosis group than in control group ( 1. 60 +/- 0. 36 vs. 1. 82 +/- 0. 51 mmol Trolox Eq / L, respectively; p = 0. 004 ).", "output": "Trolox." }, { "input": "Oxidative stress index ( OSI ) was significantly higher in fluorosis group than in control group ( 11. 5 +/- 3. 8 vs. 8. 8 +/- 3. 7, respectively; p < 0. 001 ).", "output": "There is no related enetity." }, { "input": "Correlation analysis in all the groups indicated that TAC was negatively correlated with urine fluoride ( r = - 0. 25, p = 0. 003 ), TOS was positively correlated with urine fluoride ( r = 0. 34, p < 0. 001 ) and OSI was positively correlated with urine fluoride ( r = 0. 36, p < 0. 001 ).", "output": "fluoride, fluoride, fluoride." }, { "input": "The results of our study demonstrate that oxidative stress plays an important role in the pathogenesis of the endemic fluorosis.", "output": "There is no related enetity." }, { "input": "Impact of aqueous doash extract on urinary mutagenicity in rats exposed to heterocyclic amines.", "output": "heterocyclic amines." }, { "input": "Doash ( Origanum majorana ) is an herbaceous plant found commonly in Saudi Arabia.", "output": "There is no related enetity." }, { "input": "It is used as a food flavor and a folk remedy to treat a number of diseases.", "output": "There is no related enetity." }, { "input": "The 2 - amino - 3 - methylimidazo [ 4, 5 - f ] quinoline ( IQ ) and 2 - amino - 1 - methyl - 6 - phenylimidazo [ 4, 5 - b ] pyridine ( PhIP ) are the most abundant of the heterocyclic amine carcinogens present in cooked food.", "output": "2 - amino - 3 - methylimidazo [ 4 , 5 - f ] quinoline, 2 - amino - 1 - methyl - 6 - phenylimidazo [ 4 , 5 - b ] pyridine, PhIP, heterocyclic amine." }, { "input": "In the present study, the potential of doash tea to influence carcinogen metabolism was investigated indirectly using heterocyclic amines as model mutagens, IQ and PhIP.", "output": "heterocyclic amines, PhIP." }, { "input": "Results obtained showed that doash tea had no influence on body weight in both the studies.", "output": "There is no related enetity." }, { "input": "Rats were treated with different doses of IQ ( 1, 3, 5 and 10 mg / kg ) or PhIP ( 1, 5, 10 and 20 mg / kg ).", "output": "PhIP." }, { "input": "The selected dosage was 5 mg / kg for both heterocyclic amines.", "output": "heterocyclic amines." }, { "input": "Results obtained revealed that rats treated with doash tea and given a single dose of the heterocyclic amines, whether for 1 day ( short - term ) or for 1 month ( long term ), showed a statistically significant decrease in their excretion of indirect mutagens ( IQ or PhIP ).", "output": "heterocyclic amines, PhIP." }, { "input": "Following treatment of the rats with a single oral dose of IQ or PhIP, the highest mutagenic activity determined in the presence of an activation system was excreted in the urine after 24 h, with much lower levels of mutagencity being excreted during subsequent elimination from the body.", "output": "PhIP." }, { "input": "No mutagenicity was observed in the absence of an activation system that is direct - acting mutagenicity using ( IQ and PhIP ).", "output": "PhIP." }, { "input": "Statistical analysis revealed that, in comparison with the control group, the aqueous doash extract significantly reduced the mutagenic response after 24 h.", "output": "There is no related enetity." }, { "input": "It was concluded that doash extract significantly decreased the excretion of mutagens in comparison with the control group ( water only ).", "output": "There is no related enetity." }, { "input": "Genetic and epigenetic regulation of the organic cation transporter 3, SLC22A3.", "output": "There is no related enetity." }, { "input": "Human organic cation transporter 3 ( OCT3 and SLC22A3 ) mediates the uptake of many important endogenous amines and basic drugs in a variety of tissues.", "output": "amines." }, { "input": "OCT3 is identified as one of the important risk loci for prostate cancer, and is markedly underexpressed in aggressive prostate cancers.", "output": "There is no related enetity." }, { "input": "The goal of this study was to identify genetic and epigenetic factors in the promoter region that influence the expression level of OCT3.", "output": "There is no related enetity." }, { "input": "Haplotypes that contained the common variants, g. - 81G > delGA ( rs60515630 ) ( minor allele frequency 11. 5 % in African American ) and g. - 2G > A ( rs555754 ) ( minor allele frequency > 30 % in all ethnic groups ) showed significant increases in luciferase reporter activities and exhibited stronger transcription factor - binding affinity than the haplotypes that contained the major alleles.", "output": "There is no related enetity." }, { "input": "Consistent with the reporter assays, OCT3 messenger RNA expression levels were significantly higher in Asian ( P < 0. 001 ) and Caucasian ( P < 0. 05 ) liver samples from individuals who were homozygous for g. - 2A / A in comparison with those homozygous for the g. - 2G / G allele.", "output": "There is no related enetity." }, { "input": "Studies revealed that the methylation level in the basal promoter region of OCT3 was associated with OCT3 expression level and tumorigenesis capability in various prostate cancer cell lines.", "output": "There is no related enetity." }, { "input": "The methylation level of the OCT3 promoter was higher in 62 % of prostate tumor samples compared with matched normal samples.", "output": "There is no related enetity." }, { "input": "Our studies demonstrate that genetic polymorphisms in the proximal promoter region of OCT3 alter the transcription rate of the gene and may be associated with altered expression levels of OCT3 in human liver.", "output": "There is no related enetity." }, { "input": "Aberrant methylation contributes to the reduced expression of OCT3 in prostate cancer.", "output": "There is no related enetity." }, { "input": "Accumulation patterns of some seed oil components from wild sources of Turkey.", "output": "There is no related enetity." }, { "input": "Accumulation profiles of fatty acids and alpha - tocopherol were analysed at three ripening stages in the seed oils of Primula and Echium species.", "output": "fatty acids, alpha - tocopherol." }, { "input": "Total seed oils were increased considerably with maturation, while alpha - tocopherol contents decreased in both species.", "output": "alpha - tocopherol." }, { "input": "Increased levels of ALA and oleic acid, and decrease in linoleic and palmitic acids at late ripening stages of Primula sibthorpii, and slightly fluctuations of all examined fatty acids in Echium italicum were observed.", "output": "ALA, oleic acid, linoleic and palmitic acids, fatty acids." }, { "input": "Considerable amounts of alpha - tocopherol ( 27. 4 mg / 100 g ), linoleic acid ( 42. 76 % ) and ALA ( 25. 46 % ) and GLA ( 4. 11 % ) were detected in Ribes alpinum.", "output": "alpha - tocopherol, linoleic acid, ALA, GLA." }, { "input": "Typical accumulation patterns of the examined parameters may be useful for species characterisation and biochemical monitoring of seed development in natural conditions.", "output": "There is no related enetity." }, { "input": "Mucopolysaccharidosis: cardiologic features and effects of enzyme - replacement therapy in 24 children with MPS I, II and VI.", "output": "There is no related enetity." }, { "input": "We determined the cardiologic features of children with MPS I, II and VI, and evaluated the effect of enzyme - replacement therapy ( ERT ) on cardiac disease.", "output": "There is no related enetity." }, { "input": "Twenty - four children aged 1 - 18 years with MPS I, II or VI were prospectively evaluated with echocardiogram and electrocardiogram from the start of enzyme - replacement therapy up to 6 years of treatment.", "output": "There is no related enetity." }, { "input": "At start of therapy, 66 % had abnormal cardiac geometric features.", "output": "There is no related enetity." }, { "input": "Left - ventricular mass index ( LVMI ) was increased in half of the patients, due mainly to concentric hypertrophy in MPS I and II and to eccentric hypertrophy in MPS VI.", "output": "There is no related enetity." }, { "input": "Regurgitation was most severe in a subgroup of young MPS VI patients ( < 5 years ) at the mitral valve.", "output": "There is no related enetity." }, { "input": "At baseline, all patients had abnormal valves.", "output": "There is no related enetity." }, { "input": "The ECG showed no clear rhythm or conduction abnormalities; neither, in most patients, did it reflect the hypertrophy.", "output": "There is no related enetity." }, { "input": "After ERT, the LVMI Z - score normalized in 70 % of the patients who had a Z - score > 2.", "output": "There is no related enetity." }, { "input": "LVMI Z - scores decreased significantly in patients with MPS I and MPS II ( p = 0. 04 and p = 0. 032 ).", "output": "There is no related enetity." }, { "input": "Despite ERT, valve regurgitation increased in 60 % of the patients.", "output": "There is no related enetity." }, { "input": "We conclude that all our MPS patients have cardiac abnormalities.", "output": "There is no related enetity." }, { "input": "The most severe cardiac disease was observed in a subgroup of young MPS VI patients.", "output": "There is no related enetity." }, { "input": "While ERT had an effect on LVMI and IVSd, it apparently had little or none on valve regurgitation.", "output": "There is no related enetity." }, { "input": "Structural basis for protein phosphatase 1 regulation and specificity.", "output": "There is no related enetity." }, { "input": "The ubiquitous serine / threonine protein phosphatase 1 ( PP1 ) regulates diverse, essential cellular processes such as cell cycle progression, protein synthesis, muscle contraction, carbohydrate metabolism, transcription and neuronal signaling.", "output": "serine, threonine, carbohydrate." }, { "input": "However, the free catalytic subunit of PP1, while an effective enzyme, lacks substrate specificity.", "output": "There is no related enetity." }, { "input": "Instead, it depends on a diverse set of regulatory proteins ( >= 200 ) to confer specificity towards distinct substrates.", "output": "There is no related enetity." }, { "input": "Here, we discuss recent advances in structural studies of PP1 holoenzyme complexes and summarize the new insights these studies have provided into the molecular basis of PP1 regulation and specificity.", "output": "There is no related enetity." }, { "input": "Protective effect of vitamin E and epicatechin against nicotine - induced oxidative stress in rats.", "output": "vitamin E, epicatechin, nicotine." }, { "input": "Nicotine is a major pharmacologically active and addictive component of tobacco smoke, which is regarded to be a primary risk factor in the development of cardiovascular and pulmonary diseases.", "output": "Nicotine." }, { "input": "Epicatechin is one of the most potent antioxidants present in the human diet.", "output": "Epicatechin." }, { "input": "Particularly high levels of this compound are found in tea, apples and chocolate.", "output": "There is no related enetity." }, { "input": "It has been reported that tea extracts and / or its constituents have antibacterial, antiviral, antioxidative, antitumor and antimutagenic activities.", "output": "There is no related enetity." }, { "input": "Vitamin E is a major lipid - soluble antioxidant vitamin and free radical scavenger, presents as an integral component of cellular membranes and has important biological functions.", "output": "Vitamin E." }, { "input": "The primary mechanism by which vitamin E is proposed to prevent cancer is through their antioxidant properties.", "output": "vitamin E." }, { "input": "The goal of this study is to evaluate the effect of epicatechin alone or combined with vitamin E in inhibiting the oxidative stress induced by nicotine in rats.", "output": "epicatechin, vitamin E, nicotine." }, { "input": "Results obtained indicated that there was a significant elevation in the levels of malondialdhyde ( MDA ) in nicotine injected rats.", "output": "malondialdhyde, MDA, nicotine." }, { "input": "The combined treatment ( epicatechin + Vit E ) group showed a potential reduction of these parameters more than individual treatment.", "output": "epicatechin, Vit E." }, { "input": "The activities of superoxide dismutase, catalase and glutathione peroxidase were found significantly higher in combined treated than untreated rats.", "output": "superoxide, glutathione." }, { "input": "In nicotine group, a negative significant correlation between reduced glutathione and MDA ( r = - 0. 92 ) was observed.", "output": "nicotine, glutathione, MDA." }, { "input": "In conclusion, these results suggested that the supplementation of diet with epicatechin and vitamin E provided antioxidant defense with strong chemopreventive activity against nicotine - induced carcinogenesis.", "output": "epicatechin, vitamin E, nicotine." }, { "input": "Prevention of cytotoxicity of nickel by quercetin: the role of reactive oxygen species and histone acetylation.", "output": "nickel, quercetin, oxygen." }, { "input": "Excessive exposure to nickel may cause health effects on the blood, lung, nose, kidney, reproductive system, skin and the unborn child.", "output": "nickel." }, { "input": "In the present study, we found that Ni ( 2 + ) exposure led to a time - and dose - dependent proliferation arrest and death in human leukemia HL - 60 cells.", "output": "Ni ( 2 + )." }, { "input": "In the presence of 1 mM Ni ( 2 + ), reactive oxygen species ( ROS ) generation ( indicated by the level of malondialdehyde ) increased to 323 % and histone acetylation decreased to 32 %.", "output": "Ni ( 2 + ), oxygen, malondialdehyde." }, { "input": "Interestingly, quercetin ( QU ) dose dependently prevented Ni ( 2 + ) - induced cell proliferation arrest and death from 0 to 80 mu M but showed similar activity of scavenging ROS at the concentrations of 20, 40 and 80 micro M.", "output": "quercetin, Ni ( 2 + )." }, { "input": "When the effect of QU on histone acetylation was studied, QU significantly prevented Ni ( 2 + ) - induced histone hypoacetylation at 40 or 80 micro M.", "output": "Ni ( 2 + )." }, { "input": "Moreover, increase in histone acetylation by trichostatin A could also significantly enhance the protection effect of QU at 10 or 20 micro M but not at higher concentrations.", "output": "trichostatin A." }, { "input": "Thus, our results further confirmed the critical role of ROS and histone hypoacetylation in the cytotoxicity of Ni ( 2 + ) exposure and proved that QU is a potentially useful native dietary compound to efficiently prevent Ni ( 2 + ) - caused cytotoxicity through both diminishing ROS generation and increasing histone acetylation.", "output": "Ni ( 2 + ), Ni ( 2 + )." }, { "input": "Cadmium concentrations in shrimp ( Penaeus semisulcatus and Penaeus monodon ) caught from the coastal areas in Southern Iran.", "output": "Cadmium." }, { "input": "This study was undertaken to determine the concentration of cadmium in two shrimp species, namely, Penaeus semisulcatus and Penaeus monodon caught from the coastal areas in southern Iran.", "output": "cadmium." }, { "input": "Cadmium concentration was determined by graphite furnace atomic absorption spectrophotometry in 91 shrimp samples after nitric acid / perchloric acid digestion.", "output": "Cadmium, graphite, nitric acid, perchloric acid." }, { "input": "Accuracy of the analysis was checked by various methods including the use of reference material.", "output": "There is no related enetity." }, { "input": "The mean +/- SD of cadmium concentrations in shrimp samples were 0. 128 +/- 0. 144 ( mu g / g ).", "output": "cadmium." }, { "input": "The cadmium concentrations ranged from 0. 010 to 0. 96 mu g / g of the muscle tissues of shrimp.", "output": "cadmium." }, { "input": "Higher cadmium concentration in shrimp samples was found in summer ( significant p < 0. 05 ).", "output": "cadmium." }, { "input": "The results show that the mean concentration of cadmium in shrimp is lower than the maximum allowed levels according to International standards, although the concentration of cadmium in only one sample was more than the amount recommended by Food and Agriculture Organization.", "output": "cadmium, cadmium." }, { "input": "Therefore, no risk to the consumer arises from the cadmium contents of the shrimp caught in these areas.", "output": "cadmium." }, { "input": "Selective separation of patchouli alcohol from the essential oil of Cablin potchouli by inclusion crystalline method.", "output": "patchouli alcohol." }, { "input": "In this article, we have focused on the application of non - traditional separation approach, the host - guest inclusion method, into the separation of the active component patchouli alcohol from the essential oil of Cablin potchouli Herb.", "output": "patchouli alcohol." }, { "input": "The host molecule 1, 1, 6, 6 - tetraphenylhexa - 2, 4 - diyne - 1, 6 - diol ( A ) was used to selectively recognise the guest molecule patchouli alcohol ( B ) in the essential oil of Pogostemon cablin ( Blanco ) Benth through two strong hydrogen bonding.", "output": "1 , 1 , 6 , 6 - tetraphenylhexa - 2 , 4 - diyne - 1 , 6 - diol, patchouli alcohol, hydrogen." }, { "input": "The inclusion compound was structurally determined by the single crystal X - ray diffraction.", "output": "There is no related enetity." }, { "input": "The separation effect was examined by gas chromatography for the whole essential oil and the inclusion compound, showing that the inclusion crystalline method is simple, rapid and effective for the separation of patchouli alcohol from the essential oil of C. potchouli Herb.", "output": "patchouli alcohol." }, { "input": "Toxic effects of some synthetic food colorants and / or flavor additives on male rats.", "output": "There is no related enetity." }, { "input": "The objective of the present work was to evaluate the broadest toxic effect of some synthetic additives of colorants and / or flavors on different body organs and metabolic aspects in rats.", "output": "There is no related enetity." }, { "input": "A number of chemical food color and flavor additives are routinely added during processing to improve the aesthetic appearance of the dietary items.", "output": "There is no related enetity." }, { "input": "However, many of them are toxic after prolonged use.", "output": "There is no related enetity." }, { "input": "In this experiment, a total of 100 male albino rats of Spargue Dawley strain were divided into 10 groups: G ( 1 ) was fed basal diet and served as control, G ( 2 ): basal diet + Brilliant blue ( blue dye, No. 2, 124 mg / kg diet ), G ( 3 ): basal diet + carmoisine ( red dye, No. 3, 70 mg / kg diet ), G ( 4 ): basal diet + tartrazine ( yellow dye, FD & C yellow No. 5, 75 mg / kg diet ), G ( 5 ): basal diet + trans - anethole ( 4. 5 g / kg diet ) G ( 6 ): basal diet + propylene glycol ( 0. 25 g / kg diet ), G ( 7 ): basal diet + vanillin ( 1. 25 g / kg diet ), G ( 8 ): basal diet + Brilliant blue + propylene glycol, G ( 9 ): basal diet + carmoisine + trans - anethole, G ( 10 ): basal diet + tartrazine + vanillin for 42 successive days.", "output": "Brilliant blue, carmoisine, tartrazine, trans - anethole, propylene glycol, vanillin, Brilliant blue, propylene glycol, carmoisine, trans - anethole, tartrazine, vanillin." }, { "input": "All food colorants mixed with or without flavor additives induced a significant decrease in body weight, hemoglobin concentration and red blood cell count.", "output": "There is no related enetity." }, { "input": "Also there was a significant decrease in reduced glutathione content; glutathione - S - transferase and superoxide dismutase activities in both blood and liver compared to control group.", "output": "glutathione, glutathione, S, superoxide." }, { "input": "On the other hand, a significant increase in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase activities, bilirubin, urea, creatinine, total protein and albumin were observed in all test groups when compared to control group.", "output": "alanine, aspartate, bilirubin, urea, creatinine." }, { "input": "Finally, it is advisable to limit the uses of these food colorants and / or food flavor additives especially those used by children.", "output": "There is no related enetity." }, { "input": "Steroids and phenolic constituents from the fruiting bodies of the basidiomycete Sarcodon joedes.", "output": "Steroids, phenolic." }, { "input": "Nine secondary metabolites, including four steroids, four phenolics and one cerebroside, were isolated from the methanol extract of the fruiting bodies of the basidiomycete Sarcodon joedes.", "output": "steroids, phenolics, cerebroside, methanol." }, { "input": "The isolated compounds were identified by spectroscopic analyses as ( 22E, 24R ) - 6 beta - methoxyergosta - 7, 22 - diene - 3 beta, 5 alpha - diol ( 1 ), 2 ', 3 ' - diacetoxy - 3, 4, 5 ', 6 ', 4 '' - pentahydroxy - p - terphenyl ( 2 ), cerebroside B ( 3 ), ergosta - 7, 22 - dien - 3 beta - ol ( 4 ), ergosterol peroxide ( 5 ), ( 22E, 24R ) - 3 beta - hydroxy - ergosta - 5, 22 - dien - 7 - one ( 6 ), benzoic acid ( 7 ), methyl p - hydroxybenzoate ( 8 ) and 3, 4 - dihydroxybenzoic acid ( 9 ).", "output": "( 22E , 24R ) - 6 beta - methoxyergosta - 7 , 22 - diene - 3 beta , 5 alpha - diol, 2 ' , 3 ' - diacetoxy - 3 , 4 , 5 ' , 6 ' , 4 '' - pentahydroxy - p - terphenyl, cerebroside B, ergosta - 7 , 22 - dien - 3 beta - ol, ergosterol peroxide, ( 22E , 24R ) - 3 beta - hydroxy - ergosta - 5 , 22 - dien - 7 - one, benzoic acid, methyl p - hydroxybenzoate, 3 , 4 - dihydroxybenzoic acid." }, { "input": "The cytotoxic activities of these compounds were evaluated.", "output": "There is no related enetity." }, { "input": "All these compounds were isolated from this fungus for the first time.", "output": "There is no related enetity." }, { "input": "In vitro evaluation of the protective effects of 4 - thujanol against mitomycin - C and cyclophosphamide - induced genotoxic damage in human peripheral lymphocytes.", "output": "4 - thujanol, mitomycin - C, cyclophosphamide." }, { "input": "4 - Thujanol ( sabinene hydrate ), a bicyclic monoterpene alcohol, is found in the essential oils of many aromatic and medicinal plants and is widely used as a fragrance and flavouring agent in many different products.", "output": "4 - Thujanol, sabinene hydrate, bicyclic monoterpene alcohol." }, { "input": "The aim of this study was to evaluate the protective effects of 4 - thujanol against the genotoxic effects induced by mitomycin C ( MMC ) and cyclophosphamide ( CP ) in human lymphocytes, using the chromosome aberrations, sister chromatid exchanges, and micronucleus tests, in the absence and in the presence of S9 mix, respectively.", "output": "4 - thujanol, mitomycin C, MMC, cyclophosphamide." }, { "input": "The cells were treated with 0. 25 micro g / mL MMC and 28 micro g / mL CP as alone and cotreated with 13 + 0. 25, 26 + 0. 25, and 52 + 0. 25 micro g / mL 4 - thujanol + MMC and with 13 + 28, 26 + 28, and 52 + 28 micro g / mL 4 - thujanol + CP as a mixture.", "output": "MMC, 4 - thujanol, MMC, 4 - thujanol." }, { "input": "The present study showed that 4 - thujanol was unable to reduce the genetic damage induced by MMC, in the absence of S9 mix.", "output": "4 - thujanol, MMC." }, { "input": "On the other hand, probably the metabolites of 4 - thujanol act as an antagonist and markedly antagonize CP - induced genotoxicity, in the presence of S9 mix.", "output": "4 - thujanol." }, { "input": "In general, 4 - thujanol + MMC and 4 - thujanol + CP decreased the mitotic index, proliferation index and nuclear division index to the same extent or more than those of individual exposure of MMC or CP.", "output": "4 - thujanol, MMC, 4 - thujanol, MMC." }, { "input": "In conclusion, 4 - thujanol significantly reduced ( p < 0. 001 ) the genotoxic damage induced by CP but not MMC when compared with the respective positive control alone.", "output": "4 - thujanol, MMC." }, { "input": "We can suggest that 4 - thujanol may improve the chemopreventive effects and may also reduce the harmful side effects of CP, which is widely used in chemotherapy against cancer, without reducing its antiproliferative activities.", "output": "4 - thujanol." }, { "input": "Chlorogenic acid, rutin and hyperoside content in Fragaria vesca, F. viridis and F. moschata in Lithuania.", "output": "Chlorogenic acid, rutin, hyperoside." }, { "input": "In Lithuania, two species of the genus Fragaria L.", "output": "There is no related enetity." }, { "input": "( Rosaceae ), F. vesca L. and F. viridis Weston, occur naturally in the wild and two others, F. moschata Weston and F.", "output": "There is no related enetity." }, { "input": "x ananassa Duchesne ex Rozier are found escaped from cultivation.", "output": "There is no related enetity." }, { "input": "The main objective of this study was to establish the variation pattern in the content of chlorogenic acid, rutin and hyperoside in leaves and fruits of the native Lithuanian species.", "output": "chlorogenic acid, rutin, hyperoside." }, { "input": "In this work, the chemical polymorphisms of different Fragaria species were studied by growing plants side by side under the same cultivated field conditions.", "output": "There is no related enetity." }, { "input": "F. vesca fruits had the highest rutin ( 1. 38 +/- 0. 19 mg g ( - 1 ) DM ), hyperoside ( 0. 69 +/- 0. 10 mg g ( - 1 ) DM ) and chlorogenic acid ( 2. 25 +/- 0. 34 mg g ( - 1 ) DM ) content, followed by F. viridis and F. moschata.", "output": "rutin, hyperoside, chlorogenic acid." }, { "input": "Our results showed that the leaves should be taken into account as important rutin and hyperoside contributors for strawberries.", "output": "rutin, hyperoside." }, { "input": "Bromotheoynic acid, a brominated acetylenic acid from the marine sponge Theonella swinhoei.", "output": "Bromotheoynic acid, brominated acetylenic acid." }, { "input": "A new brominated C ( 17 ) acetylenic acid ( 1 ) designated as bromotheoynic acid has been isolated from the marine sponge Theonella swinhoei, collected off the coast of Tanegashima, Kagoshima Prefecture, Japan.", "output": "brominated C ( 17 ) acetylenic acid, bromotheoynic acid." }, { "input": "The structure was determined on the basis of the analysis of its extensive 2D NMR spectroscopic data as well as HRMS.", "output": "There is no related enetity." }, { "input": "Bromotheoynic acid ( 1 ) inhibited maturation of starfish oocytes and cell division of fertilised starfish eggs.", "output": "Bromotheoynic acid." }, { "input": "Bromotheoynic acid ( 1 ) also inhibited proliferation of human leukaemia U937 and HL60 cells, human lung cancer A549 and H1299 cells, and human embryonic kidney 293 ( HEK293 ) cells.", "output": "Bromotheoynic acid." }, { "input": "Aromatic profiling of wild and rare species growing in Turkey: hypericum aviculariifolium Jaub. and Spach subsp. depilatum ( Freyn and Bornm. ) Robson var. depilatum and Hypericum pruinatum Boiss. and Bal.", "output": "There is no related enetity." }, { "input": "The volatile constituents of the rare species of Hypericum, namely Hypericum pruinatum ( as one population ) and Hypericum aviculariifolium subp. depilatum var. depilatum ( endemic, as two populations namely ' G u m u s ' and ' Yenik o y ' ) growing wild in the mountainous parts of Northern Turkey were studied for the first time.", "output": "There is no related enetity." }, { "input": "The essential oils ( EOs ) were extracted by hydrodistillation of the air - dried aerial parts and analysed by GC - FID and GC - MS.", "output": "There is no related enetity." }, { "input": "A total of 56, 49 and 50 EO components representing 98. 2 %, 96. 9 % and 99. 4 % of the total composition were identified respectively from one population for H. pruinatum and two populations for Hypericum aviculariifolium subp. depilatum var. depilatum.", "output": "There is no related enetity." }, { "input": "GC - MS profiles showed significant compositional variations not only between the two Turkish species, but also between the two populations of the same species highlighting the importance of genetic factors affecting secondary metabolite profile.", "output": "There is no related enetity." }, { "input": "Cyclo - ( His, Leu ): a new microbial diketopiperazine from a terrestrial Bacillus subtilis strain B38.", "output": "Cyclo - ( His , Leu ), diketopiperazine." }, { "input": "In continuation of our search for bioactive secondary metabolites from terrestrial Bacillus spp., a new microbial diketopiperazine, cis - cyclo - ( His, Leu ) ( 1 ) was isolated from the ethyl acetate extract of a strain B. subtilis B38, together with cis - cyclo - ( Phe, Phe ) ( 2 ), tryptophane ( 3 ), cis - cyclo - ( Leu, Tyr ) ( 4 ), cis - cyclo - ( Trp, Tyr ) ( 5 ) and macrolactin A ( 6 ).", "output": "diketopiperazine, cis - cyclo - ( His , Leu ), ethyl acetate, cis - cyclo - ( Phe , Phe ), tryptophane, cis - cyclo - ( Leu , Tyr ), cis - cyclo - ( Trp , Tyr ), macrolactin A." }, { "input": "The chemical structures of the isolated compounds were identified by comparison of their 1D, 2D NMR and HRESIMS data with authentic spectra and literatures.", "output": "There is no related enetity." }, { "input": "To the best of our knowledge, this is the first time that cyclo - ( His, Leu ) has been isolated from natural products.", "output": "cyclo - ( His , Leu )." }, { "input": "Suppression of survival signalling pathways by the phosphatase PHLPP.", "output": "There is no related enetity." }, { "input": "The recently discovered pleckstrin homology ( PH ) domain leucine - rich repeat protein phosphatase ( PHLPP ) family is emerging as a central component in suppressing cell survival pathways.", "output": "leucine." }, { "input": "Originally discovered in a rational search for a phosphatase that directly dephosphorylates and inactivates Akt, PHLPP is now known to potently suppress cell survival both by inhibiting proliferative pathways and by promoting apoptotic pathways.", "output": "There is no related enetity." }, { "input": "In the first instance, PHLPP directly dephosphorylates a conserved regulatory site ( termed the hydrophobic motif ) on Akt, protein kinase C and S6 kinase, thereby terminating signalling by these pro - survival kinases.", "output": "There is no related enetity." }, { "input": "In the second instance, PHLPP dephosphorylates and thus activates the pro - apoptotic kinase Mst1, thereby promoting apoptosis.", "output": "There is no related enetity." }, { "input": "PHLPP is deleted in a large number of cancers and the genetic deletion of one isozyme in a PTEN ( phosphatase and tensin homologue located on chromosome 1 ) + / - ( or heterozygous ) prostate cancer model results in increased tumourigenesis, underscoring the role of PHLPP as a tumour suppressor.", "output": "There is no related enetity." }, { "input": "This review summarizes the targets and cellular actions of PHLPP, with emphasis on its role as a tumour suppressor in the oncogenic phosphoinositide 3 - kinase ( PI3K ) / Akt signalling cascade.", "output": "phosphoinositide." }, { "input": "Chemical composition and antifungal activity of Artemisia nilagirica essential oil growing in northern hilly areas of India.", "output": "There is no related enetity." }, { "input": "Essential oil extracted from aerial parts of Artemisia nilagirica was analysed by gas chromatography - mass spectroscopy.", "output": "There is no related enetity." }, { "input": "Forty - three constituents amounting to 98. 16 % of the total essential oil contents were identified.", "output": "There is no related enetity." }, { "input": "The essential oil contained approximately 79. 91 % monoterpenoids and 18. 25 % sesquiterpenoids.", "output": "monoterpenoids, sesquiterpenoids." }, { "input": "alpha - Thujone ( 36. 35 % ), beta - thujone ( 9. 37 % ), germacrene D ( 6. 32 % ), 4 - terpineol ( 6. 31 % ), beta - caryophyllene ( 5. 43 % ), camphene ( 5. 47 % ) and borneol ( 4. 12 % ) were identified as the major constituents.", "output": "alpha - Thujone, beta - thujone, germacrene D, 4 - terpineol, beta - caryophyllene, camphene, borneol." }, { "input": "The essential oil exhibited significant antifungal activity against Rhizoctonia solani ( ED ( 50 ), 85. 75 mg L ( - 1 ) ), Sclerotium rolfsii ( ED ( 50 ), 87. 63 mg L ( - 1 ) ) and Macrophomina phaseolina ( ED ( 50 ), 93. 23 mg L ( - 1 ) ).", "output": "There is no related enetity." }, { "input": "This study indicated that A. nilagirica essential oil can be used to control phytopathogenic fungi infesting agricultural crops and commodities.", "output": "There is no related enetity." }, { "input": "Structural basis for the altered drug sensitivities of non - small cell lung cancer - associated mutants of human epidermal growth factor receptor.", "output": "There is no related enetity." }, { "input": "The epidermal growth factor receptor ( EGFR ) has an essential role in multiple signaling pathways, including cell proliferation and migration, through extracellular ligand binding and subsequent activation of its intracellular tyrosine kinase ( TK ) domain.", "output": "tyrosine." }, { "input": "The non - small cell lung cancer ( NSCLC ) - associated EGFR mutants, L858R and G719S, are constitutively active and oncogenic.", "output": "There is no related enetity." }, { "input": "They display sensitivity to TK inhibitors, including gefitinib and erlotinib.", "output": "gefitinib, erlotinib." }, { "input": "In contrast, the secondary mutation of the gatekeeper residue, T790M, reportedly confers inhibitor resistance on the oncogenic EGFR mutants.", "output": "There is no related enetity." }, { "input": "In this study, our biochemical analyses revealed that the introduction of the T790M mutation confers gefitinib resistance on the G719S mutant.", "output": "gefitinib." }, { "input": "The G719S / T790M double mutant has enhanced activity and retains high gefitinib - binding affinity.", "output": "gefitinib." }, { "input": "The T790M mutation increases the ATP affinity of the G719S mutant, explaining the acquired drug resistance of the double mutant.", "output": "ATP." }, { "input": "Structural analyses of the G719S / T790M double mutant, as well as the wild type and the G719S and L858R mutants, revealed that the T790M mutation stabilizes the hydrophobic spine of the active EGFR - TK conformation.", "output": "There is no related enetity." }, { "input": "The Met790 side chain of the G719S / T790M double mutant, in the apo form and gefitinib - and AMPPNP - bound forms, adopts different conformations that explain the accommodation of these ligands.", "output": "Met790, gefitinib." }, { "input": "In the L858R mutant structure, the active - site cleft is expanded by the repositioning of Phe723 within the P - loop.", "output": "Phe723." }, { "input": "Notably, the introduction of the F723A mutation greatly enhanced the gefitinib sensitivity of the wild - type EGFR in vivo, supporting our hypothesis that the expansion of the active - site cleft results in enhanced gefitinib sensitivity.", "output": "gefitinib, gefitinib." }, { "input": "Taken together, our results provide a structural basis for the altered drug sensitivities caused by distinct NSCLC - associated EGFR mutations.", "output": "There is no related enetity." }, { "input": "TGF - beta 1 - dependent L1CAM expression has an essential role in macrophage - induced apoptosis resistance and cell migration of human intestinal epithelial cells.", "output": "There is no related enetity." }, { "input": "Patients with chronic inflammatory bowel disease ( IBD ) have an increased risk to develop colorectal cancer ( CRC ) particularly after long duration of the disease.", "output": "There is no related enetity." }, { "input": "Chronic inflammation of the intestinal mucosa is characterized by a marked enrichment of immune cells such as macrophages as well as by high expression of cytokines and growth factors including transforming growth factor - beta 1 ( TGF - beta 1 ).", "output": "There is no related enetity." }, { "input": "The adhesion molecule L1CAM mediates chemoresistance and migration of tumor cells and is elevated in CRC tissues being associated with metastatic spread and poor prognosis for the patients.", "output": "There is no related enetity." }, { "input": "In this study, we examine the role of TGF - beta 1 - induced L1CAM expression and macrophages in malignant transformation of intestinal epithelial cells.", "output": "There is no related enetity." }, { "input": "We demonstrate that TGF - beta 1 stimulation leads to a Slug - dependent upregulation of L1CAM expression already in the colonic intestinal epithelial cell line NCM460 thereby enhancing cell motility and apoptosis resistance.", "output": "There is no related enetity." }, { "input": "Accordingly, NCM460 cells acquired a migratory and apoptosis - resistant phenotype if transfected with L1CAM.", "output": "There is no related enetity." }, { "input": "Immunohistochemistry of colonic biopsies revealed considerable L1CAM expression in intestinal epithelial cells in tissues from IBD patients but not in normal colonic tissues.", "output": "There is no related enetity." }, { "input": "Moreover, L1CAM expression increased with duration of disease being associated with the presence of CD33 + macrophages.", "output": "There is no related enetity." }, { "input": "Coculture with macrophages generated from monocyte colony - stimulating factor ( MCSF ) - treated monocytes led to the upregulation of Slug and L1CAM in NCM460 cells thereby elevating cell motility and apoptosis resistance.", "output": "There is no related enetity." }, { "input": "Pharmacological inhibition of TGF - beta 1 signalling abolished expression of Slug and L1CAM in cocultured NCM460 cells resulting in decreased cell migration and apoptosis resistance.", "output": "There is no related enetity." }, { "input": "In conclusion, these data provide new insights into the mechanisms by which IBD promotes malignant transformation of intestinal epithelial cells and underscore the role of L1CAM and macrophages in this scenario.", "output": "There is no related enetity." }, { "input": "Modulated release of 5 - fluorouracil from pH - sensitive and colon targeted pellets: an industrially feasible approach.", "output": "5 - fluorouracil." }, { "input": "Pellets, reliant on pH - sensitivity and time - dependency for drug delivery, provide one of the most versatile opportunities for targeting colon.", "output": "There is no related enetity." }, { "input": "5 - Fluorouracil ( 5 - FU ) loaded pellets were prepared by extrusion - spheronization using Avicel ( (R) ) PH101 as a spheronization aid and hydroxypropylmethylcellulose K4M ( HPMC K4M ) solution as a binder.", "output": "5 - Fluorouracil, 5 - FU." }, { "input": "A 3 ( 2 ) full factorial design was employed to optimize spheronization speed and time.", "output": "There is no related enetity." }, { "input": "Obtained pellets were evaluated for flow properties, pellet size, roundness and aspect ratio.", "output": "There is no related enetity." }, { "input": "Optimized batch was coated in a bottom - spray fluidized bed processor ( FBP ) with an inner coat of sustained release polymer Eudragit NE30D and an outer coat of pH - sensitive polymer Eudragit FS30D.", "output": "Eudragit NE30D, Eudragit FS30D." }, { "input": "The coating levels were statistically optimized and in vitro drug release was monitored by changing pH media method.", "output": "There is no related enetity." }, { "input": "Optimized system with 15 % inner and outer coating levels revealed t ( 50 % ) ( time required for 50 % drug release ) to be about 9 h while almost complete drug was released in 24 h ( 98. 