Input: In constrast, the mRNA and protein expression of Smad7 was upregulated.


Input: Furthermore, the expression of alpha-SMA and FSP1 was also significantly attenuated, accompanied by the increasing expression of E-cadherin, suggesting the inhibition of the epithelial-mesenchymal transition (EMT).


Input: In conclusion: C. sinensis exerted its antifibrotic effect on the SNx rats through the inhibition of the TGF-beta 1/Smad pathway.


Input: Venom toxins in the exploration of molecular, physiological and pathophysiological functions of Acid-Sensing Ion Channels.


Input: Acid-sensing ion channels (ASICs) are voltage-independent proton-gated cation channels that are largely expressed in the nervous system as well as in some non-neuronal tissues.


Input: In rodents, six different isoforms (ASIC1a, 1b, 2a, 2b, 3 and 4) can associate into homo-or hetero-trimers to form a functional channel.


Input: Specific polypeptide toxins targeting ASIC channels have been isolated from the venoms of spider (PcTx1), sea anemone (APETx2) and snakes (MitTx and mambalgins).


Input: They exhibit different and sometimes partially overlapping pharmacological profiles and are usually blockers of ASIC channels, except for MitTx which is a potent activator.


Input: This review focuses on the use of these toxins to explore the structure-function relationships, the physiological and the pathophysiological roles of ASIC channels, illustrating at the same time the therapeutic potential of some of these natural compounds.


Input: Evaluation of the positive effects on insulin-resistance and beta-cell measurements of vildagliptin in addition to metformin in type 2 diabetic patients.

vildagliptin

metformin


Input: We evaluated the positive effects of vildagliptin in addition to metformin on glycemic control and beta-cell function in type 2 diabetic patients.

vildagliptin

metformin


Input: One hundred and seventy-one type 2 diabetic patients were instructed to add vildaglipin 50mg twice a day or placebo to metformin for 12 months.

vildaglipin

metformin


Input: Body mass index (BMI), glycemic control, fasting plasma insulin (FPI), HOMA-IR, HOMA-beta, fasting plasma proinsulin (FPPr), proinsulin/fasting plasma insulin ratio (Pr/FPI ratio), C-peptide, glucagon, vaspin, visfatin, and omentin-1 were evaluated.


Input: Before, and after 12 months since the addition of vildagliptin, patients underwent a combined euglycemic hyperinsulinemic and hyperglycemic clamp, with subsequent arginine stimulation.

vildagliptin

arginine


Input: Vildagliptin + metformin were more effective than placebo + metformin in reducing body weight and BMI, glycemic control, HOMA-IR, glucagon and insulin resistance measurements.

Vildagliptin

metformin

metformin


Input: Vildagliptin + metformin gave also a better increase of HOMA-beta, and of all beta-cell parameters after the clamp.

Vildagliptin

metformin


Input: We also recorded a significant correlation between M value increase and the decrease of vaspin, visfatin, and omentin-1 obtained with vildagliptin + metformin.

vildagliptin

metformin


Input: Vildagliptin, in addition to metformin, proved to be effective in improving beta-cell function and in reducing insulin resistance measurements.

Vildagliptin

metformin


Input: 4-Hydroxytamoxifen-stimulated processing of cyclin E is mediated via G protein-coupled receptor 30 (GPR30) and accompanied by enhanced migration in MCF-7 breast cancer cells.


Input: Over-expression of cleaved cyclin E in breast tumors is closely associated with tumor progression and resistance to antiestrogens.


Input: 17 beta-Estradiol (E2) has been recently shown to induce cyclin E processing in breast cancer cells.

17 beta-Estradiol


Input: Tamoxifen has been used in patients with estrogen-sensitive breast cancer, yet resistance to antiestrogens and recurrence will appear in some of the patients after its continued use.

Tamoxifen

estrogen


Input: We therefore addressed possible effects of tamoxifen on the generation of cleaved cyclin E and its signal mechanism (s) in estrogen-responsive MCF-7 breast cancer cells that express both G protein-coupled protein (GPR) 30 and estrogen receptor alpha (ER alpha).

tamoxifen

estrogen

estrogen


Input: 4-Hydroxytamoxifen (OHT, tamoxifen' s active form) failed to prevent E2-induced proteolysis of cyclin E and migration, but rather triggered cyclin E cleavage coincident with augmented migration.

OHT

tamoxifen


Input: OHT-induced cyclin E truncation also occurred in SK-BR-3 cells that express GPR30 and lack ER alpha, but not in MDA-MB-231 cells that express neither GPR30 nor ER alpha.

OHT


Input: G1, a specific GPR 30 agonist, caused dramatic proteolysis of cyclin E and enhanced migration.


Input: Furthermore, OHT-stimulated cleavage of cyclin E and migration were tremendously attenuated by G15, a GPR30 antagonist, or siRNA against GPR30.

OHT


Input: In addition, inhibitors for EGFR or ERK1/2 remarkably suppressed OHT-induced truncation of cyclin E, suggesting involvement of EGFR signaling.

OHT


Input: Collectively, our data indicate that OHT contributes to the production of proteolyzed cyclin E via GPR30 with augmented migration in MCF-7 cells.

OHT


Input: Enhanced lithium storage in Fe2O3-SnO2-C nanocomposite anode with a breathable structure.

lithium

C


Input: A novel nanocomposite architecture of a Fe2O3-SnO2-C anode, based on clusters of Fe2O3 and SnO2 nanoparticles dispersed along the conductive chains of Super P Li (TM) carbon black (Timcal Ltd.), is presented as a breathable structure in this paper for lithium-ion batteries.

C

Li

carbon black

lithium


Input: The synthesis of the nanocomposite is achieved by combining a molten salt precipitation process and a ball milling method for the first time.

molten salt


Input: The crystalline structure, morphology, and electrochemical characterization of the synthesised product are investigated systematically.


Input: Electrochemical results demonstrate that the reversible capacity of the composite anode is 1110 mA h g (-1) at a current rate of 158 mA g (-1) with only 31% of initial irreversible capacity in the first cycle.


Input: A high reversible capacity of 502 mA h g (-1) (higher than the theoretical capacity of graphite, ~ 372 mA h g (-1)) can be obtained at a high current rate of 3950 mA g (-1).


Input: The electrochemical performance is compared favourably with those of Fe2O3-SnO2 and Fe2O3-SnO2-C composite anodes for lithium-ion batteries reported in the literature.

C

lithium


Input: This work reports a promising method for the design and preparation of nanocomposite electrodes for lithium-ion batteries.

lithium


Input: Antiaggressive activity of central oxytocin in male rats.

oxytocin


Input: RATIONALE: A substantial body of research suggests that the neuropeptide oxytocin promotes social affiliative behaviors in a wide range of animals including humans.

oxytocin


Input: However, its antiaggressive action has not been unequivocally demonstrated in male laboratory rodents.


Input: OBJECTIVE: Our primary goal was to examine the putative serenic effect of oxytocin in a feral strain (wild type Groningen, WTG) of rats that generally show a much broader variation and higher levels of intermale aggression than commonly used laboratory strains of rats.

oxytocin


Input: METHODS: Resident animals were intracerebroventricularly (icv) administered with different doses of synthetic oxytocin and oxytocin receptor antagonist, alone and in combination, in order to manipulate brain oxytocin functioning and to assess their behavioral response to an intruder.

oxytocin

oxytocin

oxytocin


Input: RESULTS: Our data clearly demonstrate that acute icv administered oxytocin produces dose-dependent and receptor-selective changes in social behavior, reducing aggression and potentiating social exploration.

oxytocin


Input: These antiaggressive effects are stronger in the more offensive rats.


Input: On the other hand, administration of an oxytocin receptor antagonist tends to increase (nonsignificantly) aggression only in low-medium aggressive animals.

oxytocin


Input: CONCLUSIONS: These results suggest that transiently enhancing brain oxytocin function has potent antiaggressive effects, whereas its attenuation tends to enhance aggressiveness.

oxytocin


Input: In addition, a possible inverse relationship between trait aggression and endogenous oxytocinergic signaling is revealed.


Input: Overall, this study emphasizes the importance of brain oxytocinergic signaling for regulating intermale offensive aggression.


Input: This study supports the suggestion that oxytocin receptor agonists could clinically be useful for curbing heightened aggression seen in a range of neuropsychiatric disorders like antisocial personality disorder, autism, and addiction.

oxytocin


Input: Coordinated conformational and compositional dynamics drive ribosome translocation.


Input: During translation elongation, the ribosome compositional factors elongation factor G (EF-G; encoded by fusA) and tRNA alternately bind to the ribosome to direct protein synthesis and regulate the conformation of the ribosome.


Input: Here, we use single-molecule fluorescence with zero-mode waveguides to directly correlate ribosome conformation and composition during multiple rounds of elongation at high factor concentrations in Escherichia coli.


Input: Our results show that EF-G bound to GTP (EF-G-GTP) continuously samples both rotational states of the ribosome, binding with higher affinity to the rotated state.

GTP

GTP


Input: Upon successful accommodation into the rotated ribosome, the EF-G-ribosome complex evolves through several rate-limiting conformational changes and the hydrolysis of GTP, which results in a transition back to the nonrotated state and in turn drives translocation and facilitates release of both EF-G-GDP and E-site tRNA.

GTP

GDP


Input: These experiments highlight the power of tracking single-molecule conformation and composition simultaneously in real time.


Input: The Acute and Chronic Effects of Monosodium L-Glutamate on Serum Iron and Total Iron-Binding Capacity in the Jugular Artery and Vein of Pigs.

Monosodium L-Glutamate


Input: We analyzed the effects of acute and chronic oral administration of monosodium L-glutamate (MSG) on serum iron (Fe) levels and total iron-binding capacity (TIBC) in piglets.

monosodium L-glutamate

MSG

iron

iron


Input: In the first experiment, 12 piglets were randomly assigned to two groups: one fed a standard diet (SD) and the other fed an SD containing MSG (10 g/kg).

MSG


Input: On day 30, serum, liver, kidney, and spleen samples were collected to determine the Fe levels.

Fe


Input: In the second experiment, six pigs were surgically fitted with a catheter in the jugular artery and vein to investigate the dynamic changes of serum Fe and TIBC.

Fe


Input: Blood samples were taken from each pig via the catheter every 30 min, for a period of 4 h.


Input: The results show that MSG increases Fe levels in the spleen (P < 0. 05) and in serum obtained from the jugular artery (P < 0. 01).

MSG

Fe


Input: In addition, TIBC in serum obtained from the jugular artery demonstrated an increasing trend in pigs fed the MSG diet; however, this trend was not observed in the jugular vein.

MSG


Input: In conclusion, MSG increases Fe retention by enhancing TIBC in serum.

MSG

Fe


Input: Lifestyle intervention and anti-obesity therapies in the polycystic ovary syndrome: impact on metabolism and fertility.


Input: Obesity is frequently present in patients with polycystic ovary syndrome (PCOS) and plays an important role in the pathogenesis of the metabolic, endocrine, and reproductive abnormalities associated with this syndrome.


Input: We aimed to summarize the effects of lifestyle changes and anti-obesity pharmacotherapy in patients with PCOS.


Input: We reviewed the literature regarding the effects of lifestyle changes and anti-obesity agents on the metabolic and endocrine abnormalities of PCOS.


Input: Lifestyle changes, including diet, exercise, and behavioral modification, appear to improve the metabolic and reproductive abnormalities of overweight and obese patients with PCOS.


Input: Therefore, lifestyle changes appear to represent the first-line management for all overweight and obese patients with PCOS.


Input: However, the optimal composition of diet and the optimal type of exercise in these patients are unknown.


