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.

docosahexaenoic acid

methylmercury


Input: Fish contains both beneficial substances e. g. docosahexaenoic acids but also harmful compounds e. g. methylmercury.

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.


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).


Input: Additionally, we analyzed impacts of both regular fish consumption and extreme fish consumption habits.


Input: At the individual level, the simulated net effects were small, encompassing a range of one IQ point in all scenarios.


Input: Fatty fish consumption, however, clearly generated a beneficial net IQ effect, and lean fish consumption evoked an adverse net IQ effect.


Input: In view of the current fish consumption pattern of Finnish mothers the benefits and risks seem to more or less compensate each other.


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.


Input: The mechanisms responsible for garlic-drug interactions and their in vivo relevance.


Input: Garlic phytochemicals and garlic supplements influence the pharmacokinetic and pharmacodynamic behavior of concomitantly ingested drugs.


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.


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.


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.


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.

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.

saquinavir

ritonavir


Input: We also assessed the probability of pharmacokinetic interactions with garlic of the novel drug darunavir and other cardiovascular drugs.

darunavir


Input: Finally, selected garlic phytochemicals were tested for their ability to influence P-glycoprotein and CYP3A4 activities.


Input: Endothelial nitric oxide synthase genotypes and haplotypes modify the responses to sildenafil in patients with erectile dysfunction.

nitric oxide

sildenafil


Input: Erectile dysfunction (ED) is usually treated with sildenafil.

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.

nitric oxide

sildenafil


Input: We studied 118 patients; 63 patients had ED secondary to radical prostatectomy (PED) and 55 had organic, clinical ED.


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.


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.

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.


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.


Input: The C-4a-Glu haplotype was more common in GR than in PR patients with PED.


Input: Conversely, the T-4b-Asp haplotype was less common in GR than in PR patients with PED.


Input: No other significant differences were found.


Input: Our findings show evidence that eNOS polymorphisms affect the responses of PED and clinical ED patients to sildenafil.

sildenafil


Input: On the benefit of magnetic magnesium nanocarrier in cardiovascular toxicity of aluminum phosphide.

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).

(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).

(25) MgPMC16

AlP


Input: Sodium bicarbonate (Bicarb; 2 mEq/kg, iv) was used as the standard therapy.

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).


Input: Later lipid peroxidation, antioxidant power, ATP/ADP ratio, and Mg concentration in the heart were evaluated.

ATP

ADP

Mg


Input: Results indicated that after AlP administration, BP and HR decreased while R-R duration increased.

AlP


Input: (25) MgPMC16 significantly increased the BP and HR at all doses used.

(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.

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.

(25) MgPMC16

Mg

(25) MgPMC16

AlP


Input: Ventilatory functions in cotton textile workers and the role of some inflammatory cytokines.


Input: Exposure to cotton dust in industrial environments causes inflammation in the airways of the exposed workers.


Input: This may manifest as respiratory complaints and changes in the respiratory functions after work shift and in the baseline of their ventilatory functions.


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).


Input: The study was conducted on 63 textile workers and 65 nonexposed subjects.


Input: Both groups were matched for age, socioeconomic status and smoking habit.


Input: The respirable dust measured in the workplace did not exceed the permissible values of the Egyptian law 1994.


Input: The bacterial counts detected were within the occupational exposure limits of the industrial settings.


Input: The results revealed that the percentage of respiratory symptoms was higher in textile workers.


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.


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.


Input: The additive effect of smoking on the ventilatory functions was not apparent.


Input: The ventilatory functions of the workers were significantly positively correlated with the duration of exposure.


Input: The cytokines were insignificantly higher in the textile workers compared to their controls.


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.


Input: In conclusion, the results supported the fact that exposure to cotton dust deteriorates ventilatory functions and elevates proinflammatory cytokine levels.


Input: Analysis of the release of cytokines can be used to evaluate the immune responses to organic dust-induced airway inflammation.


Input: Heat stress decreases testicular germ cell proliferation and increases apoptosis in short term: an immunohistochemical and ultrastructural study.


Input: Scrotal hyperthermia has been known as a cause of male infertility but the exact mechanism leading to impaired spermatogenesis is unknown.


Input: This work was aimed to investigate the role of scrotal hyperthermia on cell proliferation and apoptosis in testes.


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.


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.


Input: Control rats were treated in the same way, except the testes were immersed in a water bath maintained at 22 degrees C.