71 +/- 1. 33 % ) with highest dissolution efficiency ( DE ( 24h ) ) of 58. 71 %.", "output": "There is no related enetity." }, { "input": "The optimization model was validated; the predicted and experimental / actual values for validation batch ( M1 ) were in close tolerance and the standard error ( SE ) was also small.", "output": "There is no related enetity." }, { "input": "Drug release was also studied at pH 7. 4.", "output": "There is no related enetity." }, { "input": "Scanning electron microscopy ( SEM ) demonstrated average coating thickness to be 32. 50 +/- 3. 0 micro m.", "output": "There is no related enetity." }, { "input": "Hence, the present study provides constructive results for colon targeting of 5 - FU pellets with industrially feasible processes.", "output": "5 - FU." }, { "input": "Conditional activation of Pik3ca ( H1047R ) in a knock - in mouse model promotes mammary tumorigenesis and emergence of mutations.", "output": "There is no related enetity." }, { "input": "Oncogenic mutations in PIK3CA, which encodes the phosphoinositide - 3 - kinase ( PI3K ) catalytic subunit p110 alpha, occur in ~ 25 % of human breast cancers.", "output": "phosphoinositide." }, { "input": "In this study, we report the development of a knock - in mouse model for breast cancer where the endogenous Pik3ca allele was modified to allow tissue - specific conditional expression of a frequently found Pik3ca ( H1047R ) ( Pik3ca ( e20H1047R ) ) mutant allele.", "output": "There is no related enetity." }, { "input": "We found that activation of the latent Pik3ca ( H1047R ) allele resulted in breast tumors with multiple histological types.", "output": "There is no related enetity." }, { "input": "Whole - exome analysis of the Pik3ca ( H1047R ) - driven mammary tumors identified multiple mutations, including Trp53 mutations that appeared spontaneously during the development of adenocarinoma and spindle cell tumors.", "output": "Trp53." }, { "input": "Further, we used this model to test the efficacy of GDC - 0941, a PI3K inhibitor, in clinical development, and showed that the tumors respond to PI3K inhibition.", "output": "GDC - 0941." }, { "input": "WNT6 is a novel target gene of caveolin - 1 promoting chemoresistance to epirubicin in human gastric cancer cells.", "output": "epirubicin." }, { "input": "Resistance to chemotherapy is a major obstacle for curative treatment of human gastric cancer ( GC ).", "output": "There is no related enetity." }, { "input": "However, the underlying molecular mechanisms are largely unknown.", "output": "There is no related enetity." }, { "input": "Wingless - type MMTV integration site family members ( WNTs ) are secreted glycoproteins involved in embryogenesis and, on inappropriate expression in the adult, in cancer.", "output": "There is no related enetity." }, { "input": "Here, we show expression of WNT6 in GC patient specimens, human GC cell lines and in a mouse model of GC.", "output": "There is no related enetity." }, { "input": "In human GC cells, WNT6 expression was enhanced by caveolin - 1 ( Cav1 ), a scaffold protein of plasma membrane caveolae.", "output": "There is no related enetity." }, { "input": "WNT6 knock - down and overexpression experiments demonstrated that WNT6 increased the resistance to apoptotic cell death induced by the anthracycline chemotherapeutics epirubicin ( Epi ) and doxorubicin ( Dox ).", "output": "anthracycline, epirubicin, Epi, doxorubicin, Dox." }, { "input": "Epi increased the activity of the human WNT6 promoter through Cav1 - dependent binding of beta - catenin to the proximal WNT6 promoter.", "output": "Epi." }, { "input": "Epi increased both WNT6 / Wnt6 and Cav1 expression in human GC cells and within the tumor area of a murine model of GC ( CEA424 - SV40 TAg ).", "output": "Epi." }, { "input": "In GC patients, WNT6 expression was positively associated with the tumor stage and the nodal status, and inversely correlated with the response to ECF ( Epi, cisplatin, 5 - fluorouracil ) chemotherapy.", "output": "Epi, cisplatin, 5 - fluorouracil." }, { "input": "These results showed that WNT6 and Cav1 are upregulated by chemotherapeutics and enhance the resistance of GC cells to anthracycline drugs.", "output": "anthracycline." }, { "input": "Understanding the molecular mechanisms driving WNT6 / Cav1 - induced drug resistance will provide benefits in developing new therapies for GC.", "output": "There is no related enetity." }, { "input": "Three new alpha - glucosidase inhibitors from guggul, the oleogum resin of Commiphora wightii.", "output": "There is no related enetity." }, { "input": "Three new compounds; epi - mukulin, ( Z ) - Delta ( 1, 2 ) dehydroguggulsterone and Delta ( 6, 7 ) dehydro - 20 - hydroxygugglsterone were isolated from the n - hexane - soluble fraction ( HSF ) of the methanol extract of guggul, the oleogum resin of Commiphora wightii together with six known compounds: diasesartemin, ( + ) - epi - magnolin, ( + ) - diayangambin, gugglsterol I, ( E ) - guggulsterone and ( Z ) - guggulsterone.", "output": "epi - mukulin, ( Z ) - Delta ( 1 , 2 ) dehydroguggulsterone, Delta ( 6 , 7 ) dehydro - 20 - hydroxygugglsterone, n - hexane, methanol, diasesartemin, ( + ) - epi - magnolin, ( + ) - diayangambin, gugglsterol I, ( E ) - guggulsterone, ( Z ) - guggulsterone." }, { "input": "Their structures were elucidated on the basis of different spectroscopic data.", "output": "There is no related enetity." }, { "input": "alpha - Glucosidase inhibitory effects of HSF and the isolated compounds were evaluated calorimetrically.", "output": "There is no related enetity." }, { "input": "The HSF showed significant alpha - glucosidase inhibitory effect [ IC ( 50 ) value of 140 micro g mL ( - 1 ) ( p < 0. 05 ) ].", "output": "There is no related enetity." }, { "input": "Under the assay conditions, diasesartemin ( IC ( 50 ) = 60. 6 +/- 0. 01 micro M ) was found to be more potent than the positive control, acarbose ( IC ( 50 ) = 92. 94 +/- 0. 01 micro M ); a known alpha - glucosidase inhibitor ( p < 0. 05 ).", "output": "diasesartemin, acarbose." }, { "input": "The IC ( 50 ) values of epi - mukulin and ( Z ) - guggulsterone were found to be 159. 33 and 132. 14 micro M, respectively.", "output": "epi - mukulin, ( Z ) - guggulsterone." }, { "input": "Other compounds showed weak alpha - glucosidase inhibitory effects, < 30 % inhibition of the enzyme activity at 0. 1 mg mL ( - 1 ).", "output": "There is no related enetity." }, { "input": "Chemical constituents of Indonesian plant Protium javanicum Burm.", "output": "There is no related enetity." }, { "input": "f. and their antifeedant activities against Coptotermes formosanus Shiraki.", "output": "There is no related enetity." }, { "input": "In the continuing study of antifeedant compounds in Protium javanicum Burm.", "output": "There is no related enetity." }, { "input": "f. against Coptotermes formosanus Shiraki, 6 - desacetylnimbin ( 1 ), quercitrin ( 2 ) and myricitrin ( 3 ) were isolated from P. javanicum extract.", "output": "6 - desacetylnimbin, quercitrin, myricitrin." }, { "input": "All compounds were characterised by NMR and MS.", "output": "There is no related enetity." }, { "input": "Furthermore, the structure of 6 - desacetylnimbin was confirmed by X - ray crystallography.", "output": "6 - desacetylnimbin." }, { "input": "The antifeedant activity was evaluated with no - choice feeding tests.", "output": "There is no related enetity." }, { "input": "At a dose of 0. 5 mg, 6 - desacetylnimbin exhibited the highest antifeedant activity among the isolates.", "output": "6 - desacetylnimbin." }, { "input": "Tumor angiogenesis is enforced by autocrine regulation of high - mobility group box 1.", "output": "There is no related enetity." }, { "input": "The endothelium plays a pivotal role in the progression of solid tumors and is considered a highly relevant target for therapy.", "output": "There is no related enetity." }, { "input": "However, it emerges that current clinical angiogenesis inhibitors that act through inhibition of tumor - derived growth factors are prone to inducing drug resistance.", "output": "There is no related enetity." }, { "input": "Therefore, markers of tumor endothelial cells ( ECs ) themselves provide attractive novel therapeutic targets.", "output": "There is no related enetity." }, { "input": "In a screen for markers of tumor angiogenesis, we recently identified high - mobility group box 1 ( HMGB1 ), known to act as proinflammatory cytokine and chromatin - binding molecule.", "output": "There is no related enetity." }, { "input": "Here we report on the role of HMGB1 in angiogenesis by showing that its overexpression is associated with an increased angiogenic potential of ECs.", "output": "There is no related enetity." }, { "input": "HMGB1 stimulates the expression of players in vascular endothelial growth factor and platelet - derived growth factor signaling, both in vitro and in vivo.", "output": "There is no related enetity." }, { "input": "Importantly, we show that HMGB1 triggers and helps to sustain this proangiogenic gene expression program in ECs, additionally characterized by increased activity of matrix metalloproteinases, integrins and nuclear factor - kappa B.", "output": "There is no related enetity." }, { "input": "Moreover, we found that HMGB1 is involved in several autocrine and / or paracrine feedback mechanisms resulting in positive enforcement of HMGB1 expression, and that of its receptors, RAGE ( receptor for advanced glycation end products ) and Toll - like receptor 4 ( TLR4 ).", "output": "There is no related enetity." }, { "input": "Interference in HMGB1 expression and / or function using knockdown approaches and antibody - mediated targeting to break this vicious circle resulted in inhibited migration and sprouting of ECs.", "output": "There is no related enetity." }, { "input": "Using different in vivo models, therapeutic efficacy of HMGB1 targeting was confirmed.", "output": "There is no related enetity." }, { "input": "First, we demonstrated induction of HMGB1 expression in the chicken embryo chorioallantoic membrane ( CAM ) neovasculature following both photodynamic therapy and tumor challenge.", "output": "There is no related enetity." }, { "input": "We subsequently showed that anti - HMGB1 antibodies inhibited vessel density in both models, accompanied by a reduced vascular expression of angiogenic growth factor receptors.", "output": "There is no related enetity." }, { "input": "Collectively, these data identify HMGB1 as an important modulator of tumor angiogenesis and suggest the feasibility of targeting HMGB1 for multi - level cancer treatment.", "output": "There is no related enetity." }, { "input": "Histone deacetylase inhibitors suppress mutant p53 transcription via histone deacetylase 8.", "output": "There is no related enetity." }, { "input": "Mutation of the p53 gene is the most common genetic alteration in human cancer and contributes to malignant process by enhancing transformed properties of cells and resistance to anticancer therapy.", "output": "There is no related enetity." }, { "input": "Mutant p53 is often highly expressed in tumor cells at least, in part, due to its increased half - life.", "output": "There is no related enetity." }, { "input": "However, whether mutant p53 expression is regulated by other mechanisms in tumors is unclear.", "output": "There is no related enetity." }, { "input": "Here we found that histone deacetylase ( HDAC ) inhibitors suppress both wild - type and mutant p53 transcription in time - and dose - dependent manners.", "output": "There is no related enetity." }, { "input": "Consistent with this, the levels of wild - type and mutant p53 proteins are decreased upon treatment with HDAC inhibitors.", "output": "There is no related enetity." }, { "input": "Importantly, we found that upon knockdown of each class I HDAC, only HDAC8 knockdown leads to decreased expression of wild - type and mutant p53 proteins and transcripts.", "output": "There is no related enetity." }, { "input": "Conversely, we found that ectopic expression of wild - type, but not mutant HDAC8, leads to increased transcription of p53.", "output": "There is no related enetity." }, { "input": "Furthermore, we found that knockdown of HDAC8 results in reduced expression of HoxA5 and consequently, attenuated ability of HoxA5 to activate p53 transcription, which can be rescued by ectopic expression of HoxA5.", "output": "There is no related enetity." }, { "input": "Because of the fact that HDAC8 is required for expression of both wild - type and mutant p53, we found that targeted disruption of HDAC8 expression remarkably triggers proliferative defect in cells with a mutant, but not wild - type, p53.", "output": "There is no related enetity." }, { "input": "Together, our data uncover a regulatory mechanism of mutant p53 transcription via HDAC8 and suggest that HDAC inhibitors and especially HDAC8 - targeting agents might be explored as an adjuvant for tumors carrying a mutant p53.", "output": "There is no related enetity." }, { "input": "microRNA - 125b inhibits tube formation of blood vessels through translational suppression of VE - cadherin.", "output": "There is no related enetity." }, { "input": "Angiogenesis is controlled positively or negatively by extrinsic and intrinsic molecular cues in endothelial cells ( ECs ); in the tumor microenvironment, the action of positive regulators exceeds that of negative regulators.", "output": "There is no related enetity." }, { "input": "Thus, overinduction of negative regulators may inhibit tumor angiogenesis.", "output": "There is no related enetity." }, { "input": "MicroRNAs ( miRNAs or miRs ) are endogenous short noncoding RNAs regulating gene expression either through translational inhibition or destabilization of target mRNA.", "output": "There is no related enetity." }, { "input": "Here, we show that miR - 125b expression is transiently induced in ECs on stimulation with vascular endothelial growth factor or by ischemia.", "output": "There is no related enetity." }, { "input": "miR - 125b inhibits translation of vascular endothelial ( VE ) - cadherin mRNA and in vitro tube formation by ECs.", "output": "There is no related enetity." }, { "input": "Injection of miR - 125b into the tumor inhibited VE - cadherin expression by ECs and induced nonfunctional blood vessel formation, resulting in inhibition of tumor growth.", "output": "There is no related enetity." }, { "input": "It has been suggested that pro - angiogenic signals in ECs also upregulate anti - angiogenic molecules simultaneously via negative feedback.", "output": "There is no related enetity." }, { "input": "Because miR - 125b induction in ECs is transient after pro - angiogenic stimulation, prolonged overexpression of miR - 125b could result in blood vessel regression.", "output": "There is no related enetity." }, { "input": "Thus, miR - 125b may be useful in cancer therapy by causing the collapse of the lumen of ECs.", "output": "There is no related enetity." }, { "input": "Chemical constituents comparison between Rhizoma Smilacis Glabrae and Rhizoma Smilacis Chinae by HPLC - DAD - MS / MS.", "output": "There is no related enetity." }, { "input": "Rhizoma Smilacis Glabrae ( RSG ) and Rhizoma Smilacis Chinae ( RSC ) are two herbal materials that belong to the same genera and are both listed in the Chinese Pharmacopoeia.", "output": "There is no related enetity." }, { "input": "Chemical constituents in the two species were compared by HPLC - DAD - MS / MS.", "output": "There is no related enetity." }, { "input": "Many common constituents were found in both species, including shikimic acid, 5 - O - caffeoylshikimic acid, trans - resveratrol, taxifolin, astilbin and its three stereoisomers, engeletin and isoengeletin.", "output": "shikimic acid, 5 - O - caffeoylshikimic acid, trans - resveratrol, taxifolin, astilbin, engeletin, isoengeletin." }, { "input": "However, syringic acid was found only in RSG, while chlorogenic acid was found only in RSC.", "output": "syringic acid, chlorogenic acid." }, { "input": "Gonadal hormones and the control of reactive gliosis.", "output": "There is no related enetity." }, { "input": "Astrocytes and microglia respond to central nervous system ( CNS ) injury with changes in morphology, proliferation, migration and expression of inflammatory regulators.", "output": "There is no related enetity." }, { "input": "This phenomenon is known as reactive gliosis.", "output": "There is no related enetity." }, { "input": "Activation of astrocytes and microglia after acute neural insults, such as stroke or traumatic CNS injury, is considered to be an adaptive response that contributes to minimize neuronal damage.", "output": "There is no related enetity." }, { "input": "However, reactive gliosis may amplify CNS damage under chronic neurodegenerative conditions.", "output": "There is no related enetity." }, { "input": "Progesterone, estradiol and testosterone have been shown to control reactive gliosis in different models of CNS injury, modifying the number of reactive astrocytes and reactive microglia and the expression of anti - inflammatory and proinflammatory mediators.", "output": "Progesterone, estradiol, testosterone." }, { "input": "The actions of gonadal hormones on reactive gliosis involve different mechanisms, including the modulation of the activity of steroid receptors, such as estrogen receptors alpha and beta, the regulation of nuclear factor - kappa B mediated transcription of inflammatory molecules and the recruitment of the transcriptional corepressor c - terminal binding protein to proinflammatory promoters.", "output": "steroid, estrogen." }, { "input": "In addition, the Parkinson ' s disease related gene parkin and the endocannabinoid system also participate in the regulation of reactive gliosis by estradiol.", "output": "estradiol." }, { "input": "The control exerted by gonadal hormones on reactive gliosis may affect the response of neural tissue to trauma and neurodegeneration and may contribute to sex differences in the manifestation of neurodegenerative diseases.", "output": "There is no related enetity." }, { "input": "However, the precise functional consequences of the regulation of reactive gliosis by gonadal hormones under acute and chronic neurodegenerative conditions are still not fully clarified.", "output": "There is no related enetity." }, { "input": "A 90 - day oral ( dietary ) toxicity study of arruva, an R, R - monatin salt isomer, in Crl: CD - 1 ( ICR ) mice.", "output": "arruva, R , R - monatin." }, { "input": "R, R - Monatin [ 2R, 4R - isomer of 2 - hydroxy - 2 - ( indol - 3 - ylmethyl ) - 4 - aminoglutaric acid ] is one of four natural constituent isomers in the root bark of Sclerochitin ilicifolius; and \" arruva \" is the common / usual name that is proposed to represent R, R - monatin salt forms, which have potential use as high potency sweetener food ingredients.", "output": "R , R - Monatin, 2R , 4R - isomer of 2 - hydroxy - 2 - ( indol - 3 - ylmethyl ) - 4 - aminoglutaric acid, arruva, R , R - monatin." }, { "input": "In the present study, groups of male and female Crl: CD - 1 ( ICR ) mice were exposed to 0 ( control ), 5000, 10, 000, 20, 000, or 35, 000ppm of arruva in the diet for 90days.", "output": "arruva." }, { "input": "There were no toxicologically relevant clinical or histopathological findings in any of the test article - treated groups.", "output": "There is no related enetity." }, { "input": "Significantly lower mean body weights and cumulative body weight gains were noted in the 35, 000ppm group when compared to the control group.", "output": "There is no related enetity." }, { "input": "Mean body weights in the 35, 000ppm group males and females were 9 % and 7 % less than the control group, respectively, at week 13.", "output": "There is no related enetity." }, { "input": "In the absence of observations associated with systemic toxicity and in consideration of the magnitude of body weight difference, these effects were not considered toxicologically significant.", "output": "There is no related enetity." }, { "input": "Based on the results of this study, the dietary no - observed - adverse - effect level ( NOAEL ) of arruva for 90days in male and female mice was 35, 000ppm ( equivalent to an exposure level of 5764 and 8013mg / kg bw / day, respectively ).", "output": "arruva." }, { "input": "Grewialin and optivanin new constituents from the stem bark of Grewia optiva Drummond ex Burret ( Tiliaceae ).", "output": "Grewialin, optivanin." }, { "input": "Studies on the chemical constituents from the stem bark of Grewia optiva have led to the isolation of two new compounds, grewialin ( 1 ) and optivanin ( 2 ), along with three known constituents which were hitherto unreported from this species.", "output": "grewialin, optivanin." }, { "input": "The structures of the new constituents have been elucidated by spectral studies including 1D and 2D NMR experiments ( HSQC, HMBC, COSY, NOESY and J - resolved ) as well as HR EI - MS spectroscopic data analysis, as 2S * - ( 3 - hydroxy - 4 - methoxyphenyl ) - 3R * - methyl - 2H - [ 1, 4 ] - dioxin [ 2, 3 ] - chromen - 7 ( 3H ) - one ( 1 ); a coumarinolignan and 3 - hydroxy - 1 - ( 3 - hydroxy - 4 - methoxyphenyl ) propan - 1 - one ( 2 ).", "output": "2S * - ( 3 - hydroxy - 4 - methoxyphenyl ) - 3R * - methyl - 2H - [ 1 , 4 ] - dioxin [ 2 , 3 ] - chromen - 7 ( 3H ) - one, coumarinolignan, 3 - hydroxy - 1 - ( 3 - hydroxy - 4 - methoxyphenyl ) propan - 1 - one." }, { "input": "The known compounds were identified as beta - sitosterol, stigmasterol and lupeol by comparing their spectral data with those reported in the literature.", "output": "beta - sitosterol, stigmasterol, lupeol." }, { "input": "Berberine inhibits myofibroblast differentiation in nasal polyp - derived fibroblasts via the p38 pathway.", "output": "Berberine." }, { "input": "The purposes of this study were to determine whether berberine has any effect on phenotype changes and extracellular matrix ( ECM ) production in nasal polyp - derived fibroblasts ( NPDFs ) and to investigate the underlying molecular mechanism.", "output": "berberine." }, { "input": "NPDFs were pre - treated with berberine prior to induction by transforming growth factor ( TGF ) - beta 1.", "output": "berberine." }, { "input": "The expression of alpha - smooth muscle actin ( SMA ) and collagen type I mRNA was determined by a reverse transcription - polymerase chain reaction, and the expression of alpha - SMA protein and collagen type I was determined by western blotting and / or immunofluorescent staining.", "output": "There is no related enetity." }, { "input": "The total soluble collagen production was analysed by the SirCol collagen assay.", "output": "There is no related enetity." }, { "input": "The expression of several signaling molecules of the TGF - beta 1 pathway was evaluated by western blot analysis.", "output": "There is no related enetity." }, { "input": "In TGF - beta 1 - induced NPDFs, berberine significantly inhibited the expression of alpha - SMA and collagen type I mRNA and reduced alpha - SMA and collagen protein levels.", "output": "berberine." }, { "input": "Berberine only suppressed the expression of pp38 among the evaluated signaling molecules.", "output": "Berberine." }, { "input": "SB203580 ( a specific inhibitor of p38 kinase ) markedly suppressed the increased expression of collagen type I and alpha - SMA in TGF - beta 1 - induced NPDFs.", "output": "SB203580." }, { "input": "Berberine exerts suppressive effects on phenotype changes and ECM production in NPDFs via p38 signaling pathway interference.", "output": "Berberine." }, { "input": "The findings provide new therapeutic options for ECM production in nasal polyps.", "output": "There is no related enetity." }, { "input": "The nonhematopoietic effects of erythropoietin in skin regeneration and repair: from basic research to clinical use.", "output": "There is no related enetity." }, { "input": "Erythropoietin ( EPO ) is the main regulator of red blood cell production but there exists also a variety of nonhematopoietic properties.", "output": "There is no related enetity." }, { "input": "More recent data show that EPO is also associated with the protection of tissues suffering from ischemia and reperfusion injury as well as with improved regeneration in various organ systems, in particular the skin.", "output": "There is no related enetity." }, { "input": "This review highlights the mechanisms of EPO in the different stages of wound healing and the reparative processes in the skin emphasizing pathophysiological mechanisms and potential clinical applications.", "output": "There is no related enetity." }, { "input": "There is clear evidence that EPO effectively influences all wound - healing phases in a dose - dependent manner.", "output": "There is no related enetity." }, { "input": "This includes inflammation, tissue, and blood vessel formation as well as the remodeling of the wound.", "output": "There is no related enetity." }, { "input": "The molecular mechanism is predominantly based on an increased expression of the endothelial and inducible nitric oxide ( NO ) synthase with a consecutive rapid supply of NO as well as an increased content of vascular endothelial growth factor ( VEGF ) in the wound.", "output": "nitric oxide, NO, NO." }, { "input": "The improved understanding of the functions and regulatory mechanisms of EPO in the context of wound - healing problems and ischemia / reperfusion injury, especially during flap surgery, may lead to new considerations of this growth hormone for its regular clinical application in patients.", "output": "There is no related enetity." }, { "input": "Essential oils composition of Periploca laevigata Aiton subsp. angustifolia ( Labill. ) Markgraf ( Apocynaceae - Periplocoideae ).", "output": "There is no related enetity." }, { "input": "The essential oil of roots, branches, leaves, flowers and fruits of Periploca laevigata Aiton subsp. angustifolia ( Apocynaceae ) from Lampedusa Island has been obtained by hydrodistillation and its composition analysed.", "output": "There is no related enetity." }, { "input": "The analyses allowed the identification and quantification of 86 volatile compounds.", "output": "There is no related enetity." }, { "input": "Branches showed the higher diversity with 57 compounds followed by fruits with 33, roots with 23, flowers with 16 and leaves with six compounds, respectively.", "output": "There is no related enetity." }, { "input": "In the matrices examined three constituents, heneicosane, docosane and tricosane are in common, although with different percentages.", "output": "heneicosane, docosane, tricosane." }, { "input": "At least the most abundant compounds found in the matrices have been reported to have several biological activities.", "output": "There is no related enetity." }, { "input": "2 - Hydroxy - 4 - methoxybenzaldehyde identified in the roots as the most abundant component ( 70. 7 % ) and present with 8. 3 % in the branches is a potent tyrosinase inhibitor present in several African medicinal plants, and thus being used as an ingredient in cosmetic and other medicinal products, primarily in relation to hyperpigmentation.", "output": "2 - Hydroxy - 4 - methoxybenzaldehyde." }, { "input": "Among the compounds identified, several play a role as semiochemicals for many animals, and 28 allomones, 43 pheromones, 21 kairomones have been identified.", "output": "There is no related enetity." }, { "input": "P. laevigata subsp. angustifolia in Lampedusa Island is host to a community of visitors, and the possible ecological role of the volatiles found is briefly discussed.", "output": "There is no related enetity." }, { "input": "P21 - activated kinase 4 ( PAK4 ) is required for metaphase spindle positioning and anchoring.", "output": "There is no related enetity." }, { "input": "The oncogenic kinase PAK4 was recently found to be involved in the regulation of the G1 phase and the G2 / M transition of the cell cycle.", "output": "There is no related enetity." }, { "input": "We have also identified that PAK4 regulates Ran GTPase activity during mitosis.", "output": "There is no related enetity." }, { "input": "Here, we show that after entering mitosis, PAK4 - depleted cells maintain a prolonged metaphase - like state.", "output": "There is no related enetity." }, { "input": "In these cells, chromosome congression to the metaphase plate occurs with normal kinetics but is followed by an extended period during which membrane blebbing and spindle rotation are observed.", "output": "There is no related enetity." }, { "input": "These bipolar PAK4 - depleted metaphase - like spindles have a defective astral microtubule ( MT ) network and are not centered in the cell but are in close contact with the cell cortex.", "output": "There is no related enetity." }, { "input": "As the metaphase - like state persists, centrosome fragmentation occurs, chromosomes scatter from the metaphase plate and move toward the spindle poles with an active spindle assembly checkpoint, a phenotype that is reminiscent of cohesion fatigue.", "output": "There is no related enetity." }, { "input": "PAK4 also regulates the acto - myosin cytoskeleton and we report that PAK4 depletion results in the induction of cortical membrane blebbing during prometaphase arrest.", "output": "There is no related enetity." }, { "input": "However, we show that membrane blebs, which are strongly enriched in phospho - cofilin, are not responsible for the poor anchoring of the spindle.", "output": "phospho." }, { "input": "As PAK4 depletion interferes with the localization of components of the dynein / dynactin complexes at the kinetochores and on the astral MTs, we propose that loss of PAK4 could induce a change in the activities of motor proteins.", "output": "There is no related enetity." }, { "input": "The anxiolytic potential and psychotropic side effects of an echinacea preparation in laboratory animals and healthy volunteers.", "output": "There is no related enetity." }, { "input": "We investigated the toxicity, psychotropic side effects and anxiolytic potential of an Echinacea angustifolia extract that produced promising effects in laboratory tests performed earlier.", "output": "There is no related enetity." }, { "input": "Rats were studied in the elevated plus - maze, conditioned fear, open - field, object recognition and conditioned place preference tests.", "output": "There is no related enetity." }, { "input": "Toxicity was studied in rats after intragastric administration.", "output": "There is no related enetity." }, { "input": "The preparation decreased anxiety in the elevated plus - maze and ameliorated contextual conditioned fear.", "output": "There is no related enetity." }, { "input": "No lethality or behavioural signs of discomfort were noticed in rats treated with 1000 and 3000 mg / kg Echinacea angustifolia.", "output": "There is no related enetity." }, { "input": "The extract was without effect in tests of locomotion ( open - field ), memory ( object recognition ) and rewarding potential ( conditioned place preference ) within a wide dose range.", "output": "There is no related enetity." }, { "input": "A pharmacological formulation based on the same E. angustifolia extract was tested in human subjects.", "output": "There is no related enetity." }, { "input": "One or two tablets per day were administered for 1 week to healthy volunteers scoring high on the State - Trait Anxiety Inventory ( STAI ).", "output": "There is no related enetity." }, { "input": "The tablets contained 20 mg of the plant extract.", "output": "There is no related enetity." }, { "input": "Data were collected using a structured self - assessment diary technique.", "output": "There is no related enetity." }, { "input": "The high dose ( 2 tablets per day ) decreased STAI scores within 3 days in human subjects, an effect that remained stable for the duration of the treatment ( 7 days ) and for the 2 weeks that followed treatment.", "output": "There is no related enetity." }, { "input": "The lower dose ( 1 tablet per day ) did not affect anxiety significantly.", "output": "There is no related enetity." }, { "input": "Antitrypanosomal properties of Panax ginseng C.", "output": "There is no related enetity." }, { "input": "A.", "output": "There is no related enetity." }, { "input": "Meyer: new possibilities for a remarkable traditional drug.", "output": "There is no related enetity." }, { "input": "African trypanosomiasis is still a major health problem in many sub - Saharan countries in Africa.", "output": "There is no related enetity." }, { "input": "We investigated the effects of three preparations of Panax ginseng, Panax notoginseng, isolated ginsenosides, and the polyacetylene panaxynol on Trypanosoma brucei brucei and the human cancer cell line HeLa.", "output": "ginsenosides, polyacetylene, panaxynol." }, { "input": "Hexane extracts and the pure panaxynol were toxic and at the same time highly selective against T.", "output": "Hexane, panaxynol." }, { "input": "b. brucei, whereas methanol extracts and 12 isolated ginsenosides were significantly less toxic and showed only weak selectivity.", "output": "methanol, ginsenosides." }, { "input": "Panaxynol was cytotoxic against T.", "output": "Panaxynol." }, { "input": "b. brucei at the concentration of 0. 