Input: Anti-obesity agents that have been studied in PCOS include orlistat, sibutramine, and rimonabant.

orlistat

sibutramine

rimonabant


Input: However, the latter two agents have been withdrawn from the market because of side effects.


Input: Long-term studies with orlistat in overweight and obese diabetic patients showed greater weight loss and metabolic and cardiovascular benefits than those achieved with lifestyle changes alone.

orlistat


Input: However, there are limited data on the efficacy of orlistat in women with PCOS.

orlistat


Input: In conclusion, lifestyle changes (diet, exercise and behavioral modification), particularly when combined with anti-obesity agents, exert beneficial effects on the endocrine abnormalities of obese patients with PCOS and improve metabolic parameters.


Input: Sequential Therapy Versus Standard Triple-Drug Therapy for Helicobacter pylori Eradication: a Systematic Review of Recent Evidence.


Input: BACKGROUND: Several alternative treatment regimens for Helicobacter pylori eradication have been proposed since the efficacy of standard triple therapy has declined over time, and sequential therapy is one of them.


Input: The purpose of this systematic review is to analyze and compare the efficacy, adverse effects and cost of sequential therapy with that of standard triple therapy for H. pylori infection.


Input: METHODS: MEDLINE, EMBASE, Google Scholar and Cochrane databases were used to retrieve all relevant articles published in the English language over the last 5 years (January 2008-October 2012).


Input: Eligibility criteria were randomized controlled trials (RCTs) comparing sequential and standard triple therapies in patients with documented H. pylori infection.


Input: Eligibility and quality of the trials were assessed independently by two reviewers, and the data regarding eradication rate, adverse effects and the cost of therapy were extracted.


Input: RESULTS: Of the 17 RCTs included in the analysis (Asia 13, Europe 3, Latin America, 1), 12 reported better eradication rates with the sequential therapy, four did not find a significant difference between the two treatment regimens, and one reported a better eradication rate with standard triple therapy.


Input: All except one RCT reported no significant difference in the incidence of adverse effects between standard triple therapy and sequential therapy.


Input: Sequential therapy was cheaper than standard triple therapy in all three RCTs where a cost analysis was performed.


Input: The limitations of the RCTs included in the systematic review were that the sequential therapy regimen and the duration of standard triple therapy were not uniform.


Input: Antibiotic susceptibility tests were performed in only three RCTs.


Input: CONCLUSIONS: While the majority of the RCTs have shown superior eradication rates with sequential therapy, the largest RCT from Latin America did not find a significant difference between the two treatment regimens.


Input: Sequential therapy has good efficacy; however, further trials other than those from Asia and Italy are required to assess its superiority over existing regimens before recommending sequential therapy as the first line of treatment for H. pylori infection.


Input: Effectiveness of a Pharmacy Care Management Program for Veterans with Dyslipidemia.


Input: OBJECTIVE: To evaluate the effectiveness of a care management program provided by clinical pharmacists for veterans with dyslipidemia.


Input: DESIGN: Retrospective cohort design.


Input: SETTING: Two primary care clinics at a Veterans Affairs Medical Center.


Input: PATIENTS: An intervention (IT) cohort of 213 patients referred for management of dyslipidemia by clinical pharmacists and a control cohort of 219 patients with dyslipidemia receiving usual care (UC).


Input: METHODS: Data were obtained from electronic medical records regarding drug therapy, lipid levels, and patient characteristics.


Input: Using multivariable regression models to adjust for baseline characteristics, the primary analyses compared mean final measured values of low-density lipoprotein (LDL) cholesterol, total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and triglycerides (TGs) among the IT and UC cohorts at the final follow-up visits.

cholesterol

cholesterol

cholesterol

triglycerides


Input: Secondary analyses compared the proportion of patients achieving National Cholesterol Education Program/Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP/ATPIII) concordant LDL goals and the time to achieve LDL goals between the two groups.

Cholesterol


Input: RESULTS: Compared with the UC cohort, the adjusted difference in the mean final measured LDL for the IT cohort was-10. 4 mg/dl (95% confidence interval [CI]-16. 1 to-4. 6, p < 0. 001) and TC was-12. 7 (95% CI-21. 3 to-4. 1, p = 0. 004).


Input: There were no significant differences in the adjusted mean final measured HDL or TGs between the two groups.


Input: The NCEP/ATPIII goal LDL was met in 80. 3% of patients in the IT cohort and 65. 3% of patients in the UC cohort (odds ratio [OR], 2. 6; 95% CI 1. 6-4. 3, p < 0. 001).


Input: Time to achieve goal LDL was significantly shorter for the IT cohort compared with the UC cohort (risk ratio, 1. 8; 95% CI 1. 2-2. 8, log-rank p = 0. 002).


Input: CONCLUSION: Veterans referred to a clinical pharmacist for treatment of dyslipidemia achieved significant reductions in TC and LDL.


Input: A greater proportion of patients achieved NCEP/ATPIII goal LDL, and the time to attainment of LDL goals was shorter in the pharmacist-managed cohort, supporting a continued role for pharmacy care management in the treatment of patients with dyslipidemia.


Input: The effects of the adenosine A3 receptor agonist IB-MECA on sodium taurocholate-induced experimental acute pancreatitis.

adenosine

IB-MECA

sodium taurocholate


Input: The role of adenosine A3 receptors and their distribution in the gastrointestinal tract have been widely investigated.

adenosine


Input: Most of the reports discuss their role in intestinal inflammations.


Input: However, the role of adenosine A3 receptor agonist in pancreatitis has not been well established.

adenosine


Input: The aim of this study is (Ed note: Purpose statements should be in present tense) to evaluate the effects of the adenosine A3 receptor agonist on the course of sodium taurocholate-induced experimental acute pancreatitis (EAP).

adenosine

sodium taurocholate


Input: The experiments were performed on 80 male Wistar rats, 58 of which survived, subdivided into 3 groups: C-control rats, I-EAP group, and II-EAP group treated with the adenosine A3 receptor agonist IB-MECA (1-deoxy-1-6 [[(3-iodophenyl) methyl] amino]-9H-purin-9-yl)-N-methyl-B-D-ribofuronamide at a dose of 0. 75 mg/kg b. w.

adenosine

IB-MECA (1-deoxy-1-6 [[(3-iodophenyl) methyl] amino]-9H-purin-9-yl)-N-methyl-B-D-ribofuronamide


Input: i. p. at 48, 24, 12 and 1 h before and 1 h after the injection of 5% sodium taurocholate solution into the biliary-pancreatic duct.

sodium taurocholate


Input: Serum for alpha-amylase and lipase determinations and tissue samples for morphological examinations were collected at 2, 6, and 24 h of the experiment.


Input: In the IB-MECA group, alpha-amylase activity was decreased with statistically high significance compared to group I.

IB-MECA


Input: The activity of lipase was not significantly different among the experimental groups but higher than in the control group.


Input: The administration of IB-MECA attenuated the histological parameters of inflammation as compared to untreated animals.

IB-MECA


Input: The use of A3 receptor agonist IB-MECA attenuates EAP.

IB-MECA


Input: Our findings suggest that stimulation of adenosine A3 receptors plays a positive role in the sodium taurocholate-induced EAP in rats.

adenosine

sodium taurocholate


Input: A 7-Year Case of Furosemide-Induced Immune Thrombocytopenia.

Furosemide


Input: Immune thrombocytopenia has been attributed to many causes.


Input: Several drugs have been implicated as culprits in causing drug-induced thrombocytopenia.


Input: Although the mechanism for this type of thrombocytopenia is not well understood, at least three types of antibodies appear to be involved: drug-dependent antibodies, hapten-dependent antibodies, and drug-induced platelet-reactive autoantibodies.


Input: In this report, we describe a case in which furosemide was identified as the probable cause of drug-induced thrombocytopenia in an 84-year-old man with chronic symptomatic idiopathic thrombocytopenia for seven years before discovery.

furosemide


Input: The patient' s platelet count and daily furosemide dose, both intravenous and oral, were documented throughout his medical history.

furosemide


Input: A dose-dependent change in platelet count was observed in association with the furosemide dose.

furosemide


Input: His platelet count increased on discontinuation of furosemide and beginning of torsemide.

furosemide

torsemide


Input: Several months after discontinuation of furosemide, his platelet count increased to a 9-year high of 206 x 10 (3)/mm (3) from a low of 36 x 10 (3)/mm (3) while receiving furosemide therapy.

furosemide

furosemide


Input: Based on the observations of this case report, clinicians should more readily consider furosemide as a potential cause of thrombocytopenia.

furosemide


Input: Mesoporous Silica Nanoparticles Act as a Self-Adjuvant for Ovalbumin Model Antigen in Mice.

Silica


Input: Immunization to the model protein antigen ovalbumin (OVA) is investigated using MCM-41 mesoporous silica nanoparticles as a novel vaccine delivery vehicle and adjuvant system in mice.

silica


Input: The effects of amino surface functionalization and adsorption time on OVA adsorption to nanoparticles are assessed.

amino


Input: Amino-functionalized MCM-41 (AM-41) shows an effect on the amount of OVA binding, with 2. 5-fold increase in binding capacity (72 mg OVA/g AM-41) compared to nonfunctionalized MCM-41 (29 mg OVA/g MCM-41).

Amino


Input: Immunization studies in mice with a 10 mu g dose of OVA adsorbed to AM-41 elicits both antibody and cell-mediated immune responses following three subcutaneous injections.


Input: Immunizations at a lower 2 mu g dose of OVA adsorbed to AM-41 particles results in an antibody response but not cell-mediated immunity.


Input: The level of antibody responses following immunization with nanoformulations containing either 2 mu g or 10 mu g of OVA are only slightly lower than that in mice which receive 50 mu g OVA adjuvanted with QuilA, a crude mixture of saponins extracted from the bark of the Quillaja saponaria Molina tree.

saponins


Input: This is a significant result, since it demonstrates that AM-41 nanoparticles are self-adjuvanting and elicit immune responses at reduced antigen doses in vivo compared to a conventional delivery system.


Input: Importantly, there are no local or systemic negative effects in animals injected with AM-41.


Input: Histopathological studies of a range of tissue organs show no changes in histopathology of the animals receiving nanoparticles over a six week period.


Input: These results establish the biocompatible MCM-41 silica nanoparticles as a new method for vaccine delivery which incorporates a self-adjuvant effect.

MCM-41 silica


Input: Risk Factors for Excessive Anticoagulation Among Hospitalized Adults Receiving Warfarin Therapy Using a Pharmacist-Managed Dosing Protocol.

Warfarin


Input: STUDY OBJECTIVE: To identify specific risk factors for excessive anticoagulation, defined as an international normalized ratio (INR) higher than 5, in hospitalized adults receiving warfarin therapy using a pharmacist-managed dosing protocol.

warfarin


Input: DESIGN: Retrospective nested case-control study.


Input: SETTING: Large academic tertiary care medical center.


Input: PATIENTS: Hospitalized nonsurgical patients 18 years or older who received at least one dose of warfarin according to the pharmacist-managed protocol from January 1, 2009, to January 31, 2012, were included.

warfarin


Input: Patients who experienced an INR higher than 5 were designated as case patients; those who received warfarin for at least as many days as the case patients but who did not experience an INR more than 5 were deemed control patients.

warfarin


Input: Controls were matched to cases in a 2: 1 ratio by age, sex, INR goal, and type of warfarin therapy (new start or continuation).

warfarin


Input: MEASUREMENTS AND MAIN RESULTS: A total of 87 case patients were matched to 174 controls.


Input: Ten different hypothesized risk factors were examined.


Input: Two variables, severity of illness score (odds ratio [OR] 4. 89, p < 0. 001) and poor nutritional status (OR 4. 27, p < 0. 001), demonstrated strong independent associations with risk of excessive anticoagulation.


