Input: Improvement of neurological performance was achieved in 56. 8% of all patients, with the highest improvement rate seen in patients presenting with increased intracranial pressure and hemiparesis.


Input: Notably, the neurological benefits were independent from RPA class.


Input: In conclusion, surgical resection leads to significant neurological improvement despite poor RPA class and short overall survival.


Input: Considering the low mortality and morbidity rates, resection should be considered as a valid option to increase neurological function and quality of life for patients with BM.


Input: Molecular sensing: modulating molecular conduction through intermolecular interactions.


Input: We observe changes in the molecular conductivity of individual oligophenylene-vinylene (OPV) molecules due to interactions with small aromatic molecules.

oligophenylene-vinylene

OPV


Input: Fluorescence experiments were correlated with scanning tunneling microscopy measurements in order to determine the origin of the observed effect.


Input: Both nitrobenzene and 1, 4-dinitrobenzene decreased fluorescence intensity and molecular conductivity, while toluene had no effect.

nitrobenzene

1, 4-dinitrobenzene

toluene


Input: The observed changes in the fluorescence and conduction of OPV correlate well with the electron withdrawing ability of the interacting aromatic molecules.

OPV


Input: These results demonstrate the potential usefulness of OPV as a sensor for aromatic compounds containing electron withdrawing groups.

OPV


Input: In vitro effect of N-acetylcysteine on hepatocyte injury caused by dichlorodiphenyltrichloroethane and its metabolites.

N-acetylcysteine

dichlorodiphenyltrichloroethane


Input: The organochlorine pesticide, dichlorodiphenyltrichloroethane (DDT), is still used to combat the spread of malaria in several developing countries despite its accumulation and known hepatotoxic effects that have been demonstrated both in vitro and in vivo.

organochlorine

dichlorodiphenyltrichloroethane

DDT


Input: N-Acetylcysteine (NAC) is a recognized hepatoprotective agent that has been reported to reduce hepatotoxicity initiated by many different compounds.

N-Acetylcysteine

NAC


Input: The aim of this study was to determine whether NAC could counter in vitro hepatocyte injury induced by DDT or its two major metabolites, dichlorodiphenyldichloroethylene and dichlorodiphenyldichloroethane.

NAC

DDT

dichlorodiphenyldichloroethylene

dichlorodiphenyldichloroethane


Input: HepG2 cell cultures were used to assess the following parameters of toxicity: cellular viability, intracellular levels of reactive oxygen species (ROS), mitochondrial membrane potential and initiation of apoptosis.

oxygen


Input: None of the three test compounds induced ROS generation, yet exposure to any of the three compounds produced mitochondrial hyperpolarization, which was countered by NAC pretreatment.

NAC


Input: All three test compounds also induced apoptotic cell death, which was inhibited by NAC.

NAC


Input: Despite NAC counteracting some adverse intracellular changes due to organochlorine exposure, it appeared to aggravate the cytotoxic effects of the organochlorine compounds at low test concentrations.

NAC

organochlorine

organochlorine


Input: As the same outcome may also occur in vivo, results from the present study raise concern about the use of NAC as treatment for DDT-induced hepatotoxicity.

NAC

DDT


Input: Improving the default data analysis workflow for large autoimmune biomarker discovery studies with protoarrays.


Input: Contemporary protein microarrays like the ProtoArray (R) are used for autoimmune antibody screening studies to discover biomarker panels.


Input: For ProtoArray data analysis the software Prospector and a default workflow are suggested by the manufacturer.


Input: While analyzing a large data set of a discovery study for diagnostic biomarkers of the Parkinson' s Disease (" ParkCHIP ") we have revealed the need for distinct improvements of the suggested workflow concerning raw data acquisition, normalization and pre-selection method availability, batch effects, feature selection, and feature validation.


Input: In this work appropriate improvements of the default workflow are proposed and it is shown that completely automatic data acquisition as a batch, a re-implementation of Prospector' s pre-selection method, multivariate or hybrid feature selection, and validation of the selected protein panel using an independent test set define in combination an improved workflow for large studies.


Input: This article is protected by copyright.


Input: All rights reserved.


Input: Elucidation of in situ polycyclic aromatic hydrocarbon degradation by functional metaproteomics (protein-SIP).

polycyclic aromatic hydrocarbon


Input: Current knowledge of the physiology and phylogeny of polycyclic aromatic hydrocarbon (PAH) degrading bacteria often relies on laboratory enrichments and isolations.

polycyclic aromatic hydrocarbon

PAH


Input: In the present study, in situ microcosms consisting of activated carbon pellets (BACTRAP (R) s) were loaded with either (13) C-naphthalene or (13) C-fluorene and were subsequently exposed in the contaminant source and plume fringe region of an PAH contaminated aquifer.

carbon

(13) C-naphthalene

(13) C-fluorene

PAH


Input: Metaproteomic analysis and protein-SIP revealed Burkholderiales, Actinomycetales and Rhizobiales as the most active microorganisms in the groundwater communities.