01 micro g / mL with a selectivity index of 858, superior even to established antitrypanosomal drugs.", "output": "There is no related enetity." }, { "input": "We suggest that the inhibition of trypanothione reductase, which is only found in trypanosomes, might explain the observed selectivity.", "output": "trypanothione." }, { "input": "The high selectivity together with a cytotoxic concentration in the range of the bioavailability makes panaxynol and other polyacetylenes in general very promising lead compounds for the treatment of African trypanosomiasis.", "output": "panaxynol, polyacetylenes." }, { "input": "Androgenic and spermatogenic activity of alkylamide - rich ethanol solution extract of Anacyclus pyrethrum DC.", "output": "alkylamide, ethanol." }, { "input": "Anacyclus pyrethrum ( A. pyrethrum ) has been used as Vajikaran Rasayana ( aphrodisiac ) in traditional Indian ayurvedic medicine to treat male sexual dysfunction, including infertility.", "output": "There is no related enetity." }, { "input": "Aphrodisiac activity may be due to an increase in the production or effect of androgens, so this study sought to evaluate the androgenic and spermatogenic potential of the alkylamide - rich ethanol solution extract.", "output": "androgens, alkylamide, ethanol." }, { "input": "Male Wistar strain rats weighing between 150 and 180 g were completely randomized divided into five groups.", "output": "There is no related enetity." }, { "input": "The ethanol solution extract of A. pyrethrum was administered to groups of rats in 50, 100, and 150 mg / kg doses for a period of 28 days, and the action was compared with control and testosterone - treated rats.", "output": "ethanol, testosterone." }, { "input": "Thirteen N - alkylamides were detected in the extract by using HPLC / UV / electrospray ionization mass spectrometry method.", "output": "N - alkylamides." }, { "input": "Extract administration at all the doses produced significant increase in body weight, sperm count, motility, and viability along with serum testosterone, luteinizing hormone, and follicle - stimulating hormone concentrations.", "output": "testosterone." }, { "input": "Histoarchitecture of testis revealed increased spermatogenic activities.", "output": "There is no related enetity." }, { "input": "Seminal fructose content was also significantly increased after 28 days of treatment.", "output": "fructose." }, { "input": "Our results suggest that the ethanol solution extract of the roots of A. pyrethrum has androgenic potential and may improve male fertility by enhancing spermatogenesis.", "output": "ethanol." }, { "input": "eIF4F suppression in breast cancer affects maintenance and progression.", "output": "There is no related enetity." }, { "input": "Levels of eukaryotic initiation factor 4E ( eIF4E ) are frequently elevated in human cancers and in some instances have been associated with poor prognosis and outcome.", "output": "There is no related enetity." }, { "input": "Here we utilize transgenic and allograft breast cancer models to demonstrate that increased mammalian target of rapamycin ( mTOR ) signalling can be a significant contributor to breast cancer progression in vivo.", "output": "rapamycin." }, { "input": "Suppressing mTOR activity, as well as levels and activity of the downstream translation regulators, eIF4E and eIF4A, delayed breast cancer progression, onset of associated pulmonary metastasis in vivo and breast cancer cell invasion and migration in vitro.", "output": "There is no related enetity." }, { "input": "Translation of vascular endothelial growth factor ( VEGF ), matrix metallopeptidase 9 ( MMP9 ) and cyclin D1 mRNAs, which encode products associated with the metastatic phenotype, is inhibited upon eIF4E suppression.", "output": "There is no related enetity." }, { "input": "Our results indicate that the mTOR / eIF4F axis is an important contributor to tumor maintenance and progression programs in breast cancer.", "output": "There is no related enetity." }, { "input": "Targeting this pathway may be of therapeutic benefit.", "output": "There is no related enetity." }, { "input": "Actions of Xanthurenic acid, a putative endogenous Group II metabotropic glutamate receptor agonist, on sensory transmission in the thalamus.", "output": "Xanthurenic acid, glutamate." }, { "input": "Xanthurenic acid ( XA ), a molecule arising from tryptophan metabolism by transamination of 3 - hydroxykynurenine, has recently been identified as an endogenous Group II ( mGlu2 and mGlu3 ) metabotropic glutamate ( mGlu ) receptor ligand in vitro.", "output": "Xanthurenic acid, tryptophan, 3 - hydroxykynurenine, glutamate." }, { "input": "Impairments in Group II mGlu receptor expression and function have been implicated in the pathophysiology of schizophrenia, as have multiple steps in the kynurenine metabolism pathway.", "output": "kynurenine." }, { "input": "Therefore, we examined XA in vivo to further investigate its potential as a Group II mGlu receptor ligand using a preparation that has been previously demonstrated to efficiently reveal the action of other Group II mGlu receptor ligands in vivo.", "output": "There is no related enetity." }, { "input": "Extracellular single - neurone recordings were made in the rat ventrobasal thalamus ( VB ) in conjunction with iontophoresis of agonists, an antagonist and a positive allosteric modulator and / or intravenous ( i. v. ) injection of XA.", "output": "There is no related enetity." }, { "input": "We found the XA effect on sensory inhibition, when applied iontophoretically and i. v., was similar to that of other Group II mGlu receptor agonists in reducing inhibition evoked in the VB from the thalamic reticular nucleus upon physiological sensory stimulation.", "output": "There is no related enetity." }, { "input": "Furthermore, we postulate that XA may be the first potential endogenous allosteric agonist ( termed ' endocoid ' ) for the mGlu receptors.", "output": "There is no related enetity." }, { "input": "As the Group II receptors and kynurenine metabolism pathway have both been heavily implicated in the pathophysiology of schizophrenia, XA could play a pivotal role in antipsychotic research as this potential endocoid represents both a convergence within these two biological parameters and a novel class of Group II mGlu receptor ligand.", "output": "kynurenine." }, { "input": "This article is part of a Special Issue entitled ' Metabotropic Glutamate Receptors '.", "output": "Glutamate." }, { "input": "Sol - flame synthesis: a general strategy to decorate nanowires with metal oxide / noble metal nanoparticles.", "output": "metal oxide." }, { "input": "The hybrid structure of nanoparticle - decorated nanowires ( NP @ NW ) combines the merits of large specific surface areas for NPs and anisotropic properties for NWs and is a desirable structure for applications including batteries, dye - sensitized solar cells, photoelectrochemical water splitting, and catalysis.", "output": "There is no related enetity." }, { "input": "Here, we report a novel sol - flame method to synthesize the NP @ NW hybrid structure with two unique characteristics: ( 1 ) large loading of NPs per NW with the morphology of NP chains fanning radially from the NW core and ( 2 ) intimate contact between NPs and NWs.", "output": "There is no related enetity." }, { "input": "Both features are advantageous for the above applications that involve both surface reactions and charge transport processes.", "output": "There is no related enetity." }, { "input": "Moreover, the sol - flame method is simple and general, with which we have successfully decorated various NWs with binary / ternary metal oxide and even noble metal NPs.", "output": "metal oxide." }, { "input": "The unique aspects of the sol - flame method arise from the ultrafast heating rate and the high temperature of flame, which enables rapid solvent evaporation and combustion, and the combustion gaseous products blow out NPs as they nucleate, forming the NP chains around NWs.", "output": "There is no related enetity." }, { "input": "Improving oral absorption via drug - loaded nanocarriers: absorption mechanisms, intestinal models and rational fabrication.", "output": "There is no related enetity." }, { "input": "Although it is acknowledged that the main impediment of orally administered therapeutic agents is their extensive and changeable pre - systemic metabolism, low absorption and instability in harsh environment of the gastrointestinal ( GI ) tract are also main influential factors, resulting into inadequate and erratic drug bioavailability.", "output": "There is no related enetity." }, { "input": "To overcome these shortcomings, nanotechnology has offered new promising strategies to prevent and treat a wide variety of diseases by employing different oral drug - carrier structures capable to enhance therapeutic effects and minimize the toxicity of healthy organs or cells.", "output": "There is no related enetity." }, { "input": "This review, in general, elucidates some considerable features of in vitro oral drug delivery in three different parts.", "output": "There is no related enetity." }, { "input": "The first one summarizes the main challenges for oral drug delivery and available absorption mechanisms.", "output": "There is no related enetity." }, { "input": "The second part embodies an in - depth discussion on the role of the intestinal absorption models used to predict permeability, cellular uptake or even toxicity of nanoparticles, resulting into the design of nanocarriers with optimum efficacy for oral delivery.", "output": "There is no related enetity." }, { "input": "The third section of the literature is devoted, more particularly, to nanocarriers developed for oral absorption in the past few years, including the behavior of nanovehicles upon oral administration with respect to membrane permeability, retention properties and stability, as well as methods which may lengthen residence time in the GI environment or improve drug absorption.", "output": "There is no related enetity." }, { "input": "Precision - cut intestinal slices as in vitro tool for studies on drug metabolism.", "output": "There is no related enetity." }, { "input": "The role of the intestine in drug metabolism has long been underestimated as a consequence of the technical difficulty to discern the role of the intestine from that of the liver in in vivo experiments and of the lack of in vitro models that are sufficiently viable and fully representing the physiology and anatomy of the intestine.", "output": "There is no related enetity." }, { "input": "Recently the precision - cut slice model, which is widely used for liver and kidney, was also adapted for the small and large intestine.", "output": "There is no related enetity." }, { "input": "In this review the application of precision - cut intestinal slices ( PCIS ) for research in drug metabolism and transport is discussed.", "output": "There is no related enetity." }, { "input": "PCIS can be prepared from animal and human tissues from all regions of the intestine allowing investigation of species differences and regional gradients of activities of metabolizing enzymes.", "output": "There is no related enetity." }, { "input": "They are viable for 8 - 24 h of incubation and show high activity of drug metabolizing enzymes, representative for the in vivo activity.", "output": "There is no related enetity." }, { "input": "They have been successfully used to study drug - drug interactions such as induction, inhibition and regulation of drug metabolizing enzymes, transporters and nuclear factors.", "output": "There is no related enetity." }, { "input": "Moreover they appear to be a suitable model for studies on cold preservation of donor organs for transplantation, and allow exploring inter - organ interactions by co - incubation with precision - cut slices of other organs.", "output": "There is no related enetity." }, { "input": "Their application as model for drug - induced intestinal toxicity is still in its infancy but appears to be promising.", "output": "There is no related enetity." }, { "input": "PCIS, prepared from human and animal tissues, represent a powerful translational model for drug metabolism, transport and toxicity studies and as such contributes to the reduction and replacement of animal experiments.", "output": "There is no related enetity." }, { "input": "Topical antiinflammatory activity of essential oil of Lippia sidoides cham: possible mechanism of action.", "output": "There is no related enetity." }, { "input": "This work reports the chemical composition of the essential oil of Lippia sidoides ( EOLS ) and evaluation of the topical effect of EOLS and thymol against different irritant agents in vivo.", "output": "thymol." }, { "input": "The essential oil was obtained by hydrodistillation, and gas chromatography / mass spectrometry analysis identified the main constituents: thymol ( 84. 9 % ) and p - cymene ( 5. 33 % ).", "output": "thymol, p - cymene." }, { "input": "The antiinflammatory activity was evaluated using the mouse models of acute ear inflammation induced by croton oil, arachidonic acid, phenol or histamine, and chronic inflammation induced by croton oil.", "output": "arachidonic acid, phenol, histamine." }, { "input": "The topical application of EOLS or thymol at a dose of 2 mg / ear significantly reduced ( p < 0. 001 ) ear edema induced with arachidonic acid by 45. 1 % and 47. 4 % and reduced ear edema induced with phenol by 33. 2 % ( p < 0. 05 ) and 54. 7 % ( p < 0. 01 ) in acute ear edema.", "output": "thymol, arachidonic acid, phenol." }, { "input": "However, a proinflammatory effect of EOLS and thymol was evidenced when it was applied for more than 1 day.", "output": "thymol." }, { "input": "There were no statistical differences in antiedematogenic activity between EOLS and thymol.", "output": "thymol." }, { "input": "In conclusion, the results indicate that thymol is the constituent responsible for the topical antiinflammatory activity of EOLS.", "output": "thymol." }, { "input": "Thus, these findings could justify the popular use of L. sidoides by alternative medicine, but chronic use has an inflammatory effect.", "output": "There is no related enetity." }, { "input": "Effects of synthetic peptides on the inflammatory response and their therapeutic potential.", "output": "There is no related enetity." }, { "input": "Recently, interest in small peptide molecules as potential drug candidates has revived.", "output": "There is no related enetity." }, { "input": "In this review, two series of synthetic peptides and their selective effects on the inflammatory response have been described, focusing on the intracellular pathways involved and on their therapeutic potential.", "output": "There is no related enetity." }, { "input": "A series of F ( D ) LF ( D ) LF analogs has been synthesized, including either N - t - Boc or different N - ureido substituents.", "output": "N - t - Boc, N - ureido." }, { "input": "The free acid derivatives as they are good candidates as antiinflammatory drugs are able to antagonize the multiple neutrophil functions evoked by N - formyl - L - methionyl - L - leucyl - Lphenylalanine ( fMLF ), i. e. chemotaxis, superoxide anion production and lysozyme release.", "output": "N - formyl - L - methionyl - L - leucyl - Lphenylalanine, fMLF, superoxide." }, { "input": "Their methyl - ester derivatives are ineffective.", "output": "methyl - ester." }, { "input": "The second series of peptides derives from the endogenous protein kinase C ( PKC ) inhibitor PKI55, a 55 - amino acid protein, whose synthesis is induced by PKC activation, so that a feedback loop of inhibition is established.", "output": "amino acid." }, { "input": "In vitro experiments showed that PKI55 inhibits recombinant PKC isoforms alpha, beta 1, beta 2, gamma, delta, zeta,; to identify the minimal amino acid sequence of PKI55 protein maintaining the inhibitory effects on PKC, peptides derived from both C - and N - terminal sequences have been synthesized.", "output": "amino acid, C, N." }, { "input": "The N - terminal peptides 5 ( MLYKLHDVCRQLWFSC ), 8 ( CRQLWFSC ) and 9 ( CRQLW ), that in human neutrophils retain the inhibitory activity on PKC, decrease the chemotaxis, and, in mice, display anti - inflammatory and analgesic action, after both central and peripheral administration of very low doses.", "output": "N." }, { "input": "Furthermore, the peptide 5 shows neuroprotective activity in a model of cerebral ischemia in vitro, favouring the recovery of synaptic function.", "output": "There is no related enetity." }, { "input": "These findings suggest interesting possible therapeutic applications for these peptides.", "output": "There is no related enetity." }, { "input": "A review on the development in the field of NIDDM based thiazolidinedione PPAR gamma agonists.", "output": "thiazolidinedione." }, { "input": "Peroxisome Proliferator Activated Receptors gamma ( PPAR gamma ) are a class of ligand activated transcription factors with a prominent role in the regulation of metabolic processes.", "output": "There is no related enetity." }, { "input": "The present work aims towards examining the functional and structural features that facilitate the binding of small molecules based on Thiazolidinedione pharmacophore to PPARs.", "output": "Thiazolidinedione." }, { "input": "The intent of this article is to review all the reported thiazolidinediones and associated groups of PPAR gamma ligands.", "output": "thiazolidinediones." }, { "input": "A new triterpenoid from the rhizomes of Nelumbo nucifera.", "output": "triterpenoid." }, { "input": "A new triterpenoid, 2 alpha, 24 - diacetoxy - 3 beta - hydroxyolean - 12 - en - 28 - oic acid ( 1 ), was characterised from the rhizomes of Nelumbo nucifera Gaertn by spectroscopic and chemical methods along with four known compounds, hyptatic acid - A ( 2 alpha, 3 beta, 24 - trihydroxyolean - 12 - en - 28 - oic acid ) ( 2 ), maslinic acid ( 2 alpha, 3 beta - dihydroxyoleane - 12 - ene - 28 - oic acid ), betulin and lupeol.", "output": "triterpenoid, 2 alpha , 24 - diacetoxy - 3 beta - hydroxyolean - 12 - en - 28 - oic acid, hyptatic acid - A, 2 alpha , 3 beta , 24 - trihydroxyolean - 12 - en - 28 - oic acid, maslinic acid, 2 alpha , 3 beta - dihydroxyoleane - 12 - ene - 28 - oic acid, betulin, lupeol." }, { "input": "Vasodilatory effects of cinnamic acid via the nitric oxide - cGMP - PKG pathway in rat thoracic aorta.", "output": "cinnamic acid, nitric oxide, cGMP." }, { "input": "Cinnamic acid ( CA ) and its derivatives have a broad therapeutic spectrum that includes antimicrobial, antifungal, and antitumoral activities.", "output": "Cinnamic acid." }, { "input": "However, the vasodilative effect of CA has not been demonstrated.", "output": "There is no related enetity." }, { "input": "The present study characterizes the vasodilative activity and the mechanism of CA in rat thoracic aorta.", "output": "There is no related enetity." }, { "input": "The vasomotion of aortic strips following CA treatment was measured in an organ bath system.", "output": "There is no related enetity." }, { "input": "In addition, vascular strips and human umbilical vein endothelial cells ( HUVECs ) were used in organ bath, Western blot, nitrite, and cyclic guanosine monophosphate ( cGMP ) measurements.", "output": "nitrite, cyclic guanosine monophosphate, cGMP." }, { "input": "CA relaxed phenylephrine - precontracted aortic strips in an endothelium - dependent manner.", "output": "phenylephrine." }, { "input": "Pretreatment of the endothelium - intact aortic strips with N ( G ) - nitro - l - arginine methyl ester ( 10 ( - 4 ) M ), 1 H - [ 1, 2, 4 ] - oxadiazolole - [ 4, 3 - a ] quinoxalin - 10 - one, ( 10 ( - 6 ) M ) and methylene blue ( 10 ( - 5 ) M ) inhibited CA - induced vasorelaxation.", "output": "N ( G ) - nitro - l - arginine methyl ester, 1 H - [ 1 , 2 , 4 ] - oxadiazolole - [ 4 , 3 - a ] quinoxalin - 10 - one, methylene blue." }, { "input": "CA also increased the phosphorylation of endothelial nitric oxide synthase and nitric oxide generation in a concentration - dependent manner in HUVECs.", "output": "nitric oxide, nitric oxide." }, { "input": "In addition, cGMP generation and cGMP - dependent protein kinase G ( PKG ) expression in aortic strips were increased by CA treatment.", "output": "cGMP, cGMP." }, { "input": "Furthermore, CA - induced vasorelaxation was inhibited by the PKG inhibitor KT5823 ( 0. 3 mu M ) and the Ca ( 2 + ) - activated K ( + ) channel inhibitor tetraethylammonium ( 10 ( - 3 ) M ).", "output": "KT5823, Ca ( 2 + ), K ( + ), tetraethylammonium." }, { "input": "These findings suggest that CA exerts an endothelium - dependent vasodilation effect via the nitric oxide - cGMP - PKG - mediated pathway in rat thoracic aorta.", "output": "nitric oxide, cGMP." }, { "input": "The role of inflammation in epileptogenesis.", "output": "There is no related enetity." }, { "input": "One compelling challenge in the therapy of epilepsy is to develop anti - epileptogenic drugs with an impact on the disease progression.", "output": "There is no related enetity." }, { "input": "The search for novel targets has focused recently on brain inflammation since this phenomenon appears to be an integral part of the diseased hyperexcitable brain tissue from which spontaneous and recurrent seizures originate.", "output": "There is no related enetity." }, { "input": "Although the contribution of specific proinflammatory pathways to the mechanism of ictogenesis in epileptic tissue has been demonstrated in experimental models, the role of these pathways in epileptogenesis is still under evaluation.", "output": "There is no related enetity." }, { "input": "We review the evidence conceptually supporting the involvement of brain inflammation and the associated blood - brain barrier damage in epileptogenesis, and describe the available pharmacological evidence where post - injury intervention with anti - inflammatory drugs has been attempted.", "output": "There is no related enetity." }, { "input": "Our review will focus on three main inflammatory pathways, namely the IL - 1 receptor / Toll - like receptor signaling, COX - 2 and the TGF - beta signaling.", "output": "There is no related enetity." }, { "input": "The mechanisms underlying neuronal - glia network dysfunctions induced by brain inflammation are also discussed, highlighting novel neuromodulatory effects of classical inflammatory mediators such as cytokines and prostaglandins.", "output": "prostaglandins." }, { "input": "The increase in knowledge about a role of inflammation in disease progression, may prompt the use of specific anti - inflammatory drugs for developing disease - modifying treatments.", "output": "There is no related enetity." }, { "input": "This article is part of the Special Issue entitled ' New Targets and Approaches to the Treatment of Epilepsy '.", "output": "There is no related enetity." }, { "input": "Modulation of pyramidal cell output in the medial prefrontal cortex by mGluR5 interacting with CB1.", "output": "There is no related enetity." }, { "input": "The medial prefrontal cortex ( mPFC ) serves executive cognitive functions such as decision - making that are impaired in neuropsychiatric disorders and pain.", "output": "There is no related enetity." }, { "input": "We showed previously that amygdala - driven abnormal inhibition and decreased output of mPFC pyramidal cells contribute to pain - related impaired decision - making ( Ji et al., 2010 ).", "output": "There is no related enetity." }, { "input": "Therefore, modulating pyramidal output is desirable therapeutic goal.", "output": "There is no related enetity." }, { "input": "Targeting metabotropic glutamate receptor subtype mGluR5 has emerged as a cognitive - enhancing strategy in neuropsychiatric disorders, but synaptic and cellular actions of mGluR5 in the mPFC remain to be determined.", "output": "glutamate." }, { "input": "The present study determined synaptic and cellular actions of mGluR5 to test the hypothesis that increasing mGluR5 function can enhance pyramidal cell output.", "output": "There is no related enetity." }, { "input": "Whole - cell voltage - and current - clamp recordings were made from visually identified pyramidal neurons in layer V of the mPFC in rat brain slices.", "output": "There is no related enetity." }, { "input": "Both the prototypical mGluR5 agonist CHPG and a positive allosteric modulator ( PAM ) for mGluR5 ( VU0360172 ) increased synaptically evoked spiking ( E - S coupling ) in mPFC pyramidal cells.", "output": "CHPG, VU0360172." }, { "input": "The facilitatory effects of CHPG and VU0360172 were inhibited by an mGluR5 antagonist ( MTEP ).", "output": "CHPG, VU0360172, MTEP." }, { "input": "CHPG, but not VU0360172, increased neuronal excitability ( frequency - current [ F - I ] function ).", "output": "CHPG, VU0360172." }, { "input": "VU0360172, but not CHPG, increased evoked excitatory synaptic currents ( EPSCs ) and amplitude, but not frequency, of miniature EPSCs, indicating a postsynaptic action.", "output": "VU0360172, CHPG." }, { "input": "VU0360172, but not CHPG, decreased evoked inhibitory synaptic currents ( IPSCs ) through an action that involved cannabinoid receptor CB1, because a CB1 receptor antagonist ( AM281 ) blocked the inhibitory effect of VU0360172 on synaptic inhibition.", "output": "VU0360172, CHPG, AM281, VU0360172." }, { "input": "VU0360172 also increased and prolonged CB1 - mediated depolarization - induced suppression of synaptic inhibition ( DSI ).", "output": "VU0360172." }, { "input": "Activation of CB1 with ACEA decreased inhibitory transmission through a presynaptic mechanism.", "output": "ACEA." }, { "input": "The results show that increasing mGluR5 function enhances mPFC output.", "output": "There is no related enetity." }, { "input": "This effect can be accomplished by increasing excitability with an orthosteric agonist ( CHPG ) or by increasing excitatory synaptic drive and CB1 - mediated presynaptic suppression of synaptic inhibition ( \" dis - inhibition \" ) with a PAM ( VU0360172 ).", "output": "CHPG, VU0360172." }, { "input": "Therefore, mGluR5 may be a useful target in conditions of impaired mPFC output.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Metabotropic Glutamate Receptors '.", "output": "Glutamate." }, { "input": "Stratified medicine in psychiatry: a worrying example or new opportunity in the treatment of anxiety?", "output": "There is no related enetity." }, { "input": "Stratified medicine is a new term that figures highly in current MRC and NHS strategy.", "output": "There is no related enetity." }, { "input": "It has developed from the earlier terms individualised or personalised medicine and refers to the use of genetic and / or endophenotypic measures to allow better targeting of treatments.", "output": "There is no related enetity." }, { "input": "The best exemplar is HER2 positivity in breast cancer to determine the efficacy of Herceptin.", "output": "There is no related enetity." }, { "input": "Clinical trials of this anti - cancer drug were initially unpromising, but once the HER2 positive subgroup was identified it was found, in this subgroup only, to be highly effective.", "output": "There is no related enetity." }, { "input": "It is presumed that similar subgroups will be found for many common disorders not just cancers, and that these will lead to much better targeted treatments.", "output": "There is no related enetity." }, { "input": "Such an advance may be necessary to develop new treatments in certain fields where the development of broad - spectrum / blockbuster treatments appears to have reached the end of the road; a particular example of this is in psychiatry.", "output": "There is no related enetity." }, { "input": "In this paper we discuss this issue in relation to psychiatry using a new and interesting example of how genotyping might help rescue an apparently failed novel treatment in anxiety disorders.", "output": "There is no related enetity." }, { "input": "Extracts of Scutellaria baicalensis reduced body weight and blood triglyceride in db / db Mice.", "output": "triglyceride." }, { "input": "Scutellaria baicalensis has been extensively employed for the clinical treatment of hyperlipidemia, atherosclerosis, hypertension, dysentery, inflammatory diseases, and the common cold.", "output": "There is no related enetity." }, { "input": "The present study was performed to investigate the anti - obesity and anti - dyslipidemia effect of Scutellaria baicalensis extracts ( SBE ) in type 2 diabetic db / db mice.", "output": "There is no related enetity." }, { "input": "Male db / db mice were divided into three groups ( n = 5 ) and orally administrated vehicle ( control ), SBE 10, and 100 mg / kg body weight / day for 4 weeks everyday.", "output": "There is no related enetity." }, { "input": "Administration of SBE improves weight gain, hypertriglyceridemia, and hyperinsulinemia in db / db mice.", "output": "There is no related enetity." }, { "input": "In obese db / db mice, SBE treatment also reduced plasma alanine aminotransferase levels.", "output": "alanine." }, { "input": "In the livers of db / db mice, SBE promoted 5 ' AMP - activated protein kinase activity and restored metabolic process and insulin signaling pathways.", "output": "5 ' AMP." }, { "input": "Our data demonstrate that SBE exerts potent anti - obesity and anti - hypertriglyceride effects suggesting its useful potential function as adjuvant therapeutic agent for the treatment of weight gain and hypertriglyceridemia.", "output": "There is no related enetity." }, { "input": "A new lignan with anti - tumour activity from Polygonum perfoliatum L.", "output": "There is no related enetity." }, { "input": "The methanol extract of the tubers of Polygonum perfoliatum L. afforded a new lignan: 8 - oxo - pinoresinol ( 1 ), and five known compounds 3 ', 5 - dihydroxy - 3, 4 ', 5 ', 7 - tetramethoxy - flavone ( 2 ), catechin ( 3 ), quercetin ( 4 ), quercetin - 3 - O - beta - D - glucuronide ( 5 ) and rutin ( 6 ).", "output": "methanol, lignan, 8 - oxo - pinoresinol, 3 ' , 5 - dihydroxy - 3 , 4 ' , 5 ' , 7 - tetramethoxy - flavone, catechin, quercetin, quercetin - 3 - O - beta - D - glucuronide, rutin." }, { "input": "Their structures were established by MS, one - and two - dimensional NMR experiments.", "output": "There is no related enetity." }, { "input": "Compound 1 showed cytotoxicity against human mammary carcinoma ( Bcap - 37 ), human colon carcinoma ( RKO ), human hepatocellular carcinoma ( SMMC - 7721 ), human prostate carcinoma ( PC3 ) and human erythroleukaemia ( K562 ) cells.", "output": "There is no related enetity." }, { "input": "Tonic GABA ( A ) receptor - mediated signalling in temporal lobe epilepsy.", "output": "GABA." }, { "input": "The tonic activation of extrasynaptic GABAA receptors by extracellular GABA provides a powerful means of regulating neuronal excitability.", "output": "GABA." }, { "input": "A consistent finding from studies that have used various models of temporal lobe epilepsy is that tonic GABAA receptor - mediated conductances are largely preserved in epileptic brain ( in contrast to synaptic inhibition which is often reduced ).", "output": "There is no related enetity." }, { "input": "Tonic inhibition is therefore an attractive target for antiepileptic drugs.", "output": "There is no related enetity." }, { "input": "However, the network consequences of a commonly used approach to augment tonic GABAA receptor - mediated conductances by global manipulation of extracellular GABA are difficult to predict without understanding how epileptogenesis alters the pharmacology and GABA sensitivity of tonic inhibition, and how manipulation of tonic conductances modulates the output of individual neurons.", "output": "GABA, GABA." }, { "input": "Here we review the current literature on epilepsy - associated changes in tonic GABAA receptor - mediated signalling, and speculate about possible effects they have at the network level.", "output": "There is no related enetity." }, { "input": "This article is part of the Special Issue entitled ' New Targets and Approaches to the Treatment of Epilepsy '.", "output": "There is no related enetity." }, { "input": "Metabotropic glutamate 7 ( mGlu7 ) receptor: a target for medication development for the treatment of cocaine dependence.", "output": "glutamate, cocaine." }, { "input": "Brain glutamate has been shown to play an important role in reinstatement to drug seeking, a behavior considered to be of relevance to relapse to drug taking in humans.", "output": "glutamate." }, { "input": "Therefore, glutamate receptors, in particular metabotropic glutamate ( mGlu ) receptors, have become important targets for medication development for the treatment of drug dependence.", "output": "glutamate, glutamate." }, { "input": "In this review article, we focus on the mGlu7 receptor subtype, and discuss recent findings with AMN082, a selective mGlu7 receptor allosteric agonist, in animal models with relevance to drug dependence.", "output": "AMN082." }, { "input": "Systemic or local administration of AMN082 into the nucleus accumbens ( NAc ), a critical brain region involved in reward and drug dependence processes, inhibited the reinforcing and motivational effects of cocaine, heroin and ethanol, as assessed by the intravenous drug self - administration procedure.", "output": "AMN082, cocaine, heroin, ethanol." }, { "input": "In addition, AMN082 inhibited the reward - enhancing effects induced by cocaine, as assessed in the intracranial self - stimulation procedure, and cocaine - or cue - induced reinstatement of drug - seeking behavior.", "output": "AMN082, cocaine, cocaine." }, { "input": "In vivo microdialysis studies indicated that systemic or intra - NAc administration of AMN082 significantly decreased extracellular gamma - aminobutyric acid ( GABA ) and elevated extracellular glutamate, but had no effect on extracellular dopamine in the NAc, suggesting that a non - dopaminergic mechanism underlies the effects of AMN082 on the actions of cocaine.", "output": "AMN082, gamma - aminobutyric acid, GABA, glutamate, dopamine, AMN082, cocaine." }, { "input": "Further, data indicated that AMN082 - induced changes in glutamate were the net effect of two actions: one is the direct inhibition of glutamate release by activation of mGlu7 receptors on glutamatergic neurons; another is the indirect increases of glutamate release mediated by decreases in GABA transmission.", "output": "AMN082, glutamate, glutamate, glutamate, GABA." }, { "input": "These increases in extracellular glutamate functionally antagonized cocaine - induced inhibition of NAc - ventral pallidum GABAergic neurotransmission, and therefore, the rewarding effects of cocaine.", "output": "glutamate, cocaine, pallidum, cocaine." }, { "input": "In addition, elevated extracellular glutamate activated presynaptic mGlu2 / 3 autoreceptors which in turn inhibited cocaine priming - or cue - induced enhancement of glutamate release and reinstatement of drug - seeking behavior.", "output": "glutamate, cocaine, glutamate." }, { "input": "Taken together, these findings suggest that the mGlu7 receptor is an important target for medication development for the treatment of drug dependence.", "output": "There is no related enetity." }, { "input": "AMN082 or other mGlu7 receptor allosteric agonists may have potential as novel pharmacotherapies for cocaine addiction.", "output": "AMN082, cocaine." }, { "input": "This article is part of a Special Issue entitled ' Metabotropic Glutamate Receptors '.", "output": "Glutamate." }, { "input": "The synergistic apoptotic interaction of panaxadiol and epigallocatechin gallate in human colorectal cancer cells.", "output": "panaxadiol, epigallocatechin gallate." }, { "input": "Panaxadiol ( PD ) is a purified sapogenin of ginseng saponins, which exhibits anticancer activity.", "output": "Panaxadiol, sapogenin, saponins." }, { "input": "Epigallocatechin gallate ( EGCG ), a major catechin in green tea, is a strong botanical antioxidant.", "output": "Epigallocatechin gallate, EGCG, catechin." }, { "input": "In this study, we investigated the possible synergistic anticancer effects of PD and EGCG on human colorectal cancer cells and explored the potential role of apoptosis in the synergistic activities.", "output": "EGCG." }, { "input": "Effects of selected compounds on HCT - 116 and SW - 480 human colorectal cancer cells were evaluated by a modified trichrome stain cell proliferation analysis.", "output": "There is no related enetity." }, { "input": "Cell cycle distribution and apoptotic effects were analyzed by flow cytometry after staining with PI / RNase or annexin V / PI.", "output": "There is no related enetity." }, { "input": "Cell growth was suppressed after treatment with PD ( 10 and 20 micro m ) for 48 h.", "output": "There is no related enetity." }, { "input": "When PD ( 10 and 20 micro m ) was combined with EGCG ( 10, 20, and 30 micro m ), significantly enhanced antiproliferative effects were observed in both cell lines.", "output": "EGCG." }, { "input": "Combining 20 micro m of PD with 20 and 30 micro m of EGCG significantly decreased S - phase fractions of cells.", "output": "EGCG." }, { "input": "In the apoptotic assay, the combination of PD and EGCG significantly increased the percentage of apoptotic cells compared with PD alone ( p < 0. 01 ).", "output": "EGCG." }, { "input": "The synergistic apoptotic effects were also supported by docking analysis, which demonstrated that PD and EGCG bound in two different sites of the annexin V protein.", "output": "EGCG." }, { "input": "Data from this study suggested that apoptosis might play an important role in the EGCG - enhanced antiproliferative effects of PD on human colorectal cancer cells.", "output": "EGCG." }, { "input": "HPLC analysis of Stephania rotunda extracts and correlation with antiplasmodial activity.", "output": "There is no related enetity." }, { "input": "Stephania rotunda ( Menispermaceae ), a creeper commonly found in the mountainous areas of Cambodia, has been mainly used for the treatment of fever and malaria.", "output": "There is no related enetity." }, { "input": "Thus, the aim of this study is to investigate the chemical composition and antiplasmodial activity of different samples of S. rotunda and compare their antiplasmodial activity with their alkaloid content.", "output": "There is no related enetity." }, { "input": "Sixteen samples from different parts ( roots, stem, and tuber ) of S. rotunda were collected from four regions of Cambodia ( Battambang, Pailin, Siem Reap, and Kampot ).", "output": "There is no related enetity." }, { "input": "Reversed - phase HPLC was used to determine the content of three bioactive alkaloids ( cepharanthine, tetrahydropalmatine, and xylopinine ).", "output": "cepharanthine, tetrahydropalmatine, xylopinine." }, { "input": "These three alkaloids have been found in all samples from Battambang and Pailin ( samples I - IX ), whereas only tetrahydropalmatine was present in samples from Siem Reap and Kampot ( samples X - XVI ).", "output": "tetrahydropalmatine." }, { "input": "The analyzed extracts were evaluated for their antiplasmodial activity on W2 strain of Plasmodium falciparum.", "output": "There is no related enetity." }, { "input": "Among them, 13 extracts were significantly active with inhibitory concentration 50 ( IC ( 50 ) ) from 1. 2 to 3. 7 micro g / mL and 2 extracts were moderately active ( IC ( 50 ) = 6. 1 and 10 micro g / mL, respectively ), whereas sample XI was not active ( IC ( 50 ) = 19. 