Input: Administration of interacting drugs that highly potentiate warfarin' s effect (OR 2. 26, p = 0. 011) and concurrent diarrheal illness (OR 4. 75, p < 0. 001) also displayed a statistically significant risk for excessive anticoagulation.

warfarin


Input: CONCLUSION: Even in a highly standardized system for warfarin dosing by a pharmacist-managed protocol, higher disease severity and poor nutritional status placed hospitalized patients at greater risk of experiencing excessive anticoagulation.

warfarin


Input: In addition, administration of interacting drugs that highly potentiate warfarin' s effect or the occurrence of diarrheal illness may predict increased risk.

warfarin


Input: 5'-Trityl-Substituted Thymidine Derivatives as a Novel Class of Antileishmanial Agents: Leishmania infantum EndoG as a Potential Target.

Thymidine


Input: Two series of 5'-triphenylmethyl (trityl)-substituted thymidine derivatives were synthesized and tested against Leishmania infantum axenic promastigotes and amastigotes.

5'-triphenylmethyl (trityl)

thymidine


Input: Several of these compounds show significant antileishmanial activity, with IC50 values in the low micromolar range.


Input: Among these, 3'-O-(isoleucylisoleucyl)-5'-O-(3, 3, 3-triphenylpropanoyl) thymidine displays particularly good activity against intracellular amastigotes.

3'-O-(isoleucylisoleucyl)-5'-O-(3, 3, 3-triphenylpropanoyl) thymidine


Input: Assays performed to characterize the nature of parasite cell death in the presence of the tritylthymidines indicated significant alterations in mitochondrial transmembrane potential, an increase in superoxide concentrations, and also significant decreases in DNA degradation during the cell death process.

tritylthymidines

superoxide


Input: Results point to the mitochondrial nuclease LiEndoG as a target for the action of this family of compounds.


Input: Effect of chromium (VI) exposure on antioxidant defense status and trace element homeostasis in acute experiment in rat.

chromium (VI)


Input: Occupational exposure to hexavalent chromium (Cr (VI)) compounds is of concern in many Cr-related industries and their surrounding environment.

hexavalent chromium

Cr (VI)

Cr


Input: Cr (VI) is a proven toxin and carcinogen.

Cr (VI)


Input: The Cr (VI) compounds are easily absorbed, can diffuse across cell membranes, and have strong oxidative potential.

Cr (VI)


Input: Despite intensive studies of Cr (VI) pro-oxidative effects, limited data exist on the influence of Cr (VI) on selenoenzymes thioredoxin reductase (TrxR) and glutathione peroxidase (GPx)-important components of antioxidant defense system.

Cr (VI)

Cr (VI)

glutathione


Input: This study investigates the effect of Cr (VI) exposure on antioxidant defense status, with focus on these selenoenzymes, and on trace element homeostasis in an acute experiment in rat.

Cr (VI)


Input: Male Wistar rats (130-140g) were assigned to two groups of 8 animals: I. control; and II.


Input: Cr (VI) treated.

Cr (VI)


Input: The animals in Cr (VI) group were administered a single dose of K2Cr2O7 (20 mg/kg, intraperitoneally (ip)).

Cr (VI)


Input: The control group received saline solution.


Input: After 24 h, the animals were sacrificed and the liver and kidneys were examined for lipid peroxidation (LP; thiobarbituric acid reactive substances (TBARS) concentration), the level of reduced glutathione (GSH) and the activities of GPx-1, TrxR-1, and glutathione reductase (GR).

thiobarbituric acid

glutathione

GSH

glutathione


Input: Samples of tissues were also used to estimate Cr accumulation and alterations in zinc, copper, and iron levels.

Cr

zinc

copper

iron


Input: The acute Cr (VI) exposure caused an increase in both hepatic and renal LP (by 70%, p < 0. 01 and by 15%, p < 0. 05, respectively), increased hepatic GSH level and GPx-1 activity, and decreased renal GPx-1 activity.

Cr (VI)

GSH


Input: The activity of GR was not changed.


Input: A significant inhibitory effect of Cr (VI) was found on TrxR-1 activity in both the liver and the kidneys.

Cr (VI)


Input: The ability of Cr (VI) to cause TrxR inhibition could contribute to its cytotoxic effects.

Cr (VI)


Input: Further investigation of oxidative responses in different in vivo models may enable the development of strategies to protect against Cr (VI) oxidative damage.

Cr (VI)


Input: Optimization of conventional water treatment plant using dynamic programming.


Input: In this research, the mathematical models, indicating the capability of various units, such as rapid mixing, coagulation and flocculation, sedimentation, and the rapid sand filtration are used.


Input: Moreover, cost functions were used for the formulation of conventional water and wastewater treatment plant by applying Clark' s formula (Clark, 1982).


Input: Also, by applying dynamic programming algorithm, it is easy to design a conventional treatment system with minimal cost.


Input: The application of the model for a case reduced the annual cost.


Input: This reduction was approximately in the range of 4. 5-9. 5% considering variable limitations.


Input: Sensitivity analysis and prediction of system' s feedbacks were performed for different alterations in proportion from parameters optimized amounts.


Input: The results indicated (1) that the objective function is more sensitive to design flow rate (Q), (2) the variations in the alum dosage (A), and (3) the sand filter head loss (H).

alum


Input: Increasing the inflow by 20%, the total annual cost would increase to about 12. 6%, while 20% reduction in inflow leads to 15. 2% decrease in the total annual cost.


Input: Similarly, 20% increase in alum dosage causes 7. 1% increase in the total annual cost, while 20% decrease results in 7. 9% decrease in the total annual cost.

alum


Input: Furthermore, the pressure decrease causes 2. 95 and 3. 39% increase and decrease in total annual cost of treatment plants.


Input: Effects of aluminum chloride on some trace elements and erythrocyte osmotic fragility in rats.

aluminum chloride


Input: Aluminum (Al) is a nonessential, toxic element to which humans are constantly exposed as a result of an increase in industrialization and improving technology practices.

Aluminum

Al


Input: The aim of the study was to investigate the effects of different durations and doses of Al exposure on serum and tissue element levels and erythrocyte osmotic fragility in rats.

Al


Input: A total of 40 male Wistar Albino rats were divided into five groups: control, group I (3 weeks, 8 mg/kg), group II (6 weeks, 8 mg/kg), group III (3 weeks, 16 mg/kg), and group IV (6 weeks, 16 mg/kg).


Input: Al chloride (AlCl3) was injected intraperitoneally (i. p.) five times a week.

Al chloride


Input: At the end of the experimental period, levels of Al, iron (Fe), copper (Cu), and zinc (Zn) in serum, liver, and kidney tissues were measured using inductively coupled plasma optical emission spectrometry.

Al

iron

Fe

copper

Cu

zinc

Zn


Input: Osmotic fragility was determined using a spectrophotometer.


Input: The results of the experiment indicate that Al induced a statistically significant increase in Al and Fe concentrations in liver and serum as well as in Cu in the kidney.

Al

Al

Fe

Cu


Input: The Fe concentration in serum and kidney tissues was significantly lower in all the groups.

Fe


Input: As a result of our study, it may be concluded that tissue Al accumulation may lead to an increase in osmotic fragility of erythrocytes and abnormal trace element levels.

Al


Input: MYCN and HDAC2 cooperate to repress miR-183 signaling in neuroblastoma.


Input: MYCN is a master regulator controlling many processes necessary for tumor cell survival.


Input: Here, we unravel a microRNA network that causes tumor suppressive effects in MYCN-amplified neuroblastoma cells.


Input: In profiling studies, histone deacetylase (HDAC) inhibitor treatment most strongly induced miR-183.


Input: Enforced miR-183 expression triggered apoptosis, and inhibited anchorage-independent colony formation in vitro and xenograft growth in mice.


Input: Furthermore, the mechanism of miR-183 induction was found to contribute to the cell death phenotype induced by HDAC inhibitors.


Input: Experiments to identify the HDAC (s) involved in miR-183 transcriptional regulation showed that HDAC2 depletion induced miR-183.


Input: HDAC2 overexpression reduced miR-183 levels and counteracted the induction caused by HDAC2 depletion or HDAC inhibitor treatment.


Input: MYCN was found to recruit HDAC2 in the same complexes to the miR-183 promoter, and HDAC2 depletion enhanced promoter-associated histone H4 pan-acetylation, suggesting epigenetic changes preceded transcriptional activation.


Input: These data reveal miR-183 tumor suppressive properties in neuroblastoma that are jointly repressed by MYCN and HDAC2, and suggest a novel way to bypass MYCN function.


Input: Thermostated Hamiltonian Dynamics with Log-Oscillators.


Input: With this work we present two new methods for the generation of thermostated, manifestly Hamiltonian dynamics and provide corresponding illustrations.


Input: The basis for this new class of thermostats are the peculiar thermodynamics as exhibited by logarithmic oscillators.


Input: These two schemes are best suited when applied to systems with a small number of degrees of freedom.


Input: Dual-Responsive Capsules with Tunable Low Critical Solution Temperatures and Their Loading and Release Behavior.


Input: Dual-responsive capsules sensitive to pH and temperature changes were successfully prepared by grafting random copolymer brushes of 2-(2-methoxyethoxy) ethyl methacrylate (MEO2MA) and oligo (ethylene glycol) methacrylate (OEGMA) from polydopamine (Pdop)-coated SiO2 via a surface-initiated atom-transfer radical polymerization (SI-ATRP) method with subsequent removal of the SiO2 core.

2-(2-methoxyethoxy) ethyl methacrylate

oligo (ethylene glycol) methacrylate

OEGMA

polydopamine

Pdop


Input: The uptake and release properties of the resulting capsules are highly affected by changes in the pH values and temperature of the solution.


Input: The capsules can take up cationic dye rhodamine 6G (Rh6G) at high pH and T < LCST but not at low pH and T > LCST.

rhodamine 6G


Input: In contrast, the capsules can release Rh6G at pH < 7 and temperature below the LCST, but release is less efficient under the opposite conditions.


Input: This dual-responsive property was also observed for the anionic dye methyl orange.

methyl orange


Input: Development and Therapeutic Implications of Selective Histone Deacetylase 6 Inhibitors.


Input: The ensuing Perspective provides an in depth look at the numerous disease states in which histone deacetylase 6 (HDAC6) has been implicated.


Input: The physiological pathways, protein-protein interactions and non-histone substrates relating to different pathological conditions are discussed with regard to HDAC6.


Input: Furthermore, the compounds and methods used to modulate HDAC6 activity are profiled.


Input: The latter half of this Perspective analyzes reported HDAC6 selective inhibitors in terms of structure, potency and selectivity over the other HDAC isoforms with the intent of providing a comprehensive overview of the molecular tools available.


Input: Potential obstacles and future directions of HDAC6 research are also presented.


Input: Antifungal Agents from Pseudallescheria boydii SNB-CN73 Isolated from a Nasutitermes sp.


Input: Termite.


Input: Defense mutualisms between social insects and microorganisms have been described in the literature.


Input: The present article describes the discovery of a Pseudallescheria boydii strain isolated from Nasutitermes sp.


Input: The microbial symbiont produces two antifungal metabolites: tyroscherin and N-methyltyroscherin, a compound not previously described in the literature.

tyroscherin

N-methyltyroscherin


Input: Methylation of tyroscherin has confirmed the structure of N-methyltyroscherin.

tyroscherin

N-methyltyroscherin


Input: Both compounds are effective antifungal agents with favorable selectivity indices for Candida albicans and Trichophyton rubrum.


Input: Sciadopitysin: active component from Taxus chinensis for anti-Alzheimer' s disease.