Input: Hyperthermia-exposed rats were killed under 50 mg/kg ketamine anaesthesia and tissue samples were obtained for biochemical and histopathological investigations.

ketamine


Input: Hyperthermia treatment significantly decreased the testicular antioxidant system, including decreases in the glutathione level, superoxide dismutase, and glutathione peroxidase activities.

glutathione

superoxide

glutathione


Input: Moreover, exposure to hyperthermia resulted in lipid peroxidation increase in testes.


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.

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.


Input: Scrotal hyperthermia is one of the major factors that impair spermatogenesis in testis.


Input: This heat stress is shown to be closely associated with oxidative stress, followed by apoptosis of germ cells.


Input: A genomic approach to predict synergistic combinations for breast cancer treatment.


Input: We leverage genomic and biochemical data to identify synergistic drug regimens for breast cancer.


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.

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.

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).

VPA

SAHA


Input: In particular, VPA and SAHA upregulate key cyclin-dependent kinase (CDK) inhibitors.

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.


Input: Together, these results led us to hypothesize that VPA and SAHA may interact synergistically with CDK inhibitors such as PD-033299.

VPA

SAHA


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.


Input: Therefore, synergistic relationships between HDAC and CDK inhibitors may provide an effective combinatorial regimen for breast cancer.


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.


Input: Chemical constituents and allelopathic and antioxidant activities of Alchorneopsis floribunda M u ll.


Input: Arg.


Input: (Euphorbiaceae).


Input: Chemical investigation of extracts from the stems and leaves of Alchorneopsis floribunda M u ll.


Input: Arg., collected in the Amazon region, was performed.


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).

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).

isocorilagin

2, 2-diphenyl-1-picrylhydrazyl

isocorilagin

Trolox

butylated hydroxyanisole


Input: This is the first chemical study of the genus Alchorneopsis (Euphorbiaceae).


Input: Evaluation of total oxidative status and total antioxidant capacity in patients with endemic fluorosis.


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.


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.


Input: The urine fluoride levels and plasma TOS and TAC levels were measured.

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).

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).


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).

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).


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).

fluoride

fluoride

fluoride


Input: The results of our study demonstrate that oxidative stress plays an important role in the pathogenesis of the endemic fluorosis.


Input: Impact of aqueous doash extract on urinary mutagenicity in rats exposed to heterocyclic amines.

heterocyclic amines


Input: Doash (Origanum majorana) is an herbaceous plant found commonly in Saudi Arabia.


Input: It is used as a food flavor and a folk remedy to treat a number of diseases.


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.

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.

heterocyclic amines

PhIP


Input: Results obtained showed that doash tea had no influence on body weight in both the studies.


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).

PhIP


Input: The selected dosage was 5 mg/kg for both heterocyclic amines.

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).

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.

PhIP


Input: No mutagenicity was observed in the absence of an activation system that is direct-acting mutagenicity using (IQ and PhIP).

PhIP


Input: Statistical analysis revealed that, in comparison with the control group, the aqueous doash extract significantly reduced the mutagenic response after 24 h.


Input: It was concluded that doash extract significantly decreased the excretion of mutagens in comparison with the control group (water only).


Input: Genetic and epigenetic regulation of the organic cation transporter 3, SLC22A3.


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.

amines


Input: OCT3 is identified as one of the important risk loci for prostate cancer, and is markedly underexpressed in aggressive prostate cancers.


Input: The goal of this study was to identify genetic and epigenetic factors in the promoter region that influence the expression level of OCT3.


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.


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.


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.


Input: The methylation level of the OCT3 promoter was higher in 62% of prostate tumor samples compared with matched normal samples.


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.


Input: Aberrant methylation contributes to the reduced expression of OCT3 in prostate cancer.


Input: Accumulation patterns of some seed oil components from wild sources of Turkey.


Input: Accumulation profiles of fatty acids and alpha-tocopherol were analysed at three ripening stages in the seed oils of Primula and Echium species.

fatty acids

alpha-tocopherol


Input: Total seed oils were increased considerably with maturation, while alpha-tocopherol contents decreased in both species.

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.

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.

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.


Input: Mucopolysaccharidosis: cardiologic features and effects of enzyme-replacement therapy in 24 children with MPS I, II and VI.


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.


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.


Input: At start of therapy, 66% had abnormal cardiac geometric features.


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.


Input: Regurgitation was most severe in a subgroup of young MPS VI patients (< 5 years) at the mitral valve.


Input: At baseline, all patients had abnormal valves.


Input: The ECG showed no clear rhythm or conduction abnormalities; neither, in most patients, did it reflect the hypertrophy.


Input: After ERT, the LVMI Z-score normalized in 70% of the patients who had a Z-score > 2.


Input: LVMI Z-scores decreased significantly in patients with MPS I and MPS II (p = 0. 04 and p = 0. 032).