6 micro g / mL ).", "output": "There is no related enetity." }, { "input": "A comparison between antiplasmodial activity and concentration of the three bioactive alkaloids in S. rotunda extracts has been realized.", "output": "There is no related enetity." }, { "input": "Preventive effects of North American ginseng ( Panax quinquefolius ) on diabetic retinopathy and cardiomyopathy.", "output": "There is no related enetity." }, { "input": "Ginseng ( Araliaceae ) has multiple pharmacological actions because of its diverse phytochemical constituents.", "output": "There is no related enetity." }, { "input": "The aims of the present study are to evaluate the preventive effects of North American ginseng on diabetic retinopathy and cardiomyopathy and to delineate the underlying mechanisms of such effects.", "output": "There is no related enetity." }, { "input": "Models of both type 1 ( C57BL / 6 mice with streptozotocin - induced diabetes ) and type 2 diabetes ( db / db mice ) and age - matched and sex - matched controls were examined.", "output": "streptozotocin." }, { "input": "Alcoholic ginseng root ( 200 mg / kg body weight, daily oral gavage ) extract was administered to groups of both type 1 and type 2 diabetic mice for 2 or 4 months.", "output": "There is no related enetity." }, { "input": "Dysmetabolic state in the diabetic mice was significantly improved by ginseng treatment.", "output": "There is no related enetity." }, { "input": "In both the heart and retina of diabetic animals, ginseng treatment significantly prevented oxidative stress and diabetes - induced upregulations of extracellular matrix proteins and vasoactive factors.", "output": "There is no related enetity." }, { "input": "Ginseng treatment in the diabetic animals resulted in enhancement of stroke volume, ejection fraction, cardiac output, and left ventricle pressure during systole and diastole and diminution of stroke work.", "output": "There is no related enetity." }, { "input": "In addition, mRNA expressions of atrial natriuretic factor and brain natriuretic factor ( molecular markers for cardiac hypertrophy ) were significantly diminished in ginseng - treated diabetic mice.", "output": "There is no related enetity." }, { "input": "These data indicate that North American ginseng prevents the diabetes - induced retinal and cardiac biochemical and functional changes probably through inhibition of oxidative stress.", "output": "There is no related enetity." }, { "input": "Evaluation of food - drug interaction of guava leaf tea.", "output": "There is no related enetity." }, { "input": "Guava leaf tea ( GLT ) contains guava leaf polyphenol ( Gvpp ), which regulates the absorption of dietary carbohydrate from the intestines.", "output": "polyphenol, carbohydrate." }, { "input": "Borderline diabetics, who are at high risk of development of diabetes, take GLT to suppress a rapid increase of blood sugar level after meals.", "output": "sugar." }, { "input": "However, patients with diabetes in whom diabetic drugs or warfarin as a blood thinner are prescribed also take GLT with the expectation of glycemic control.", "output": "warfarin." }, { "input": "Therefore, we studied whether GLT had potential for inhibition or induction of cytochrome P450 ( CYP ) and an influence on the action of warfarin.", "output": "warfarin." }, { "input": "Extract of guava leaf ( GvEx ) consists of carbohydrate and polyphenols, which are Gvpp, quercetin, and ellagic acid.", "output": "carbohydrate, polyphenols, quercetin, ellagic acid." }, { "input": "These polyphenols, but not GvEx, showed a certain level of inhibition of human - cDNA - expressed CYPs.", "output": "polyphenols." }, { "input": "In a comparison of GLT and grapefruit juice, GLT showed weaker inhibition of CYP activities and of midazolam 1 ' - hydroxylation than grapefruit juice.", "output": "midazolam." }, { "input": "Furthermore, neither liver weight nor CYP3A expression in the liver was changed in rats that received GvEx for 90 days compared with the control group.", "output": "There is no related enetity." }, { "input": "When rats were concomitantly treated with GLT and warfarin, the prolongation of clotting time of blood by warfarin was not influenced.", "output": "warfarin, warfarin." }, { "input": "These data suggest that GLT is unlikely to interact with drugs.", "output": "There is no related enetity." }, { "input": "A new phenylethanoid glucoside from Plantago depressa Willd.", "output": "phenylethanoid glucoside." }, { "input": "Chemical research of Plantago depressa Willd. led to one new phenylethanoid glucoside with alpha - L - rhamnosyl ( 1 --> 2 ) - beta - D - glucose structure, together with four known compounds.", "output": "phenylethanoid glucoside, alpha - L - rhamnosyl ( 1 --> 2 ) - beta - D - glucose." }, { "input": "These five compounds ( 1 - 5 ) were isolated from the family Plantaginaceae for the first time; the chemotaxonomic significance of cerebrosides was also discussed.", "output": "cerebrosides." }, { "input": "Chemical composition of essential oil from Calligonum polygonoides Linn.", "output": "There is no related enetity." }, { "input": "The essential oil from air dried buds and roots of Calligonum polygonoides Linn., has been extracted from dry steam distillation and analysed for chemical composition by gas chromatography - mass spectrometry.", "output": "There is no related enetity." }, { "input": "In total, 27 and 10 compounds were analysed qualitatively and quantitatively, accounting for 68. 42 % and 82. 12 % total contents of the essential oils of buds and roots, respectively.", "output": "There is no related enetity." }, { "input": "It contains a complex mixture of terpenoids, hydrocarbons, phenolic compounds, acid derivatives and ketones.", "output": "terpenoids, hydrocarbons, phenolic, ketones." }, { "input": "The main component of essential oil was ethyl homovanillate ( 11. 79 % ) in buds and drimenol ( 29. 42 % ) in roots.", "output": "ethyl homovanillate, drimenol." }, { "input": "The effects of temperature and salinity on 17 - alpha - ethynylestradiol uptake and its relationship to oxygen consumption in the model euryhaline teleost ( Fundulus heteroclitus ).", "output": "17 - alpha - ethynylestradiol, oxygen." }, { "input": "The synthetic estrogen 17 - alpha - ethynylestradiol ( EE2 ), a component of birth control and hormone replacement therapy, is discharged into the environment via wastewater treatment plant ( WWTP ) effluents.", "output": "estrogen, 17 - alpha - ethynylestradiol, EE2." }, { "input": "The present study employed radiolabeled EE2 to examine impacts of temperature and salinity on EE2 uptake in male killifish ( Fundulus heteroclitus ).", "output": "EE2, EE2." }, { "input": "Fish were exposed to a nominal concentration of 100ng / L EE2 for 2h.", "output": "EE2." }, { "input": "The rate of EE2 uptake was constant over the 2h period.", "output": "EE2." }, { "input": "Oxygen consumption rates ( MO ( 2 ) ), whole body uptake rates, and tissue - specific EE2 distribution were determined.", "output": "Oxygen, EE2." }, { "input": "In killifish acclimated to 18 degrees C at 16ppt ( 50 % sea water ), MO ( 2 ) and EE2 uptake were both lower after 24h exposure to 10 degrees C and 4 degrees C, and increased after 24h exposure to 26 degrees C.", "output": "EE2." }, { "input": "Transfer to fresh water ( FW ) for 24h lowered EE2 uptake rate, and long - term acclimation to fresh water reduced it by 70 %.", "output": "EE2." }, { "input": "Both long - term acclimation to 100 % sea water ( 32ppt ) and a 24h transfer to 100 % sea water also reduced EE2 uptake rate by 50 % relative to 16ppt.", "output": "EE2." }, { "input": "Tissue - specific accumulation of EE2 was highest ( 40 - 60 % of the total ) in the liver plus gall bladder across all exposures, and the vast majority of this was in the bile at 2h, regardless of temperature or salinity.", "output": "EE2." }, { "input": "The carcass was the next highest accumulator ( 30 - 40 % ), followed by the gut ( 10 - 20 % ) with only small amounts in gill and spleen.", "output": "There is no related enetity." }, { "input": "Killifish chronically exposed ( 15 days ) to 100ng / L EE2 displayed no difference in EE2 uptake rate or tissue - specific distribution.", "output": "EE2, EE2." }, { "input": "Drinking rate, measured with radiolabeled polyethylene glycol - 4000, was about 25 times greater in 16ppt - acclimated killifish relative to FW - acclimated animals.", "output": "polyethylene glycol - 4000." }, { "input": "However, drinking accounted for less than 30 % of gut accumulation, and therefore a negligible percentage of whole body EE2 uptake rates.", "output": "EE2." }, { "input": "In general, there were strong positive relationships between EE2 uptake rates and MO ( 2 ), suggesting similar uptake pathways of these lipophilic molecules across the gills.", "output": "EE2." }, { "input": "These data will be useful in developing a predictive model of how key environmental parameter variations ( salinity, temperature, dissolved oxygen ) affect EE2 uptake in estuarine fish, to determine optimal timing and location of WWTP discharges.", "output": "oxygen, EE2." }, { "input": "One new antitumour cassane - type diterpene from Caesalpinia crista.", "output": "cassane, diterpene." }, { "input": "1 alpha - acetoxy - 5 alpha, 7 beta - dihydroxycassa - 11, 13 ( 15 ) - diene - 16, 12 - lactone, a new cassane - type diterpene was isolated from Caesalpinia crista.", "output": "1 alpha - acetoxy - 5 alpha , 7 beta - dihydroxycassa - 11 , 13 ( 15 ) - diene - 16 , 12 - lactone, cassane, diterpene." }, { "input": "The structure of this compound was elucidated by analysis of NMR spectra, and the relative configuration was established by NOE experiment.", "output": "There is no related enetity." }, { "input": "The new compound was evaluated for antitumour activity against T47D, DU145 and showed significant inhibitory activities.", "output": "There is no related enetity." }, { "input": "MUC1 - C oncoprotein as a target in breast cancer: activation of signaling pathways and therapeutic approaches.", "output": "There is no related enetity." }, { "input": "Mucin 1 ( MUC1 ) is a heterodimeric protein formed by two subunits that is aberrantly overexpressed in human breast cancer and other cancers.", "output": "There is no related enetity." }, { "input": "Historically, much of the early work on MUC1 focused on the shed mucin subunit.", "output": "There is no related enetity." }, { "input": "However, more recent studies have been directed at the transmembrane MUC1 - C - terminal subunit ( MUC1 - C ) that functions as an oncoprotein.", "output": "There is no related enetity." }, { "input": "MUC1 - C interacts with EGFR ( epidermal growth factor receptor ), ErbB2 and other receptor tyrosine kinases at the cell membrane and contributes to activation of the PI3K AKT and mitogen - activated protein kinase kinase ( MEK ) extracellular signal - regulated kinase ( ERK ) pathways.", "output": "tyrosine." }, { "input": "MUC1 - C also localizes to the nucleus where it activates the Wnt / beta - catenin, signal transducer and activator of transcription ( STAT ) and NF ( nuclear factor ) - kappa B RelA pathways.", "output": "There is no related enetity." }, { "input": "These findings and the demonstration that MUC1 - C is a druggable target have provided the experimental basis for designing agents that block MUC1 - C function.", "output": "There is no related enetity." }, { "input": "Notably, inhibitors of the MUC1 - C subunit have been developed that directly block its oncogenic function and induce death of breast cancer cells in vitro and in xenograft models.", "output": "There is no related enetity." }, { "input": "On the basis of these findings, a first - in - class MUC1 - C inhibitor has entered phase I evaluation as a potential agent for the treatment of patients with breast cancers who express this oncoprotein.", "output": "There is no related enetity." }, { "input": "beta - Eudesmol induces JNK - dependent apoptosis through the mitochondrial pathway in HL60 cells.", "output": "beta - Eudesmol." }, { "input": "beta - eudesmol, a natural sesquiterpenol present in a variety of Chinese herbs, is known to inhibit the proliferation of human tumor cells.", "output": "beta - eudesmol, sesquiterpenol." }, { "input": "However, the molecular mechanisms of the effect of beta - eudesmol on human tumor cells are unknown.", "output": "beta - eudesmol." }, { "input": "In the present study, we report the cytotoxic effect of beta - eudesmol on the human leukemia HL60 cells and its molecular mechanisms.", "output": "beta - eudesmol." }, { "input": "The cytotoxic effect of beta - eudesmol on HL60 cells was associated with apoptosis, which was characterized by the presence of DNA fragmentation.", "output": "beta - eudesmol." }, { "input": "beta - eudesmol - induced apoptosis was accompanied by cleavage of caspase - 3, caspase - 9, and poly ( ADP - ribose ) polymerase; downregulation of Bcl - 2 expression; release of cytochrome c from mitochondria; and decrease in mitochondrial membrane potential ( MMP ).", "output": "beta - eudesmol, poly ( ADP - ribose )." }, { "input": "Activation of c - Jun N - terminal kinases ( JNK ) mitogen - activated protein kinases was observed in beta - eudesmol - treated HL60 cells, and the inhibitor of JNK blocked the beta - eudesmol - induced apoptosis, downregulation of Bcl - 2, and the loss of MMP.", "output": "N, beta - eudesmol, beta - eudesmol." }, { "input": "These data suggest that beta - eudesmol induces apoptosis in HL60 cells via the mitochondrial apoptotic pathway, which is controlled through JNK signaling.", "output": "beta - eudesmol." }, { "input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "A new triterpenoid saponin from Glinus oppositifolius with alpha - glucosidase inhibitory activity.", "output": "triterpenoid saponin." }, { "input": "Evaluation of alpha - glucosidase inhibitory activity led to the isolation of six triterpene saponins from the aerial parts of Glinus oppositifolius including one new and five known constituents.", "output": "triterpene saponins." }, { "input": "The structure of the new saponin, glinoside C ( 1 ), was established as 16 - O - ( beta - D - glucopyranosyl ) - 3 beta, 12 beta, 16 beta, 21 alpha, 22 - pentahydroxy hopane by extensive use of 1 - D, 2 - D NMR and mass spectral techniques.", "output": "saponin, glinoside C, 16 - O - ( beta - D - glucopyranosyl ) - 3 beta , 12 beta , 16 beta , 21 alpha , 22 - pentahydroxy hopane." }, { "input": "The other constituents identified were 3 - O - ( beta - D - xylopyranosyl ) - spergulagenin A ( 2 ), spergulacin ( 3 ), spergulin A ( 4 ), spergulacin A ( 5 ) and spergulin B ( 6 ).", "output": "3 - O - ( beta - D - xylopyranosyl ) - spergulagenin A, spergulacin, spergulin A, spergulacin A, spergulin B." }, { "input": "Compound 1 exhibited the greatest inhibition of the enzyme with IC50 of 127 +/- 30 micro M.", "output": "There is no related enetity." }, { "input": "Kinetics study for the compound 1 demonstrated mixed type of inhibition ( Ki = 157. 9 micro M ).", "output": "There is no related enetity." }, { "input": "Optimization of PLGA nanoparticles formulation containing L - DOPA by applying the central composite design.", "output": "PLGA, L - DOPA." }, { "input": "The aim of this work was to prepare L - DOPA loaded poly ( D, L - lactide - co - glycolide ) ( PLGA ) nanoparticles by a modified water - in - oil - in - water ( W ( 1 ) / O / W ( 2 ) ) emulsification solvent evaporation method.", "output": "L - DOPA, poly ( D , L - lactide - co - glycolide ), PLGA." }, { "input": "A central composite design was applied for optimization of the formulation parameters and for studying the effects of three independent variables: PLGA concentration, polyvinyl alcohol ( PVA ) concentration and organic solvent removal rate on the particle size and the entrapment efficiency ( response variables ).", "output": "PLGA, polyvinyl alcohol, PVA." }, { "input": "Second - order models were obtained to adequately describe the influence of the independent variables on the selected responses.", "output": "There is no related enetity." }, { "input": "The analysis of variance showed that the three independent variables had significant effects ( p < 0. 05 ) on the responses.", "output": "There is no related enetity." }, { "input": "The experimental results were in perfect accordance with the predictions estimated by the models.", "output": "There is no related enetity." }, { "input": "Using the desirability approach and overlay contour plots, the optimal preparation area can be highlighted.", "output": "There is no related enetity." }, { "input": "It was found that the optimum values of the responses could be obtained at higher concentration of PLGA ( 5 %, w / v ) and PVA ( 6 %, w / v ); and faster organic solvent removal rate ( 700 rpm ).", "output": "PLGA, PVA." }, { "input": "The corresponding particle size was 256. 2 nm and the entrapment efficiency was 62. 19 %.", "output": "There is no related enetity." }, { "input": "FTIR investigation confirmed that the L - DOPA and PLGA polymer maintained its backbone structure in the fabrication of nanoparticles.", "output": "L - DOPA, PLGA." }, { "input": "The scanning electron microscopic images of nanoparticles showed that all particles had spherical shape with porous outer skin.", "output": "There is no related enetity." }, { "input": "The results suggested that PLGA nanoparticles might represent a promising formulation for brain delivery of L - DOPA.", "output": "PLGA, L - DOPA." }, { "input": "The preparation of L - DOPA loaded PLGA nanoparticles can be optimized by the central composite design.", "output": "L - DOPA, PLGA." }, { "input": "Impact of early - life stress, on group III mGlu receptor levels in the rat hippocampus: effects of ketamine, electroconvulsive shock therapy and fluoxetine treatment.", "output": "ketamine, fluoxetine." }, { "input": "The glutamatergic system is increasingly being viewed as a promising target for the development of novel treatments for depression.", "output": "There is no related enetity." }, { "input": "The group III metabotropic glutamate ( mGlu ) receptors ( mGlu ( 4, 7 ) and ( 8 ) receptors ) in particular are beginning to show promise in this respect.", "output": "glutamate." }, { "input": "It remains unclear how antidepressant medications modulate mGlu receptors.", "output": "There is no related enetity." }, { "input": "In this study we investigated the effects of three antidepressant treatments ( fluoxetine, ketamine and electroconvulsive shock therapy ( ECT ) ).", "output": "fluoxetine, ketamine." }, { "input": "Ketamine is an NMDA receptor antagonist which possess a rapid antidepressant therapeutic profile and moreover is effective in cases of treatment - resistant depression.", "output": "Ketamine, NMDA." }, { "input": "Furthermore, ECT is also a therapeutic strategy possessing increased efficacy compared to conventional monoamine based therapies.", "output": "monoamine." }, { "input": "The effect these two highly efficacious treatments have on hippocampal group III mGlu receptors remains completely unexplored.", "output": "There is no related enetity." }, { "input": "To redress this deficit we investigated the effects these treatments and the prototypical selective serotonin reuptake inhibitor ( SSRI ) fluoxetine would have on hippocampal group III mGlu receptor mRNA levels in na i ve Sprague - Dawley rats and rats which had undergone early - life stress in the form of the maternal separation ( MS ) procedure.", "output": "serotonin, fluoxetine." }, { "input": "We found MS significantly reduced mGlu ( 4 ) receptor expression and fluoxetine reversed this MS induced change.", "output": "fluoxetine." }, { "input": "ECT and ketamine treatment significantly reduced mGlu ( 4 ) receptor expression in non - separated ( NS ) animals while having no effect in MS animals.", "output": "ketamine." }, { "input": "Fluoxetine and ECT significantly increased mGlu ( 7 ) receptor expression in NS animals.", "output": "Fluoxetine." }, { "input": "This work demonstrates changes to mGlu ( 4 ) receptor expression may be a lasting molecular change which occurs due to early - life stress.", "output": "There is no related enetity." }, { "input": "Taken together our data shows there are selective changes to group III mGlu receptors under basal and early - life stress conditions.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Metabotropic Glutamate Receptors '.", "output": "Glutamate." }, { "input": "In vitro biomonitoring of the genotoxic and oxidative potentials of two commonly eaten insects in southwestern Nigeria.", "output": "There is no related enetity." }, { "input": "In this study, the cytogenetic and oxidative effects of water soluble extracts of two commonly eaten insects, Zonocerus variegatus ( Orthoptera: Pyrgomorphidae ) and Oryctes boas ( Solanales: Solanaceae ), in southwestern Nigeria were evaluated on cultured human blood cells.", "output": "There is no related enetity." }, { "input": "The extracts were added to the cultures at various concentrations ( 0 - 2000 ppm ).", "output": "There is no related enetity." }, { "input": "The chromosome aberration and micronucleus tests were used to find out the DNA and chromosomal damage potentials in vitro by aqueous insect extracts.", "output": "There is no related enetity." }, { "input": "To assess the oxidative effects of these insect extracts, total antioxidant capacity ( TAC ) and total oxidant status ( TOS ) levels were also measured.", "output": "There is no related enetity." }, { "input": "Our results indicated that these extracts did not show genotoxic effects at the tested concentrations.", "output": "There is no related enetity." }, { "input": "However, the extracts caused dose - dependent alterations in both TAC and TOS levels.", "output": "There is no related enetity." }, { "input": "Based on the findings, it was concluded that the studied insects can be consumed safely, but it is necessary to consider the cellular damages that are likely to appear depending on the oxidative stress.", "output": "There is no related enetity." }, { "input": "We also suggest that this in vitro approach for oxidative and genotoxicity assessments may be useful to compare the potential health risks of edible insects.", "output": "There is no related enetity." }, { "input": "The role of diallyl sulfides and dipropyl sulfides in the in vitro antimicrobial activity of the essential oil of garlic, Allium sativum L., and Leek, Allium porrum L.", "output": "diallyl sulfides, dipropyl sulfides." }, { "input": "The in vitro antibacterial activity of essential oils ( EOs ) obtained from fresh bulbs of garlic, Allium sativum L., and leek, Allium porrum L.", "output": "There is no related enetity." }, { "input": "( Alliaceae ), was studied.", "output": "There is no related enetity." }, { "input": "A. sativum ( garlic ) EO showed a good antimicrobial activity against Staphylococcus aureus ( inhibition zone 14. 8 mm ), Pseudomonas aeruginosa ( inhibition zone 21. 1 mm ), and Escherichia coli ( inhibition zone 11. 0 mm ), whereas the EO of A. porrum ( leek ) had no antimicrobial activity.", "output": "There is no related enetity." }, { "input": "The main constituents of the garlic EO were diallyl monosulfide, diallyl disulfide ( DADS ), diallyl trisulfide, and diallyl tetrasulfide.", "output": "diallyl monosulfide, diallyl disulfide, DADS, diallyl trisulfide, diallyl tetrasulfide." }, { "input": "The EO of A. porrum was characterized by the presence of dipropyl disulfide ( DPDS ), dipropyl trisulfide, and dipropyl tetrasulfide.", "output": "dipropyl disulfide, DPDS, dipropyl trisulfide, dipropyl tetrasulfide." }, { "input": "The antimicrobial activities of the DADS and DPDS were also studied.", "output": "DADS, DPDS." }, { "input": "The results obtained suggest that the presence of the allyl group is fundamental for the antimicrobial activity of these sulfide derivatives when they are present in Allium or in other species ( DADS inhibition zone on S. aureus 15. 9 mm, P. aeruginosa 21. 9 mm, E. coli 11. 4 mm ).", "output": "allyl, sulfide, DADS." }, { "input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "MicroRNA - 7 functions as an anti - metastatic microRNA in gastric cancer by targeting insulin - like growth factor - 1 receptor.", "output": "There is no related enetity." }, { "input": "Metastasis is a major clinical obstacle in the treatment of gastric cancer ( GC ) and it accounts for the majority of cancer - related mortality.", "output": "There is no related enetity." }, { "input": "MicroRNAs have recently emerged as regulators of metastasis by acting on multiple signaling pathways.", "output": "There is no related enetity." }, { "input": "In this study, we found that miR - 7 is significantly downregulated in highly metastatic GC cell lines and metastatic tissues.", "output": "There is no related enetity." }, { "input": "Both gain - of - function and loss - of - function experiments showed that increased miR - 7 expression significantly reduced GC cell migration and invasion, whereas decreased miR - 7 expression dramatically enhanced cell migration and invasion.", "output": "There is no related enetity." }, { "input": "In vivo metastasis assays also demonstrated that overexpression of miR - 7 markedly inhibited GC metastasis.", "output": "There is no related enetity." }, { "input": "Moreover, the insulin - like growth factor - 1 receptor ( IGF1R ) oncogene, which is often mutated or amplified in human cancers and functions as an important regulator of cell growth and tumor invasion, was identified as a direct target of miR - 7.", "output": "There is no related enetity." }, { "input": "Silencing of IGF1R using small interefering RNA ( siRNA ) recapitulated the anti - metastatic function of miR - 7, whereas restoring the IGF1R expression attenuated the function of miR - 7 in GC cells.", "output": "There is no related enetity." }, { "input": "Furthermore, we found that suppression of Snail by miR - 7, through targeting IGF1R, increased E - cadherin expression and partially reversed the epithelial - mesenchymal transition ( EMT ).", "output": "There is no related enetity." }, { "input": "Finally, analyses of miR - 7 and IGF1R levels in human primary GC with matched lymph node metastasis tissue arrays revealed that miR - 7 is inversely correlated with IGF1R expression.", "output": "There is no related enetity." }, { "input": "The present study provides insight into the specific biological behavior of miR - 7 in EMT and tumor metastasis.", "output": "There is no related enetity." }, { "input": "Targeting this novel miR - 7 / IGF1R / Snail axis would be helpful as a therapeutic approach to block GC metastasis.", "output": "There is no related enetity." }, { "input": "Flavonoids and saponins from Zizyphus incurva.", "output": "Flavonoids, saponins." }, { "input": "A new flavonol triglycoside, myricetin - 3 - O - [ beta - xylopyranosyl - ( 1 - 2 ) - alpha - rhamnopyranoside ] - 4 ' - O - alpha - rhamnopyranoside, named as bayarin ( 1 ), was isolated from the aerial parts of Zizyphus incurva Roxb.", "output": "flavonol triglycoside, myricetin - 3 - O - [ beta - xylopyranosyl - ( 1 - 2 ) - alpha - rhamnopyranoside ] - 4 ' - O - alpha - rhamnopyranoside, bayarin." }, { "input": "( Rhamnaceae ) along with eight known compounds: six flavonoids and two saponins.", "output": "flavonoids, saponins." }, { "input": "All of these compounds were isolated for the first time from this plant.", "output": "There is no related enetity." }, { "input": "Structures of these compounds were elucidated on the basis of spectroscopic data.", "output": "There is no related enetity." }, { "input": "Rapid characterisation of flavonoids from Sophora alopecuroides L. by HPLC / DAD / ESI - MSn.", "output": "flavonoids." }, { "input": "An HPLC / DAD / ESI - MSn method was established to characterise flavonoids in the seeds of Sophora alopecuroides L.", "output": "flavonoids." }, { "input": "All the flavonoids exhibited abundant [ M - H ] - ions, which triggered data - dependent multistage mass spectrometry fragmentations.", "output": "flavonoids, H." }, { "input": "Characteristic UV spectra were used to confirm flavonoid subtypes.", "output": "flavonoid." }, { "input": "In total, 22 flavonoids and two phenolic compounds were detected and identified.", "output": "flavonoids, phenolic." }, { "input": "Five of them were identified by comparing with reference standards, and the others were characterised based on the retention behaviour, multistage fragmentation feature and UV absorption.", "output": "There is no related enetity." }, { "input": "A total of 19 compounds were reported from S. alopecuroides for the first time.", "output": "There is no related enetity." }, { "input": "This method accomplished rapid profiling of flavonoid constituents in S. alopecuroides L.", "output": "flavonoid." }, { "input": "cAMP regulation of airway smooth muscle function.", "output": "cAMP." }, { "input": "Agonists activating beta ( 2 ) - adrenoceptors ( beta ( 2 ) ARs ) on airway smooth muscle ( ASM ) are the drug of choice for rescue from acute bronchoconstriction in patients with both asthma and chronic obstructive pulmonary disease ( COPD ).", "output": "There is no related enetity." }, { "input": "Moreover, the use of long - acting beta - agonists combined with inhaled corticosteroids constitutes an important maintenance therapy for these diseases.", "output": "corticosteroids." }, { "input": "beta - Agonists are effective bronchodilators due primarily to their ability to antagonize ASM contraction.", "output": "There is no related enetity." }, { "input": "The presumed cellular mechanism of action involves the generation of intracellular cAMP, which in turn can activate the effector molecules cAMP - dependent protein kinase ( PKA ) and Epac.", "output": "cAMP, cAMP." }, { "input": "Other agents such as prostaglandin E ( 2 ) and phosphodiesterase inhibitors that also increase intracellular cAMP levels in ASM, can also antagonize ASM contraction, and inhibit other ASM functions including proliferation and migration.", "output": "prostaglandin E ( 2 ), cAMP." }, { "input": "Therefore, beta ( 2 ) ARs and cAMP are key players in combating the pathophysiology of airway narrowing and remodeling.", "output": "cAMP." }, { "input": "However, limitations of beta - agonist therapy due to drug tachyphylaxis related to beta ( 2 ) AR desensitization, and recent findings regarding the manner in which beta ( 2 ) ARs and cAMP signal, have raised new and interesting questions about these well - studied molecules.", "output": "cAMP." }, { "input": "In this review we discuss current concepts regarding beta ( 2 ) ARs and cAMP in the regulation of ASM cell functions and their therapeutic roles in asthma and COPD.", "output": "cAMP." }, { "input": "Anxiolytic - but not antidepressant - like activity of Lu AF21934, a novel, selective positive allosteric modulator of the mGlu 4 receptor.", "output": "Lu AF21934." }, { "input": "Previous studies demonstrated that the Group III mGlu receptor - selective orthosteric agonist, LSP1 - 2111 produced anxiolytic - but not antidepressant - like effects upon peripheral administration.", "output": "LSP1 - 2111." }, { "input": "Herein, we report the pharmacological actions of Lu AF21934, a novel, selective, and brain - penetrant positive allosteric modulator ( PAM ) of the mGlu ( 4 ) receptor in the stress - induced hyperthermia ( SIH ), four - plate, marble - burying and Vogel ' s conflict tests.", "output": "Lu AF21934." }, { "input": "In all models, except Vogel ' s conflict test, a dose - dependent anxiolytic - like effect was seen.", "output": "There is no related enetity." }, { "input": "The anti - hyperthermic effect of Lu AF21934 ( 5 mg / kg ) in the SIH test was inhibited by the benzodiazepine receptor antagonist flumazenil ( 10 mg / kg ) and was not serotonin - dependent, as it persisted in serotonin - deficient mice and upon blockade of either 5 - HT ( 1A ) receptors by WAY100635, or 5 - HT ( 2A / 2C ) receptors by ritanserin.", "output": "Lu AF21934, benzodiazepine, flumazenil, serotonin, serotonin, 5 - HT, WAY100635, 5 - HT, ritanserin." }, { "input": "These results suggest that the GABAergic system, but not the serotonergic system, is involved in the mechanism of the anxiolytic - like phenotype of Lu AF21934 in rodents.", "output": "Lu AF21934." }, { "input": "Lu AF21934 did not produce antidepressant - like effects in the tail suspension test ( TST ) in mice; however, it decreased the basal locomotor activity of mice that were not habituated to activity cages.", "output": "Lu AF21934." }, { "input": "This article is part of a Special Issue entitled ' Metabotropic Glutamate Receptors '.", "output": "Glutamate." }, { "input": "Intraspecific variability of the essential oil of Calamintha nepeta subsp. nepeta from Southern Italy ( Apulia ).", "output": "There is no related enetity." }, { "input": "The essential oil of 46 spontaneous plants of Calamintha nepeta ( L. ) Savi subsp. nepeta growing wild in Sud, Italy ( Salento, Apulia ), were investigated by GC / MS.", "output": "There is no related enetity." }, { "input": "Fifty - seven components were identified in the oil representing over the 98 % of the total oil composition.", "output": "There is no related enetity." }, { "input": "Four chemotypes were identified: piperitone oxide, piperitenone oxide, piperitone - menthone and pulegone.", "output": "piperitone oxide, piperitenone oxide, piperitone, menthone, pulegone." }, { "input": "Screening of venezuelan medicinal plant extracts for cytostatic and cytotoxic activity against tumor cell lines.", "output": "There is no related enetity." }, { "input": "There are estimated to be more than 20, 000 species of plants in Venezuela, of which more than 1500 are used for medicinal purposes by indigenous and local communities.", "output": "There is no related enetity." }, { "input": "Only a relatively small proportion of these have been evaluated in terms of their potential as antitumor agents.", "output": "There is no related enetity." }, { "input": "In this study, we screened 308 extracts from 102 species for cytostatic and cytotoxic activity against a panel of six tumor cell lines using a 24 - h sulphorhodamine B assay.", "output": "sulphorhodamine B." }, { "input": "Extracts from Clavija lancifolia, Hamelia patens, Piper san - vicentense, Physalis cordata, Jacaranda copaia, Heliotropium indicum, and Annona squamosa were the most cytotoxic, whereas other extracts from Calotropis gigantea, Hyptis dilatata, Chromolaena odorata, Siparuna guianensis, Jacaranda obtusifolia, Tapirira guianensis, Xylopia aromatica, Protium heptaphyllum, and Piper arboreum showed the greatest cytostatic activity.", "output": "There is no related enetity." }, { "input": "These results confirm previous reports on the cytotoxic activities of the abovementioned plants as well as prompting further studies on others such as C. lancifolia and H. dilatata that have not been so extensively studied.", "output": "There is no related enetity." }, { "input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "The interaction between mGluR1 and the calcium channel Cav 2. 1 preserves coupling in the presence of long Homer proteins.", "output": "calcium." }, { "input": "Group I metabotropic glutamate receptors ( mGluR1 and 5 ) are G protein coupled receptors that regulate neuronal activity in a number of ways.", "output": "glutamate." }, { "input": "Some of the most well studied functions of group I mGluRs, such as initiation of multiple forms of mGluR - dependent long - term depression, require receptor localization near the post - synaptic density ( PSD ).", "output": "There is no related enetity." }, { "input": "This localization is in turn dependent on the Homer family of scaffolding proteins which bind to a small motif on the distal C - termini of mGluR1 and 5, localize the receptors near the PSD, strengthen coupling to post - synaptic effectors and simultaneously uncouple the mGluRs from extra - synaptic effectors such as voltage dependent ion channels.", "output": "C." }, { "input": "Here the selectivity of this uncoupling process was examined by testing the ability of Homer - 2b to uncouple mGluR1 from multiple voltage dependent calcium channels including Ca ( V2. 2 ) ( N - type ), Ca ( V3. 2 ) ( T - type ), and Ca ( V2. 1 ) ( P / Q - type ) expressed in rat sympathetic neurons from the superior cervical ganglion ( SCG ).", "output": "calcium, Ca, Ca, Ca." }, { "input": "Of these, only the mGluR1 - Ca ( V2. 1 ) modulatory pathway was insensitive to Homer - 2b expression.", "output": "There is no related enetity." }, { "input": "Uncoupling from this channel was achieved by co - expression of an mGluR1 C - terminal protein designed to disrupt a previously described direct interaction between these two proteins, suggesting that this interaction allows incorporation of Ca ( V2. 