Sciadopitysin


Input: Five taxane diterpenoids derived from the 95% ethanol extract of Taxus chinensis were tested for the inhibitory activities on amyloid-beta (A beta) peptide aggregation.

taxane diterpenoids

ethanol


Input: Using thioflavin-T fluorescence assay, sciadopitysin was found to exhibit the most potency against A beta aggregation and the formation of fibrils.

thioflavin-T

sciadopitysin


Input: Further cellular assay indicated that sciadopitysin increased the cell viability of SH-SY5Y cell and demonstrated neuroprotection against A beta protein-induced insult in primary cortical neurons.

sciadopitysin


Input: According to the authors' best knowledge, this is the first report that sciadopitysin can inhibit the A beta aggregation and reduce A beta-induced toxicity in the primary cortical neurons.

sciadopitysin


Input: Nanocarrier-based topical drug delivery for an antifungal drug.


Input: Abstract Objective: The conventional liposomal amphotericin B causes many unwanted side effects like blood disorder, nephrotoxicity, dose-dependent side effects, highly variable oral absorption and formulation-related instability.

amphotericin B


Input: The objective of the present investigation was to develop cost-effective nanoemulsion as nanocarreir for enhanced and sustained delivery of amphotericin B into the skin.

amphotericin B


Input: Methods and characterizations: Different oil-in-water nanoemulsions were developed by varying the composition of hydrophilic (Tween (R) 80) surfactants and co-surfactant by the spontaneous titration method.

Tween


Input: The developed formulation were characterized, optimized, evaluated and compared for the skin permeation with commercial formulation (fungisome 0. 01% w/w).


Input: Optimized formulations loaded with amphotericin B were screened using varied concentrations of surfactants and co-surfactants as decided by the ternary phase diagram.

amphotericin B


Input: Results and discussion: The maximum% transmittance obtained were 96. 9 +/- 1. 0%, 95. 9 +/- 3. 0% and 93. 7 +/- 1. 2% for the optimized formulations F-I, F-III and F-VI, respectively.


Input: These optimized nanoemulsions were subjected to thermodynamic stability study to get the most stable nanoemulsions (F-I).


Input: The results of the particle size and zeta potential value were found to be 67. 32 +/- 0. 8 nm and-3. 7 +/- 1. 2 mV for the final optimized nanoemulsion F-I supporting transparency and stable nanoemulsion for better skin permeation.


Input: The steady state transdermal flux for the formulations was observed between 5. 89 +/- 2. 06 and 18. 02 +/- 4. 3 micro g/cm (2)/h whereas the maximum enhancement ratio were found 1. 85-and 3. 0-fold higher than fungisome and drug solution, respectively, for F-I.


Input: The results of the skin deposition study suggests that 231. 37 +/- 3. 6 micro g/cm (2) drug deposited from optimized nanoemulsion F-I and 2. 11-fold higher enhancement ratio as compared to fungisome.


Input: Optimized surfactants and co-surfactant combination-mediated transport of the drug through the skin was also tried and the results were shown to have facilitated drug permeation and skin perturbation (SEM).


Input: Conclusion: The combined results suggested that amphotericin B nanoemulsion could be a better option for localized topical drug delivery and have greater potential as an effective, efficient and safe approach.

amphotericin B


Input: Gold-Catalyzed Cycloisomerization of 1, 6-Diyne Carbonates and Esters to 2, 4a-Dihydro-1H-fluorenes.

1, 6-Diyne Carbonates and Esters

2, 4a-Dihydro-1H-fluorenes


Input: A synthetic method to prepare 2, 4a-dihydro-1H-fluorenes efficiently from gold (I)-catalyzed 1, 2-acyloxy migration/cyclopropenation/Nazarov cyclization of 1, 6-diyne carbonates and esters is described.

2, 4a-dihydro-1H-fluorenes

gold (I)

1, 2-acyloxy

1, 6-diyne carbonates and esters


Input: The suggested reaction pathway provides rare examples of [2, 3]-sigmatropic rearrangement in this class of compounds as well as the involvement of an in situ formed cyclopropene intermediate in gold catalysis.

cyclopropene


Input: Experimental and ONIOM (QM: QM') (our own n-layered integrated molecular orbital and molecular mechanics (quantum mechanics: quantum mechanics')) computational studies based on the proposed Au carbenoid species provide insight into this unique selectivity.

Au


Input: How Graphene Slides: Measurement and Theory of Strain-Dependent Frictional Forces between Graphene and SiO2.

Graphene

Graphene


Input: Strain, bending rigidity, and adhesion are interwoven in determining how graphene responds when pulled across a substrate.

graphene


Input: Using Raman spectroscopy of circular, graphene-sealed microchambers under variable external pressure, we demonstrate that graphene is not firmly anchored to the substrate when pulled.

graphene

graphene


Input: Instead, as the suspended graphene is pushed into the chamber under pressure, the supported graphene outside the microchamber is stretched and slides, pulling in an annulus.

graphene

graphene


Input: Analyzing Raman G band line scans with a continuum model extended to include sliding, we extract the pressure dependent sliding friction between the SiO2 substrate and mono-, bi-, and trilayer graphene.

graphene


Input: The sliding friction for trilayer graphene is directly proportional to the applied load, but the friction for monolayer and bilayer graphene is inversely proportional to the strain in the graphene, which is in violation of Amontons' law.

graphene

graphene

graphene


Input: We attribute this behavior to the high surface conformation enabled by the low bending rigidity and strong adhesion of few layer graphene.

graphene


Input: Understanding Morphology-Controlled Synthesis of Zinc Nanoparticles and Their Characteristics of Hydrolysis Reaction.

Zinc


Input: Two-step thermochemical water-splitting cycle based on a Zn/ZnO redox pair is considered as a potential route for carbon-free production of hydrogen because the first hydrolysis step of the cycle highly depends on the method of preparation and the resultant particle characteristics, such as size, morphology, surface state, and initial oxide content.

Zn

ZnO

carbon

hydrogen

oxide


Input: Here, employing a conventional evaporation and condensation method, we successfully produce three types of Zn nanoparticles ranging from nanorods, mesoporous nanorods with nanospheres on their surfaces, and fully sintered nanocrystals.

Zn


Input: The achievement in morphology control is realized simply by changing the injection position of the quenching gas.


Input: We found that the resultant hydrolysis kinetics is highly dependent on the morphology and porosity of the Zn nanoparticles.

Zn


Input: Finally, a series of simple mathematical modeling is made in an effort to understand the formation mechanism of Zn nanoparticles.

Zn


Input: Modeling of multiple equilibria in the self-aggregation of di-n-decyldimethylammonium chloride/octaethylene glycol monododecyl ether/cyclodextrin ternary systems.

di-n-decyldimethylammonium chloride

octaethylene glycol monododecyl ether


Input: The surface tension equations of binary surfactant mixtures (di-n-decyldimethylammonium chloride and octaethylene glycol monododecyl ether) are established by combining the Szyszkowski equation of surfactant solutions, the ideal or nonideal mixing theory and the phase separation model.

di-n-decyldimethylammonium chloride

octaethylene glycol monododecyl ether


Input: For surfactant mixtures, the surface tension at the air-water interface is calculated using nonideal theory due to synergism between the two adsorbed surfactant types.


Input: The incorporation of cyclodextrin complexation model to the surface tension equations gives a robust model for the description of the surface tension isotherms of binary, ternary and more complex systems involving numerous inclusion complexes.


Input: The surface tension data obtained experimentally shows excellent agreement with the theoretical model below and above the formation of micelles.


Input: The strong synergistic effect observed between the two surfactants is disrupted by the presence of CDs, leading to ideal behavior of ternary systems.


Input: Indeed, depending on the nature of the cyclodextrin (i. e. <F061>, <F062> or <F067>) which allows a tuning of the cavity size, the binding constants with the surfactants are modified as well as the surface properties due to strong modification of equilibria involved in the ternary mixture.

cyclodextrin (i. e. <F061>, <F062> or <F067>)


Input: Superparamagnetic Hollow Hybrid Nanogels as a Potential Guidable Vehicle System of Stimuli-Mediated MR Imaging and Multiple Cancer Therapeutics.


Input: Hollow hybrid nanogels were prepared first by co-assembly of the citric acid-coated superparamagnetic iron oxide nanoparticles (SPIONs) (44 wt%) with the graft copolymer (56 wt%) comprising acrylic acid and 2-methacryloylethyl acrylate units as the backbone and poly (ethylene glycol) and poly (N-isopropylacrylamide) as the grafts in aqueous phase of pH 3. 0 into the hybrid vesicle structure, followed by in situ covalent stabilization via the photo-initiated polymerization of MEA residues within vesicles.

citric acid

iron oxide

acrylic acid

2-methacryloylethyl acrylate

poly (ethylene glycol)

poly (N-isopropylacrylamide)

MEA


Input: The resultant hollow nanogels, though slightly swollen, satisfactorily retain the structural integrity while the medium pH being adjusted to 7. 4.


Input: Confining SPION clusters to such a high level (44 wt%) within the pH-responsive thin gel layer remarkably enhances the transverse relaxivity (r2) and renders the MR imaging highly pH-tunable.


Input: For example, with the pH being adjusted from 4. 0 to 7. 4, the r2 value can be dramatically increased from 138. 5 to 265. 5 mM-1 s-1.


Input: The DOX-loaded hybrid nanogels also exhibit accelerated drug release in response to both pH reduction and temperature increase due to the substantial disruption of the interactions between drug molecules and copolymer components.


Input: With magnetic transport guidance toward the target and subsequent exposure to alternating magnetic field, this DOX-loaded nanogel system possessing combined capabilities of hyperthermia and stimuli-triggered drug release showed superior in vitro cytotoxicity against HeLa cells as compared to the case with only free drug or hyperthermia alone.


Input: This work demonstrates that the hollow inorganic/organic hybrid nanogels show great potential to serve as a multimodal theranostic vehicle functionalized with such desirable features as guidable delivery of stimuli-mediated diagnostic imaging and hyperthermia/chemotherapies.


Input: Dual Stimuli-Responsive Poly (N-isopropylacrylamide)-b-poly (l-histidine) Chimeric Materials for the Controlled Delivery of Doxorubicin into Liver Carcinoma.

Poly (N-isopropylacrylamide)-b-poly (l-histidine)

Doxorubicin


Input: A series of dual stimuli responsive synthetic polymer bioconjugate chimeric materials, poly (N-isopropylacrylamide) 55-block-poly (l-histidine) n [p (NIPAM) 55-b-p (His) n] (n = 50, 75, 100, 125), have been synthesized by employing reversible addition-fragmentation chain transfer polymerization of NIPAM, followed by ring-opening polymerization of alpha-amino acid N-carboxyanhydrides.

poly (N-isopropylacrylamide) 55-block-poly (l-histidine) n

p (NIPAM) 55-b-p (His) n

NIPAM

alpha-amino acid N-carboxyanhydrides


Input: The dual stimuli responsive properties of the resulting biocompatiable and membrenolytic p (NIPAM) 55-b-p (His) n polymers are investigated for their use as a stimuli responsive drug carrier for tumor targeting.

p (NIPAM) 55-b-p (His) n


Input: Highly uniform self-assembled micelles (~ 55 nm) fabricated by p (NIPAM) 55-b-p (His) n polymers display sharp thermal and pH responses in aqueous media.

p (NIPAM) 55-b-p (His) n


Input: An anticancer drug, doxorubicin (Dox), is effectively encapsulated in the micelles and the controlled Dox release is investigated in different temperature and pH conditions.

doxorubicin

Dox

Dox


Input: Antitumor effect of the released Dox is also assessed using the HepG2 human hepatocellular carcinoma cell lines.