Input: Despite ERT, valve regurgitation increased in 60% of the patients.


Input: We conclude that all our MPS patients have cardiac abnormalities.


Input: The most severe cardiac disease was observed in a subgroup of young MPS VI patients.


Input: While ERT had an effect on LVMI and IVSd, it apparently had little or none on valve regurgitation.


Input: Structural basis for protein phosphatase 1 regulation and specificity.


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.

serine

threonine

carbohydrate


Input: However, the free catalytic subunit of PP1, while an effective enzyme, lacks substrate specificity.


Input: Instead, it depends on a diverse set of regulatory proteins (>= 200) to confer specificity towards distinct substrates.


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.


Input: Protective effect of vitamin E and epicatechin against nicotine-induced oxidative stress in rats.

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.

Nicotine


Input: Epicatechin is one of the most potent antioxidants present in the human diet.

Epicatechin


Input: Particularly high levels of this compound are found in tea, apples and chocolate.


Input: It has been reported that tea extracts and/or its constituents have antibacterial, antiviral, antioxidative, antitumor and antimutagenic activities.


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.

Vitamin E


Input: The primary mechanism by which vitamin E is proposed to prevent cancer is through their antioxidant properties.

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.

epicatechin

vitamin E

nicotine


Input: Results obtained indicated that there was a significant elevation in the levels of malondialdhyde (MDA) in nicotine injected rats.

malondialdhyde

MDA

nicotine


Input: The combined treatment (epicatechin + Vit E) group showed a potential reduction of these parameters more than individual treatment.

epicatechin

Vit E


Input: The activities of superoxide dismutase, catalase and glutathione peroxidase were found significantly higher in combined treated than untreated rats.

superoxide

glutathione


Input: In nicotine group, a negative significant correlation between reduced glutathione and MDA (r =-0. 92) was observed.

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.

epicatechin

vitamin E

nicotine


Input: Prevention of cytotoxicity of nickel by quercetin: the role of reactive oxygen species and histone acetylation.

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.

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.

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%.

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.

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.

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.

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.

Ni (2 +)

Ni (2 +)


Input: Cadmium concentrations in shrimp (Penaeus semisulcatus and Penaeus monodon) caught from the coastal areas in Southern Iran.

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.

cadmium


Input: Cadmium concentration was determined by graphite furnace atomic absorption spectrophotometry in 91 shrimp samples after nitric acid/perchloric acid digestion.

Cadmium

graphite

nitric acid

perchloric acid


Input: Accuracy of the analysis was checked by various methods including the use of reference material.


Input: The mean +/- SD of cadmium concentrations in shrimp samples were 0. 128 +/- 0. 144 (mu g/g).

cadmium


Input: The cadmium concentrations ranged from 0. 010 to 0. 96 mu g/g of the muscle tissues of shrimp.

cadmium


Input: Higher cadmium concentration in shrimp samples was found in summer (significant p < 0. 05).

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.

cadmium

cadmium


Input: Therefore, no risk to the consumer arises from the cadmium contents of the shrimp caught in these areas.

cadmium


Input: Selective separation of patchouli alcohol from the essential oil of Cablin potchouli by inclusion crystalline method.

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.

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.

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.


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.

patchouli alcohol


Input: Toxic effects of some synthetic food colorants and/or flavor additives on male rats.


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.


Input: A number of chemical food color and flavor additives are routinely added during processing to improve the aesthetic appearance of the dietary items.


Input: However, many of them are toxic after prolonged use.


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.

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.


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.

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.

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.


Input: Steroids and phenolic constituents from the fruiting bodies of the basidiomycete Sarcodon joedes.

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.

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).

(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.


Input: All these compounds were isolated from this fungus for the first time.


Input: In vitro evaluation of the protective effects of 4-thujanol against mitomycin-C and cyclophosphamide-induced genotoxic damage in human peripheral lymphocytes.

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.

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.

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.

MMC

MMC


Input: The present study showed that 4-thujanol was unable to reduce the genetic damage induced by MMC, in the absence of S9 mix.

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.


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.

MMC

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.

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.


Input: Chlorogenic acid, rutin and hyperoside content in Fragaria vesca, F. viridis and F. moschata in Lithuania.

Chlorogenic acid

rutin

hyperoside


Input: In Lithuania, two species of the genus Fragaria L.


Input: (Rosaceae), F. vesca L. and F. viridis Weston, occur naturally in the wild and two others, F. moschata Weston and F.


Input: x ananassa Duchesne ex Rozier are found escaped from cultivation.


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.

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.