1 ) into the mGluR1 / Homer signaling complex, thereby preserving modulation in the presence of scaffolding Homer proteins.", "output": "C, Ca." }, { "input": "This article is part of a Special Issue entitled ' Metabotropic Glutamate Receptors '.", "output": "Glutamate." }, { "input": "Pharmacological profiling of native group II metabotropic glutamate receptors in primary cortical neuronal cultures using a FLIPR.", "output": "glutamate." }, { "input": "The group II metabotropic glutamate ( mGlu ) receptors comprised of the mGlu2 and mGlu3 receptor subtypes have gained recognition in recent years as potential targets for psychiatric disorders, including anxiety and schizophrenia.", "output": "glutamate." }, { "input": "In addition to studies already indicating which subtype mediates the anxiolytic and anti - psychotic effects observed in disease models, studies to help further define the preferred properties of selective group II mGlu receptor ligands will be essential.", "output": "There is no related enetity." }, { "input": "Comparison of the in vitro properties of these ligands to their in vivo efficacy and tolerance profiles may help provide these additional insights.", "output": "There is no related enetity." }, { "input": "We have developed a relatively high - throughput native group II mGlu receptor functional assay to aid this characterisation.", "output": "There is no related enetity." }, { "input": "We have utilised dissociated primary cortical neuronal cultures, which after 7 days in vitro have formed functional synaptic connections and display periodic and spontaneous synchronised calcium ( Ca ( 2 + ) ) oscillations in response to intrinsic action potential bursts.", "output": "calcium, Ca ( 2 + )." }, { "input": "We herein demonstrate that in addition to non - selective group II mGlu receptor agonists, ( 2R, 4R ) - APDC, LY379268 and DCG - IV, a selective mGlu2 agonist, LY541850, and mGlu2 positive allosteric modulators, BINA and CBiPES, inhibit the frequency of synchronised Ca ( 2 + ) oscillations in primary cultures of rat and mouse cortical neurons.", "output": "( 2R , 4R ) - APDC, LY379268, DCG - IV, LY541850, Ca ( 2 + )." }, { "input": "Use of cultures from wild - type, mGlu2 ( - / - ), mGlu3 ( - / - ) and mGlu2 / 3 ( - / - ) mice allowed us to further probe the contribution of mGlu2 and mGlu3, and revealed LY541850 to be a partial mGlu2 agonist and a full mGlu3 antagonist.", "output": "LY541850." }, { "input": "Overnight pre - treatment of cultures with these ligands revealed a preferred desensitisation profile after treatment with a positive allosteric modulator.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Metabotropic Glutamate Receptors '.", "output": "Glutamate." }, { "input": "Glycine release is regulated by metabotropic glutamate receptors sensitive to mGluR2 / 3 ligands and activated by N - acetylaspartylglutamate ( NAAG ).", "output": "Glycine, glutamate, N - acetylaspartylglutamate, NAAG." }, { "input": "The presence of metabotropic glutamate receptors ( mGluRs ) of group II modulating glycine exocytosis from glycinergic nerve endings of mouse spinal cord was investigated.", "output": "glutamate, glycine." }, { "input": "Purified synaptosomes were selectively prelabeled with [ ( 3 ) H ] glycine through the neuronal transporter GlyT2 and subsequently depolarized by superfusion with 12 mM KCl.", "output": "[ ( 3 ) H ] glycine, KCl." }, { "input": "The selective mGluR2 / 3 agonist LY379268 inhibited the K ( + ) - evoked overflow of [ ( 3 ) H ] glycine in a concentration - dependent manner ( EC ( 50 ) about 0. 2 nM ).", "output": "LY379268, K ( + ), [ ( 3 ) H ] glycine." }, { "input": "The effect of LY379268 was prevented by the selective mGluR2 / 3 antagonist LY341495 ( IC ( 50 ) about 1 nM ).", "output": "LY379268, LY341495." }, { "input": "N - acetylaspartylglutamate ( NAAG ) inhibited [ ( 3 ) H ] glycine overflow with extraordinary potency ( EC ( 50 ) about 50 fmol ).", "output": "N - acetylaspartylglutamate, NAAG, [ ( 3 ) H ] glycine." }, { "input": "In contrast, glutamate was ineffective up to 0. 1 nM, excluding that glutamate contamination of commercial NAAG samples is responsible for the reported activity of NAAG at mGluR3.", "output": "glutamate, glutamate, NAAG, NAAG." }, { "input": "LY341495 antagonized the NAAG inhibition of [ ( 3 ) H ] glycine release.", "output": "LY341495, NAAG, [ ( 3 ) H ] glycine." }, { "input": "The effect of a combination of maximally effective concentrations of LY379268 and NAAG exhibited no additivity.", "output": "LY379268, NAAG." }, { "input": "The non - hydrolysable NAAG analogue N - acetylaspartyl - beta - linked glutamate ( beta - NAAG ) antagonized NAAG and LY379268.", "output": "NAAG, N - acetylaspartyl - beta - linked glutamate, beta - NAAG, NAAG, LY379268." }, { "input": "In conclusion, our results show that glycinergic nerve endings in spinal cord are endowed with group II mGluRs mediating inhibition of glycine exocytosis.", "output": "glycine." }, { "input": "NAAG can activate these presynaptic receptors with extremely high affinity and with characteristics compatible with the reported mGluR3 pharmacology.", "output": "NAAG." }, { "input": "This article is part of a Special Issue entitled ' Metabotropic Glutamate Receptors '.", "output": "Glutamate." }, { "input": "Attenuation of methamphetamine seeking by the mGluR2 / 3 agonist LY379268 in rats with histories of restricted and escalated self - administration.", "output": "methamphetamine, LY379268." }, { "input": "Recent findings implicate group II metabotropic glutamate receptors ( mGluR ( 2 / 3 ) ) in the reinforcing effects of psychostimulants and have identified these receptors as potential treatment targets for drug addiction.", "output": "glutamate." }, { "input": "Here, we investigated the effects of mGluR ( 2 / 3 ) stimulation on cue - and drug - primed reinstatement in rats with different histories of methamphetamine ( METH ) self - administration training, under two conditions: 16 daily sessions of short access ( 90 min / day, ShA ), or 8 daily sessions of short access followed by 8 sessions of long access ( 6 h / day, LgA ).", "output": "methamphetamine, METH." }, { "input": "Following self - administration and subsequent extinction training, rats were pretreated with the selective mGluR ( 2 / 3 ) agonist LY379268 ( variable dose, 0 - 3 mg / kg ), exposed to METH - paired cues or a priming injection of METH ( 1 mg / kg ), and tested for reinstatement of METH - seeking behavior.", "output": "LY379268, METH, METH, METH." }, { "input": "LgA rats self - administered greater amounts of METH during the second half of training, but when pretreated with vehicle, ShA and LgA rats showed cue - and drug - primed reinstatement at equivalent response rates.", "output": "METH." }, { "input": "However, LgA rats demonstrated greater sensitivity to mGluR ( 2 / 3 ) stimulation with attenuated responding during cue - induced reinstatement after 0. 3 mg / kg and higher doses of LY379268, whereas ShA rats decreased cue - induced reinstatement behavior following 1. 0 mg / kg and 3. 0 mg / kg LY379268.", "output": "LY379268, LY379268." }, { "input": "Additionally, both LgA and ShA rats exhibited decreased METH - primed reinstatement behavior following 0. 3 mg / kg and higher doses of LY379268.", "output": "METH, LY379268." }, { "input": "A separate group of control rats was trained to self - administer sucrose pellets, and demonstrated attenuated cue - induced sucrose - seeking behavior following 1. 0 and 3. 0 mg / kg LY379268.", "output": "LY379268." }, { "input": "Together, the results indicate that LY379268 has differential attenuating effects on cue - induced reinstatement behavior in rats with different histories of METH intake.", "output": "LY379268, METH." }, { "input": "This article is part of a Special Issue entitled ' Metabotropic Glutamate Receptors '.", "output": "Glutamate." }, { "input": "Stathmin 1 is a potential novel oncogene in melanoma.", "output": "There is no related enetity." }, { "input": "In previous studies, we demonstrated that miR - 193b expression is reduced in melanoma relative to benign nevi, and also that miR - 193b represses cyclin D1 and Mcl - 1 expression.", "output": "There is no related enetity." }, { "input": "We suggested that stathmin 1 ( STMN1 ) might be a target of miR - 193b.", "output": "There is no related enetity." }, { "input": "STMN1 normally regulates microtubule dynamics either by sequestering free tubulin heterodimers or by promoting microtubule catastrophe.", "output": "There is no related enetity." }, { "input": "Increased expression of STMN1 has been observed in a variety of human malignancies, but its association with melanoma is unknown.", "output": "There is no related enetity." }, { "input": "We now report that STMN1 is upregulated during the progression of melanoma relative to benign nevi, and that STMN1 is directly regulated by miR - 193b.", "output": "There is no related enetity." }, { "input": "Using an experimental cell culture approach, overexpression of miR - 193b using synthetic microRNAs repressed STMN1 expression, whereas inhibition of miR - 193b with anti - miR oligos increased STMN1 expression in melanoma cells.", "output": "There is no related enetity." }, { "input": "The use of a luciferase reporter assay confirmed that miR - 193b directly regulates STMN1 by targeting the 3 ' - untranslated region of STMN1 mRNA.", "output": "There is no related enetity." }, { "input": "We further demonstrated that STMN1 is overexpressed in malignant melanoma compared with nevi in two independent melanoma cohorts, and that its level is inversely correlated with miR - 193b expression.", "output": "There is no related enetity." }, { "input": "However, STMN1 expression was not significantly associated with patient survival, Breslow depth, mitotic count or patient age.", "output": "There is no related enetity." }, { "input": "STMN1 knockdown by small - interfering RNA in melanoma cells drastically repressed cell proliferation and migration potential, whereas ectopic expression of STMN1 using lentivirus increased cell proliferation and migration rates.", "output": "There is no related enetity." }, { "input": "Subsequent gene expression analysis indicated that interconnected cytoskeletal networks are directly affected following STMN1 knockdown.", "output": "There is no related enetity." }, { "input": "In addition, we identified deregulated genes associated with proliferation and migration, and revealed that p21 ( Cip1 / Waf1 ) and p27 ( Kip ) could be downstream effectors of STMN1 signaling.", "output": "There is no related enetity." }, { "input": "Taken together, our study suggests that downregulation of miR - 193b may contribute to increased STMN1 expression in melanoma, which consequently promotes migration and proliferation of tumor cells.", "output": "There is no related enetity." }, { "input": "The p44 / wdr77 - dependent cellular proliferation process during lung development is reactivated in lung cancer.", "output": "There is no related enetity." }, { "input": "During lung development, cells proliferate for a defined length of time before they begin to differentiate.", "output": "There is no related enetity." }, { "input": "Factors that control this proliferative process and how this growth process is related to lung cancer are currently unknown.", "output": "There is no related enetity." }, { "input": "Here, we found that the WD40 - containing protein ( p44 / wdr77 ) was expressed in growing epithelial cells at the early stages of lung development.", "output": "There is no related enetity." }, { "input": "In contrast, p44 / wdr77 expression was diminished in fully differentiated epithelial cells in the adult lung.", "output": "There is no related enetity." }, { "input": "Loss of p44 / wdr77 gene expression led to cell growth arrest and differentiation.", "output": "There is no related enetity." }, { "input": "Re - expression of p44 / wdr77 caused terminally differentiated cells to re - enter the cell cycle.", "output": "There is no related enetity." }, { "input": "Our findings suggest that p44 / wdr77 is essential and sufficient for proliferation of lung epithelial cells.", "output": "There is no related enetity." }, { "input": "P44 / Wdr77 was re - expressed in lung cancer, and silencing p44 / wdr77 expression strongly inhibited growth of lung adenocarcinoma cells in tissue culture and abolished growth of lung adenocarcinoma tumor xenografts in mice.", "output": "There is no related enetity." }, { "input": "The growth arrest induced by loss of p44 / wdr77 expression was partially through the p21 - Rb signaling.", "output": "There is no related enetity." }, { "input": "Our results suggest that p44 / wdr77 controls cellular proliferation during lung development, and this growth process is reactivated during lung tumorigenesis.", "output": "There is no related enetity." }, { "input": "Two new phenolic glycosides from Inula cappa DC.", "output": "phenolic glycosides." }, { "input": "Two new phenolic glycosides were isolated from the ethanol extract of the roots of Inula cappa DC.", "output": "phenolic glycosides, ethanol." }, { "input": "Their structures were defined as 4 - [ ( 6 - O - ( E ) - caffeoyl ) - beta - D - glucopyranosyl ] vanillic acid ( 1 ) and 3 - O - [ beta - D - apiofurarnosyl - ( 1 - 6 ) - beta - D - glucopyranoxy ] - 6 - hydroxy - p - cymene ( 2 ) on the basis of spectral analysis.", "output": "4 - [ ( 6 - O - ( E ) - caffeoyl ) - beta - D - glucopyranosyl ] vanillic acid, 3 - O - [ beta - D - apiofurarnosyl - ( 1 - 6 ) - beta - D - glucopyranoxy ] - 6 - hydroxy - p - cymene." }, { "input": "In vitro characterization of organophosphorus compound hydrolysis by native and recombinant human prolidase.", "output": "organophosphorus." }, { "input": "Human prolidase is a binuclear metalloenzyme, which can potentially function as a catalytic bioscavenger for organophosphorus ( OP ) nerve agents.", "output": "organophosphorus." }, { "input": "Although the biochemical properties of native prolidase purified from human erythrocytes, liver, kidney, and fibroblast cells are well known, it is very poorly characterized with regard to its OP hydrolyzing activity.", "output": "There is no related enetity." }, { "input": "Also, the high cost of purification of large quantities of native enzyme limits its use as a bioscavenger.", "output": "There is no related enetity." }, { "input": "Thus, recombinant human prolidase with similar biochemical properties to those of native enzyme would be more suitable as a catalytic bioscavenger.", "output": "There is no related enetity." }, { "input": "In this study, we established an Escherichia coli expression system, which produced a large amount of tagged human liver prolidase that was purified to over 95 % purity from the soluble fraction of cell lysate by affinity chromatography on Streptavidin - agarose resin.", "output": "There is no related enetity." }, { "input": "The catalytic properties of the recombinant enzyme were compared in vitro with those of highly purified prolidase I isolated from human erythrocytes.", "output": "There is no related enetity." }, { "input": "The catalytic properties of recombinant prolidase overlap with those of the erythrocyte - derived native enzyme.", "output": "There is no related enetity." }, { "input": "Both enzymes efficiently hydrolyzed diisopropylfluorophosphate, sarin, soman, tabun and cyclosarin, but were much less efficient at hydrolyzing paraoxon and methyl paraoxon.", "output": "diisopropylfluorophosphate, sarin, soman, tabun, cyclosarin, paraoxon, methyl paraoxon." }, { "input": "These results suggest that human prolidase expressed in E. coli is suitable for further development as a catalytic bioscavenger for OP nerve agents.", "output": "There is no related enetity." }, { "input": "Theoretical study of the pH - dependent antioxidant properties of vitamin C.", "output": "vitamin C." }, { "input": "Molecules acting as antioxidants capable of scavenging reactive oxygen species ( ROS ) are of utmost importance in the living cell.", "output": "oxygen." }, { "input": "Vitamin C is known to be one of these molecules.", "output": "Vitamin C." }, { "input": "In this study we have analyzed the reactivity of vitamin C toward the [ Formula: see text ] and [ Formula: see text ] ROS species, in all acidic, neutral and basic media.", "output": "vitamin C." }, { "input": "In order to do so, density functional theory ( DFT ) have been used.", "output": "There is no related enetity." }, { "input": "More concretely, the meta - GGA functional MPW1B95 have been used.", "output": "There is no related enetity." }, { "input": "Two reaction types have been studied in each case: addition to the ring atoms, and hydrogen / proton abstraction.", "output": "hydrogen." }, { "input": "Our results show that [ Formula: see text ] is the most reactive species, while [ Formula: see text ] displays low reactivity.", "output": "There is no related enetity." }, { "input": "In all three media, vitamin C reactions with two hydroxyl radicals show a wide variety of possible products.", "output": "vitamin C, hydroxyl." }, { "input": "Cooperation between p53 and the telomere - protecting shelterin component Pot1a in endometrial carcinogenesis.", "output": "There is no related enetity." }, { "input": "Type II endometrial cancer ( EMCA ) represents only 10 % of all EMCAs, but accounts for 40 % of EMCA - related mortality.", "output": "There is no related enetity." }, { "input": "Previous studies of human tumors have shown an association between Type II tumors and damaged telomeres.", "output": "There is no related enetity." }, { "input": "We hypothesized that the lack of murine Type II EMCA models is due to the extremely long telomeres in laboratory mouse strains.", "output": "There is no related enetity." }, { "input": "We previously showed that telomerase - null mice with critically short telomeres developed endometrial lesions histologically resembling endometrial intraepithelial carcinoma ( EIC ), the accepted precursor for Type II EMCA.", "output": "There is no related enetity." }, { "input": "However, these mice did not develop invasive endometrial adenocarcinoma, and instead succumbed prematurely to multi - organ failure.", "output": "There is no related enetity." }, { "input": "Here, we modeled critical telomere attrition by conditionally inactivating Pot1a, a component of the shelterin complex that stabilizes telomeres, within endometrial epithelium.", "output": "There is no related enetity." }, { "input": "Inactivation of Pot1a by itself did not stimulate endometrial carcinogenesis, and did not result in detectable DNA damage or apoptosis in endometrium.", "output": "There is no related enetity." }, { "input": "However, simultaneous inactivation of Pot1a and p53 resulted in EIC - like lesions by 9 months indistinguishable from those seen in late generation telomerase - null mice.", "output": "There is no related enetity." }, { "input": "These lesions progressed to invasive endometrial adenocarcinomas as early as 9 months of age with metastatic disease in 100 % of the animals by 15 months.", "output": "There is no related enetity." }, { "input": "These tumors were poorly differentiated endometrial adenocarcinomas with prominent nuclear atypia, resembling human Type II cancers.", "output": "There is no related enetity." }, { "input": "Furthermore, these tumors were aneuploid with double - stranded DNA breaks and end - to - end telomere fusions and most were tetraploid or near - tetraploid.", "output": "There is no related enetity." }, { "input": "These studies lend further support to the hypothesis that telomeric instability has a critical role in Type II endometrial carcinogenesis and provides an intriguing in - vivo correlate to recent studies implicating telomere - dependent tetraploidization as an important mechanism in carcinogenesis.", "output": "There is no related enetity." }, { "input": "Hyperinakin, a new anti - inflammatory phloroglucinol derivative from Hypericum nakamurai.", "output": "Hyperinakin, phloroglucinol." }, { "input": "Phytochemical investigation of Hypericum nakamurai ( Masamune ) Robson has led to the isolation of three phloroglucinol derivatives 1 - 3.", "output": "phloroglucinol." }, { "input": "The structures of these compounds were determined by the analysis of their spectroscopic data ( IR, mass and UV ), and by the application of 1 - D and 2 - D - NMR techniques.", "output": "There is no related enetity." }, { "input": "Hyperinakin ( 1 ) is a new compound.", "output": "Hyperinakin." }, { "input": "The anti - inflammatory activities of compounds 1 - 3 were also tested and evaluated.", "output": "There is no related enetity." }, { "input": "A biogenetic pathway for compounds 1 - 3 was also proposed.", "output": "There is no related enetity." }, { "input": "Recurrent gene deletions and the evolution of adaptive cyanogenesis polymorphisms in white clover ( Trifolium repens L. ).", "output": "There is no related enetity." }, { "input": "Understanding the molecular evolution of genes that underlie intraspecific polymorphisms can provide insights into the process of adaptive evolution.", "output": "There is no related enetity." }, { "input": "For adaptive polymorphisms characterized by gene presence / absence ( P / A ) variation, underlying loci commonly show signatures of long - term balancing selection, with gene - presence and gene - absence alleles maintained as two divergent lineages.", "output": "There is no related enetity." }, { "input": "We examined the molecular evolution of two unlinked P / A polymorphisms that underlie a well - documented adaptive polymorphism for cyanogenesis ( hydrogen cyanide release with tissue damage ) in white clover.", "output": "hydrogen cyanide." }, { "input": "Both cyanogenic and acyanogenic plants occur in this species, and the ecological forces that maintain this chemical defence polymorphism have been studied for several decades.", "output": "There is no related enetity." }, { "input": "Using a sample of 65 plants, we investigated the molecular evolution of sequences flanking the two underlying cyanogenesis genes: Ac / ac ( controlling the presence / absence of cyanogenic glucosides ) and Li / li ( controlling the presence / absence of their hydrolysing enzyme, linamarase ).", "output": "cyanogenic glucosides." }, { "input": "A combination of genome walking, PCR assays, DNA sequence analysis and Southern blotting was used to test whether these adaptive P / A polymorphisms show evidence of long - term balancing selection, or whether gene - absence alleles have evolved repeatedly through independent deletion events.", "output": "There is no related enetity." }, { "input": "For both loci, we detect no signatures of balancing selection in the closest flanking genomic sequences.", "output": "There is no related enetity." }, { "input": "Instead, we find evidence for variation in the size of the deletions characterizing gene - absence alleles.", "output": "There is no related enetity." }, { "input": "These observations strongly suggest that both of these polymorphisms have been evolving through recurrent gene deletions over time.", "output": "There is no related enetity." }, { "input": "We discuss the genetic mechanisms that could account for this surprising pattern and the implications of these findings for mechanisms of rapid adaptive evolution in white clover.", "output": "There is no related enetity." }, { "input": "Regulation of gene expression in human prostate cancer cells with artificially constructed promoters that are activated in response to ultrasound stimulation.", "output": "There is no related enetity." }, { "input": "We chose promoters responsive to sonication in LNCap cells, a prostate cancer cell line, out of a library composed of DNA fragments constructed by linking the TATA box sequence to randomly combined cis - acting elements of transcription factors activated in response to radiation in prostate cancer cells.", "output": "There is no related enetity." }, { "input": "When a plasmid containing the luciferase gene under control of a promoter was transfected into LNCap cells and sonicated with 1 MHz ultrasound at 0. 5 W / cm ( 2 ), 10 % DF for 60s, 13 promoters showed more than 10 - fold enhancement compared with their counterparts without sonication 12h after sonication.", "output": "There is no related enetity." }, { "input": "As to their responsiveness to sonication, the best two promoters were then compared to clone 880 - 8, a derivative from clone 880 that was created by random introduction of point mutations and was shown to have an improved response to X - ray irradiation.", "output": "There is no related enetity." }, { "input": "We then took clone 880 - 8 for further analyses since it showed the highest enhancement to sonication, though not statistically significant from the others.", "output": "There is no related enetity." }, { "input": "Next, we employed a retrovirus vector and stably introduced the luciferase gene under control of clone 880 - 8 into LNCap cells to establish a cell line.", "output": "There is no related enetity." }, { "input": "When the cell line was sonicated with 1 MHz ultrasound at 0. 5 W / cm ( 2 ), 10 % DF for 60s, luciferase expression was enhanced up to 14. 8 - fold 12h after sonication.", "output": "There is no related enetity." }, { "input": "We then established another cell line by replacing the luciferase gene with the fcy:: fur gene, a suicide gene, and when the cell line was sonicated with 1 MHz ultrasound at 0. 5 W / cm ( 2 ), 10 % DF for 60s, expression of the gene was enhanced, showing the maximum expression 12 - 24h after sonication.", "output": "There is no related enetity." }, { "input": "When the cells were incubated in medium containing 5 - fluorocytosine, cell survival ratio decreased dose dependently with 5 - fluorocytosine only after sonication treatment, suggesting this promoter could be utilized for gene expression control with ultrasound.", "output": "5 - fluorocytosine, 5 - fluorocytosine." }, { "input": "Genetic determinants of neuronal vulnerability to apoptosis.", "output": "There is no related enetity." }, { "input": "Apoptosis is a common mode of cell death that contributes to neuronal loss associated with neurodegeneration.", "output": "There is no related enetity." }, { "input": "Single - nucleotide polymorphisms ( SNPs ) in chromosomal DNA are contributing factors dictating natural susceptibility of humans to disease.", "output": "nucleotide." }, { "input": "Here, the most common SNPs affecting neuronal vulnerability to apoptosis are reviewed in the context of neurological disorders.", "output": "There is no related enetity." }, { "input": "Polymorphic variants in genes encoding apoptotic proteins, either from the extrinsic ( FAS, TNF - alpha, CASP8 ) or the intrinsic ( BAX, BCL2, CASP3, CASP9 ) pathways could be highly valuable in the diagnosis of neurodegenerative diseases and stroke.", "output": "There is no related enetity." }, { "input": "Interestingly, the Arg72Pro SNP in TP53, the gene encoding tumor suppressor p53, was recently revealed a biomarker of poor prognosis in stroke due to its ability to modulate neuronal apoptotic death.", "output": "There is no related enetity." }, { "input": "Search for new SNPs responsible for genetic variability to apoptosis will ensure the implementation of novel diagnostic and prognostic tools, as well as therapeutic strategies against neurological diseases.", "output": "There is no related enetity." }, { "input": "Dissolved gas and ultrasonic cavitation - - a review.", "output": "There is no related enetity." }, { "input": "The physics and chemistry of nonlinearly oscillating acoustic cavitation bubbles are strongly influenced by the dissolved gas in the surrounding liquid.", "output": "There is no related enetity." }, { "input": "Changing the gas alters among others the luminescence spectrum, and the radical production of the collapsing bubbles.", "output": "There is no related enetity." }, { "input": "An overview of experiments with various gas types and concentration described in literature is given and is compared to mechanisms that lead to the observed changes in luminescence spectra and radical production.", "output": "There is no related enetity." }, { "input": "The dissolved gas type changes the bubble adiabatic ratio, thermal conductivity, and the liquid surface tension, and consequently the hot spot temperature.", "output": "There is no related enetity." }, { "input": "The gas can also participate in chemical reactions, which can enhance radical production or luminescence of a cavitation bubble.", "output": "There is no related enetity." }, { "input": "With this knowledge, the gas content in cavitation can be tailored to obtain the desired output.", "output": "There is no related enetity." }, { "input": "Towards an understanding and control of cavitation activity in 1 MHz ultrasound fields.", "output": "There is no related enetity." }, { "input": "Various industrial processes such as sonochemical processing and ultrasonic cleaning strongly rely on the phenomenon of acoustic cavitation.", "output": "There is no related enetity." }, { "input": "As the occurrence of acoustic cavitation is incorporating a multitude of interdependent effects, the amount of cavitation activity in a vessel is strongly depending on the ultrasonic process conditions.", "output": "There is no related enetity." }, { "input": "It is therefore crucial to quantify cavitation activity as a function of the process parameters.", "output": "There is no related enetity." }, { "input": "At 1 MHz, the active cavitation bubbles are so small that it is becoming difficult to observe them in a direct way.", "output": "There is no related enetity." }, { "input": "Hence, another metrology based on secondary effects of acoustic cavitation is more suitable to study cavitation activity.", "output": "There is no related enetity." }, { "input": "In this paper we present a detailed analysis of acoustic cavitation phenomena at 1 MHz ultrasound by means of time - resolved measurements of sonoluminescence, cavitation noise, and synchronized high - speed stroboscopic Schlieren imaging.", "output": "There is no related enetity." }, { "input": "It is shown that a correlation exists between sonoluminescence, and the ultraharmonic and broadband signals extracted from the cavitation noise spectra.", "output": "There is no related enetity." }, { "input": "The signals can be utilized to characterize different regimes of cavitation activity at different acoustic power densities.", "output": "There is no related enetity." }, { "input": "When cavitation activity sets on, the aforementioned signals correlate to fluctuations in the Schlieren contrast as well as the number of nucleated bubbles extracted from the Schlieren Images.", "output": "There is no related enetity." }, { "input": "This additionally proves that signals extracted from cavitation noise spectra truly represent a measure for cavitation activity.", "output": "There is no related enetity." }, { "input": "The cyclic behavior of cavitation activity is investigated and related to the evolution of the bubble populations in the ultrasonic tank.", "output": "There is no related enetity." }, { "input": "It is shown that cavitation activity is strongly linked to the occurrence of fast - moving bubbles.", "output": "There is no related enetity." }, { "input": "The origin of this \" bubble streamers \" is investigated and their role in the initialization and propagation of cavitation activity throughout the sonicated liquid is discussed.", "output": "There is no related enetity." }, { "input": "Finally, it is shown that bubble activity can be stabilized and enhanced by the use of pulsed ultrasound by conserving and recycling active bubbles between subsequent pulsing cycles.", "output": "There is no related enetity." }, { "input": "The potential of nicotinic enhancement of cognitive remediation training in schizophrenia.", "output": "There is no related enetity." }, { "input": "Cognitive deficits in schizophrenia are critically important predictors of long - term psychosocial outcome and are not significantly ameliorated by currently available medications.", "output": "There is no related enetity." }, { "input": "Cognitive remediation training has shown promise for alleviating cognitive symptoms of schizophrenia, but the clinical significance has often been limited by small effect sizes.", "output": "There is no related enetity." }, { "input": "Approaches that achieve larger improvement involve time requirements that can be cost - prohibitive within the current clinical care system.", "output": "There is no related enetity." }, { "input": "This mini - review evaluates the theoretical potential of a pharmacological enhancement strategy of cognitive remediation training with nicotinic acetylcholine receptor ( nAChR ) agonists.", "output": "acetylcholine." }, { "input": "nAChR agonists can facilitate sensory processing, alertness, attention, learning and memory.", "output": "There is no related enetity." }, { "input": "While these effects may be too subtle and short - lasting to be of clinical relevance as a primary treatment of cognitive deficits, they constitute an ideal effects profile for enhancing training benefits.", "output": "There is no related enetity." }, { "input": "Several mechanisms are described through which repeated coupling of cognitive training challenges with nAChR stimulation may enhance and accelerate cognitive remediation training effects, advancing such interventions into more effective and practicable treatments of some of the most debilitating symptoms of schizophrenia.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "Enhanced mGlu5 - receptor dependent long - term depression at the Schaffer collateral - CA1 synapse of congenitally learned helpless rats.", "output": "There is no related enetity." }, { "input": "Alterations of the glutamatergic system have been implicated in the pathophysiology and treatment of major depression.", "output": "There is no related enetity." }, { "input": "In order to investigate the expression and function of mGlu5 receptors in an animal model for treatment - resistant depression we used rats bred for congenital learned helplessness ( cLH ) and the control strain, bred for resistance against inescapable stress, congenitally. not learned helpless rats ( cNLH ).", "output": "There is no related enetity." }, { "input": "Western blot analysis showed an increased expression of mGlu5 ( but not mGlu1a ) receptors in the hippocampus of cLH rats, as compared with control cNLH rats.", "output": "There is no related enetity." }, { "input": "We also examined mGlu1 / 5 receptor signaling by in vivo measurement of DHPG - stimulated polyphosphoinositides hydrolysis.", "output": "DHPG, polyphosphoinositides." }, { "input": "Stimulation of ( 3 ) H - inositolmonophosphate formation induced by i. c. v. injection of DHPG was enhanced by about 50 % in the hippocampus of cLH rats.", "output": "( 3 ) H - inositolmonophosphate, DHPG." }, { "input": "Correspondingly, DHPG - induced long - term depression ( LTD ) at Schaffer collateral / CA1 pyramidal cell synapses was amplified in hippocampal slices of cLH rats, whereas LTD induced by low frequency stimulation of the Schaffer collaterals did not change.", "output": "DHPG." }, { "input": "Moreover, these effects were associated with decreased basal dendritic spine density of CA1 pyramidal cell in cLH rats.", "output": "There is no related enetity." }, { "input": "These data raise the attractive possibility that changes in the expression and function of mGlu5 receptors in the hippocampus might underlie the changes in synaptic plasticity associated with the depressive - like phenotype of cLH rats.", "output": "There is no related enetity." }, { "input": "However, chronic treatment of cLH rats with MPEP did not reverse learned helplessness, indicating that the enhanced mGlu5 receptor function is not the only player in the behavioral phenotype of this genetic model of depression.", "output": "MPEP." }, { "input": "This article is part of a Special Issue entitled ' Metabotropic Glutamate Receptors '.", "output": "Glutamate." }, { "input": "A variant in the carboxyl - terminus of connexin 40 alters GAP junctions and increases risk for tetralogy of Fallot.", "output": "carboxyl." }, { "input": "GJA5 gene ( MIM no. 121013 ), localized at 1q21. 1, encodes for the cardiac gap junction protein connexin 40.", "output": "There is no related enetity." }, { "input": "In humans, copy number variants of chromosome 1q21. 1 have been associated with variable phenotypes comprising congenital heart disease ( CHD ), including isolated TOF.", "output": "There is no related enetity." }, { "input": "In mice, the deletion of Gja5 can cause a variety of complex CHDs, in particular of the cardiac outflow tract, corresponding to TOF in many cases.", "output": "There is no related enetity." }, { "input": "In the present study, we screened for mutations in the GJA5 gene 178 unrelated probands with isolated TOF.", "output": "There is no related enetity." }, { "input": "A heterozygous nucleotide change ( c. 793C > T ) in exon 2 of the gene leading to the p. Pro265Ser variant at the carboxyl - terminus of the protein was found in two unrelated sporadic patients, one with classic anatomy and one with pulmonary atresia.", "output": "nucleotide, carboxyl." }, { "input": "This GJA5 missense substitution was not observed in 1568 ethnically - matched control chromosomes.", "output": "There is no related enetity." }, { "input": "Immunofluorescent staining and confocal microscopy revealed that cells expressing the mutant protein form sparse or no visible gap - junction plaques in the region of cell - cell contact.", "output": "There is no related enetity." }, { "input": "Moreover, analysis of the transfer of the gap junction permanent tracer lucifer yellow showed that cells expressing the mutant protein have a reduced rate of dye transfer compared with wild - type cells.", "output": "There is no related enetity." }, { "input": "Finally, use of a zebrafish model revealed that microinjection of the GJA5 - p. Pro265Ser mutant disrupts overall morphology of the heart tube in the 37 % ( 22 / 60 ) of embryos, compared with the 6 % ( 4 / 66 ) of the GJA5 wild - type - injected embryos.", "output": "There is no related enetity." }, { "input": "These findings implicate GJA5 gene as a novel susceptibility gene for TOF.", "output": "There is no related enetity." }, { "input": "A newly identified locus for benign adult familial myoclonic epilepsy on chromosome 3q26. 