Dox


Input: Dox molecules released from the [p (NIPAM) 55-b-p (His) n] micelles remain biologically active and have stimuli responsive capability to kill cancer cells.

Dox

p (NIPAM) 55-b-p (His) n


Input: The self-assembling ability of these hybrid materials into uniform micelles and their efficiency to encapsulate Dox makes them a promising drug carrier to cancer cells.

Dox


Input: The new chimeric materials thus display tunable properties that can make them useful for a molecular switching device and controlled drug delivery applications needing responses to temperature and pH for the improvement of cancer chemotherapy.


Input: Structural Characterization and Molecular Order of Rodlike Mesogens with Three-and Four-Ring Core by XRD and (13) C NMR Spectroscopy.

(13) C


Input: Structural characterizations using XRD and (13) C NMR spectroscopy of two rodlike mesogens consisting of (i) three phenyl ring core with a polar cyano terminal and (ii) four phenyl ring core with flexible dodecyl terminal chain are presented.

(13) C

phenyl

cyano

phenyl

dodecyl


Input: The three-ring-core mesogen with cyano terminal exhibits enantiotropic smectic A phase while the four-ring mesogen reveals polymesomorphism and shows enantiotropic nematic, smectic C, and tilted hexatic phases.

cyano


Input: The molecular organization in the three-ring mesogen is found to be partial bilayer smectic Ad type, and the interdigitation of the molecules in the neighboring layers is attributed to the presence of the polar terminal group.


Input: For the four-ring mesogen, the XRD results confirm the existence of the smectic C and the tilted hexatic mesophases.


Input: A thermal variation of the layer spacing across the smectic C phase followed by a discrete jump at the transition to the tilted hexatic phase is also observed.


Input: The tilt angles have been estimated to be about 45 degrees in the smectic C phase and about 40 degrees in tilted hexatic phase.


Input: (13) C NMR results indicate that in the mesophase the molecules are aligned parallel to the magnetic field.

(13) C


Input: From the (13) C-(1) H dipolar couplings determined from the 2D experiments, the overall order parameter for the three-ring mesogen in its smectic A phase has been estimated to be 0. 72 while values ranging from 0. 88 to 0. 44 have been obtained for the four-ring mesogen as it passes from the tilted hexatic to the nematic phase.

(13) C

(1) H


Input: The orientations of the different rings of the core unit with respect to each other and also with respect to the long axis of the molecule have also been obtained.


Input: Novel pharmacokinetic studies of the Chinese formula Huang-Lian-Jie-Du-Tang in MCAO rats.


Input: Our previous studies showed that after oral administration of an Huang-Lian-Jie-Du-Tang (HLJDT) decoction, there is a higher concentration of the pure components, berberine, baicalin and gardenoside in the plasma of Middle cerebral artery occlusion (MCAO) rats than in sham-operated rats, The aim of the present study was to determine whether these components could be reliably measured in MCAO rat tissues.

berberine

baicalin

gardenoside


Input: First, the plasma concentration-time profiles of berberine, palmatine, baicalin, baicalein and gardenoside were characterised in MCAO rats after oral administration of the aqueous extract of HLJDT.

berberine

palmatine

baicalin

baicalein

gardenoside


Input: Subsequently, liver, lung and kidney tissues were obtained from sudden death MCAO rats in the absorption phase (0. 25h), the distribution phase (1. 0h) and the elimination phase (8. 0h) after administration of the HLJDT aqueous extract.


Input: An HPLC method was developed and validated for the determination of the distribution characteristics of berberine, palmatine, baicalin, baicalein and gardenoside simultaneously from the above-mentioned rat tissues.

berberine

palmatine

baicalin

baicalein

gardenoside


Input: The results indicated that berberine, palmatine, baicalin and baicalein distributed rapidly and accumulated at high levels in the lung, while gardenoside distributed widely in the lung and the kidney.

berberine

palmatine

baicalin

baicalein

gardenoside


Input: To the best of our knowledge, this is the first report to describe the distribution of the active ingredients derived from HLJDT in MCAO rat tissues.


Input: The tissue distribution results provide a biopharmaceutical basis for the design of the clinic application of HLJDT in cerebrovascular disease.


Input: Anti-adipogenic activity of compounds isolated from Idesia polycarpa on 3T3-L1 cells.


Input: Recently, obesity is a complex multifactorial chronic disease increasing the risk for type 2 diabetes, coronary heart disease and hypertension, and has become a major worldwide health problem.


Input: In the course of screening natural products employing 3T3-L1 cells as an in vitro system, the methanol extract of Idesia polycarpa Maxim.

methanol


Input: Fruits (Flacourtiaceae) significantly inhibited adipocyte differentiation by measuring lipid contents using oil red O staining.


Input: One new compound, 6-(oxymethyl)-2-hydroxyphenyl-O-beta-d-glucopyranosyl-(1 --> 6)-beta-d-glucopyranoside (8), was isolated along with nine known compounds (1-7 and 9-10) from CHCl3 and n-BuOH fractions of the methanol extract of I. polycarpa fruits.

6-(oxymethyl)-2-hydroxyphenyl-O-beta-d-glucopyranosyl-(1 --> 6)-beta-d-glucopyranoside

n-BuOH

methanol


Input: Among them, idescarpin (1) with 1-hydroxy-6-oxo-2-cyclohexenecarboxylate moiety showed the most potent inhibitory activity on adipocyte differentiation with IC50 values of 23. 2 mu M.

idescarpin

1-hydroxy-6-oxo-2-cyclohexenecarboxylate


Input: Idescarpin (1) dramatically suppressed the induction of C/EBP alpha expression, whereas it significantly increased the induction of PPAR gamma expression, supported by quantitative real time PCR and Western blot analysis.

Idescarpin


Input: The down-regulation in mRNA levels of SREBP1c, SCD-1, and FAS by idescarpin (1) during adipocyte differentiation revealed that the inhibition of adipocyte differentiation was mediated by the regulation of lipogenesis.

idescarpin


Input: Taken together, we suggest that idescarpin (1) shows a great potential against obesity and diabetes though the anti-adipogenic activity and the up-regulation of PPAR gamma.

idescarpin


Input: Identification of substituted 2-thio-6-oxo-1, 6-dihydropyrimidines as inhibitors of human lactate dehydrogenase.

2-thio-6-oxo-1, 6-dihydropyrimidines

lactate


Input: A novel 2-thio-6-oxo-1, 6-dihydropyrimidine-containing inhibitor of human lactate dehydrogenase (LDH) was identified by high-throughput screening (IC50 = 8. 1 mu M).

2-thio-6-oxo-1, 6-dihydropyrimidine

lactate


Input: Biochemical, surface plasmon resonance, and saturation transfer difference NMR experiments indicated that the compound specifically associated with human LDHA in a manner that required simultaneous binding of the NADH co-factor.

NADH


Input: Structural variation of the screening hit resulted in significant improvements in LDHA biochemical inhibition activity (best IC50 = 0. 48 mu M).


Input: A crystal structure of an optimized compound bound to human LDHA was obtained and explained many of the observed structure-activity relationships.


Input: High salt intake does not produce additional impairment in the coronary artery relaxation of spontaneously hypertensive aged rats.


Input: The effect of a salt-based diet on the coronary responsiveness in aged hypertensive rats (SHR) still unclear.


Input: We investigated the effects of high salt intake on the relaxation properties of coronary arteries of aged SHRs.


Input: Male SHR (32week-old) received drink water (SHR) or 1% NaCl solution (SHR-Salt) for 8weeks.

NaCl


Input: Isolated coronary segments were subjected to concentration-response curves to acetylcholine (ACh) in the presence or absence of L-NAME (100 mu mol), enalaprilate (10 mu M), losartan (10 mu M), and spironolactone (100 mu M).

acetylcholine

ACh

L-NAME

enalaprilate

losartan

spironolactone


Input: Salt intake did not increase blood pressure in old SHRs, but caused ventricular hypertrophy.


Input: The endothelium-dependent relaxation in SHRs was lower than in Wistar rats.


Input: However, salt intake did not add further impairment.


Input: Both enalaprilate and losartan reduced the vasodilator response in coronary arteries from Wistar, but did not affect SHR-salt rats.

enalaprilate

losartan


Input: Conversely, losartan attenuated the impaired ACh relaxation observed in SHR.

losartan

ACh


Input: Spironolactone reduced the relaxation induced by ACh in coronary arteries from Wistar rats but not in SHR.

Spironolactone


Input: The renin-angiotensin-aldosterone system participates in the impaired coronary relaxation in aged SHR, but does not participate in deleterious effects under increased salt intake, indicating that age could differentiate the effects of high sodium intake in coronary arteries of SHR.

aldosterone

sodium


Input: Aspidin BB, a phloroglucinol derivative, induces cell cycle arrest and apoptosis in human ovarian HO-8910 cells.

Aspidin BB

phloroglucinol


Input: Aspidin BB, an effective phloroglucinol derivative from Dryopteris fragrans (L.) Schott, has been previously reported to exert high biological activities.

Aspidin BB

phloroglucinol


Input: In this study, we analyzed the underlying mechanisms of aspidin BB on human ovarian cancer cell line, HO-8910.

aspidin BB


Input: Aspidin BB significantly inhibited HO-8910 cell proliferation in a dose-and time-dependent manner.

Aspidin BB


Input: The IC50 values were 15. 02, 25. 79 and 68. 81 mu M after 72, 48 and 24h treatment, respectively.


Input: Meanwhile, aspidin BB markedly induced apoptosis evidenced by characteristic apoptotic morphological changes, nuclear DNA fragmentation, annexin V-FITC/propidium iodide (PI) double staining and S peak.

aspidin BB

propidium iodide


Input: Western blot analysis showed that aspidin BB suppressed Bcl-2 expression and enhanced Bax expression to desintegrate the outer mitochondrial membrane, then caused cytochrome c release which led to the activation of effector caspase-3, and further cleaved the poly ADP-ribose polymerase (PARP) in the nucleus, finally induced cell apoptosis.

aspidin BB

poly ADP-ribose


Input: Furthermore, aspidin BB provoked S phase arrest in HO-8910 cells with up-regulation of pRb, E2F1, CDK2, cyclin E and cyclin A proteins.

aspidin BB


Input: Taken together, these findings support the conclusion that aspidin BB exhibits cytotoxicity towards human ovarian cancer HO-8910 cells through induction of apoptosis via mitochondrial pathway and arresting cell cycle progression in S phase.

aspidin BB


Input: Cyclopenta [c] phenanthrenes-Chemistry and biological activity.

Cyclopenta [c] phenanthrenes


Input: Despite cyclopenta-fused polycyclic aromatic hydrocarbons (CP-PAHs) having been detected in the environment, the ability of these compounds to induce cellular and tissue responses remains poorly characterized.

cyclopenta-fused polycyclic aromatic hydrocarbons

CP-PAHs


Input: In this review, we look at the chemistry and biological activity of the cyclopenta [c] phenanthrenes (CP [c] Ph) as potential chemicals of concern in the process of risk assessment.

cyclopenta [c] phenanthrenes

CP [c] Ph


Input: The first part of the review deals with the environmental occurrence and chemistry of CP-PAHs, focusing on available methods of CP [c] Ph chemical synthesis.

CP-PAHs

CP [c] Ph


Input: The most interesting structural feature of the CP [c] Ph is the presence of a pseudo fjord-region constructed by the cyclopentane ring.

CP [c] Ph

cyclopentane


Input: This compound can be treated either as a structurally similar one to B [c] Ph, or as a phenanthrene skeleton with an electrodonating alkyl substituent in the bay-region of the molecule.

B [c] Ph

phenanthrene

alkyl


Input: The second thread, providing available data on the adverse effects of CP [c] Ph compounds on cells and tissues of living organisms, mainly fish, improves our understanding of these possible environmental hazards.