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.

rutin

hyperoside

chlorogenic acid


Input: Our results showed that the leaves should be taken into account as important rutin and hyperoside contributors for strawberries.

rutin

hyperoside


Input: Bromotheoynic acid, a brominated acetylenic acid from the marine sponge Theonella swinhoei.

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.

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.


Input: Bromotheoynic acid (1) inhibited maturation of starfish oocytes and cell division of fertilised starfish eggs.

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.

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.


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.


Input: The essential oils (EOs) were extracted by hydrodistillation of the air-dried aerial parts and analysed by GC-FID and GC-MS.


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.


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.


Input: Cyclo-(His, Leu): a new microbial diketopiperazine from a terrestrial Bacillus subtilis strain B38.

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).

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.


Input: To the best of our knowledge, this is the first time that cyclo-(His, Leu) has been isolated from natural products.

cyclo-(His, Leu)


Input: Suppression of survival signalling pathways by the phosphatase PHLPP.


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.

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.


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.


Input: In the second instance, PHLPP dephosphorylates and thus activates the pro-apoptotic kinase Mst1, thereby promoting apoptosis.


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.


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.

phosphoinositide


Input: Chemical composition and antifungal activity of Artemisia nilagirica essential oil growing in northern hilly areas of India.


Input: Essential oil extracted from aerial parts of Artemisia nilagirica was analysed by gas chromatography-mass spectroscopy.


Input: Forty-three constituents amounting to 98. 16% of the total essential oil contents were identified.


Input: The essential oil contained approximately 79. 91% monoterpenoids and 18. 25% sesquiterpenoids.

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.

alpha-Thujone

beta-thujone

germacrene D

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)).


Input: This study indicated that A. nilagirica essential oil can be used to control phytopathogenic fungi infesting agricultural crops and commodities.


Input: Structural basis for the altered drug sensitivities of non-small cell lung cancer-associated mutants of human epidermal growth factor receptor.


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.

tyrosine


Input: The non-small cell lung cancer (NSCLC)-associated EGFR mutants, L858R and G719S, are constitutively active and oncogenic.


Input: They display sensitivity to TK inhibitors, including gefitinib and erlotinib.

gefitinib

erlotinib


Input: In contrast, the secondary mutation of the gatekeeper residue, T790M, reportedly confers inhibitor resistance on the oncogenic EGFR mutants.


Input: In this study, our biochemical analyses revealed that the introduction of the T790M mutation confers gefitinib resistance on the G719S mutant.

gefitinib


Input: The G719S/T790M double mutant has enhanced activity and retains high gefitinib-binding affinity.

gefitinib


Input: The T790M mutation increases the ATP affinity of the G719S mutant, explaining the acquired drug resistance of the double mutant.

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.


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.

gefitinib


Input: In the L858R mutant structure, the active-site cleft is expanded by the repositioning of Phe723 within the P-loop.


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.

gefitinib

gefitinib


Input: Taken together, our results provide a structural basis for the altered drug sensitivities caused by distinct NSCLC-associated EGFR mutations.


Input: TGF-beta 1-dependent L1CAM expression has an essential role in macrophage-induced apoptosis resistance and cell migration of human intestinal epithelial cells.


Input: Patients with chronic inflammatory bowel disease (IBD) have an increased risk to develop colorectal cancer (CRC) particularly after long duration of the disease.


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).


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.


Input: In this study, we examine the role of TGF-beta 1-induced L1CAM expression and macrophages in malignant transformation of intestinal epithelial cells.


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.


Input: Accordingly, NCM460 cells acquired a migratory and apoptosis-resistant phenotype if transfected with L1CAM.


Input: Immunohistochemistry of colonic biopsies revealed considerable L1CAM expression in intestinal epithelial cells in tissues from IBD patients but not in normal colonic tissues.


Input: Moreover, L1CAM expression increased with duration of disease being associated with the presence of CD33 + macrophages.


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.


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.


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.


Input: Modulated release of 5-fluorouracil from pH-sensitive and colon targeted pellets: an industrially feasible approach.


Input: Pellets, reliant on pH-sensitivity and time-dependency for drug delivery, provide one of the most versatile opportunities for targeting colon.


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.


Input: A 3 (2) full factorial design was employed to optimize spheronization speed and time.


Input: Obtained pellets were evaluated for flow properties, pellet size, roundness and aspect ratio.


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.

Eudragit NE30D

Eudragit FS30D


Input: The coating levels were statistically optimized and in vitro drug release was monitored by changing pH media method.


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%.


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.


Input: Drug release was also studied at pH 7. 4.


Input: Scanning electron microscopy (SEM) demonstrated average coating thickness to be 32. 50 +/- 3. 0 micro m.