32 - 3q28.", "output": "There is no related enetity." }, { "input": "Benign Adult Familial Myoclonic Epilepsy ( BAFME ) is an autosomal dominant disorder characterized by adult - onset cortical tremor or action myoclonus predominantly in the upper limbs, and generalized seizures.", "output": "There is no related enetity." }, { "input": "We investigated a Thai BAFME family.", "output": "There is no related enetity." }, { "input": "Clinical and electrophysiological studies revealed that 13 were affected with BAFME.", "output": "There is no related enetity." }, { "input": "There were a total of 24 individuals studied.", "output": "There is no related enetity." }, { "input": "Genetic analysis by genome - wide linkage study ( GWLS ) was performed using 400 microsatellite markers and excluded linkage of the previous BAFME loci, 8q23. 3 - q24. 1, and 2p11. 1 - q12. 2.", "output": "There is no related enetity." }, { "input": "GWLS showed that the disease - associated region in our Thai family was linked to a newly identified locus on chromosome 3q26. 32 - 3q28.", "output": "There is no related enetity." }, { "input": "This locus represents the fourth chromosomal region for BAFME.", "output": "There is no related enetity." }, { "input": "Sonoluminescence quenching and cavitation bubble temperature measurements in an ionic liquid.", "output": "There is no related enetity." }, { "input": "A comparison between the temperatures within imploding acoustic cavitation bubbles and the extent of sonoluminescence ( SL ) quenching by C ( 1 ) - C ( 5 ) aliphatic alcohols in 1 - ethyl - 3 - methylimidazolium ethylsulfate ( [ EMIM ] [ EtSO ( 4 ) ], a well known imidazolium based room temperature ionic liquid ( RTIL ) ), has been made at an ultrasound frequency of 213 kHz.", "output": "aliphatic alcohols, 1 - ethyl - 3 - methylimidazolium ethylsulfate, [ EMIM ] [ EtSO ( 4 ) ], imidazolium." }, { "input": "The temperatures obtained ranged from 3500 +/- 200K, in neat [ EMIM ] [ EtSO ( 4 ) ], to about 3200 +/- 200K in RTIL - alcohol containing solutions.", "output": "[ EMIM ] [ EtSO ( 4 ) ], alcohol." }, { "input": "It was also found that the SL intensity decreased with increasing concentration ( up to 1M ) of the alcohols to a greater extent compared with the relative changes to the bubble temperatures.", "output": "alcohols." }, { "input": "Both the extent of the reduction in the bubble temperatures and the SL quenching were much smaller than those obtained in comparable aqueous solutions containing aliphatic alcohols.", "output": "aliphatic alcohols." }, { "input": "Possible reasons for the differences in the observed trends between water / alcohol and [ EMIM ] [ EtSO ( 4 ) ] / alcohol systems under sonication at 213 kHz are discussed.", "output": "alcohol, [ EMIM ] [ EtSO ( 4 ) ], alcohol." }, { "input": "GABAergic activity in autism spectrum disorders: an investigation of cortical inhibition via transcranial magnetic stimulation.", "output": "There is no related enetity." }, { "input": "Mounting evidence suggests a possible role for gamma - aminobutyric acid ( GABA ) in the neuropathophysiology of autism spectrum disorders ( ASD ), but the extent of this impairment is unclear.", "output": "gamma - aminobutyric acid, GABA." }, { "input": "A non - invasive, in vivo measure of GABA involves transcranial magnetic stimulation ( TMS ) of the primary motor cortex to probe cortical inhibition.", "output": "GABA." }, { "input": "Individuals diagnosed with ASD ( high - functioning autism or Asperger ' s disorder ) ( n = 36 [ 28 male ]; mean age: 26. 00 years ) and a group of healthy individuals ( n = 34 [ 23 male ]; mean age: 26. 21 years ) ( matched for age, gender, and cognitive function ) were administered motor cortical TMS paradigms putatively measuring activity at GABAA and GABAB receptors ( i. e., short and long interval paired pulse TMS, cortical silent period ).", "output": "There is no related enetity." }, { "input": "All cortical inhibition paradigms yielded no difference between ASD and control groups.", "output": "There is no related enetity." }, { "input": "There was, however, evidence for short interval cortical inhibition ( SICI ) deficits among those ASD participants who had experienced early language delay, suggesting that GABA may be implicated in an ASD subtype.", "output": "GABA." }, { "input": "The current findings do not support a broad role for GABA in the neuropathophysiology of ASD, but provide further indication that GABAA could be involved in ASD where there is a delay in language acquisition.", "output": "GABA." }, { "input": "This article is part of the Special Issue entitled ' Neurodevelopmental Disorders '.", "output": "There is no related enetity." }, { "input": "Pharmacological treatment of tic disorders and Tourette Syndrome.", "output": "There is no related enetity." }, { "input": "The present review gives an overview of current pharmacological treatment options of tic disorders and Tourette Syndrome ( TS ).", "output": "There is no related enetity." }, { "input": "After a short summary on phenomenology, clinical course and comorbid conditions we review indications for pharmacological treatment in detail.", "output": "There is no related enetity." }, { "input": "Unfortunately, standardized and large enough drug trials in TS patients fulfilling evidence based medicine standards are still scarce.", "output": "There is no related enetity." }, { "input": "Treatment decisions are often guided by individual needs and personal experience of treating clinicians.", "output": "There is no related enetity." }, { "input": "The present recommendations for pharmacological tic treatment are therefore based on both scientific evidence and expert opinion.", "output": "There is no related enetity." }, { "input": "As first - line treatment of tics risperidone ( best evidence level for atypical antipsychotics ) or tiapride ( largest clinical experience in Europe and low rate of adverse reactions ) are recommended.", "output": "risperidone, tiapride." }, { "input": "Aripiprazole ( still limited but promising data with low risk for adverse reactions ) and pimozide ( best evidence of the typical antipsychotics ) are agents of second choice.", "output": "Aripiprazole, pimozide." }, { "input": "In TS patients with comorbid attention deficit hyperactivity disorder ( ADHD ) atomoxetine, stimulants or clonidine should be considered, or, if tics are severe, a combination of stimulants and risperidone.", "output": "atomoxetine, clonidine, risperidone." }, { "input": "When mild to moderate tics are associated with obsessive - compulsive symptoms, depression or anxiety sulpiride monotherapy can be helpful.", "output": "sulpiride." }, { "input": "In more severe cases the combination of risperidone and a selective serotonin reuptake inhibitor should be given.", "output": "risperidone, serotonin." }, { "input": "In summary, further studies, particularly randomized, double - blind, placebo - controlled trials including larger and / or more homogenous patient groups over longer periods are urgently needed to enhance the scientific basis for drug treatment in tic disorders.", "output": "There is no related enetity." }, { "input": "This article is part of the Special Issue entitled ' Neurodevelopmental Disorders '.", "output": "There is no related enetity." }, { "input": "Cognitive enhancement as a treatment for drug addictions.", "output": "There is no related enetity." }, { "input": "Drug addiction continues to be an important public health problem, with an estimated 22. 6 million current illicit drug users in the United States alone.", "output": "There is no related enetity." }, { "input": "For many addictions, including cocaine, methamphetamine, and marijuana addiction, there are no approved pharmacological treatments.", "output": "cocaine, methamphetamine." }, { "input": "Behavioral treatments are effective but effects vary widely across individuals.", "output": "There is no related enetity." }, { "input": "Treatments that are effective across multiple addictions are greatly needed, and accumulating evidence suggests that one such approach may be pharmacological or behavioral interventions that enhance executive inhibitory control in addicts.", "output": "There is no related enetity." }, { "input": "Current evidence indicates that most forms of chronic drug use may be associated with significant cognitive impairments, especially in attention, working memory, and response inhibition functions.", "output": "There is no related enetity." }, { "input": "In some studies, these impairments predict poor treatment retention and outcome.", "output": "There is no related enetity." }, { "input": "A number of cognitive enhancing agents, including galantamine, modafinil, atomoxetine, methylphenidate, and guanfacine, have shown promising findings in human studies.", "output": "galantamine, modafinil, atomoxetine, methylphenidate, guanfacine." }, { "input": "Specific behavioral interventions, including cognitive remediation, also show promise.", "output": "There is no related enetity." }, { "input": "However, whether improvement of selective cognitive functions reduces drug use behavior remains to be determined.", "output": "There is no related enetity." }, { "input": "Cognitive enhancement to improve treatment outcomes is a novel strategy worthy of future research, as are related questions such as whether these approaches may be broadly beneficial to most addicts or best reserved for substance users with specific demonstrated cognitive impairments.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "Pinosylvin Induces Cell Survival, Migration and Anti - Adhesiveness of Endothelial Cells via Nitric Oxide Production.", "output": "Pinosylvin, Nitric Oxide." }, { "input": "Pinosylvin is a phenolic compound mainly found in the Pinus species.", "output": "Pinosylvin, phenolic." }, { "input": "To determine the vascular functions of pinosylvin, we first examined both proliferation and apoptosis of bovine aortic endothelial cells ( BAECs ) in the presence of pinosylvin.", "output": "pinosylvin, pinosylvin." }, { "input": "When BAECs were treated with pinosylvin, etoposide - or starvation - induced apoptosis was shown to be significantly reduced.", "output": "pinosylvin, etoposide." }, { "input": "The anti - apoptotic effect of pinosylvin was mediated by inhibition of caspase - 3.", "output": "pinosylvin." }, { "input": "Moreover, pinosylvin was shown to activate endothelial nitric oxide synthetase ( eNOS ).", "output": "pinosylvin, nitric oxide." }, { "input": "At 1 pM, pinosylvin appeared to have a cell - proliferative effect in the endothelial cell.", "output": "pinosylvin." }, { "input": "The pinosylvin - induced cell proliferation was declined by treatment with L - NAME, an eNOS inhibitor.", "output": "pinosylvin, L - NAME." }, { "input": "Then, we found that pinosylvin had a stimulatory effect on cell migration and tube formation.", "output": "pinosylvin." }, { "input": "These stimulatory effects suggest that pinosylvin is likely to act as a pro - angiogenic factor.", "output": "pinosylvin." }, { "input": "Yet another effect of pinosylvin was inhibition of lipopolysaccharide - induced THP - 1 cell adhesion to endothelial cells.", "output": "pinosylvin." }, { "input": "Altogether, we propose that pinosylvin may be utilized as a phytotherapic agent for the prevention of cardiovascular inflammatory diseases.", "output": "pinosylvin." }, { "input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Dihydroxy - Isosteviol Methyl Ester from Pulsatilla nigricans Induces Apoptosis in HeLa Cells: Its Cytoxicity and Interaction with Calf Thymus DNA.", "output": "Dihydroxy - Isosteviol Methyl Ester." }, { "input": "Dihydroxy - isosteviol methyl ester ( DIME ), the principal biological compound isolated from the medicinal plant Pulsatilla nigricans ( Fam: Ranunculaceae ) having the molecular formula of C21 H34 O3 ( molecular weight 334. 25 ), was administered to cervical cancer cells ( HeLa ) in vitro to evaluate its possible apoptotic ( anti - cancer ) potentials.", "output": "Dihydroxy - isosteviol methyl ester, DIME, C21 H34 O3." }, { "input": "We analyzed the expression of p53, Bax, Bcl2, Apaf and caspase 3 signal proteins and analyzed the early apoptotic events in HeLa cells induced by DIME using protocols like Annexin V - FITC and PI staining.", "output": "DIME." }, { "input": "DIME caused a significant decrease in cell viability, induced nuclear condensation and inter - nucleosomal DNA fragmentation.", "output": "DIME." }, { "input": "We further studied the interaction of DIME with calf thymus DNA as target through circular - dichroism spectra.", "output": "DIME." }, { "input": "Results showed that DIME interacted with DNA, bringing indiscernible changes in structure and conformation.", "output": "DIME." }, { "input": "Thus, DIME showed its capability to induce apoptosis in cancer cells, signifying its utility in drug design as a possible candidate for chemoprevention.", "output": "DIME." }, { "input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Genome - wide patterns of standing genetic variation in a marine population of three - spined sticklebacks.", "output": "There is no related enetity." }, { "input": "Since the end of the Pleistocene, the three - spined stickleback ( Gasterosteus aculeatus ) has repeatedly colonized and adapted to various freshwater habitats probably originating from ancestral marine populations.", "output": "There is no related enetity." }, { "input": "Standing genetic variation and the underlying genomic architecture both have been speculated to contribute to recent adaptive radiations of sticklebacks.", "output": "There is no related enetity." }, { "input": "Here, we expand on the current genomic resources of this fish by providing extensive genome - wide variation data from six individuals from a marine ( North Sea ) stickleback population.", "output": "There is no related enetity." }, { "input": "Using next - generation sequencing and a combination of paired - end and mate - pair libraries, we detected a wide size range of genetic variation.", "output": "There is no related enetity." }, { "input": "Among the six individuals, we found more than 7 % of the genome is polymorphic, consisting of 2599111 SNPs, 233464 indels and structural variation ( SV ) ( > 50 bp ) such as 1054 copy - number variable regions ( deletions and duplications ) and 48 inversions.", "output": "There is no related enetity." }, { "input": "Many of these polymorphisms affect gene and coding sequences.", "output": "There is no related enetity." }, { "input": "Based on SNP diversity, we determined outlier regions concordant with signatures expected under adaptive evolution.", "output": "There is no related enetity." }, { "input": "As some of these outliers overlap with pronounced regions of copy - number variation, we propose the consideration of such SV when analysing SNP data from re - sequencing approaches.", "output": "There is no related enetity." }, { "input": "We further discuss the value of this resource on genome - wide variation for further investigation upon the relative contribution of standing variation on the parallel evolution of sticklebacks and the importance of the genomic architecture in adaptive radiation.", "output": "There is no related enetity." }, { "input": "Structure - based optimization of oxadiazole - based GSK - 3 inhibitors.", "output": "oxadiazole." }, { "input": "Inhibition of glycogen synthase kinase - 3 ( GSK - 3 ) induces neuroprotective effects, e. g. decreases beta - amyloid production and reduces tau hyperphosphorylation, which are both associated with Alzheimer ' s disease ( AD ).", "output": "There is no related enetity." }, { "input": "The two isoforms of GSK - 3 in mammalians are GSK - 3 alpha and beta, which share 98 % homology in their catalytic domains.", "output": "There is no related enetity." }, { "input": "We investigated GSK - 3 inhibitors based on 2 different scaffolds in order to elucidate the demands of the ATP - binding pocket [ 1 ].", "output": "ATP." }, { "input": "Particularly, the oxadiazole scaffold provided potent and selective GSK - 3 inhibitors.", "output": "oxadiazole." }, { "input": "For example, the most potent inhibitor of the present series, the acetamide 26d, is characterized by an IC50 of 2 nM for GSK - 3 alpha and 17 nM for GSK - 3 beta.", "output": "acetamide." }, { "input": "In addition, the benzodioxane 8g showed up to 27 - fold selectivity for GSK - 3 alpha over GSK - 3 beta, with an IC50 of 35 nM for GSK - 3 alpha.", "output": "benzodioxane." }, { "input": "Two GSK - 3 inhibitors were further profiled for efficacy and toxicity in the wild - type ( wt ) zebrafish embryo assay to evaluate simultaneously permeability and safety.", "output": "There is no related enetity." }, { "input": "Dual inhibitor of PDE7 and GSK - 3 - VP1. 15 acts as antipsychotic and cognitive enhancer in C57BL / 6J mice.", "output": "There is no related enetity." }, { "input": "Cognitive deficit is a core of schizophrenia and it is not effectively treated by the available antipsychotic drugs, hence new and more effective therapy is needed.", "output": "There is no related enetity." }, { "input": "Schizophrenia is considered as a pathway disorder where Disrupted - In - Schizophrenia - 1 ( DISC1 ) is important molecular player that regulates multiple cellular cascades.", "output": "There is no related enetity." }, { "input": "We recently reported synergistic action between phosphodiesterase - 4 ( PDE4 ) and glycogen synthase kinase - 3 ( GSK - 3 ) as DISC1 interacting proteins.", "output": "There is no related enetity." }, { "input": "In the current study we characterized behavioural effects of a newly developed compound, VP1. 15 that inhibits both PDE7 and GSK - 3 with main focus on its antipsychotic and cognitive capacities.", "output": "There is no related enetity." }, { "input": "VP1. 15 reduced ambulation in C57BL / 6J mice in a dose - dependent manner ( 7. 5 mg / kg and 3 mg / kg, respectively ) and, hence, lower dose was chosen for the further analysis.", "output": "There is no related enetity." }, { "input": "VP1. 1. 5 facilitated pre - pulse inhibition ( PPI ), reversed amphetamine - but not MK - 801 - induced PPI deficit.", "output": "amphetamine, MK - 801." }, { "input": "The drug was able to ameliorate the disrupted latent inhibition ( LI ) induced by the increased number of conditioning trials and reversed amphetamine - induced LI deficit, supporting further its antipsychotic effects.", "output": "amphetamine." }, { "input": "The drug also significantly improved episodic memory in the spatial object recognition test, facilitated working memory in Y - maze and enhanced cued fear memory, but had no effect on executive function in the Puzzle box and contextual fear conditioning.", "output": "There is no related enetity." }, { "input": "Taken together, VP1. 15 elicited antipsychotic effects and also facilitated cognitive domains in mice, suggesting that multitarget drugs, affecting molecular substrates from the same pathway, perhaps could be antipsychotics of new - generation that open a new possibilities in drug discoveries.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "The novel phosphodiesterase 10A inhibitor THPP - 1 has antipsychotic - like effects in rat and improves cognition in rat and rhesus monkey.", "output": "THPP - 1." }, { "input": "Phosphodiesterase 10A ( PDE10A ) is a novel target for the treatment of schizophrenia that may address multiple symptomatic domains associated with this disorder.", "output": "There is no related enetity." }, { "input": "PDE10A is highly expressed in the brain and functions to metabolically inactivate the important second messengers cAMP and cGMP.", "output": "cAMP, cGMP." }, { "input": "Here we describe effects of a potent and orally bioavailable PDE10A inhibitor [ 2 - ( 6 - chloropyridin - 3 - yl ) - 4 - ( 2 - methoxyethoxy ) - 7, 8 - dihydropyrido [ 4, 3 - d ] pyrimidin - 6 ( 5H ) - yl ] ( imidazo [ 1, 5 - a ] pyridin - 1 - yl ) methanone ] ( THPP - 1 ) on striatal signaling pathways, in behavioral tests that predict antipsychotic potential, and assays that measure episodic - like memory in rat and executive function in rhesus monkey.", "output": "2 - ( 6 - chloropyridin - 3 - yl ) - 4 - ( 2 - methoxyethoxy ) - 7 , 8 - dihydropyrido [ 4 , 3 - d ] pyrimidin - 6 ( 5H ) - yl ] ( imidazo [ 1 , 5 - a ] pyridin - 1 - yl ) methanone, THPP - 1." }, { "input": "THPP - 1 exhibits nanomolar potency on the PDE10A enzyme, demonstrates excellent pharmacokinetic properties in multiple preclinical animal species, and is selective for PDE10A over other PDE families of enzymes.", "output": "THPP - 1." }, { "input": "THPP - 1 significantly increased phosphorylation of proteins in the striatum involved in synaptic plasticity, including the a - amino - 3 - hydroxy - 5 - methylisoxazole - 4 - proprionic acid receptor ( AMPA ) GluR1 subunit, extracellular receptor kinase ( ERK ), and cAMP - response element binding protein ( CREB ).", "output": "THPP - 1, a - amino - 3 - hydroxy - 5 - methylisoxazole - 4 - proprionic acid, AMPA, cAMP." }, { "input": "THPP - 1 produced dose - dependent effects in preclinical assays predictive of antipsychotic activity including attenuation of MK - 801 - induced psychomotor activation and condition avoidance responding in rats.", "output": "THPP - 1, MK - 801." }, { "input": "At similar plasma exposures, THPP - 1 significantly increased object recognition memory in rat and attenuated a ketamine - induced deficit in the object retrieval detour task in rhesus monkey.", "output": "THPP - 1, ketamine." }, { "input": "These findings suggest that PDE10A inhibitors have the potential to impact multiple symptomatic domains of schizophrenia including positive symptoms and cognitive impairment.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "Quetiapine ameliorates stress - induced cognitive inflexibility in rats.", "output": "Quetiapine." }, { "input": "The antidepressant action of quetiapine has been demonstrated in clinical and preclinical studies.", "output": "quetiapine." }, { "input": "Nevertheless, little is known about its effectiveness in the treatment of frontal - like cognitive disturbances that may be associated with stress - related disorder.", "output": "There is no related enetity." }, { "input": "Therefore, the aim of the present study was to investigate whether quetiapine would prevent and / or reverse stress - induced cognitive impairments in a rat model of prefrontal cortex ( PFC ) - dependent attentional set - shifting task ( ASST ).", "output": "quetiapine." }, { "input": "Because quetiapine augmentation to selective serotonin reuptake inhibitors ( SSRIs ) has recently been proven to be beneficial in neuropsychiatric disorders, a separate experiment was designed to assess the impact of combined administration of inactive doses of quetiapine and escitalopram on ASST performance in rats.", "output": "quetiapine, serotonin, quetiapine, escitalopram." }, { "input": "According to our previous studies, 1 h daily exposure to restraint stress for 7 days significantly and specifically impaired extra - dimensional ( ED ) set - shifting ability of rats.", "output": "There is no related enetity." }, { "input": "Quetiapine ( 2. 5 mg / kg, PO ) given to rats prior to the restraint sessions completely prevented this stress - induced cognitive inflexibility.", "output": "Quetiapine." }, { "input": "Similar effect was demonstrated after pretreatment with the alpha 1 - adrenoceptor antagonist, prazosin ( 1 mg / kg, IP ).", "output": "prazosin." }, { "input": "Moreover, acute administration of quetiapine before the test reversed set - shifting deficits in stressed rats ( 0. 63, 1. 25 and 2. 5 mg / kg, PO ) and improved ED performance of cognitively unimpaired control animals ( 1. 25 and 2. 5 mg / kg, PO ).", "output": "quetiapine." }, { "input": "Finally, the combined administration of inactive doses of quetiapine ( 0. 63 and 0. 3 mg / kg in control and stressed rats, respectively ) and escitalopram ( 0. 3 mg / kg, IP ) facilitated set - shifting performance in either control or stressed rats.", "output": "quetiapine, escitalopram." }, { "input": "In conclusion, quetiapine administration either prevented or reversed stress - induced cognitive inflexibility in rats.", "output": "quetiapine." }, { "input": "In addition to promoting of set - shifting by itself, quetiapine also enhanced the procognitive efficacy of escitalopram.", "output": "quetiapine, escitalopram." }, { "input": "The potential contribution of the antagonism at alpha 1 - adrenoceptors to the mechanisms underlying the protective action of quetiapine requires further evaluation.", "output": "quetiapine." }, { "input": "These findings may have therapeutic implications for the treatment of frontal - like disturbances, particularly cognitive inflexibility, in stress - related psychiatric disorders.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "Modified - release prednisone decreases complaints and fatigue compared to standard prednisolone in patients with adrenal insufficiency.", "output": "prednisone, prednisolone." }, { "input": "Patients with adrenal insufficiency ( AI ) receive first glucocorticoid replacement dose after waking, resulting in a 3 - 5 h delay compared to physiological secretion.", "output": "There is no related enetity." }, { "input": "Impaired quality of life ( QoL ) and fatigue might be due to this delayed dose scheme.", "output": "There is no related enetity." }, { "input": "Modified - release glucocorticoid preparations might have therapeutic advantages.", "output": "There is no related enetity." }, { "input": "Exploratory pilot study including 14 patients with AI was conducted in a single university center.", "output": "There is no related enetity." }, { "input": "Patients on morning dose prednisolone ( 5 mg ) were included, switched to modified - release prednisone ( 5 mg ) at 10 PM for 3 months, and then switched back on standard prednisolone.", "output": "prednisolone, prednisone, prednisolone." }, { "input": "3 standardized questionnaires ( GBB - 24, MFI, and AddiQoL ) investigating complaints and fatigue were completed at baseline, after 3, and 6 months.", "output": "There is no related enetity." }, { "input": "Data regarding clinical and hormonal parameters were assessed.", "output": "There is no related enetity." }, { "input": "Modified - release prednisone showed significant improvement in one of 4 scales of GBB - 24 and positive trends to better scores in 3 of 4 scales.", "output": "prednisone." }, { "input": "The global score of discomfort improved significantly.", "output": "There is no related enetity." }, { "input": "The MFI showed also significant improvement in 3 of 5 scales and positive trend to better scores in 2 scales.", "output": "There is no related enetity." }, { "input": "Significant changes to better scores were seen in 4 out of 30 items of the AddiQoL.", "output": "There is no related enetity." }, { "input": "Modified - release prednisone showed decreased complaints and fatigue compared to standard prednisolone indicating importance of glucocorticoid increase in early morning hours before waking.", "output": "prednisone, prednisolone." }, { "input": "Bioactivity of Diosmetin Glycosides Isolated from the Epicarp of Date Fruits, Phoenix dactylifera, on the Biochemical Profile of Alloxan Diabetic Male Rats.", "output": "Diosmetin Glycosides, Alloxan." }, { "input": "The new natural flavonoid compounds - diosmetin 7 - O - beta - L - arabinofuranosyl ( 1 --> 2 ) beta - D - apiofuranoside ( 1 ) and diosmetin 7 - O - beta - D - apiofuranoside ( 2 ) - were isolated from the acetone extract of date fruits epicarp belonging to family Arecaceae ( Palmae ).", "output": "flavonoid, diosmetin 7 - O - beta - L - arabinofuranosyl ( 1 --> 2 ) beta - D - apiofuranoside, diosmetin 7 - O - beta - D - apiofuranoside, acetone." }, { "input": "Elucidation of their chemical structures was determined by different spectroscopic methods in addition to the chemical and physical methods of analysis.", "output": "There is no related enetity." }, { "input": "These compounds were assessed for their biological activity on alloxan diabetic rats.", "output": "alloxan." }, { "input": "A dose of 1. 5 ml of ( 1 ) and ( 2 ) suspensions / 100 gm b.", "output": "There is no related enetity." }, { "input": "wt were orally administrated to alloxan diabetic rats for 30 days.", "output": "alloxan." }, { "input": "The treatment of diabetic rats with these compounds resulted in marked improvement of the different biochemical results, i. e. the serum glucose level ( highly significant, from 330 + 5. 5 mg / dL to 140 + 1. 2 mg / dL ) treated with ( 1 ); liver functions markedly developed both by AST and ALT levels, ( reduced significantly from 68. 3 + 4. 8 mu / L to 54 + 5. 5 mu / L and from 61. 0 + 3. 6 mu / L to 40. 1 + 3. 6 mu / L, respectively ) treated with ( 2 ), accompanying with mild decrease in both cholesterol and triglycerides levels with ( 1 ) or ( 2 ).", "output": "glucose, cholesterol, triglycerides." }, { "input": "Decrease of TBARS level was observed in whole blood when treated with ( 1 ) or ( 2 ), while levels of glutathione peroxidase and superoxide dismutase were increased in liver.", "output": "glutathione, superoxide." }, { "input": "Serum testosterone level was highly significantly increased ( from 705. 1 + 3. 6 mg / 100 ml to 720 + 4. 7 mg / 100 ml ), total acid phosphatase and prostate acid phosphatase activities were highly significantly decreased ( from 16. 9 + 0. 28 mu / L to 10. 7 + 1. 2 mu / L and from 9. 7 + 0. 7 mu / L to 6. 5 + 1 mu / L, respectively ) for compound ( 1 ).", "output": "testosterone." }, { "input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Haplotype analysis of the 185delAG BRCA1 mutation in ethnically diverse populations.", "output": "There is no related enetity." }, { "input": "The 185delAG * BRCA1 mutation is encountered primarily in Jewish Ashkenazi and Iraqi individuals, and sporadically in non - Jews.", "output": "There is no related enetity." }, { "input": "Previous studies estimated that this is a founder mutation in Jewish mutation carriers that arose before the dispersion of Jews in the Diaspora ~ 2500 years ago.", "output": "There is no related enetity." }, { "input": "The aim of this study was to assess the haplotype in ethnically diverse 185delAG * BRCA1 mutation carriers, and to estimate the age at which the mutation arose.", "output": "There is no related enetity." }, { "input": "Ethnically diverse Jewish and non - Jewish 185delAG * BRCA1 mutation carriers and their relatives were genotyped using 15 microsatellite markers and three SNPs spanning 12. 5 MB, encompassing the BRCA1 gene locus.", "output": "There is no related enetity." }, { "input": "Estimation of mutation age was based on a subset of 11 markers spanning a region of ~ 5 MB, using a previously developed algorithm applying the maximum likelihood method.", "output": "There is no related enetity." }, { "input": "Overall, 188 participants ( 154 carriers and 34 noncarriers ) from 115 families were included: Ashkenazi, Iraq, Kuchin - Indians, Syria, Turkey, Iran, Tunisia, Bulgaria, non - Jewish English, non - Jewish Malaysian, and Hispanics.", "output": "There is no related enetity." }, { "input": "Haplotype analysis indicated that the 185delAG mutation arose 750 - 1500 years ago.", "output": "There is no related enetity." }, { "input": "In Ashkenazim, it is a founder mutation that arose 61 generations ago, and with a small group of founder mutations was introduced into the Hispanic population ( conversos ) ~ 650 years ago, and into the Iraqi - Jewish community ~ 450 years ago.", "output": "There is no related enetity." }, { "input": "The 185delAG mutation in the non - Jewish populations in Malaysia and the UK arose at least twice independently.", "output": "There is no related enetity." }, { "input": "We conclude that the 185delAG * BRCA1 mutation resides on a common haplotype among Ashkenazi Jews, and arose about 61 generations ago and arose independently at least twice in non - Jews.", "output": "There is no related enetity." }, { "input": "Role of AMPK in pancreatic beta cell function.", "output": "There is no related enetity." }, { "input": "Pharmacological activation of AMP activated kinase ( AMPK ) by metformin has proven to be a beneficial therapeutic approach for the treatment of type II diabetes.", "output": "metformin." }, { "input": "Despite improved glucose regulation achieved by administration of small molecule activators of AMPK, the potential negative impact of enhanced AMPK activity on insulin secretion by the pancreatic beta cell is an important consideration.", "output": "glucose." }, { "input": "In this review, we discuss our current understanding of the role of AMPK in central functions of the pancreatic beta cell, including glucose - stimulated insulin secretion ( GSIS ), proliferation, and survival.", "output": "glucose." }, { "input": "In addition we discuss the controversy surrounding the role of AMPK in insulin secretion, underscoring the merits and caveats of methods used to date.", "output": "There is no related enetity." }, { "input": "Enhancement of cognitive function in models of brain disease through environmental enrichment and physical activity.", "output": "There is no related enetity." }, { "input": "This review will provide an overview of the non - drug based approaches that have been demonstrated to enhance cognitive function of the compromised brain, primarily focussed on the two most widely adopted paradigms of environmental enrichment and enhanced physical exercise.", "output": "There is no related enetity." }, { "input": "Environmental enrichment involves the generation of novelty and complexity in animal housing conditions which facilitates enhanced sensory and cognitive stimulation as well as physical activity.", "output": "There is no related enetity." }, { "input": "In a wide variety of animal models of brain disorders, environmental enrichment and exercise have been found to have beneficial effects, including cognitive enhancement, delayed disease onset, enhanced cellular plasticity and associated molecular processes.", "output": "There is no related enetity." }, { "input": "Potential cellular and molecular mechanisms will also be discussed, which have relevance for the future development of ' enviromimetics ', drugs which could mimic or enhance the beneficial effects of environmental stimulation.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "Human neuronal coenzyme Q10 deficiency results in global loss of mitochondrial respiratory chain activity, increased mitochondrial oxidative stress and reversal of ATP synthase activity: implications for pathogenesis and treatment.", "output": "coenzyme Q10, ATP." }, { "input": "Disorders of coenzyme Q ( 10 ) ( CoQ ( 10 ) ) biosynthesis represent the most treatable subgroup of mitochondrial diseases.", "output": "coenzyme Q ( 10 ), CoQ ( 10 )." }, { "input": "Neurological involvement is frequently observed in CoQ ( 10 ) deficiency, typically presenting as cerebellar ataxia and / or seizures.", "output": "CoQ ( 10 )." }, { "input": "The aetiology of the neurological presentation of CoQ ( 10 ) deficiency has yet to be fully elucidated and therefore in order to investigate these phenomena we have established a neuronal cell model of CoQ ( 10 ) deficiency by treatment of neuronal SH - SY5Y cell line with para - aminobenzoic acid ( PABA ).", "output": "CoQ ( 10 ), CoQ ( 10 ), para - aminobenzoic acid, PABA." }, { "input": "PABA is a competitive inhibitor of the CoQ ( 10 ) biosynthetic pathway enzyme, COQ2.", "output": "PABA, CoQ ( 10 )." }, { "input": "PABA treatment ( 1 mM ) resulted in a 54 % decrease ( 46 % residual CoQ ( 10 ) ) decrease in neuronal CoQ ( 10 ) status ( p < 0. 01 ).", "output": "PABA, CoQ ( 10 ), CoQ ( 10 )." }, { "input": "Reduction of neuronal CoQ ( 10 ) status was accompanied by a progressive decrease in mitochondrial respiratory chain enzyme activities, with a 67. 