CP [c] Ph


Input: The data show that CP [c] Ph is less potent at inducing CYP1A gene expression in rainbow trout than benzo [a] pyrene (B [a] P), a well-known Ah-receptor agonist.

CP [c] Ph

benzo [a] pyrene

B [a] P


Input: Interestingly, the CP [c] Ph dependent up-regulation of CYP1A mRNA is positively correlated with the incidences of clastogenic changes in rainbow trout erythrocytes.

CP [c] Ph


Input: CP [c] Ph has, comparably to B [a] P, a potential to repress expression of tumor suppressor p53, in the head kidney of rainbow trout.

CP [c] Ph

B [a] P


Input: Furthermore, estrogen responsive genes in fish liver, ER alpha and VTG, are not induced by CP [c] Ph, suggesting that the compound has no endocrine disrupting potential.

estrogen

CP [c] Ph


Input: However, some CP [c] Phs show mutagenic activity when investigated in the Ames test, and exhibit genotoxic properties in in vitro micronucleus assay.

CP [c] Phs


Input: The above characteristics suggest that CP-PAHs are chemicals of concern for which potential pathways of exposure should be further identified.

CP-PAHs


Input: Steroid hormone synthesis in mitochondria.

Steroid


Input: Mitochondria are essential sites for steroid hormone biosynthesis.

steroid


Input: Mitochondria in the steroidogenic cells of the adrenal, gonad, placenta and brain contain the cholesterol side-chain cleavage enzyme, P450scc, and its two electron-transfer partners, ferredoxin reductase and ferredoxin.

cholesterol


Input: This enzyme system converts cholesterol to pregnenolone and determines net steroidogenic capacity, so that it serves as the chronic regulator of steroidogenesis.

cholesterol

pregnenolone


Input: Several other steroidogenic enzymes, including 3 beta-hydroxysteroid dehydrogenase, 11 beta-hydroxylase and aldosterone synthase also reside in mitochondria.

3 beta-hydroxysteroid

aldosterone


Input: Similarly, the mitochondria of renal tubular cells contain two key enzymes participating in the activation and degradation of vitamin D.

vitamin D


Input: The access of cholesterol to the mitochondria is regulated by the steroidogenic acute regulatory protein, StAR, serving as the acute regulator of steroidogenesis.

cholesterol


Input: StAR action requires a complex multi-component molecular machine on the outer mitochondrial membrane (OMM).


Input: Components of this machine include the 18kDa translocator protein (TSPO), the voltage-dependent anion chanel (VDAC-1), TSPO-associated protein 7 (PAP7, ACBD3), and protein kinase A regulatory subunit 1 alpha (PKAR1A).


Input: The precise fashion in which these proteins interact and move cholesterol from the OMM to P450scc, and the means by which cholesterol is loaded into the OMM, remain unclear.

cholesterol

cholesterol


Input: Human deficiency diseases have been described for StAR and for all the mitochondrial steroidogenic enzymes, but not for the electron transfer proteins or for the components of the cholesterol import machine.

cholesterol


Input: Quality of Care of People With Type 2 Diabetes in Eight European Countries: Findings from the Guideline Adherence to Enhance Care (GUIDANCE) study.


Input: OBJECTIVESWe sought to determine levels of adherence in eight European countries to recommendations for the management of type 2 diabetes and to investigate factors associated with key intermediate outcomes. RESEARCH DESIGN AND METHODSGUIDANCE was a cross-sectional study including retrospective data extraction from the medical records of people with type 2 diabetes recruited, using a shared protocol, from primary and specialist care sites in the following eight European countries: Belgium, France, Germany, Italy, Ireland, Sweden, the Netherlands, and the United Kingdom.


Input: The dataset for analysis comprised 7, 597 cases.


Input: Proportions meeting process and outcome criteria were determined, including between-country variations.


Input: Logistic regression was used to investigate potential predictors of meeting targets for HbA1c, blood pressure, and LDL cholesterol. RESULTSIn the total sample, adherence to process recommendations was high for some measures, for example, HbA1c recorded in past 12 months in 97. 6% of cases.

cholesterol


Input: Target achievement for intermediate outcome measures was lower, with only 53. 6% having HbA1c < 7%.


Input: Considerable between-country variation was identified for both processes and outcomes.


Input: The following characteristics were associated with an increased likelihood of meeting targets for all three measures considered (HbA1c, blood pressure, LDL cholesterol): shorter diagnosis of diabetes; having one or more macrovascular complications; lower BMI; being prescribed lipid-lowering medication; and no current antihypertensive prescribing. CONCLUSIONSCompared with earlier reports, we have suggested some encouraging positive trends in Europe in relation to meeting targets for the management of people with type 2 diabetes, but there is still scope for further improvement and greater between-country consistency.

cholesterol


Input: Effects of Traditional Chinese Medicine Wuzhi Capsule on Pharmacokinetics of Tacrolimus in Rats.

Tacrolimus


Input: Wuzhi capsule (WZC) is a preparation of an ethanol herbal extract of Schisandra sphenanthera (Nan-Wuweizi), with its main active ingredients including schisandrin, schisandrol B, schisantherin A, schisanhenol and deoxyshisandrin.

ethanol

schisandrin

schisandrol B

schisantherin A

schisanhenol

deoxyshisandrin


Input: WZC and tacrolimus are often co-administered for the treatment of drug-induced hepatitis in organ transplant recipients in China.

tacrolimus


Input: Recently, it was reported that WZC could significantly increase the blood concentration of tacrolimus.

tacrolimus


Input: The purpose of this study was to investigate whether and how WZC affects the pharmacokinetics of tacrolimus in rats.

tacrolimus


Input: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used to determine the plasma concentration of tacrolimus.

tacrolimus


Input: The results showed that WZC increased the mean plasma concentration of tacrolimus.

tacrolimus


Input: Compared with administration of tacrolimus alone (Cmax, 18. 87 +/- 10. 29 ng/mL; AUC0 & --> t, 40. 98 +/- 37. 07), a single intragastric administered dose of WZC increased, the pharmacokinetic parameters of tacrolimus (Cmax, 59. 42 +/- 30. 32 ng/mL; AUC0 --> t, 239. 71 +/- 28. 86) by five folds in rat plasma.

tacrolimus

tacrolimus


Input: After pretreatment with WZC for 12 days, there were still significant increases in AUC0 --> t (from 40. 98 +/- 37. 07 to 89. 21 +/- 26. 39 h ng/mL; p < 0. 05) and Cmax (from 18. 87 +/- 10. 29 to 43. 16 +/- 10. 61 ng/mL; p < 0. 05) of tacrolimus compared with oral of tacrolimus alone, suggesting that WZC increased the exposure of tacrolimus by one or more mechanisms.

tacrolimus

tacrolimus

tacrolimus


Input: The increase in tacolimus Cmax by WZC was dose dependent.

tacolimus


Input: The effect of WZC on Tacrolimus AUC0 --> t also increased with dose with a maximal effect observed at 450 mg/kg (825. 34 ng h/mL).

Tacrolimus


Input: No further increases in tacolimus AUC0 --> t were observed at WZC dose above 450 mg/kg.

tacolimus


Input: It is suggested that due to the effect of WZC on the pharmacokinetics of tacrolimus, the herb-drug interaction between WZC and tacrolimus should be taken into considered in clinical practice.

tacrolimus

tacrolimus


Input: Improved group contribution parameter set for the application of solubility parameters to melt extrusion.


Input: Hot-melt extrusion is gaining importance for the production of amorphous solid solutions; in parallel, predictive tools for estimating drug solubility in polymers are increasingly demanded.


Input: The Hansen solubility parameter (SP) approach is well acknowledged for its predictive power of the miscibility of liquids as well as the solubility of some amorphous solids in liquid solvents.


Input: By solely using the molecular structure, group contribution (GC) methods allow the calculation of Hansen SPs.


Input: The GC parameter sets available were derived from liquids and polymers which conflicts with the object of prediction, the solubility of solid drugs.


Input: The present study takes a step from the liquid based SPs toward their application to solid solutes.


Input: On the basis of published experimental Hansen SPs of solid drugs and excipients only, a new GC parameter set was developed.


Input: In comparison with established parameter sets by van Krevelen/Hoftyzer, Beerbower/Hansen, Breitkreutz and Stefanis/Panayiotou, the new GC parameter set provides the highest overall predictive power for solubility experiments (correlation coefficient r =-0. 87 to-0. 91) as well as for literature data on melt extrudates and casted films (r =-0. 78 to-0. 96).


Input: Porphyrin sensitizers with pi-extended pull units for dye-sensitized solar cells.

Porphyrin


Input: New pi-extended porphyrin dyes with long alkoxyl chains at the ortho positions of the meso-phenyls, and meta di-tert-butylphenyl-substituted porphyrins, and were synthesized for dye-sensitized solar cells, and their optical, electrochemical and photovoltaic properties were investigated and compared with those of and.

porphyrin

meso-phenyls

meta di-tert-butylphenyl-substituted porphyrins


Input: The absorption spectra of showed a slight red shift of Soret bands and blue shift of Q bands as compared to the meta-substituted porphyrins due to the electron-donating effects of dioctyloxy substituents at the ortho-positions of the meso-phenyl rings.

meta-substituted porphyrins

dioctyloxy

meso-phenyl


Input: Replacement of the carboxyl with a cyanoacrylic acid as the anchoring group results in significant broadening and red shifts of the absorptions, which is due to the strong electronic coupling between the pull unit and the porphyrin ring facilitated by the C [triple bond, length as m-dash] C triple bond.

carboxyl

cyanoacrylic acid

porphyrin

C

C


Input: The electrochemical studies and quantum-chemical calculations (DFT) indicated that the ortho alkoxy-substituted sensitizers exhibit lower oxidation potential, i. e. a higher HOMO energy level, and their HOMO-LUMO gaps are comparable to the meta-substituted analogues.


Input: The photovoltaic measurements confirmed that the ortho-octyloxy groups in the two meso-phenyls of and play a significant role in preventing dye aggregation thereby enhancing the corresponding short-circuit current density and open-circuit voltage.

ortho-octyloxy

meso-phenyls


Input: The power conversion efficiency (eta) of is 8. 04%, which is 11% higher than that of, whereas the efficiency of is 6. 03%, which is 135% higher than that of.


Input: On the other hand, the poor performance of and is due to the floppy structural nature and limited molecular rigidity of the cyanoacrylic acid anchor.

cyanoacrylic acid


Input: Mitochondria as a Target of Environmental Toxicants.


Input: Enormous strides have recently been made in our understanding of the biology and pathobiology of mitochondria.


Input: Many diseases have been identified as caused by mitochondrial dysfunction, and many pharmaceuticals have been identified as previously unrecognized mitochondrial toxicants.


Input: A much smaller but growing literature indicates that mitochondria are also targeted by environmental pollutants.


Input: We briefly review the importance of mitochondrial function and maintenance for health, based on the genetics of mitochondrial diseases and the toxicities resulting from pharmaceutical exposure.


Input: We then discuss how the principles of mitochondrial vulnerability illustrated by those fields might apply to environmental contaminants, with particular attention to factors that may modulate vulnerability including genetic differences, epigenetic interactions, tissue characteristics, and developmental stages.


Input: Finally, we review the literature related to environmental mitochondrial toxicants, with a particular focus on those toxicants that target mitochondrial DNA.


Input: We conclude that the fields of environmental toxicology and environmental health should focus more strongly on mitochondria.