Input: Hence, the present study provides constructive results for colon targeting of 5-FU pellets with industrially feasible processes.


Input: Conditional activation of Pik3ca (H1047R) in a knock-in mouse model promotes mammary tumorigenesis and emergence of mutations.


Input: Oncogenic mutations in PIK3CA, which encodes the phosphoinositide-3-kinase (PI3K) catalytic subunit p110 alpha, occur in ~ 25% of human breast cancers.

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.


Input: We found that activation of the latent Pik3ca (H1047R) allele resulted in breast tumors with multiple histological types.


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.


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.


Input: WNT6 is a novel target gene of caveolin-1 promoting chemoresistance to epirubicin in human gastric cancer cells.

epirubicin


Input: Resistance to chemotherapy is a major obstacle for curative treatment of human gastric cancer (GC).


Input: However, the underlying molecular mechanisms are largely unknown.


Input: Wingless-type MMTV integration site family members (WNTs) are secreted glycoproteins involved in embryogenesis and, on inappropriate expression in the adult, in cancer.


Input: Here, we show expression of WNT6 in GC patient specimens, human GC cell lines and in a mouse model of GC.


Input: In human GC cells, WNT6 expression was enhanced by caveolin-1 (Cav1), a scaffold protein of plasma membrane caveolae.


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).

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.

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).

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.

Epi

cisplatin


Input: These results showed that WNT6 and Cav1 are upregulated by chemotherapeutics and enhance the resistance of GC cells to anthracycline drugs.

anthracycline


Input: Understanding the molecular mechanisms driving WNT6/Cav1-induced drug resistance will provide benefits in developing new therapies for GC.


Input: Three new alpha-glucosidase inhibitors from guggul, the oleogum resin of Commiphora wightii.


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.

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.


Input: alpha-Glucosidase inhibitory effects of HSF and the isolated compounds were evaluated calorimetrically.


Input: The HSF showed significant alpha-glucosidase inhibitory effect [IC (50) value of 140 micro g mL (-1) (p < 0. 05)].


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).

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.

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).


Input: Chemical constituents of Indonesian plant Protium javanicum Burm.


Input: f. and their antifeedant activities against Coptotermes formosanus Shiraki.


Input: In the continuing study of antifeedant compounds in Protium javanicum Burm.


Input: f. against Coptotermes formosanus Shiraki, 6-desacetylnimbin (1), quercitrin (2) and myricitrin (3) were isolated from P. javanicum extract.

quercitrin

myricitrin


Input: All compounds were characterised by NMR and MS.


Input: Furthermore, the structure of 6-desacetylnimbin was confirmed by X-ray crystallography.


Input: The antifeedant activity was evaluated with no-choice feeding tests.


Input: At a dose of 0. 5 mg, 6-desacetylnimbin exhibited the highest antifeedant activity among the isolates.


Input: Tumor angiogenesis is enforced by autocrine regulation of high-mobility group box 1.


Input: The endothelium plays a pivotal role in the progression of solid tumors and is considered a highly relevant target for therapy.


Input: However, it emerges that current clinical angiogenesis inhibitors that act through inhibition of tumor-derived growth factors are prone to inducing drug resistance.


Input: Therefore, markers of tumor endothelial cells (ECs) themselves provide attractive novel therapeutic targets.


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.


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.


Input: HMGB1 stimulates the expression of players in vascular endothelial growth factor and platelet-derived growth factor signaling, both in vitro and in vivo.


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.


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).


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.


Input: Using different in vivo models, therapeutic efficacy of HMGB1 targeting was confirmed.


Input: First, we demonstrated induction of HMGB1 expression in the chicken embryo chorioallantoic membrane (CAM) neovasculature following both photodynamic therapy and tumor challenge.


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.


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.


Input: Histone deacetylase inhibitors suppress mutant p53 transcription via histone deacetylase 8.


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.


Input: Mutant p53 is often highly expressed in tumor cells at least, in part, due to its increased half-life.


Input: However, whether mutant p53 expression is regulated by other mechanisms in tumors is unclear.


Input: Here we found that histone deacetylase (HDAC) inhibitors suppress both wild-type and mutant p53 transcription in time-and dose-dependent manners.


Input: Consistent with this, the levels of wild-type and mutant p53 proteins are decreased upon treatment with HDAC inhibitors.


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.


Input: Conversely, we found that ectopic expression of wild-type, but not mutant HDAC8, leads to increased transcription of p53.


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.


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.


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.


Input: microRNA-125b inhibits tube formation of blood vessels through translational suppression of VE-cadherin.