5 % decrease in cellular ATP production at 46 % residual CoQ ( 10 ).", "output": "CoQ ( 10 ), ATP, CoQ ( 10 )." }, { "input": "Mitochondrial oxidative stress increased four - fold at 77 % and 46 % residual CoQ ( 10 ).", "output": "CoQ ( 10 )." }, { "input": "A 40 % increase in mitochondrial membrane potential was detected at 46 % residual CoQ ( 10 ) with depolarisation following oligomycin treatment suggesting a reversal of complex V activity.", "output": "CoQ ( 10 )." }, { "input": "This neuronal cell model provides insights into the effects of CoQ ( 10 ) deficiency on neuronal mitochondrial function and oxidative stress, and will be an important tool to evaluate candidate therapies for neurological conditions associated with CoQ ( 10 ) deficiency.", "output": "CoQ ( 10 ), CoQ ( 10 )." }, { "input": "Evaluation of potential Myt1 kinase inhibitors by TR - FRET based binding assay.", "output": "There is no related enetity." }, { "input": "In the human cell cycle, the Myt1 kinase is a crucial regulator of the G2 / M transition.", "output": "There is no related enetity." }, { "input": "Because this membrane - associated kinase is hard to obtain and assay, there is a distinct lack of data so far.", "output": "There is no related enetity." }, { "input": "Here we report the derivatization of a glycoglycerolipid which was shown previously to be active in a Myt1 activity assay.", "output": "There is no related enetity." }, { "input": "These compounds were tested in a binding assay together with a set of common kinase inhibitors against a full - length Myt1 expressed in a human cell line.", "output": "There is no related enetity." }, { "input": "Dasatinib exhibited nanomolar affinity whereas broad coverage inhibitors such as sunitinib and staurosporine derivatives did not show any effect.", "output": "Dasatinib, sunitinib, staurosporine." }, { "input": "We also carried out docking studies for the most potent compounds allowing further insights into the inhibitor interaction of this kinase.", "output": "There is no related enetity." }, { "input": "The glycoglycerolipids showed no significant effects in the binding assay, endorsing the idea of a mechanism of action distant from the active site.", "output": "There is no related enetity." }, { "input": "Nicotine improves performance in an attentional set shifting task in rats.", "output": "Nicotine." }, { "input": "A large number of studies in both humans and experimental animals have demonstrated nicotine - induced improvements in various aspects of cognitive function, including attention and memory.", "output": "nicotine." }, { "input": "The prefrontal cortex ( PFC ) is thought to be critically involved in the modulation of executive function and these attentional processes are enhanced by nicotine acting at nicotinic acetylcholine receptors.", "output": "nicotine, acetylcholine." }, { "input": "The involvement of nicotinic processes on cognitive flexibility in particular has not been specifically investigated.", "output": "There is no related enetity." }, { "input": "The effects of nicotine on attentional flexibility were therefore evaluated using the rodent attentional set shifting task in rats.", "output": "nicotine." }, { "input": "Nicotine injected both acutely and following repeated pre - exposure significantly improved both intradimensional and extradimensional set shifting performance in the task.", "output": "Nicotine." }, { "input": "Further investigation of the acute effects of nicotine demonstrated this improvement in attentional flexibility to be dose - dependent.", "output": "nicotine." }, { "input": "These results implicate the nicotinic receptor system in the mediation of processes underlying cognitive flexibility and suggest that nicotine improves attentional flexibility in rats, both within and between perceptual dimensions of a compound stimulus.", "output": "nicotine." }, { "input": "Nicotine - induced alterations in prefrontal circuitry may underlie these effects on cognitive flexibility.", "output": "Nicotine." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "Co - learning facilitates memory in mice: a new avenue in social neuroscience.", "output": "There is no related enetity." }, { "input": "Social context affects brain function but our understanding of its neurobiology is at an early stage.", "output": "There is no related enetity." }, { "input": "The mere presence of one individual can alter the cognitive capacities of another and social learning has been demonstrated in many species, including the mouse.", "output": "There is no related enetity." }, { "input": "We asked several questions: 1.", "output": "There is no related enetity." }, { "input": "How can active engagement of two familiar mice in the same learning activity ( co - learning ) alter their memory?", "output": "There is no related enetity." }, { "input": "2.", "output": "There is no related enetity." }, { "input": "Under which environmental conditions ( aversive vs non - aversive ) can we expect the memory to be enhanced, impaired, or not affected?", "output": "There is no related enetity." }, { "input": "3.", "output": "There is no related enetity." }, { "input": "Can a genetic factor modify the co - learning effect on memory?", "output": "There is no related enetity." }, { "input": "More specifically, can co - learning correct memory deficits in autistic - like BTBR inbred mice with deficient sociability?", "output": "There is no related enetity." }, { "input": "We demonstrated that pairs of familiar inbred mice of the same or different genotypes ( C57BL / 6J and BTBR ) that were habituated to new objects and their spatial location, had enhanced episodic memory in the spatial object recognition test, whereas individually - trained animals failed to solve this task.", "output": "There is no related enetity." }, { "input": "Notably, the co - learning effect was genotype - dependent.", "output": "There is no related enetity." }, { "input": "BTBR mice paired with BTBR cage - mates in the habituation session modestly ameliorated their performance in the object recognition test but co - learning with a familiar C57BL / 6J mouse completely normalized episodic memory deficit.", "output": "There is no related enetity." }, { "input": "Next, we explored the co - learning effect on fear memory in these inbred strains.", "output": "There is no related enetity." }, { "input": "Interestingly, mice of both genotypes displayed significantly enhanced contextual fear memory once they had been conditioned together with BTBR animals.", "output": "There is no related enetity." }, { "input": "The same influence of BTBR presence was observed on cued fear memory in C57BL / 6J mice, whereas a modest co - learning effect was found on cued fear conditioning in the BTBR strain.", "output": "There is no related enetity." }, { "input": "Taken together, we demonstrated for the first time the co - learning effect on cognitive capacities in mice, which can be modified by genetic background and environmental conditions.", "output": "There is no related enetity." }, { "input": "The possible implications of this methodological approach in social neuroscience are discussed.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "Passive stiffness of airway smooth muscle: the next target for improving airway distensibility and treatment for asthma?", "output": "There is no related enetity." }, { "input": "Reduced airway distensibility due to increased airway stiffness is a characteristic of asthma.", "output": "There is no related enetity." }, { "input": "Airway stiffness is determined by the property and structural organization of the various elements of the airway wall, and is often divided into active and passive components.", "output": "There is no related enetity." }, { "input": "Active stiffness is thought to be associated with activation of muscle cells in the airway wall.", "output": "There is no related enetity." }, { "input": "This component of stiffness can be inhibited when active force produced by the muscle is abolished.", "output": "There is no related enetity." }, { "input": "Passive stiffness, on the other hand, is thought to stem from non - muscle component of the airway wall, especially the collagen / elastin fibrous network of the extracellular matrix within which the muscle cells are embedded.", "output": "There is no related enetity." }, { "input": "In this brief review, the notion that passive stiffness is exclusively extracellular in origin is challenged.", "output": "There is no related enetity." }, { "input": "Recent evidence suggests that a substantial portion of the passive stiffness of an in vitro preparation of tracheal smooth muscle is calcium sensitive and is regulated by Rho - kinase, although the underlying mechanism and the details of regulation for the development of this intracellular passive stiffness are still largely unknown.", "output": "calcium." }, { "input": "To reduce airway stiffness different lines of attack must be tailored to different components of the stiffness.", "output": "There is no related enetity." }, { "input": "The regulatable passive stiffness is distinct from the relatively permanent stiffness of the extracellular matrix and the stiffness associated with active muscle contraction.", "output": "There is no related enetity." }, { "input": "To improve airway distensibility during asthma exacerbation, a comprehensive approach to reduce overall airway stiffness should therefore include a strategy for targeting the regulatable passive stiffness.", "output": "There is no related enetity." }, { "input": "Harmonization of description and classification of fetal observations: achievements and problems still unresolved: report of the 7th Workshop on the Terminology in Developmental Toxicology Berlin, 4 - 6 May 2011.", "output": "There is no related enetity." }, { "input": "This article summarizes the 7th Workshop on the Terminology in Developmental Toxicology held in Berlin, May 4 - 6, 2011.", "output": "There is no related enetity." }, { "input": "The series of Berlin Workshops has been mainly concerned with the harmonization of terminology and classification of fetal anomalies in developmental toxicity studies.", "output": "There is no related enetity." }, { "input": "The main topics of the 7th Workshop were knowledge on the fate of anomalies after birth, use of Version 2 terminology for maternal - fetal observations and non - routinely used species, reclassification of \" grey zone \" anomalies and categorization of fetal observations for human health risk assessment.", "output": "There is no related enetity." }, { "input": "The paucity of data on health consequences of the postnatal permanence of fetal anomalies is relevant and further studies are needed.", "output": "There is no related enetity." }, { "input": "The Version 2 terminology is an important step forward and the terms listed in this glossary are considered also to be appropriate for most observations in non - routinely used species.", "output": "There is no related enetity." }, { "input": "Continuation of the Berlin Workshops was recommended.", "output": "There is no related enetity." }, { "input": "Topics suggested for the next Workshop were grouping of fetal observations for reporting and statistical analysis.", "output": "There is no related enetity." }, { "input": "Natural anthocyanins from phytoresources and their chemical researches.", "output": "anthocyanins." }, { "input": "Anthocyanins are a class of naturally occurring polyphenols which have been most widely studied in recent decades for the rapid development of relative techniques.", "output": "Anthocyanins, polyphenols." }, { "input": "This article first reviews the various anthocyanin resources including fruits, flowers, vegetables and beverages.", "output": "anthocyanin." }, { "input": "Besides the direct extraction from natural resources, anthocyanins can also be obtained by semi - or total synthesis.", "output": "anthocyanins." }, { "input": "After the introduction of new representative anthocyanins found in the past few years and the major relationships between structures and stability, modern separation and analysis technologies in related studies were summarised, which play an important role in chemical researches of anthocyanins.", "output": "anthocyanins, anthocyanins." }, { "input": "Classification of Aurora kinase inhibitors by self - organizing map ( SOM ) and support vector machine ( SVM ).", "output": "There is no related enetity." }, { "input": "The Aurora kinase family ( consisting of Aurora - A, - B and - C ) is an important group of enzymes that controls several aspects of cell division in mammalian cells.", "output": "There is no related enetity." }, { "input": "In this study, 512 compounds of Aurora - A and - B inhibitors were collected.", "output": "There is no related enetity." }, { "input": "They were classified into three classes: dual Aurora - A and Aurora - B inhibitors, selective inhibitors of Aurora - A and selective inhibitors of Aurora - B by Self - Organizing Map ( SOM ) and Support Vector Machine ( SVM ).", "output": "There is no related enetity." }, { "input": "The prediction accuracies of the models ( based on the training / test set splitting using SOM method ) for the test set were 92. 2 % for SOM1 and 93. 8 % for SVM1, respectively.", "output": "There is no related enetity." }, { "input": "In addition, the extended connectivity fingerprints ( ECFP _ 4 ) for all the molecules were calculated and structure - activity relationship of Aurora kinase inhibitors was summarized, which may be helpful to find the important structural features of inhibitors relating to the selectivity to Aurora kinases.", "output": "There is no related enetity." }, { "input": "Role of metabotropic glutamate receptor 1 in the basolateral amygdala - driven prefrontal cortical deactivation in inflammatory pain in the rat.", "output": "glutamate." }, { "input": "Plastic changes in the amygdala and limbic cortex networks have been widely shown in chronic pain.", "output": "There is no related enetity." }, { "input": "We have here investigated the role of group I metabotropic glutamate receptors ( mGluRs ) in the basolateral amygdala ( BLA ) pre - infra - limbic ( PL - IL ) divisions of the medial prefrontal cortex ( mPFC ) neuron connections after carrageenan - induced inflammatory pain in the rat.", "output": "glutamate." }, { "input": "Intra - plantar injection of carrageenan decreased either spontaneous or mechanically / electrically evoked activity of PL cortex pyramidal neurons which responded with excitation in a way prevented by CPCOOEt, a selective mGluR1 antagonist, though not by MPEP, a selective mGluR5 antagonist.", "output": "CPCOOEt, MPEP." }, { "input": "Accordingly, intra - BLA microinjection of DHPG, a group I mGluR agonist, caused PL cortex neuron activity depression, antagonized by CPCCOEt.", "output": "DHPG, CPCCOEt." }, { "input": "CPCOOEt, but not MPEP, reduced also carrageenan - induced mechanical allodynia.", "output": "CPCOOEt, MPEP." }, { "input": "The PL cortex cell deactivation in inflammatory pain condition was associated with increased GABA ( conversely glutamate was decreased ) in the PL / IL cortex.", "output": "GABA, glutamate." }, { "input": "The local application of bicuculline, a GABA ( A ) receptor selective antagonist, reduced mechanical allodynia.", "output": "bicuculline, GABA." }, { "input": "An over - expression of mGluR1, but not mGluR5, have been observed in the PL - IL cortex after inflammatory pain suggesting an increased mGluR1 - dependent cross - talk among BLA and IL - PL cortex neurons in inflammatory pain conditions.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Metabotropic Glutamate Receptors '.", "output": "Glutamate." }, { "input": "Emerging role of AMP - activated protein kinase in endocrine control of metabolism in the liver.", "output": "AMP." }, { "input": "This review summarizes the emerging role of AMP - activated protein kinase ( AMPK ) in mediating endocrine regulation of metabolic fluxes in the liver.", "output": "AMP." }, { "input": "There are a number of hormones which, when acting on the liver, alter AMPK activation.", "output": "There is no related enetity." }, { "input": "Here we describe those hormones associated with activation and de - activation of AMPK and the potential mechanisms for changes in AMPK activation state.", "output": "There is no related enetity." }, { "input": "The actions of these hormones, in many cases, are consistent with downstream effects of AMPK signaling thus strengthening the circumstantial case for AMPK - mediated hormone action.", "output": "There is no related enetity." }, { "input": "In recent years, genetic mouse models have also been used in an attempt to establish the role of AMPK in hormone - stimulated metabolism in the liver.", "output": "There is no related enetity." }, { "input": "Few experiments have, however, firmly established a causal relationship between hormone action at the liver and AMPK signaling.", "output": "There is no related enetity." }, { "input": "Rectifying behavior of charge transfer complexes of tetrakis ( dimethylamino ) ethene with acceptor molecules: a theoretical study.", "output": "tetrakis ( dimethylamino ) ethene." }, { "input": "The effect of electric field induced electron transfer on the rectification properties of molecular rectifiers based on charge transfer complexes of tetrakis ( dimethylamino ) ethane ( TDAE ) with acceptor molecules was explored.", "output": "tetrakis ( dimethylamino ) ethane, TDAE." }, { "input": "The current - voltage curves and the rectification ratios ( RR ) for two different molecular rectifiers were obtained using a direct ab initio method at M06 / LACVP ( d ) level of theory in the range from - 2 to + 2 V.", "output": "There is no related enetity." }, { "input": "The highest RR of 25. 7 was determined for the complex of TDAE with 2 - nitropyrene - 4, 5, 9, 10 - tetraone at 0. 5 V ( D1 ), while another rectifier [ complex of TDAE with 2, 7 - dimethyl nitropyrene - 4, 5, 9, 10 - tetraone ( D2 ) ] showed a maximum RR of only 2. 9 at 0. 3 V.", "output": "TDAE, 2 - nitropyrene - 4 , 5 , 9 , 10 - tetraone, TDAE, 2 , 7 - dimethyl nitropyrene - 4 , 5 , 9 , 10 - tetraone." }, { "input": "The electric field induced electron transfer occurring in D1 creates a one - way conducting channel consisting of two SOMOs involving the entire D1 complex.", "output": "There is no related enetity." }, { "input": "In the case of D2, no electron transfer occurs at the applied bias voltages due to the relatively high energy difference between HOMO and LUMO.", "output": "There is no related enetity." }, { "input": "Increased expression of P450scc and CYP17 in development of endogenous hyperandrogenism in a rat model of PCOS.", "output": "There is no related enetity." }, { "input": "The objective of the present study was to characterize the effect of insulin plus hCG on the expression of steroidogenic enzymes ( P450scc and CYP17 ) in polycystic ovaries of rats.", "output": "There is no related enetity." }, { "input": "Changes in estrous cycle, ovarian morphology, hormonal levels, and protein levels by immunohistochemistry and western - blot were determined.", "output": "There is no related enetity." }, { "input": "Rats treated with insulin plus hCG displayed abnormal estrous cycles with increasing androgen biosynthesis.", "output": "androgen." }, { "input": "Meanwhile, insulin plus hCG resulted in multiple large cysts with diminished granulosa layers and increased thecal layers and stromal - interstitial tissue.", "output": "There is no related enetity." }, { "input": "Moreover, there was an increase in the expression of P450scc and CYP17 in thecal and stromal cells in our PCOS rat model compared with control rats.", "output": "There is no related enetity." }, { "input": "These results indicate that administration of insulin with hCG can synergistically result in endogenous hyperandrogenism which may partially upregulate the expression of steroidogenic enzymes in ovarian tissue.", "output": "There is no related enetity." }, { "input": "beta - Orcinol - type depsides from the lichen Thamnolia vermicularis.", "output": "beta - Orcinol." }, { "input": "A phytochemical investigation of a herb tea made from Thamnolia vermicularis led to the isolation of three new beta - orcinol - type depsides ( 1, 2 and 3 ), along with seven known compounds hypothamnolic acid ( 4 ), 3 ' - methylevenic acid ( 5 ), baeomycesic acid ( 6 ), squamatic acid ( 7 ), methyl 3 ' - methyllecanorate ( 8 ), barbatinic acid ( 9 ) and atranorin ( 10 ).", "output": "beta - orcinol, depsides, hypothamnolic acid, 3 ' - methylevenic acid, baeomycesic acid, squamatic acid, methyl 3 ' - methyllecanorate, barbatinic acid, atranorin." }, { "input": "The structures of the new compounds were determined on the basis of spectroscopic evidence, including 1 - D and 2 - D NMR and ESI - MS techniques.", "output": "There is no related enetity." }, { "input": "AMPAKINE enhancement of social interaction in the BTBR mouse model of autism.", "output": "AMPAKINE." }, { "input": "Autism is a neurodevelopmental disorder in which the first diagnostic symptom is unusual reciprocal social interactions.", "output": "There is no related enetity." }, { "input": "Approximately half of the children diagnosed with an autism spectrum disorder also have intellectual impairments.", "output": "There is no related enetity." }, { "input": "General cognitive abilities may be fundamental to many aspects of social cognition.", "output": "There is no related enetity." }, { "input": "Cognitive enhancers could conceivably be of significant benefit to children and adults with autism.", "output": "There is no related enetity." }, { "input": "AMPAKINE compounds are a novel class of pharmacological agents that act as positive modulators of AMPA receptors to enhance excitatory glutamatergic neurotransmission.", "output": "AMPAKINE, AMPA." }, { "input": "This class of compounds was reported to improve learning and memory in several rodent and non - human primate tasks, and to normalize respiratory abnormalities in a mouse model of Rett syndrome.", "output": "There is no related enetity." }, { "input": "Here we evaluate the actions of AMPA compounds in adult male and female BTBR mice, a well characterized mouse model of autism.", "output": "AMPA." }, { "input": "Acute treatment with CX1837 and CX1739 reversed the deficit in sociability in BTBR mice on the most sensitive parameter, time spent sniffing a novel mouse as compared to time spent sniffing a novel object.", "output": "CX1837, CX1739." }, { "input": "The less sensitive parameter, time in the chamber containing the novel mouse versus time in the chamber containing the novel object, was not rescued by CX1837 or CX1739 treatment.", "output": "CX1837, CX1739." }, { "input": "Preliminary data with CX546, in which beta - cyclodextrin was the vehicle, revealed behavioral effects of the acute intraperitoneal and oral administration of vehicle alone.", "output": "CX546, beta - cyclodextrin." }, { "input": "To circumvent the artifacts introduced by the vehicle administration, we employed a novel treatment regimen using pellets of peanut butter for drug delivery.", "output": "There is no related enetity." }, { "input": "Absence of vehicle treatment effects when CX1837 and CX1739 were given in the peanut butter pellets, to multiple cohorts of BTBR and B6 control mice, confirmed that the pharmacologically - induced improvements in sociability in BTBR were not confounded by the administration procedures.", "output": "CX1837, CX1739." }, { "input": "The highest dose of CX1837 improved the cognitive deficit in novel object recognition in BTBR.", "output": "CX1837." }, { "input": "No drug effects were detected on the high levels of repetitive self - grooming in BTBR.", "output": "There is no related enetity." }, { "input": "In open field tests, CX1837 and CX1739 did not induce hyperactivity or sedation in either strain.", "output": "CX1837, CX1739." }, { "input": "It is interesting to speculate that the ability of CX1837 and CX1739 to restore aspects of sociability in BTBR mice could utilize synaptic mechanisms regulating social cognition, suggesting a potential pharmacological target for interventions to treat symptoms of autism.", "output": "CX1837, CX1739." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "Androgen insensitivity syndrome.", "output": "Androgen." }, { "input": "Androgen insensitivity syndrome ( AIS ) is a disorder caused by a mutation of the gene encoding the androgen receptor ( AR; Xq11 - q12 ).", "output": "Androgen, androgen." }, { "input": "The prevalence of AIS has been estimated to be one case in every 20, 000 to 64, 000 newborn males for the complete syndrome ( CAIS ), and the prevalence is unknown for the partial syndrome ( PAIS ).", "output": "There is no related enetity." }, { "input": "The symptoms range from phenotypically normal males with impaired spermatogenesis to phenotypically normal women with primary amenorrhea.", "output": "There is no related enetity." }, { "input": "Various forms of ambiguous genitalia have been observed at birth.", "output": "There is no related enetity." }, { "input": "The diagnosis is confirmed by determining the exact mutation in the AR gene.", "output": "There is no related enetity." }, { "input": "PAIS individuals require precise diagnosis as early as possible so that the sex can be assigned, treatment can be recommended, and they can receive proper genetic counseling.", "output": "There is no related enetity." }, { "input": "After birth, differential diagnosis should be performed using other forms of abnormal sexual differentiation of primary amenorrhea.", "output": "There is no related enetity." }, { "input": "The treatment of AIS is based on reinforcement sexual identity, gonadectomy planning, and hormone replacement therapy.", "output": "There is no related enetity." }, { "input": "The prognosis for CAIS is good if the testicular tissue is removed at the appropriate time.", "output": "There is no related enetity." }, { "input": "For PAIS, the prognosis depends on the ambiguity of the genitalia and physical and psychosocial adjustment to the assigned sex.", "output": "There is no related enetity." }, { "input": "Deep understanding of the interaction between thienorphine and UDP - glucuronosyltransferase ( UGT ) isoforms.", "output": "thienorphine, UDP." }, { "input": "Thienorphine has been demonstrated to be a potent, long - acting partial opioid agonist.", "output": "Thienorphine." }, { "input": "It is being developed as a good candidate to treat opioid dependence.", "output": "There is no related enetity." }, { "input": "The thienorphine ' s glucuronide was detected after thienorphine was incubated with human liver microsomes ( HLMs ).", "output": "thienorphine, thienorphine." }, { "input": "Recombinant UGT isoforms screening experiment and enzyme kinetic study showed that UGT1A1 completely contributed to the glucuronidation of thienorphine.", "output": "thienorphine." }, { "input": "Among the tested UGT isoforms, UGT1A3 and UGT2B7 were inhibited by thienorphine, with other UGT isoforms negligibly influenced.", "output": "thienorphine." }, { "input": "The inhibition type is competitive, and inhibition kinetic parameters ( K ( i ) ) were 1. 65 and 5. 27 mu M for UGT1A3 and UGT2B7, respectively.", "output": "There is no related enetity." }, { "input": "However, due to low plasma concentration of thienorphine, in vivo drug - drug interaction might not occur.", "output": "thienorphine." }, { "input": "Adnexal torsion in children and adolescents: new trends to conservative surgical approach - - our experience and review of literature.", "output": "There is no related enetity." }, { "input": "The purpose of this study is to discuss the surgical treatment for ovarian torsion in children and adolescents with a focus on the procedures of adnexal conservation surgery and its frequency in the literature of the last 10 years.", "output": "There is no related enetity." }, { "input": "We retrospectively reviewed the medical charts of 127 operative ovarian lesions including 30 ovarian torsions ( 23. 6 % ) treated in two pediatric centers over a 10 - year period.", "output": "There is no related enetity." }, { "input": "Age at presentation, presenting symptoms, diagnostic studies, surgical procedure and pathological findings were analyzed.", "output": "There is no related enetity." }, { "input": "Mean age was 13. 7 years.", "output": "There is no related enetity." }, { "input": "Conservative surgery has been performed in 46. 7 % of the cases and laparoscopic approach in 40 %.", "output": "There is no related enetity." }, { "input": "Ovarian torsion occurred in 56. 7 % on ovaries with functional lesion, in 23. 3 % on normal adnexa and in 20 % on ovaries with benign neoplasm.", "output": "There is no related enetity." }, { "input": "The article includes a literature review ( 2000 - 2010 ) and a statistical analysis which shows a slow increase in conservative surgery from 28 to 45 %.", "output": "There is no related enetity." }, { "input": "Laparoscopic surgery accounts for 23. 5 %.", "output": "There is no related enetity." }, { "input": "Literature review shows 40. 5 % normal adnexa, 33. 2 % non - neoplastic lesions, 25. 3 % benign neoplasms and 1 % malignant neoplasms.", "output": "There is no related enetity." }, { "input": "The surgical treatment of children and adolescents presenting adnexal torsion should be practiced as an emergency and it should be more conservative as possible in order to maximize the future reproductive potential.", "output": "There is no related enetity." }, { "input": "Silibinin protects H9c2 cardiac cells from oxidative stress and inhibits phenylephrine - induced hypertrophy: potential mechanisms.", "output": "Silibinin, phenylephrine." }, { "input": "Cardiac hypertrophy is the main response of the heart to various extrinsic and intrinsic stimuli, and it is characterized by specific molecular and phenotypic changes.", "output": "There is no related enetity." }, { "input": "Recent in vitro and in vivo studies indicate the involvement of reactive oxygen species in the hypertrophic response.", "output": "oxygen." }, { "input": "In this study, silibinin, a plant flavonolignan extracted from milk thistle with potent antioxidant activity, was evaluated for its effects in ( a ) preventing hydrogen peroxide ( H2O2 ) - induced cellular damage and ( b ) blocking the phenylephrine - induced hypertrophic response.", "output": "silibinin, flavonolignan, hydrogen peroxide, H2O2, phenylephrine." }, { "input": "Using the in vitro model of embryonic rat heart - derived H9c2 cells, we showed that silibinin has a rather safe profile as concentrations up to 200 mu M did not affect cell viability.", "output": "silibinin." }, { "input": "Pretreatment of H9c2 cells with silibinin resulted in better protection of H9c2 cells under conditions of H2O2 - induced cellular stress compared to untreated cells as indicated by cell viability and DNA fragmentation assays.", "output": "silibinin, H2O2." }, { "input": "Furthermore, silibinin attenuated the phenylephrine - induced hypertrophic response as evidenced by the measurement of cell surface, up - regulation of atrial natriuretic peptide and increase of cellular protein levels.", "output": "silibinin, phenylephrine." }, { "input": "Moreover, silibinin repressed the phenylephrine - induced phosphorylation of ERK1 / 2 kinases, while it appeared to inhibit the weakly activated by phenylephrine phosphorylation of Akt.", "output": "silibinin, phenylephrine, phenylephrine." }, { "input": "Based on our results, silibinin may attenuate the phenylephrine - induced hypertrophic response of H9c2 cells via antioxidant mechanisms involving mainly the inhibition of the intracellular signaling pathways mediated by ERK1 / 2 MAPKs and Akt.", "output": "silibinin, phenylephrine." }, { "input": "Modafinil effects on cognition and emotion in schizophrenia and its neurochemical modulation in the brain.", "output": "Modafinil." }, { "input": "Modafinil is a central nervous system wake promoting agent used for the treatment of excessive daytime sleeping.", "output": "Modafinil." }, { "input": "Its vigilance promoting properties and low abuse potential has intrigued the scientific community and has led to use it as a cognitive enhancer, before its neural functions were understood.", "output": "There is no related enetity." }, { "input": "Here, we review the effects of modafinil in human cognition and emotion and its specific actions on symptoms in patients with schizophrenia and whether these are consistently effective throughout the literature.", "output": "modafinil." }, { "input": "We also performed a systematic review on the effects of modafinil on neurotransmitter signalling in different areas of the brain in order to better understand the neuromechanisms of its cognitive and emotional enhancing properties.", "output": "modafinil." }, { "input": "A review of its effects in schizophrenia suggests that modafinil facilitates cognitive functions, with pro - mnemonic effects and problem solving improvements.", "output": "modafinil." }, { "input": "Emotional processing also appears to be enhanced by the drug, although to date there are only a limited number of studies.", "output": "There is no related enetity." }, { "input": "The systematic review on the neurochemical modulation of the modafinil suggests that its mnemonic enhancing properties might be the result of glutamatergic and dopaminergic increased neuronal activation in the hippocampus and in the prefrontal cortex respectively.", "output": "modafinil." }, { "input": "Other neurotransmitters were also activated by modafinil in various limbic brain areas, suggesting that the drug acts on these brain regions to influence emotional responses.", "output": "modafinil." }, { "input": "These reviews seek to delineate the neuronal mechanisms by which modafinil affects cognitive and emotional function.", "output": "modafinil." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "Current understanding of TRPM7 pharmacology and drug development for stroke.", "output": "There is no related enetity." }, { "input": "The initial excitement and countless efforts to find a pharmacological agent that disrupts the excitotoxic pathway of ischemic neuronal death have only led to disappointing clinical trials.", "output": "There is no related enetity." }, { "input": "Currently, a thrombolytic agent called recombinant tissue plasminogen activator ( rt - PA ) is the only pharmacological treatment available for patients with acute ischemic stroke in most countries.", "output": "There is no related enetity." }, { "input": "Even though its efficacy has been confirmed repeatedly, rt - PA is considerably underused due to reasons including a short therapeutic window and repeated complications associated with its use.", "output": "There is no related enetity." }, { "input": "A search for alternative mechanisms that may operate dependently or independently with the well - established excitotoxic mechanism has led researchers to the discovery of newly described non - glutamate mechanisms.", "output": "glutamate." }, { "input": "Among the latter, transient receptor potential melastatin 7 ( TRPM7 ) is one of the important nonglutamate mechanisms in stroke, which has been evaluated in both in - vitro and in - vivo.", "output": "There is no related enetity." }, { "input": "In this review, we will discuss the current state of pharmacological treatments of ischemic stroke and provide evidence that TRPM7 is a promising therapeutic target of stroke.", "output": "There is no related enetity." }, { "input": "Altered gene expression involved in insulin signaling pathway in type II diabetic osteoporosis rats model.", "output": "There is no related enetity." }, { "input": "It is well established that both estrogen loss and type II diabetes mellitus ( DMII ) can impair bone metabolism, but whether estrogen loss exacerbates the effects of DMII is unclear.", "output": "estrogen, estrogen." }, { "input": "Therefore, we determined if ovariectomy ( OVX ) of rats on a long - term high - fat / sugar diet and injection of a low dose of streptozotocin ( DMII ) decreased bone mineral density ( BMD ) more than OVX or DMII alone.", "output": "sugar, streptozotocin." }, { "input": "Bone insulin signaling is known to support bone metabolism; therefore, we also tested the hypothesis that OVX DMII rats ( DOVX ) would exhibit greater reductions in the expression of proteins important in insulin signaling, including IRS - 1, IRS - 2, and IGF - 1.", "output": "There is no related enetity." }, { "input": "As hypothesized, BMD and plasma estrogen levels were decreased more in DOVX rats than in rats following OVX ( NOVX ) or DMII ( DS ) alone.", "output": "estrogen." }, { "input": "IGF - 1 expression was decreased in the liver, kidney, skeletal muscle, and bone of DOVX, DS, and NOVX rats; however, the decrease was larger and occurred sooner in DOVX rats.", "output": "There is no related enetity." }, { "input": "While IRS - 1 and IRS - 2 decreased in most groups in all tissues examined, the expression patterns differed in both a group - and tissue - dependent fashion.", "output": "There is no related enetity." }, { "input": "In conclusion, these data demonstrate that estrogen loss and DMII induced by a high - fat / sugar diet interact to produce osteoporosis and support the hypothesis that the bone loss may be mediated at least in part by concurrent decreases in the insulin signaling proteins in bone.", "output": "estrogen, sugar." }, { "input": "Egis - 11150: a candidate antipsychotic compound with procognitive efficacy in rodents.", "output": "Egis - 11150." }, { "input": "Classical antipsychotics, e. g. haloperidol, chlorpromazine, are potent at controlling the positive symptoms of schizophrenia but frequently elicit extrapyramidal motor side - effects.", "output": "haloperidol, chlorpromazine." }, { "input": "The introduction of atypical antipsychotics such as risperidone, olanzapine and clozapine has obviated this problem, but none of the current drugs seem to improve the cognitive deficits accompanying schizophrenia.", "output": "risperidone, olanzapine, clozapine." }, { "input": "Thus there is an unmet need for agents that not only suppress the psychotic symptoms but also ameliorate the impairment of cognition.", "output": "There is no related enetity." }, { "input": "Here, we report the preclinical properties of a candidate antipsychotic, Egis - 11150, that shows marked pro - cognitive efficacy.", "output": "Egis - 11150." }, { "input": "Egis - 11150 displayed high affinity for adrenergic alpha ( 1 ), alpha ( 2c ), 5 - HT ( 2A ) 5 - HT 7, moderate affinity for adrenergic alpha ( 2a ) and D 2 receptors.", "output": "Egis - 11150, 5 - HT." }, { "input": "It was a functional antagonist on all of the above receptors, with the exception of 5 - HT 7 receptors, where it was an inverse agonist.", "output": "There is no related enetity." }, { "input": "Phencyclidine - induced hypermotility in mice and inhibition of conditioned avoidance response in rats were assessed to estimate efficacy against the positive and social withdrawal test in rats was used to predict efficacy against the negative symptoms of schizophrenia.", "output": "Phencyclidine." }, { "input": "Passive - avoidance learning, novel object recognition and radial maze tests in rats were used to assess pro - cognitive activity, while phencyclidine - induced disruption of prepulse inhibition in mice was examined to test for effects on attention.", "output": "phencyclidine." }, { "input": "Egis - 11150 ( 0. 