Input: Proteins identified of the naphthalene degradation pathway showed a relative (13) C isotope abundance of approximately 50 atom% demonstrating that the identified naphthalene degrading bacteria gained at least 80% of their carbon by PAH degradation.

naphthalene

(13) C

naphthalene

carbon

PAH


Input: Although the microbial community grown on the fluorene-BACTRAPs showed a structure similar to the naphthalene-BACTRAPs, the identification of fluorene degraders and degradation pathways failed in situ.

fluorene

naphthalene

fluorene


Input: In complementary laboratory microcosms, a clear enrichment in proteins related to Rhodococcus and possible fluorene degradation enzymes was observed.

fluorene


Input: This result demonstrates the impact of laboratory conditions on microbial community structure and activity of certain species and underlines the need on in situ exploration of microbial community functions.


Input: In situ microcosms in combination with protein-SIP may be a significant tool for in situ identification of metabolic key players as well as degradation pathways.


Input: This article is protected by copyright.


Input: All rights reserved.


Input: Folate-Conjugated PEG on Single Walled Carbon Nanotubes for Targeting Delivery of Doxorubicin to Cancer Cells.

Folate

PEG

Carbon

Doxorubicin


Input: A highly effective drug carrier is constructed by coating folic acid-terminated poly (ethylene glycol) (PEG-FA) on single walled carbon nanotubes (SWNTs) in a facile non-covalent method.

folic acid

poly (ethylene glycol)

PEG

carbon


Input: The anti-cancer drug, doxorubicin (DOX), is further loaded on the surface of SWNTs at a very high loading efficiency, 149. 3 +/- 4. 1%.

doxorubicin

DOX


Input: The drug system (DOX/PEG-FA/SWNTs) exhibits excellent stability under neutral pH conditions such as serum, but dramatically releases DOX at reduced pH typical of the tumour environment and intracellular lysosomes and endosomes.

DOX

PEG

DOX


Input: With the help of FA, DOX/PEG-FA/SWNTs tend to selectively attach onto cancer cells and enter the lysosomes or endosomes by clathrin-mediated endocytosis.

DOX

PEG


Input: This can greatly improve the pharmaceutical efficiency and reduce potential side effects.


Input: Physiotherapeutic approach in early and late post-menopausal Brazilian women.


Input: Abstract To evaluate changes in joints after physiotherapy in post-menopausal women, specifically to identify clinical responses to the measurements of flexibility, functional capacity and joint pain in early and late post-menopausal women at a multi-disciplinary health education programme.


Input: A total of 69 women participated in the Integral Program for the Attention to Climacteric Women at the Department of Gynecology-Federal University of Sao Paulo and were sorted into two groups of early (n = 32) and late (n = 37) post-menopause.


Input: The average age of menopause was 47. 9 +/- 5. 6 years.


Input: The Blatt Kupperman Menopausal Index scores for the early (baseline = 12. 8 +/- 6. 1) and late (baseline = 14. 1 +/- 7. 7) post-menopausal groups after the programme were 8. 4 +/- 7. 1 and 9. 4 +/- 8. 1, respectively.


Input: Both groups presented improvements regarding functional capacity (p < 0. 01) and complaints of pain (p < 0. 001) after the intervention.


Input: The group of early post-menopausal women had better flexibility for hip flexion (p < 0. 001), and the late post-menopausal group showed greater improvement in shoulder flexion (p < 0. 001), extension (p < 0. 001) and elbow flexion (p < 0. 001).


Input: After multi-disciplinary approach, both early and late post-menopausal groups experienced decrease in intensity of climacteric symptoms, reduction in pain intensity and improvement in functional capacity, but the flexibility was different between both the groups.


Input: Structural identification of (1 --> 6)-alpha-D-glucan, a key responsible for the health benefits of longan, and evaluation of anticancer activity.


Input: Longan is a delicious subtropical fruit with great health-beneficial effects.


Input: It has been utilised for disease prevention and health care since ancient age.


Input: To explore the chemicals responsible for the health benefits, water-soluble polysaccharides were extracted from longan flesh in this work.


Input: A pure polysaccharide (LPS1) was obtained through column purification.


Input: Analysis by gas chromatography showed LPS1 was a homopolysaccharide of glucose with glycosidic linkage of --> 6)-D-Glc-(1 -->.

glucose


Input: Nuclear magnetic resonance (NMR) spectra indicated that the con fi guration of anomeric carbon in glucose residual was alpha-form.

carbon

glucose


Input: The polysaccharide structure was further confirmed to be (1 --> 6)-alpha-D-glucan by chemcial shift of C6.


Input: The molecular weight of LPS1 was calculated to be 108 kDa, which had 661 glucose residuals.

glucose


Input: Anticancer assay showed that LPS1 had anticancer activity against the growth of HepG2 cells to a certain extent.


Input: However, it did not show any cytotoxicity against MCF-7 breast cancer cells.