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.


Input: Thus, overinduction of negative regulators may inhibit tumor angiogenesis.


Input: MicroRNAs (miRNAs or miRs) are endogenous short noncoding RNAs regulating gene expression either through translational inhibition or destabilization of target mRNA.


Input: Here, we show that miR-125b expression is transiently induced in ECs on stimulation with vascular endothelial growth factor or by ischemia.


Input: miR-125b inhibits translation of vascular endothelial (VE)-cadherin mRNA and in vitro tube formation by ECs.


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.


Input: It has been suggested that pro-angiogenic signals in ECs also upregulate anti-angiogenic molecules simultaneously via negative feedback.


Input: Because miR-125b induction in ECs is transient after pro-angiogenic stimulation, prolonged overexpression of miR-125b could result in blood vessel regression.


Input: Thus, miR-125b may be useful in cancer therapy by causing the collapse of the lumen of ECs.


Input: Chemical constituents comparison between Rhizoma Smilacis Glabrae and Rhizoma Smilacis Chinae by HPLC-DAD-MS/MS.


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.


Input: Chemical constituents in the two species were compared by HPLC-DAD-MS/MS.


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.

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.

syringic acid

chlorogenic acid


Input: Gonadal hormones and the control of reactive gliosis.


Input: Astrocytes and microglia respond to central nervous system (CNS) injury with changes in morphology, proliferation, migration and expression of inflammatory regulators.


Input: This phenomenon is known as reactive gliosis.


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.


Input: However, reactive gliosis may amplify CNS damage under chronic neurodegenerative conditions.


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.

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.

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.

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.


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.


Input: A 90-day oral (dietary) toxicity study of arruva, an R, R-monatin salt isomer, in Crl: CD-1 (ICR) mice.

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.

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.

arruva


Input: There were no toxicologically relevant clinical or histopathological findings in any of the test article-treated groups.


Input: Significantly lower mean body weights and cumulative body weight gains were noted in the 35, 000ppm group when compared to the control group.


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.


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.


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).

arruva


Input: Grewialin and optivanin new constituents from the stem bark of Grewia optiva Drummond ex Burret (Tiliaceae).

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.

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).

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.

beta-sitosterol

stigmasterol

lupeol


Input: Berberine inhibits myofibroblast differentiation in nasal polyp-derived fibroblasts via the p38 pathway.

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.

berberine


Input: NPDFs were pre-treated with berberine prior to induction by transforming growth factor (TGF)-beta 1.

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.


Input: The total soluble collagen production was analysed by the SirCol collagen assay.


Input: The expression of several signaling molecules of the TGF-beta 1 pathway was evaluated by western blot analysis.


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.

berberine


Input: Berberine only suppressed the expression of pp38 among the evaluated signaling molecules.

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.


Input: Berberine exerts suppressive effects on phenotype changes and ECM production in NPDFs via p38 signaling pathway interference.

Berberine


Input: The findings provide new therapeutic options for ECM production in nasal polyps.


Input: The nonhematopoietic effects of erythropoietin in skin regeneration and repair: from basic research to clinical use.


Input: Erythropoietin (EPO) is the main regulator of red blood cell production but there exists also a variety of nonhematopoietic properties.


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.


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.


Input: There is clear evidence that EPO effectively influences all wound-healing phases in a dose-dependent manner.


Input: This includes inflammation, tissue, and blood vessel formation as well as the remodeling of the wound.


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.

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.


Input: Essential oils composition of Periploca laevigata Aiton subsp. angustifolia (Labill.) Markgraf (Apocynaceae-Periplocoideae).


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.


Input: The analyses allowed the identification and quantification of 86 volatile compounds.


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.


Input: In the matrices examined three constituents, heneicosane, docosane and tricosane are in common, although with different percentages.

heneicosane

docosane

tricosane


Input: At least the most abundant compounds found in the matrices have been reported to have several biological activities.


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.


Input: Among the compounds identified, several play a role as semiochemicals for many animals, and 28 allomones, 43 pheromones, 21 kairomones have been identified.


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.


Input: P21-activated kinase 4 (PAK4) is required for metaphase spindle positioning and anchoring.


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.


Input: We have also identified that PAK4 regulates Ran GTPase activity during mitosis.


Input: Here, we show that after entering mitosis, PAK4-depleted cells maintain a prolonged metaphase-like state.


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.


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.


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.


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.


Input: However, we show that membrane blebs, which are strongly enriched in phospho-cofilin, are not responsible for the poor anchoring of the spindle.

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.


Input: The anxiolytic potential and psychotropic side effects of an echinacea preparation in laboratory animals and healthy volunteers.