Input: In ovo effects of two organophosphate flame retardants, TCPP and TDCPP, on pipping success, development, mRNA expression and thyroid hormone levels in chicken embryos.

organophosphate

TCPP

TDCPP


Input: Tris (1-chloro-2-propyl) phosphate (TCPP) and tris (1, 3-dichloro-2-propyl) phosphate (TDCPP) are organic flame retardants detected in the environment and biota for which toxicological data for avian species are limited.

Tris (1-chloro-2-propyl) phosphate

TCPP

tris (1, 3-dichloro-2-propyl) phosphate

TDCPP


Input: In this study, domestic chicken eggs were injected with TCPP or TDCPP (maximum dose = 51600 and 45000 ng/g egg, respectively) to determine dose-dependent effects on pipping success, development, hepatic messenger RNA (mRNA) expression levels of genes associated with xenobiotic metabolism and the thyroid hormone (TH) pathway, and TH levels following 20-22 days of incubation.

TCPP

TDCPP


Input: Neither compound reduced pipping success; however, TCPP significantly delayed pipping at 9240 and 51600 ng/g and reduced tarsus length at 51600 ng/g.

TCPP


Input: TDCPP exposure resulted in significant decreases in head plus bill length, embryo mass and gallbladder size at 45000 ng/g and reduced plasma free T4 levels at 7640 ng/g.

TDCPP


Input: Type I deiodinase, liver fatty-acid binding protein and cytochrome P450 (CYP) 3A37 mRNA levels were significantly induced by TCPP, while TDCPP induced CYP3A37 and CYP2H1.

TCPP

TDCPP


Input: Chemical analysis of egg contents at incubation days 0, 5, 11, 18, and 19 revealed that > 92% of the injected TCPP or TDCPP concentration was detectable up to day 5; however, < 1% was detected by day 19.

TCPP

TDCPP


Input: The observed phenotypic responses to TCPP and TDCPP exposure may be associated with disruption of the TH-axis, which is critical for normal growth and development in birds.

TCPP

TDCPP


Input: The effects of TDCPP on the gallbladder indicate that the disturbance of lipid metabolism is a likely target in its mechanism of toxicity.

TDCPP


Input: Improved Nutritive Quality and Salt Resistance in Transgenic Maize by Simultaneously Overexpression of a Natural Lysine-Rich Protein Gene, SBgLR, and an ERF Transcription Factor Gene, TSRF1.

Lysine


Input: Maize (Zea mays L.), as one of the most important crops in the world, is deficient in lysine and tryptophan.

lysine

tryptophan


Input: Environmental conditions greatly impact plant growth, development and productivity.


Input: In this study, we used particle bombardment mediated co-transformation to obtain marker-free transgenic maize inbred X178 lines harboring a lysine-rich protein gene SBgLR from potato and an ethylene responsive factor (ERF) transcription factor gene, TSRF1, from tomato.

lysine

ethylene


Input: Both of the target genes were successfully expressed and showed various expression levels in different transgenic lines.


Input: Analysis showed that the protein and lysine content in T1 transgenic maize seeds increased significantly.

lysine


Input: Compared to non-transformed maize, the protein and lysine content increased by 7. 7% to 24. 38% and 8. 70% to 30. 43%, respectively.

lysine


Input: Moreover, transgenic maize exhibited more tolerance to salt stress.


Input: When treated with 200 mM NaCl for 48 h, both non-transformed and transgenic plant leaves displayed wilting and losing green symptoms and dramatic increase of the free proline contents.

NaCl

proline


Input: However, the degree of control seedlings was much more serious than that of transgenic lines and much more increases of the free proline contents in the transgenic lines than that in the control seedlings were observed.

proline


Input: Meanwhile, lower extent decreases of the chlorophyll contents were detected in the transgenic seedlings.


Input: Quantitative RT-PCR was performed to analyze the expression of ten stress-related genes, including stress responsive transcription factor genes, ZmMYB59 and ZmMYC1, proline synthesis related genes, ZmP5CS1 and ZmP5CS2, photosynthesis-related genes, ZmELIP, ZmPSI-N, ZmOEE, Zmrbcs and ZmPLAS, and one ABA biosynthesis related gene, ZmSDR.

proline


Input: The results showed that with the exception of ZmP5CS1 and ZmP5CS2 in line 9-10 and 19-11, ZmMYC1 in line 19-11 and ZmSDR in line 19-11, the expression of other stress-related genes were inhibited in transgenic lines under normal conditions.


Input: After salt treatment, the expressions of the ten stress-related genes were significantly induced in both wild-type (WT) and transgenic lines.


Input: However, compared to WT, the increases of ZmP5CS1 in all these three transgenic lines and ZmP5CS2 in line 9-10 were less than WT plants.


Input: This study provides an effective approach of maize genetic engineering for improved nutritive quality and salt tolerance.


Input: Synthesis and Characterization of 5-(1, 2, 4-Triazol-3-yl) tetrazoles with various energetic functionalities.

5-(1, 2, 4-Triazol-3-yl) tetrazoles


Input: In this contribution the synthesis and full structural as well as spectroscopic characterization of three 5-(1, 2, 4-triazol-3-yl) tetrazoles along with selected energetic moieties like nitro, nitrimino, and azido groups are presented.

5-(1, 2, 4-triazol-3-yl) tetrazoles

nitro

nitrimino

azido


Input: The main goal is a comparative study on the influence of those variable energetic moieties on structural and energetic properties.


Input: A complete characterization including IR and Raman as well as multinuclear NMR spectroscopy of all compounds is presented.


Input: Additionally, X-ray crystallographic measurements were performed and reveal insights into structural characteristics as well as inter-and intramolecular interactions.


Input: The standard enthalpies of formation were calculated for all compounds at the CBS-4M level of theory and reveal high positive heats of formation for all compounds.


Input: The calculated detonation parameters (using the EXPLO5. 05 program) are in the range of 8000 m s (-1) (8097 m s (-1) (5), 8020 m s (-1) (6), 7874 m s (-1) (7)).


Input: As expected, the measured impact and friction sensitivities as well as decomposition temperatures strongly depend on the energetic moiety at the triazole ring.

triazole


Input: The C <F8FF> C connection of a triazole ring with its opportunity to introduce a large variety of energetic moieties and a tetrazole ring, implying a large energy content, leads to the selective synthesis of primary and secondary explosives.

C <F8FF> C

triazole

tetrazole


Input: Novel acetylated chalcone and biflavonoid glycosides from Trigonosciadium brachytaenium (Boiss.) Alava.

acetylated chalcone

biflavonoid glycosides


Input: A new acetylated chalcone glycoside, trans-2', 6'-dihydroxy-4'-O-(4''-acetyl-rhamnoside)-4-methoxychalcone (1) and a new biflavonoid glycosides, 5, 3', 5'', 4'''-tetrahydroxy-3''', 5''' dimethoxy-biflavone (4' --> 8'')-7-O-((2-rhamnoside) rhamnoside) (2) were isolated from the ethyl acetate soluble fraction of the methanol extract obtained from Trigonosciadium brachytaenium and have been purified by column chromatography and preparative TLC.

acetylated chalcone glycoside

trans-2', 6'-dihydroxy-4'-O-(4''-acetyl-rhamnoside)-4-methoxychalcone

biflavonoid glycosides

5, 3', 5'', 4'''-tetrahydroxy-3''', 5''' dimethoxy-biflavone (4' --> 8'')-7-O-((2-rhamnoside) rhamnoside)

ethyl acetate

methanol


Input: Those structures were elucidated by UV, (1) H NMR and (13) C NMR, HMBC, EI-MS and IR spectra.

(1) H

(13) C


Input: The antioxidant activity of ethyl acetate extract was evaluated by 1, 1-diphenyl-2-picrylhydrazyl method.

ethyl acetate

1, 1-diphenyl-2-picrylhydrazyl


Input: The results indicate that ethyl acetate extract from aerial part of T. brachytaenium possesses considerable antioxidant activity.

ethyl acetate


Input: Dual Targeting of the Adenosine A2A Receptors and Monoamine Oxidase B by 4H-3, 1-Benzothiazin-4-ones.

Adenosine

Monoamine


Input: Blockade of A2A adenosine receptors (A2AARs) and inhibition of monoamine oxidase B (MAO-B) in brain are considered attractive strategies for the treatment of neurodegenerative diseases such as Parkinson' s disease (PD).

adenosine

monoamine


Input: In the present study benzothiazinones, e. g. 2-(3-chlorophenoxy)-N-(4-oxo-4H-3, 1-benzothiazin-2-yl) acetamide (13), were identified as a novel class of potent MAO-B inhibitors (IC50 human MAO-B: 1. 63 nM).

benzothiazinones

2-(3-chlorophenoxy)-N-(4-oxo-4H-3, 1-benzothiazin-2-yl) acetamide


Input: Benzothiazinones with large substituents in the 2-position, e. g. methoxy-cinnamoylamino, phenylbutyrylamino, or chlorobenzylpiperazinylbenzamido residues (14, 17, 27, 28) showed high affinity and selectivity for A2AARs (Ki human A2AAR: 39. 5-69. 5 nM).

Benzothiazinones

methoxy

cinnamoylamino

phenylbutyrylamino

chlorobenzylpiperazinylbenzamido


Input: By optimizing benzothiazinones for both targets the first potent, dual-acting A2AAR/MAO-B inhibitors with a non-xanthine structure were developed.

benzothiazinones

xanthine


Input: The best derivative was N-(4-oxo-4H-3, 1-benzothiazin-2-yl)-4-phenylbutanamide (17, Ki human A2A 39. 5 nM, IC50 human MAO-B 34. 9 nM; selective versus other AR subtypes and MAO-A), which inhibited A2AAR-induced cAMP accumulation and showed competitive, reversible MAO B inhibition.

N-(4-oxo-4H-3, 1-benzothiazin-2-yl)-4-phenylbutanamide


Input: The new compounds may be useful tools for validating the A2AAR/MAO-B dual target approach in PD.


Input: Green Tea Polyphenols Improve Bone Microarchitecture in High-Fat-Diet-Induced Obese Female Rats Through Suppressing Bone Formation and Erosion.

Polyphenols


Input: Abstract This study evaluates the effects of green tea polyphenols (GTPs) on bone microarchitecture in high-fat-diet (HFD)-induced obese female rats.

polyphenols


Input: Thirty-six 3-month-old female rats were fed either a control diet or a HFD for 4 months.


Input: Animals in the control group continued on the control diet for another 4 months.


Input: Animals in the HFD group were divided into two groups, with 0. 5 g/100 mL GTP (the HFD + GTP group) or without GTP (the HFD group) in drinking water, in addition to the HFD for another 4 months.


Input: Compared to the control group, the HFD group increased bone formation and erosion rates at the tibia, decreased trabecular volume and thickness, but had no impact on bone mineral density (BMD), trabecular number (Tb. N), and separation.


Input: Compared to the control group, the HFD + GTP group demonstrates a greater Tb. N at the proximal tibia, and a greater trabecular thickness at the femur and the lumbar vertebrae, but a smaller trabecular separation (Tb. Sp) and mineralizing surface at the proximal tibia, and a reduced endocortical mineral apposition rate (MAR) at the tibia shaft.


Input: Relative to the HFD group, the HFD + GTP group demonstrates (1) a higher BMD at the femur, a greater trabecular volume, thickness, and number at the proximal tibia, a larger cortical area and thickness at the tibial shaft, and a greater trabecular volume and thickness at the femur and the lumbar vertebrae, (2) a smaller Tb. Sp, MAR, bone formation rate, and eroded surface at the tibia.


Input: We concluded that GTP supplementation in drinking water improves bone microarchitecture in the HFD-induced obese female rats, possibly through suppressing bone turnover, resulting in a larger net bone volume.


Input: Effect of Lycopene Supplementation on Oxidative Stress: An Exploratory Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Lycopene


Input: Abstract Lycopene is a potentially useful compound for preventing and treating cardiovascular diseases and cancers.