01 - 0. 3 mg / kg, ip. ) was effective in all of the preclinical models of schizophrenia examined.", "output": "Egis - 11150." }, { "input": "Moreover, a robust pro - cognitive profile was apparent.", "output": "There is no related enetity." }, { "input": "In summary, work in preclinical models indicates that Egis - 11150 is a potential treatment for controlling the psychosis as well as the cognitive dysfunction in schizophrenia.", "output": "Egis - 11150." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "Propranolol restores cognitive deficits and improves amyloid and Tau pathologies in a senescence - accelerated mouse model.", "output": "Propranolol." }, { "input": "Ageing is associated with a deterioration of cognitive performance and with increased risk of neurodegenerative disorders.", "output": "There is no related enetity." }, { "input": "Hypertension is the most - prevalent modifiable risk factor for cardiovascular morbidity and mortality worldwide, and clinical data suggest that hypertension is a risk factor for Alzheimer ' s disease ( AD ).", "output": "There is no related enetity." }, { "input": "In the present study we tested whether propranolol, a beta - receptor antagonist commonly used as antihypertensive drug, could ameliorate the cognitive impairments and increases in AD - related markers shown by the senescence - accelerated mouse prone - 8 ( SAMP8 ).", "output": "propranolol." }, { "input": "Propranolol administration ( 5 mg / kg for 3 weeks ) to 6 - month - old SAMP8 mice attenuated cognitive memory impairments shown by these mice in the novel object recognition test.", "output": "Propranolol." }, { "input": "In the hippocampus of SAMP8 mice it has been found increases in A beta ( 42 ) levels, the principal constituent of amyloid plaques observed in AD, accompanied by both an increased expression of the cleaving enzyme BACE1 and a decreased expression of the degrading enzyme IDE.", "output": "There is no related enetity." }, { "input": "All these effects were reversed by propranolol treatment.", "output": "propranolol." }, { "input": "Tau hyperphosphorylation ( PHF - 1 epitope ) shown by SAMP8 mice at this age was also decreased in the hippocampus of propranolol - treated mice, an effect probably related to a decrease in JNK1 expression.", "output": "propranolol." }, { "input": "Interestingly, propranolol also phosphorylated Akt in SAMP8 mice, which was associated with an increase of glycogen synthase kinase - 3 beta phosphorylation, contributing therefore to the reductions in Tau hyperphosphorylation.", "output": "propranolol." }, { "input": "Synaptic pathology in SAMP8 mice, as shown by decreases in synaptophysin and BDNF, was also counteracted by propranolol treatment.", "output": "propranolol." }, { "input": "Overall, propranolol might be beneficial in age - related brain dysfunction and could be an emerging candidate for the treatment of other neurodegenerative diseases.", "output": "propranolol." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "Metabolism and disposition of [ 14C ] n - butyl - p - hydroxybenzoate in male and female Harlan Sprague Dawley rats following oral administration and dermal application.", "output": "[ 14C ] n - butyl - p - hydroxybenzoate." }, { "input": "n - Butyl - p - hydroxybenzoate ( n - butylparaben, BPB ) is an antioxidant used in foods, pharmaceuticals and cosmetics.", "output": "n - Butyl - p - hydroxybenzoate, n - butylparaben, BPB." }, { "input": "This study investigated the disposition of ring - labelled [ ( 14 ) C ] BPB in Harlan Sprague Dawley rats, and in rat and human hepatocytes.", "output": "[ ( 14 ) C ] BPB." }, { "input": "BPB was rapidly cleared in hepatocytes from rat ( t ( 1 / 2 ) = 3 - 4 min ) and human ( t ( 1 / 2 ) = 20 - 30 min ).", "output": "BPB." }, { "input": "The major metabolites detected in rat hepatocytes were hydroxybenzoic acid and in human hepatocytes were hydroxybenzoic acid and hydroxyhippuric acid.", "output": "hydroxybenzoic acid, hydroxybenzoic acid, hydroxyhippuric acid." }, { "input": "[ ( 14 ) C ] BPB was administered to male rats orally at 10, 100 or 1000 mg / kg, intravenously at 10 mg / kg and dermally at 10 and 100 mg / kg; female rats were administered oral doses at 10 mg / kg.", "output": "[ ( 14 ) C ] BPB." }, { "input": "Oral doses of BPB were well - absorbed ( > 83 % ) and eliminated chiefly in urine ( 83 - 84 % ); <= 1 % of the radioactivity remained in tissues at 24 h or 72 h after dosing.", "output": "BPB." }, { "input": "About 4 % and 8 %, respectively, of 100 mg / kg dermal doses were absorbed in 24 h and 72 h, and about 50 % of a 10 mg / kg dose was absorbed in 72 h.", "output": "There is no related enetity." }, { "input": "Metabolites detected in urine included those previously reported, BPB - glucuronide, BPB - sulfate, hydroxybenzoic acid and hydroxyhippuric acid, but also novel metabolites arising from ring hydroxylation followed by glucuronidation and sulfation.", "output": "BPB - glucuronide, BPB - sulfate, hydroxybenzoic acid, hydroxyhippuric acid." }, { "input": "Fertility and endocrine outcome after robot - assisted laparoscopic myomectomy ( RALM ).", "output": "There is no related enetity." }, { "input": "Introduction: Laparoscopic myomectomy has recently gained wide acceptance but this procedure remains technically highly demanding and concerns have been raised about the increased blood loss and an higher risk of postoperative uterine rupture of the pregnant uterus.", "output": "There is no related enetity." }, { "input": "Objective: The aim of the present study is to evaluate the fertility and endocrine outcome in women underwent robot - assisted laparoscopic myomectomy ( RALM ).", "output": "There is no related enetity." }, { "input": "Methods: Data from 48 RALM performed in our department between the years 2007 and 2011 have been collected.", "output": "There is no related enetity." }, { "input": "Conception rate, abortion rate, incidence of feto - maternal morbidity or severe pregnancy and labor - related complications were reported; FSH and AMH levels and ultrasound valuation of AFC has been made before and 6 months after operation.", "output": "There is no related enetity." }, { "input": "Number of cesarean sections and vaginal deliveries were described.", "output": "There is no related enetity." }, { "input": "Results: The average age of the patients was 35 years and median Body Mass Index was 23 kg / m ( 2 ) ( range 18 - 35 kg / m ( 2 ) ).", "output": "There is no related enetity." }, { "input": "Seven women ( 13 % ) became pregnant after RALM with eight pregnancies.", "output": "There is no related enetity." }, { "input": "One pregnancy is actually on going; there were six deliveries with caesarian section and one spontaneous delivery.", "output": "There is no related enetity." }, { "input": "No spontaneous abortions.", "output": "There is no related enetity." }, { "input": "No uterine ruptures occurred.", "output": "There is no related enetity." }, { "input": "No significant modification of ovarian function was found after myomectomy.", "output": "There is no related enetity." }, { "input": "Conclusion: RALM seems to have a favorable impact on the reproductive outcome of young patients with no impact on the ovarian function.", "output": "There is no related enetity." }, { "input": "Sour Cherry Seed Kernel Extract Increases Heme Oxygenase - 1 Expression and Decreases Representation of CD3 + TNF - alpha + and CD3 + IL - 8 + Subpopulations in Peripheral Blood Leukocyte Cultures from Type 2 Diabetes Patients.", "output": "Heme." }, { "input": "The present study evaluates a hypothesis that sour cherry ( Prunus cerasus ) seed extracts ( SCE ) modulate CD3 + T lymphocyte activity in ways predictive of potential for uses of SCE in management of inflammatory diseases.", "output": "There is no related enetity." }, { "input": "Peripheral blood mononuclear cells ( PBMC ) from 12 type 2 diabetes ( T2DM ) patients and eight healthy control subjects were cultured 24 h with 100 ng / ml lipopolysaccharide ( LPS ) to increase inflammatory signaling and co - incubated with 0. 5 - 100 micro g / ml SCE.", "output": "There is no related enetity." }, { "input": "Cultures were evaluated by two - color flow cytometry for percent representation of CD3 + IL8 + and CD3 + TNF - alpha + cells which express interleukin - 8 ( IL - 8 ), and tumor necrosis factor - alpha, ( TNF - alpha + ) respectively, and by enzyme - linked immunoassay for lymphocyte - associated heme oxygenase - 1 ( HO - 1, known to be induced by SCE ).", "output": "heme." }, { "input": "SCE dosage ranges of 0. 5 - 100 micro g / ml in cell cultures significantly suppressed LPS - increased CD3 + TNF - alpha + and CD3 + IL8 + representation from all participants ( p < 0. 05 ), with greater pharmacological effect noted in suppression of CD3 + TNF - alpha + noted in cells from T2DM patients versus healthy control subjects.", "output": "There is no related enetity." }, { "input": "These effects correlated with increased HO - 1 expression in SCE - treated PBMC from all subjects ( p < 0. 05 ).", "output": "There is no related enetity." }, { "input": "Since TNF - alpha and IL - 8 are diagnostic / prognostic biomarkers for many inflammatory syndromes, the capacity of SCE to down - regulate representation of cells that express them suggests potential for therapeutic use of SCE in T2DM and other diseases.", "output": "There is no related enetity." }, { "input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Combined effects of treatment with vitamin C, vitamin E and selenium on the skin of diabetic rats.", "output": "vitamin C, vitamin E, selenium." }, { "input": "The aim of this study was to investigate the effects of vitamin C, vitamin E and selenium ( Se ) on the skin tissue of streptozotocin - induced diabetic rats.", "output": "vitamin C, vitamin E, selenium, Se, streptozotocin." }, { "input": "Swiss albino rats were divided into four groups: control, control + antioxidants, diabetic, diabetic + antioxidants groups.", "output": "There is no related enetity." }, { "input": "Diabetes was induced by intraperitoneal injection of 65 mg / kg streptozotocin.", "output": "streptozotocin." }, { "input": "Vitamin C ( 250 mg / kg ), vitamin E ( 250 mg / kg ) and Se ( 0. 2 mg / kg ) were given by gavage technique to rats of one diabetic and one control group for 30 days.", "output": "Vitamin C, vitamin E, Se." }, { "input": "In the diabetic group, the levels of serum urea and creatinine, skin lipid peroxidation and nonenzymatic glycosylation levels increased, but skin glutathione levels decreased.", "output": "urea, creatinine, glutathione." }, { "input": "Treatment with vitamin C, vitamin E and Se reversed these effects.", "output": "vitamin C, vitamin E, Se." }, { "input": "The present study showed that vitamin C, vitamin E and Se exerted antioxidant effects and consequently may prevent skin damage caused by streptozotocin - induced diabetes.", "output": "vitamin C, vitamin E, Se, streptozotocin." }, { "input": "Dopamine D 2 - agonist rotigotine effects on cortical excitability and central cholinergic transmission in Alzheimer ' s disease patients.", "output": "Dopamine, rotigotine." }, { "input": "Dopamine is a neurotransmitter involved in several brain functions ranging from emotions control, movement organization to memory formation.", "output": "Dopamine." }, { "input": "It is also involved in the regulation of mechanisms of synaptic plasticity.", "output": "There is no related enetity." }, { "input": "However, its role in Alzheimer ' s disease ( AD ) pathogenesis is still puzzling.", "output": "There is no related enetity." }, { "input": "Several recent line of research instead indicates a clear role for dopamine in both amyloid beta formation as well as in cognitive decline progression.", "output": "dopamine." }, { "input": "In particular it has been shown that dopamine D 2 - like receptors ( namely D 3 and D 2 ) could be mostly responsible for dopamine dysfunction in AD.", "output": "dopamine, dopamine." }, { "input": "Here we aimed to study the effects of the dopamine agonist Rotigotine on cortical excitability and on central cholinergic transmission in cases of AD.", "output": "dopamine, Rotigotine." }, { "input": "Rotigotine is a dopamine agonist with a pharmacological profile with high affinity for D 3 and D 2 receptors.", "output": "Rotigotine, dopamine." }, { "input": "We used paired pulse protocols assessing short intracortical inhibition ( SICI ) and intracortical facilitation ( ICF ) to asses cortical excitability over the primary motor cortex and Short Latency Afferent Inhibition ( SLAI ) protocols, to verify the effects of the drug on central cholinergic transmission in a group of AD patients compared to age - matched controls.", "output": "There is no related enetity." }, { "input": "We observed that rotigotine induces unexpected changes in both cortical excitability ( increased ) and central cholinergic transmission ( restored ) of AD patients.", "output": "rotigotine." }, { "input": "These unexpected effects might depend on the dopamine D 2 - like receptors dysfunction previously described in AD brains.", "output": "dopamine." }, { "input": "The current findings could indicate that future strategies aimed to ameliorate symptoms of the related AD cognitive decline could also involve some dopaminergic drugs.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "Absorption of TAK - 491, a new angiotensin II receptor antagonist, in animals.", "output": "TAK - 491, angiotensin II." }, { "input": "The absorption process in animals of TAK - 491, designed as ester - based prodrug with medoxomil moiety, was evaluated.", "output": "TAK - 491, ester, medoxomil." }, { "input": "In the plasma of rats and dogs, TAK - 536, the pharmacologically active metabolite, was present as the main component with hardly detectable concentrations of TAK - 491 after oral administration of TAK - 491.", "output": "TAK - 536, TAK - 491, TAK - 491." }, { "input": "In the rat portal plasma, TAK - 536 was also present as the main component with hardly detectable concentrations of TAK - 491 after jejunal loop injection of TAK - 491, suggesting TAK - 491 was absorbed from small intestine and hydrolyzed almost completely during absorption.", "output": "TAK - 536, TAK - 491, TAK - 491, TAK - 491." }, { "input": "Caco - 2 study indicated the permeability of TAK - 491 was improved by prodrug modification and the compound could be mainly transferred as TAK - 491.", "output": "TAK - 491, TAK - 491." }, { "input": "This is well consistent with the facts that the AUC and T ( max ) of TAK - 536 after oral administration of TAK - 491 were higher and shorter than those after oral administration of TAK - 536 in dogs Hydrolysis of TAK - 491 is observed not only by the intestinal and hepatic S9 fraction, but also by plasma and human serum albumin.", "output": "TAK - 536, TAK - 491, TAK - 536, TAK - 491." }, { "input": "However, medoxomil alcohol wasn ' t detected during the hydrolysis of TAK - 491.", "output": "medoxomil alcohol, TAK - 491." }, { "input": "These metabolic features of TAK - 491 were similar to olmesartan medoxomil, suggesting the hydrolytic pathway and enzymes for TAK - 491 when catalyzing to TAK - 536 would be the same as olmesartan medoxomil.", "output": "TAK - 491, olmesartan medoxomil, TAK - 491, TAK - 536, olmesartan medoxomil." }, { "input": "Synthesis, characterization, screening and docking analysis of 4 - anilinoquinazoline derivatives as tyrosine kinase inhibitors.", "output": "4 - anilinoquinazoline, tyrosine." }, { "input": "We report here the design and synthesis of a series of 4 - anilinoquinazoline derivatives, of which 7 compounds were crystallographically characterized, as epidermal growth factor receptor ( EGFR ) inhibitors by modifications on the aniline ring or at the 6 - alkoxy site of the 6, 7 - dimethoxy - 4 - anilinoquinazoline pharmacophore.", "output": "4 - anilinoquinazoline, aniline, 6 - alkoxy, 6 , 7 - dimethoxy - 4 - anilinoquinazoline." }, { "input": "The relative inhibition efficiency on EGFR of all as - prepared compounds were measured and ordered, and the IC50 values of nine highly active compounds were determined by ELISA.", "output": "There is no related enetity." }, { "input": "Docking studies indicated that all 4 - anilinoquinazoline derivatives could be inserted into the ATP - binding pocket of the EGFR via indirect docking, and that the modifications at the 3 ' - position of the anilino group and 6 - alkoxy site of the quinazoline ring have little interference with the formation of the two essential H - bonds between the N3 of the quinazoline ring and Thr766 through a water molecule, and the N1 of the quinazoline ring and N - H of Met769.", "output": "4 - anilinoquinazoline, ATP, anilino, 6 - alkoxy, quinazoline, H, quinazoline, Thr766, quinazoline, N - H, Met769." }, { "input": "The displacing of the phenyl at 4 - position with pyridinyl dramatically reduces the activity of the quinazoline pharmacophore, the resulting derivative ( 10 ) being the least active compound.", "output": "phenyl, pyridinyl, quinazoline." }, { "input": "The docking results also showed that the formation of new H - bonds between the N - H of the ethylenediamine group linked to the 6 - alkoxy site and Asp776 / Cys773 in the binding pocket of EGFR makes compounds 19 ( IC50 = 12. 1 +/- 1. 6 nM ) and 20 ( IC50 = 13. 6 +/- 0. 8 nM ) the most potent EGFR inhibitors in this class and worthy of further modification to obtain more potent anticancer compounds.", "output": "H, N - H, ethylenediamine, 6 - alkoxy, Asp776, Cys773." }, { "input": "Small molecule modulation of nuclear receptor conformational dynamics: implications for function and drug discovery.", "output": "There is no related enetity." }, { "input": "Nuclear receptors are targets for a wide range of ligands, both natural and synthetic, that regulate their activity and provide a means to pharmacologically modulate the receptor.", "output": "There is no related enetity." }, { "input": "Recent emphasis in the nuclear receptor field has focused on selective nuclear receptor modulators, which can display graded transcriptional responses and tissue selective pharmacological responses that deviate from the prototypical agonist or antagonist.", "output": "There is no related enetity." }, { "input": "Understanding the molecular mechanism of action of these selective modulators will provide significant insight toward the development of the next generation of modulators.", "output": "There is no related enetity." }, { "input": "Although most nuclear receptor structural studies have primarily focused on obtaining ligand - receptor cocrystal structures, recent studies implicate an important role for protein dynamics in the mechanism of action of nuclear receptor ligands.", "output": "There is no related enetity." }, { "input": "Here we review nuclear receptor studies reporting how ligands modulate the conformational dynamics of the nuclear receptor ligand - binding domain ( LBD ).", "output": "There is no related enetity." }, { "input": "A particular emphasis is placed on protein NMR and hydrogen / deuterium exchange ( HDX ) techniques and how they provide complementary information that, when combined with crystallography, provide detailed insight into the function of nuclear receptors.", "output": "hydrogen, deuterium." }, { "input": "Gelucire 44 / 14 based immediate release formulations for poorly water - soluble drugs.", "output": "There is no related enetity." }, { "input": "Here, we aim to evaluate Gelucire 44 / 14 as non - ionic surface - active excipient to produce immediate - release solid dosage forms for poorly water - soluble drugs.", "output": "There is no related enetity." }, { "input": "Gelucires are polyethylene glycol ( PEG ) glycerides composed of mono -, di - and triglycerides and mono - and diesters of PEG.", "output": "polyethylene glycol, PEG, mono - , di - and triglycerides, PEG." }, { "input": "They are inert semi - solid waxy amphiphilic excipients with surface - active properties that spontaneously form a fine dispersion or emulsion upon contact with water.", "output": "There is no related enetity." }, { "input": "Monolithic Gelucire 44 / 14 structures are prone to prolonged erosion times, thereby slowing down drug dissolution.", "output": "There is no related enetity." }, { "input": "To overcome this issue, we combine either granulation or spray - drying, followed by compression into tablets, with an optimized composition of disintegration promoting agents.", "output": "There is no related enetity." }, { "input": "This formulation strategy allows obtaining nearly 100 % drug release within 10 min dissolution time.", "output": "There is no related enetity." }, { "input": "Modeling the structure and proton transfer pathways of the mutant His - 107 - Tyr of human carbonic anhydrase II.", "output": "His, Tyr." }, { "input": "We present molecular modeling of the structure and possible proton transfer pathways from the surface of the protein to the zinc - bound water molecule in the active site of the mutant His - 107 - Tyr of human carbonic anhydrase II ( HCAII ).", "output": "zinc, His, Tyr." }, { "input": "No high - resolution structure or crystal structure is available till now for this particular mutant due to its lack of stability at physiological temperature.", "output": "There is no related enetity." }, { "input": "Our analysis utilizes as starting point a series of structures derived from high - resolution crystal structure of the wild type protein.", "output": "There is no related enetity." }, { "input": "While many of the structures investigated do not reveal a complete path between the zinc bound water and His - 64, several others do indicate the presence of a transient connection even when His - 64 is present in its outward conformation.", "output": "zinc, His, His." }, { "input": "Mutation at the residue 107 also reveals the formation of a new path into the active site.", "output": "There is no related enetity." }, { "input": "Competing contributions from His - 64 sidechain rotation from its outward conformation are also evaluated in terms of optimal path analysis.", "output": "His." }, { "input": "No indication of a lower catalytic efficiency of the mutant is evident from our results under the condition of thermal stability of the mutant.", "output": "There is no related enetity." }, { "input": "Oxysterol generation and liver X receptor - dependent reverse cholesterol transport: not all roads lead to Rome.", "output": "Oxysterol, cholesterol." }, { "input": "Cell cholesterol metabolism is a tightly regulated process, dependent in part on activation of nuclear liver X receptors ( LXRs ) to increase expression of genes mediating removal of excess cholesterol from cells in the reverse cholesterol transport pathway.", "output": "cholesterol, cholesterol, cholesterol." }, { "input": "LXRs are thought to be activated predominantly by oxysterols generated enzymatically from cholesterol in different cell organelles.", "output": "oxysterols, cholesterol." }, { "input": "Defects resulting in slowed release of cholesterol from late endosomes and lysosomes or reduction in sterol - 27 - hydroxylase activity lead to specific blocks in oxysterol production and impaired LXR - dependent gene activation.", "output": "cholesterol, sterol, oxysterol." }, { "input": "This block does not appear to be compensated by oxysterol production in other cell compartments.", "output": "oxysterol." }, { "input": "The purpose of this review is to summarize current knowledge about oxysterol - dependent activation by LXR of genes involved in reverse cholesterol transport, and what these defects of cell cholesterol homeostasis can teach us about the critical pathways of oxysterol generation for expression of LXR - dependent genes.", "output": "oxysterol, cholesterol, cholesterol, oxysterol." }, { "input": "The mGlu 5 positive allosteric modulator LSN2463359 differentially modulates motor, instrumental and cognitive effects of NMDA receptor antagonists in the rat.", "output": "LSN2463359, NMDA." }, { "input": "Metabotropic glutamate 5 ( mGlu 5 ) receptors are known to functionally interact with N - methyl - d - aspartate ( NMDA ) receptors at both neuronal and behavioural levels, in a manner that may be of relevance to the treatment of schizophrenia.", "output": "glutamate, N - methyl - d - aspartate, NMDA." }, { "input": "We have previously described a novel mGlu 5 positive allosteric modulator ( PAM ), LSN2463359 and provided evidence of its ability to attenuate aspects of the behavioural response to administration of the competitive NMDA receptor antagonist, SDZ 220, 581.", "output": "LSN2463359, NMDA, SDZ 220 , 581." }, { "input": "In addition, LSN2463359 was found to selectively attenuate reversal learning deficits observed in the neurodevelopmental MAM E17 model but not in the acute phencyclidine ( PCP ) model.", "output": "LSN2463359, phencyclidine, PCP." }, { "input": "In the present study, the interactions between this mGlu 5 PAM and the NMDA receptor were explored further by assessing the effects of LSN2463359 against some of the motor, instrumental and cognitive effects induced by the non - competitive NMDA receptor antagonists PCP and MK - 801, the competitive NMDA receptor antagonist SDZ 220, 581 and the GluN2B selective NMDA receptor antagonist, Ro 63 - 1908.", "output": "NMDA, LSN2463359, NMDA, PCP, MK - 801, NMDA, SDZ 220 , 581, NMDA, Ro 63 - 1908." }, { "input": "LSN2463359 had either no or minor impact on locomotor hyperactivity induced by either PCP or SDZ 220, 581.", "output": "LSN2463359, PCP, SDZ 220 , 581." }, { "input": "However, in rats lever pressing for food rewards under a variable interval 30s schedule of instrumental responding, the drug clearly attenuated not only the suppression of response rate induced by SDZ 220, 581 but also the stimulation of response rate induced by Ro 63 - 1908.", "output": "SDZ 220 , 581, Ro 63 - 1908." }, { "input": "In contrast, LSN2463359 failed to alter both of the instrumental effects induced by the open channel blockers PCP and MK - 801.", "output": "LSN2463359, PCP, MK - 801." }, { "input": "In addition, although PCP and SDZ 220, 581 induced similar deficits in a discrimination and reversal learning task, LSN2463359 was again only able to reverse the deficit induced by SDZ 220, 581.", "output": "PCP, SDZ 220 , 581, LSN2463359, SDZ 220 , 581." }, { "input": "The results indicate that the interactions between mGlu 5 and NMDA receptors are dependent on both the mechanism of the blockade of the receptor and the behavioural domain under investigation.", "output": "NMDA." }, { "input": "Our work has implications for the preclinical use of NMDA receptor antagonists in the prediction of potential therapeutic efficacy in the search for novel treatments for schizophrenia.", "output": "NMDA." }, { "input": "Positive allosteric modulators of the mGlu 5 receptor certainly question the predictive validity of such approaches.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "In vitro characterisation of the novel positive allosteric modulators of the mGlu 5 receptor, LSN2463359 and LSN2814617, and their effects on sleep architecture and operant responding in the rat.", "output": "LSN2463359, LSN2814617." }, { "input": "The demonstrated functional interaction of metabotropic glutamate 5 ( mGlu 5 ) receptors with N - methyl - d - aspartate ( NMDA ) receptors has prompted speculation that their activation may offer a potential treatment for aspects of schizophrenia.", "output": "glutamate, N - methyl - d - aspartate, NMDA." }, { "input": "Development of selective mGlu 5 agonists has been difficult, but several different positive allosteric modulator ( PAM ) molecules have now been identified.", "output": "There is no related enetity." }, { "input": "This study describes two novel mGlu 5 PAMs, LSN2463359 ( N - ( 1 - methylethyl ) - 5 - ( pyridin - 4 - ylethynyl ) pyridine - 2 - carboxamide ) and LSN2814617 [ ( 7S ) - 3 - tert - butyl - 7 - [ 3 - ( 4 - fluorophenyl ) - 1, 2, 4 - oxadiazol - 5 - yl ] - 5, 6, 7, 8 - tetrahydro [ 1, 2, 4 ] triazolo [ 4, 3 - A ] pyridine ], which are useful tools for this field of research.", "output": "LSN2463359, N - ( 1 - methylethyl ) - 5 - ( pyridin - 4 - ylethynyl ) pyridine - 2 - carboxamide, LSN2814617, ( 7S ) - 3 - tert - butyl - 7 - [ 3 - ( 4 - fluorophenyl ) - 1 , 2 , 4 - oxadiazol - 5 - yl ] - 5 , 6 , 7 , 8 - tetrahydro [ 1 , 2 , 4 ] triazolo [ 4 , 3 - A ] pyridine." }, { "input": "Both compounds are potent and selective potentiators of human and rat mGlu 5 receptors in vitro, displaying curve shift ratios of two to three fold in the concentration - response relationship to glutamate or the glutamate receptor agonist, DHPG, with no detectable intrinsic agonist properties.", "output": "glutamate, glutamate, DHPG." }, { "input": "Both compounds displaced the mGlu 5 receptor antagonist radioligand, [ (3) H ] MPEP in vitro and, following oral administration reached brain concentrations sufficient to occupy hippocampal mGlu 5 receptors as measured in vivo by dose - dependent displacement from the hippocampus of intravenously administered MPEPy.", "output": "[ (3) H ] MPEP, MPEPy." }, { "input": "In vivo EEG studies demonstrated that these mGlu 5 PAMs have marked wake - promoting properties but little in the way of rebound hypersomnolence.", "output": "There is no related enetity." }, { "input": "In contrast, the previously described mGlu 5 PAMs CDPPB and ADX47273 showed relatively poor evidence of in vivo target engagement in either receptor occupancy assays or EEG disturbance.", "output": "CDPPB, ADX47273." }, { "input": "Wake - promoting doses of LSN2463359 and LSN2814617 attenuated deficits in performance induced by the competitive NMDA receptor antagonist SDZ 220, 581 in two tests of operant behaviour: the variable interval 30 s task and the DMTP task.", "output": "LSN2463359, LSN2814617, NMDA, SDZ 220 , 581." }, { "input": "These effects were lost if the dose of either compound extended into the range which disrupted performance in the baseline DMTP task.", "output": "There is no related enetity." }, { "input": "However, the improvements in response accuracy induced by the mGlu 5 potentiators in SDZ 220, 581 - treated rats were not delay - dependent and, therefore, perhaps more likely reflected optimization of general arousal than specific beneficial effects on discrete cognitive processes.", "output": "SDZ 220 , 581." }, { "input": "The systematic profiling of LSN2463359 and LSN2814617 alongside other previously described molecules will help determine more precisely how mGlu 5 potentiator pharmacology might provide therapeutic benefit.", "output": "LSN2463359, LSN2814617." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "The development and application of small molecule modulators of SF3b as therapeutic agents for cancer.", "output": "There is no related enetity." }, { "input": "The identification of potent spliceosome modulators that demonstrate antitumor activity indicates that this complex may be a target for drug development.", "output": "There is no related enetity." }, { "input": "Several natural products have been demonstrated to bind to the SF3b1 subunit of this macromolecule and these agents modulate alternative RNA splicing.", "output": "There is no related enetity." }, { "input": "In this article we describe their biological properties, discuss the validity of the spliceosome as a therapeutic target, and propose that alteration of alternative splicing represents a viable approach for inducing tumor - selective cytotoxicity.", "output": "There is no related enetity." }, { "input": "Size of TiO ( 2 ) nanoparticles influences their phototoxicity: an in vitro investigation.", "output": "TiO ( 2 )." }, { "input": "To uncover the size influence of TiO ( 2 ) nanoparticles on their potential toxicity, the cytotoxicity of different - sized TiO ( 2 ) nanoparticles with and without photoactivation was tested.", "output": "TiO ( 2 ), TiO ( 2 )." }, { "input": "It was demonstrated that without photoactivation, TiO ( 2 ) nanoparticles were inert up to 100 mu g / ml.", "output": "TiO ( 2 )." }, { "input": "On the contrary, with photoactivation, the toxicity of TiO ( 2 ) nanoparticles significantly increased, which correlated well with the specific surface area of the particles.", "output": "TiO ( 2 )." }, { "input": "Our results also suggest that the generation of hydroxyl radicals and reactive oxygen species ( ROS ) - mediated damage to the surface - adsorbed biomolecules could be the two major reasons for the cytotoxicity of TiO ( 2 ) nanoparticles after photoactivation.", "output": "hydroxyl, oxygen, TiO ( 2 )." }, { "input": "Higher ROS generation from smaller particles was detected under both biotic and abiotic conditions.", "output": "There is no related enetity." }, { "input": "Smaller particles could adsorb more proteins, which was confirmed by thermogravimetric analysis.", "output": "There is no related enetity." }, { "input": "To further investigate the influence of the generation of hydroxyl radicals and adsorption of protein, poly ( ethylene - alt - maleic anhydride ) ( PEMA ) and chitosan were used to coat TiO ( 2 ) nanoparticles.", "output": "hydroxyl, poly ( ethylene - alt - maleic anhydride ), PEMA, TiO ( 2 )." }, { "input": "The results confirmed that surface coating of TiO ( 2 ) nanoparticles could reduce such toxicity after photoactivation, by hindering adsorption of biomolecules and generation of hydroxyl radical (. OH ) during photoactivation.", "output": "TiO ( 2 ), hydroxyl, . OH." }, { "input": "Fibroblast growth factor 23 inhibits extrarenal synthesis of 1, 25 - dihydroxyvitamin D in human monocytes.", "output": "1 , 25 - dihydroxyvitamin D." }, { "input": "Vitamin D is a potent stimulator of monocyte innate immunity, and this effect is mediated via intracrine conversion of 25 - hydroxyvitamin D ( 25OHD ) to 1, 25 - dihydroxyvitamin D ( 1, 25 ( OH ) ( 2 ) D ).", "output": "Vitamin D, 25 - hydroxyvitamin D, 25OHD, 1 , 25 - dihydroxyvitamin D, 1 , 25 ( OH ) ( 2 ) D." }, { "input": "In the kidney, synthesis of 1, 25 ( OH ) ( 2 ) D is suppressed by fibroblast growth factor 23 ( FGF23 ), via transcriptional suppression of the vitamin D - activating enzyme 1 alpha - hydroxylase ( CYP27B1 ).", "output": "1 , 25 ( OH ) ( 2 ) D, vitamin D." }, { "input": "We hypothesized that FGF23 also suppresses CYP27B1 in monocytes, with concomitant effects on intracrine responses to 1, 25 ( OH ) ( 2 ) D.", "output": "1 , 25 ( OH ) ( 2 ) D." }, { "input": "Healthy donor peripheral blood mononuclear cell monocytes ( PBMCm ) and peritoneal dialysate monocyte ( PDm ) effluent from kidney disease patients were assessed at baseline to confirm the presence of mRNA for FGF23 receptors ( FGFRs ), with Klotho and FGFR1 being more strongly expressed than FGFR2 / 3 / 4 in both cell types.", "output": "There is no related enetity." }, { "input": "Immunohistochemistry showed coexpression of Klotho and FGFR1 in PBMCm and PDm, with this effect being enhanced following treatment with FGF23 in PBMCm but not PDm.", "output": "There is no related enetity." }, { "input": "Treatment with FGF23 activated mitogen - activated protein kinase ( MAPK ) and protein kinase B ( Akt ) pathways in PBMCm, demonstrating functional FGFR signaling in these cells.", "output": "There is no related enetity." }, { "input": "FGF23 treatment of PBMCm and PDm decreased expression of mRNA for CYP27B1.", "output": "There is no related enetity." }, { "input": "In PBMCm this was associated with downregulation of 25OHD to 1, 25 ( OH ) ( 2 ) D metabolism, and concomitant suppression of intracrine induced 24 - hydroxylase ( CYP24A1 ) and antibacterial cathelicidin ( LL37 ).", "output": "25OHD, 1 , 25 ( OH ) ( 2 ) D." }, { "input": "FGF23 suppression of CYP27B1 was particularly pronounced in PBMCm treated with interleukin - 15 to stimulate synthesis of 1, 25 ( OH ) ( 2 ) D.", "output": "1 , 25 ( OH ) ( 2 ) D." }, { "input": "These data indicate that FGF23 can inhibit extra - renal expression of CYP27B1 and subsequent intracrine responses to 1, 25 ( OH ) ( 2 ) D in two different human monocyte models.", "output": "1 , 25 ( OH ) ( 2 ) D." }, { "input": "Elevated expression of FGF23 may therefore play a crucial role in defining immune responses to vitamin D and this, in turn, may be a key determinant of infection in patients with chronic kidney disease ( CKD ).", "output": "vitamin D." }, { "input": "A crown - ether loop - derivatized oligothiophene doubly attached on gold surface as cation - binding switchable molecular junction.", "output": "crown - ether, oligothiophene." } ] }