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.


Input: Rats were studied in the elevated plus-maze, conditioned fear, open-field, object recognition and conditioned place preference tests.


Input: Toxicity was studied in rats after intragastric administration.


Input: The preparation decreased anxiety in the elevated plus-maze and ameliorated contextual conditioned fear.


Input: No lethality or behavioural signs of discomfort were noticed in rats treated with 1000 and 3000 mg/kg Echinacea angustifolia.


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.


Input: A pharmacological formulation based on the same E. angustifolia extract was tested in human subjects.


Input: One or two tablets per day were administered for 1 week to healthy volunteers scoring high on the State-Trait Anxiety Inventory (STAI).


Input: The tablets contained 20 mg of the plant extract.


Input: Data were collected using a structured self-assessment diary technique.


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.


Input: The lower dose (1 tablet per day) did not affect anxiety significantly.


Input: Antitrypanosomal properties of Panax ginseng C.


Input: A.


Input: Meyer: new possibilities for a remarkable traditional drug.


Input: African trypanosomiasis is still a major health problem in many sub-Saharan countries in Africa.


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.

ginsenosides

polyacetylene panaxynol


Input: Hexane extracts and the pure panaxynol were toxic and at the same time highly selective against T.

Hexane

panaxynol


Input: b. brucei, whereas methanol extracts and 12 isolated ginsenosides were significantly less toxic and showed only weak selectivity.

methanol

ginsenosides


Input: Panaxynol was cytotoxic against T.

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.


Input: We suggest that the inhibition of trypanothione reductase, which is only found in trypanosomes, might explain the observed selectivity.

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.

panaxynol

polyacetylenes


Input: Androgenic and spermatogenic activity of alkylamide-rich ethanol solution extract of Anacyclus pyrethrum DC.

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.


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.

androgens

alkylamide

ethanol


Input: Male Wistar strain rats weighing between 150 and 180 g were completely randomized divided into five groups.


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.

ethanol

testosterone


Input: Thirteen N-alkylamides were detected in the extract by using HPLC/UV/electrospray ionization mass spectrometry method.

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.

testosterone


Input: Histoarchitecture of testis revealed increased spermatogenic activities.


Input: Seminal fructose content was also significantly increased after 28 days of treatment.

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.

ethanol


Input: eIF4F suppression in breast cancer affects maintenance and progression.


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.


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.

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.


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.


Input: Our results indicate that the mTOR/eIF4F axis is an important contributor to tumor maintenance and progression programs in breast cancer.


Input: Targeting this pathway may be of therapeutic benefit.


Input: Actions of Xanthurenic acid, a putative endogenous Group II metabotropic glutamate receptor agonist, on sensory transmission in the thalamus.

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.

Xanthurenic acid

tryptophan

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.

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.


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.


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.


Input: Furthermore, we postulate that XA may be the first potential endogenous allosteric agonist (termed' endocoid') for the mGlu receptors.


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.

kynurenine


Input: This article is part of a Special Issue entitled' Metabotropic Glutamate Receptors'.

Glutamate


Input: Sol-flame synthesis: a general strategy to decorate nanowires with metal oxide/noble metal nanoparticles.

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.


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.


Input: Both features are advantageous for the above applications that involve both surface reactions and charge transport processes.


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.

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.


Input: Improving oral absorption via drug-loaded nanocarriers: absorption mechanisms, intestinal models and rational fabrication.


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.


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.


Input: This review, in general, elucidates some considerable features of in vitro oral drug delivery in three different parts.


Input: The first one summarizes the main challenges for oral drug delivery and available absorption mechanisms.


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.


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.


Input: Precision-cut intestinal slices as in vitro tool for studies on drug metabolism.


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.


Input: Recently the precision-cut slice model, which is widely used for liver and kidney, was also adapted for the small and large intestine.


Input: In this review the application of precision-cut intestinal slices (PCIS) for research in drug metabolism and transport is discussed.


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.


Input: They are viable for 8-24 h of incubation and show high activity of drug metabolizing enzymes, representative for the in vivo activity.


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.


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.


Input: Their application as model for drug-induced intestinal toxicity is still in its infancy but appears to be promising.


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.


Input: Topical antiinflammatory activity of essential oil of Lippia sidoides cham: possible mechanism of action.


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.

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%).

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.

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.

thymol

arachidonic acid

phenol


Input: However, a proinflammatory effect of EOLS and thymol was evidenced when it was applied for more than 1 day.

thymol


Input: There were no statistical differences in antiedematogenic activity between EOLS and thymol.

thymol


Input: In conclusion, the results indicate that thymol is the constituent responsible for the topical antiinflammatory activity of EOLS.

thymol


Input: Thus, these findings could justify the popular use of L. sidoides by alternative medicine, but chronic use has an inflammatory effect.