Lycopene


Input: Studies on the effects of lycopene on oxidative stress offer insights into its mechanism of action and provide evidence-based rationale for its supplementation.

lycopene


Input: In this analysis, randomized controlled trials of the effects of oral lycopene supplementation on any valid outcomes of oxidative stress were identified and pooled through a search of international journal databases and reference lists of relevant publications.

lycopene


Input: Two reviewers extracted data from each of the identified studies.


Input: Only studies of sufficient quality were included.


Input: Twelve parallel trials and one crossover trial were included in the systematic review, and six trials provided data for quantitative meta-analysis.


Input: Our results indicate that lycopene supplementation significantly decreases the DNA tail length, as determined using comet assays, with a mean difference (MD) of-6. 27 [95% confidence interval (CI)-10. 74,-1. 90] (P =. 006) between the lycopene intervention groups and the control groups.

lycopene

lycopene


Input: Lycopene supplementation does not significantly prolong the lag time of low-density lipoprotein (MD 3. 76 [95% CI-2. 48, 10. 01]; P =. 24).

Lycopene


Input: Lycopene possibly alleviates oxidative stress; however, biomarker research for oxidative stress needs be more consistent with the outcomes in lycopene intervention trials for disease prevention.

Lycopene

lycopene


Input: Possible Therapeutic Uses of Salvia triloba and Piper nigrum in Alzheimer' s Disease-Induced Rats.


Input: Abstract This study aimed to investigate the role of Salvia triloba L. and Piper nigrum extracts in ameliorating neuroinflammatory insults characteristic of Alzheimer' s disease (AD) in an experimentally induced rat model.


Input: Adult male Sprague-Dawley rats were classified into Group 1 (n = 10): normal healthy animals serving as the negative control group; Group 2 (n = 60): the AD-induced group.


Input: After AD induction, animals in the AD-induced group were divided randomly and equally into 6 subgroups.


Input: The first subgroup served as AD control; the second one, which served as positive control, was treated orally with the conventional therapy for AD (rivastigmine) at a dose of 0. 3 mg/kg body weight (b. w.) daily for 3 months.

rivastigmine


Input: The third and fourth subgroups were, respectively, treated orally with the S. triloba extract at a dose of 750 and 375 mg/kg b. w. daily for 3 months.


Input: The fifth and sixth subgroups were, respectively, treated orally with the P. nigrum extract at a dose of 187. 5 and 93. 75 mg/kg b. w. daily for 3 months.


Input: Levels of brain acetylcholine (Ach), serum and brain acetylcholinesterase (AchE) activity, C-reactive protein (CRP), total nuclear factor kappa-B (NF-kappa B), and monocyte chemoattractant protein-1 (MCP-1) were estimated.

acetylcholine


Input: The results showed that administration of AlCl3 resulted in a significant elevation in the levels of AchE activity, CRP, NF-kappa B, and MCP-1 accompanied with a significant depletion in the Ach level.


Input: Treatment of AD rats with each of the selected medicinal plant extracts caused marked improvement in the measured biochemical parameters.


Input: In conclusion, S. triloba and P. nigrum methanolic extracts have potent anti-inflammatory effects against neuroinflammation characterizing AD.


Input: Bio-based Chitosan/Polybenzoxazine Crosslinked Films: Preparation in Aqueous Media and Synergistic Improvements in Thermal and Mechanical Properties.

Polybenzoxazine


Input: A novel class of polymer blends has been prepared from main-chain type benzoxazine polymer (MCBP) and chitosan (CTS), a modified biomacromolecule.

benzoxazine


Input: A water-soluble, main-chain type benzoxazine polymer, MCBP (BA-tepa), was synthesized from the reaction of bisphenol-A (BA), tetraethylenepentamine (TEPA) and formalin.

benzoxazine

bisphenol-A

tetraethylenepentamine

TEPA

formalin


Input: The structure of the MCBP (BA-tepa) was confirmed by proton nuclear magnetic resonance spectroscopy (1H-NMR) and Fourier transform infrared spectroscopy (FT-IR).


Input: The polymer blends were prepared by mixing MCBP (BA-tepa) and chitosan (CTS) in aqueous acetic acid solution (1%).

acetic acid


Input: The CTS/MCBP (BA-tepa) films are crosslinked by thermal treatment via the ring-opening polymerization of benzoxazine structures in the main chain to produce AB-crosslinked network.

benzoxazine


Input: Differential scanning calorimetry and FT-IR were used to study the effects of chitosan on the polymerization behavior of benzoxazine.

benzoxazine


Input: Hydrogen bonding between polybenzoxazine and chitosan structures was also observed.

Hydrogen

polybenzoxazine


Input: The mechanical and thermal properties of crosslinked CTS/MCBP (BA-tepa) films were evaluated and the results show unusual levels of synergism.


Input: In particular, the tensile strength and thermal stability were significantly enhanced in a non-linear fashion.


Input: Keywords: Polybenzoxazine; chitosan; crosslinked films; mechanical and thermal properties.

Polybenzoxazine


Input: Hydrodynamic Effects on the Relative Rotational Velocity of Associating Proteins.


Input: Hydrodynamic steering effects on the barnase-barstar association were studied through the analysis of the proteins' relative rotational velocity.


Input: We considered the two proteins approaching each other in a response to their electrostatic attraction and employed a method that accounts for the long range and the many-body character of hydrodynamic interactions as well as complicated shapes of proteins.


Input: Hydrodynamic steering effects are clearly seen when attractive forces are applied to proteins geometric centers (resulting in zero torques) and the attraction acts along the line that connects centers of geometry of proteins in their crystallographic complex.


Input: When we rotate barstar relative to barnase around this line by an angle in the range of (-90 (o), 60 (o)), the rotational velocity arising solely due to hydrodynamic interactions restores orientation of proteins that is observed in the crystal structure.


Input: However, as in reality both electrostatic forces and torques act on proteins, and these forces and torques depend on protein-protein distance and the relative orientation of binding partners, we investigated also more realistic situations employing continuum electrostatics calculations based on atomistic proteins models.


Input: Overall, we conclude that hydrodynamic interactions aid barnase and barstar in assuming a proper relative orientation upon complex formation.


Input: Development of a method for extraction and assay of human erythrocyte acetylcholinesterase and pesticide inhibition.


Input: A method of extracting membranes from red blood cells (RBCs) is described, which were in turn used to assay acetylcholinesterase (AChE) activity.


Input: The evidence for the enzyme activity was established by selective inhibition using 1, 5-bis (4-allyldimethylammoniumphenyl) pentan-3-one dibromide, tetraisopropyl pyrophosphoramide and neostigmine.

1, 5-bis (4-allyldimethylammoniumphenyl) pentan-3-one dibromide

tetraisopropyl pyrophosphoramide

neostigmine


Input: Blood samples were exposed to three organophosphorus (dichlorvos, chlorpyrifos and diazinon) and two carbamate (carbaryl and carbofuran) pesticides.

organophosphorus

dichlorvos

chlorpyrifos

diazinon

carbamate

carbaryl

carbofuran


Input: Afterwards AChE activities in RBC membranes were determined.


Input: The concentrations capable to inhibit the enzyme activity by 50% (IC50) for the pesticides were 10. 66 micro M (dichlorvos), 21. 42 micro M (chlorpyrifos), 109. 98 micro M (carbaryl) and 5. 44 micro M (carbofuran).

dichlorvos

chlorpyrifos

carbaryl

carbofuran


Input: The results related to 20% enzyme inhibition (level used in the estimation of threshold limits for anticholinesterase compounds) were below those acceptable daily intake values enacted by relevant national and international regulations.


Input: These results suggest that the proposed AChE extraction from RBC and assay could be a suitable method for monitoring occupational exposure to pesticides.


Input: Species tree reconstruction of a poorly resolved clade of salamanders (Ambystomatidae) using multiple nuclear loci.


Input: The analysis of diverse data sets can yield different phylogenetic estimates that challenge systematists to explain the source of discordance.


Input: The mole salamanders (family Ambystomatidae) are a classic example of this phylogenetic conflict.


Input: Previous attempts to resolve the ambystomatid species tree using allozymic, morphological, and mitochondrial sequence data have yielded different estimates, making it unclear which data source best approximates ambystomatid phylogeny and which ones yield phylogenetically inaccurate reconstructions.


Input: To shed light on this conflict, we present the first multi-locus DNA sequence-based phylogenetic study of the Ambystomatidae.


Input: We utilized a range of analyses, including coalescent-based methods of species-tree estimation that account for incomplete lineage sorting within a locus and concordance-based methods that estimate the number of sampled loci that support a particular clade.


Input: We repeated these analyses with the removal of individual loci to determine if any a locus has a disproportionate effect on our phylogenetic results.


Input: Collectively, these results robustly resolved many deep and relatively shallow clades within Ambystoma, including the placement of A. gracile and A. talpoideum as the sister clade to a clade containing all remaining ambystomatids, and the placement of A. maculatum as the sister lineage to all remaining ambystomatids excluding A. gracile and A. talpoideum.


Input: Both Bayesian coalescent and concordance methods produced similar results, highlighting strongly supported branches in the species tree.


Input: Furthermore, coalescent-based analyses that excluded loci produced overlapping species-tree posterior distributions, suggesting that no particular locus-including mtDNA-disproportionately contributed to our species-tree estimates.


Input: Overall, our phylogenetic estimates have greater similarity with previous allozyme and mitochondrial sequence-based phylogenetic estimates.


Input: However, intermediate depths of divergence in the ambystomatid species tree remain unresolved, potentially highlighting a region of rapid species radiation or a hard polytomy, and which limits our ability to comment on previous morphologically-based taxonomic groups.


Input: Identification of an Allosteric Modulator of Serotonin Transporter with Novel Mechanism of Action.

Serotonin


Input: Serotonin transporters (SERT) play an essential role in the termination and regulation of serotonin signaling in the brain.

Serotonin

serotonin


Input: SERT is also the target of antidepressants and psychostimulants.


Input: Molecules with novel activities and modes of interaction with regard to SERT function are of great scientific and clinical interest.


Input: We explored structural regions outside the putative serotonin translocation pathway to identify potential binding sites for allosteric transporter modulators (ATMs).

serotonin


Input: Mutational studies revealed a pocket of amino acids outside the orthosteric substrate binding sites located in the interface between extracellular loops 1 and 3 that when mutated affect transporter function.

amino acids


Input: Using the structure of the bacterial transporter homologue leucine transporter as a template, we developed a structural model of SERT.

leucine


Input: We performed molecular dynamics simulations to further characterize the allosteric pocket that was identified by site-directed mutagenesis studies and employed this pocket in a virtual screen for small-molecule modulators of SERT function.


Input: In functional transport assays, we found that one of the identified molecules, ATM7, increased the reuptake of serotonin, possibly by facilitating the interaction of serotonin with transport-ready conformations of SERT when concentrations of serotonin were low and rate limiting.

serotonin

serotonin

serotonin


Input: In addition, ATM7 potentiates 3, 4-methylenedioxy-N-methylamphetamine (MDMA, " Ecstasy ")-induced reversed transport by SERT.

3, 4-methylenedioxy-N-methylamphetamine

MDMA


Input: Taking advantage of a conformationally sensitive residue in transmembrane domain 6, we demonstrate that ATM7 mechanistically stabilizes an outward-facing conformation of SERT.


Input: Taken together these observations demonstrate that ATM7 acts through a novel mechanism that involves allosteric modulation of SERT function.


Input: GIRK-like and TRPC-like conductances mediate thyrotropin-releasing hormone-induced increases in excitability in thalamic paraventricular nucleus neurons.

thyrotropin