Input: Effects of synthetic peptides on the inflammatory response and their therapeutic potential.


Input: Recently, interest in small peptide molecules as potential drug candidates has revived.


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.


Input: A series of F (D) LF (D) LF analogs has been synthesized, including either N-t-Boc or different N-ureido substituents.

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.

N-formyl-L-methionyl-L-leucyl-Lphenylalanine

fMLF

superoxide


Input: Their methyl-ester derivatives are ineffective.

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.

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.

amino acid

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.

N


Input: Furthermore, the peptide 5 shows neuroprotective activity in a model of cerebral ischemia in vitro, favouring the recovery of synaptic function.


Input: These findings suggest interesting possible therapeutic applications for these peptides.


Input: A review on the development in the field of NIDDM based thiazolidinedione PPAR gamma agonists.

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.


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.

Thiazolidinedione


Input: The intent of this article is to review all the reported thiazolidinediones and associated groups of PPAR gamma ligands.

thiazolidinediones


Input: A new triterpenoid from the rhizomes of Nelumbo nucifera.

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.

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.

cinnamic acid

nitric oxide

cGMP


Input: Cinnamic acid (CA) and its derivatives have a broad therapeutic spectrum that includes antimicrobial, antifungal, and antitumoral activities.

Cinnamic acid


Input: However, the vasodilative effect of CA has not been demonstrated.


Input: The present study characterizes the vasodilative activity and the mechanism of CA in rat thoracic aorta.


Input: The vasomotion of aortic strips following CA treatment was measured in an organ bath system.


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.

nitrite

cyclic guanosine monophosphate

cGMP


Input: CA relaxed phenylephrine-precontracted aortic strips in an endothelium-dependent manner.

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.

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.

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.

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).

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.

nitric oxide

cGMP


Input: The role of inflammation in epileptogenesis.


Input: One compelling challenge in the therapy of epilepsy is to develop anti-epileptogenic drugs with an impact on the disease progression.


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.


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.


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.


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.


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.

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.


Input: This article is part of the Special Issue entitled' New Targets and Approaches to the Treatment of Epilepsy'.


Input: Modulation of pyramidal cell output in the medial prefrontal cortex by mGluR5 interacting with CB1.


Input: The medial prefrontal cortex (mPFC) serves executive cognitive functions such as decision-making that are impaired in neuropsychiatric disorders and pain.


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).


Input: Therefore, modulating pyramidal output is desirable therapeutic goal.


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.

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.


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.


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.

CHPG


Input: The facilitatory effects of CHPG and VU0360172 were inhibited by an mGluR5 antagonist (MTEP).

CHPG

MTEP


Input: CHPG, but not VU0360172, increased neuronal excitability (frequency-current [F-I] function).

CHPG


Input: VU0360172, but not CHPG, increased evoked excitatory synaptic currents (EPSCs) and amplitude, but not frequency, of miniature EPSCs, indicating a postsynaptic action.

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.

CHPG


Input: VU0360172 also increased and prolonged CB1-mediated depolarization-induced suppression of synaptic inhibition (DSI).


Input: Activation of CB1 with ACEA decreased inhibitory transmission through a presynaptic mechanism.

ACEA


Input: The results show that increasing mGluR5 function enhances mPFC output.


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).

CHPG


Input: Therefore, mGluR5 may be a useful target in conditions of impaired mPFC output.


Input: This article is part of a Special Issue entitled' Metabotropic Glutamate Receptors'.

Glutamate


Input: Stratified medicine in psychiatry: a worrying example or new opportunity in the treatment of anxiety?


Input: Stratified medicine is a new term that figures highly in current MRC and NHS strategy.


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.


Input: The best exemplar is HER2 positivity in breast cancer to determine the efficacy of Herceptin.


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.


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.


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.


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.


Input: Extracts of Scutellaria baicalensis reduced body weight and blood triglyceride in db/db Mice.

triglyceride


Input: Scutellaria baicalensis has been extensively employed for the clinical treatment of hyperlipidemia, atherosclerosis, hypertension, dysentery, inflammatory diseases, and the common cold.


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.


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.


Input: Administration of SBE improves weight gain, hypertriglyceridemia, and hyperinsulinemia in db/db mice.


Input: In obese db/db mice, SBE treatment also reduced plasma alanine aminotransferase levels.

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.

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.


Input: A new lignan with anti-tumour activity from Polygonum perfoliatum L.