Input: Hybrid Molecule from O (2)-(2, 4-Dinitrophenyl) diazeniumdiolate and Oleanolic Acid: a GST pi Activated Nitric Oxide Prodrug with Selective Anti-human Hepatocellular Carcinoma Activity and Improved Stability.

O (2)-(2, 4-Dinitrophenyl) diazeniumdiolate

Oleanolic Acid

Nitric Oxide


Input: A series of hybrids from O (2)-(2, 4-dinitrophenyl) diazeniumdiolate and oleanolic acid (OA) were designed, synthesized, and biologically evaluated as novel nitric oxide (NO) releasing prodrugs which could be activated by glutathione S-transferase pi (GST pi) overexpressed in a number of cancer cells.

O (2)-(2, 4-dinitrophenyl) diazeniumdiolate

oleanolic acid

nitric oxide

NO

glutathione


Input: It was discovered that the most active compound 21 released high levels of NO selectively in HCC cells but not in the normal cells, and exhibited potent antiproliferative activity in vitro as well as remarkable tumor-retarding effects in vivo.

NO


Input: Compared with the reported GST pi-activated prodrugs JS-K and PABA/NO, 21 exhibited remarkably improved stability in the absence of GST pi.

PABA

NO


Input: Importantly, the decomposition of 21 occurred in the presence of GST pi, and was much more effective than in GST alpha.


Input: Additionally, 21 induced HepG2 cells apoptosis by arresting cell cycle at G2/M phase, activating both the mitochondria-mediated pathway and the MAPKs pathway, as well as enhancing the intracellular production of ROS.


Input: Rationale for the higher reactivity of interfacial sites in methanol decomposition on Au13/TiO2 (110).

methanol

Au13/TiO2 (110)


Input: Interfacial and perimeter sites have been known for their high activity in various reactions on supported gold nanoparticles.


Input: We find that the higher activity of interfacial sites in Au13/TiO2 (110) towards methanol decomposition originates from charge-transfer-induced Coulomb interaction among the gold, reactant, and reducible TiO2 support, brought about through the formation of an ionic O-Au bond between gold and methoxy in such sites, which turns the participating perimeter gold atom cationic.

Au13/TiO2 (110)

methanol

O-Au

methoxy


Input: A direct result of such charge-transfer-induced repulsive interaction between cationic gold and positively charged C moiety of methoxy is activation of the positively charged C moiety of methoxy, as manifested by the pronounced elongation of O-C bond length and the tilting of the methoxy axis, which facilitate reaction of methoxy through C-H scission with the bridge oxygen atoms that are readily available from the reducible support.

C

methoxy

C

methoxy

O-C

methoxy

methoxy

C-H

oxygen


Input: More generally, our proposed mechanism for the reactivity of the gold/TiO2 interface should hold for oxidation of organic molecules with the structure of R-O-R', where R and R' are (saturated) hydrocarbons.

R-O-R'

(saturated) hydrocarbons


Input: Cadmium-Based Quantum Dot Induced Autophagy Formation for Cell Survival via Oxidative Stress.

Cadmium


Input: Quantum dots (QDs) are one of most utilized nanomaterials in nanocrystalline semiconductors.


Input: QDs emit near-infrared fluorescence and can be applied as probes for detecting vasculature and imaging in biological systems.


Input: Since QDs have potential in clinical application, the toxicity of QDs needs to be carefully evaluated.


Input: In our present study, we elucidate the cytotoxic mechanisms of QDs using a mouse renal adenocarcinoma (RAG) cell line.


Input: QDs in RAG cells increased intracellular reactive oxygen species (ROS) levels and induced autophagy at 6 h, leading to subsequent apoptosis at 24 h.

oxygen


Input: QDs entered the cells and were located within the endoplasmic reticulum (ER), endosome, and lysosome at 6 h and endosome, lysosome, and mitochondria at 24 h.


Input: However, QDs only affected mitochondrial function and did not induce ER stress.


Input: N-Acetylcysteine, an antioxidant agent, reduced intracellular ROS levels and decreased QD-induced autophagy but enhanced QD-induced cell death.

N-Acetylcysteine


Input: Moreover, 3-methylamphetamine (an autophagy inhibitor) also reduced the cell viability in QD-treated cells.


Input: These findings suggest that ROS plays an essential role in the regulation of QD-induced autophagy, which subsequently enhances cell survival.


Input: Taken together, these results suggest that oxidative stress-induced autophagy is a defense/survival mechanism against the cytotoxicity of QD.


Input: MicroRNA-32 (miR-32) regulates phosphatase and tensin homologue (PTEN) expression and promotes growth, migration, and invasion in colorectal carcinoma cells.


Input: BACKGROUND: Colorectal carcinoma (CRC) is one of the leading causes of cancer-related mortality worldwide.


Input: MicroRNAs (miRNAs, miRs) play important roles in carcinogenesis.


Input: MiR-32 has been shown to be upregulated in CRC.


Input: In this study, we identified the potential effects of miR-32 on some important biological properties of CRC cells, and clarified the regulation of PTEN by miR-32.


Input: METHODS: The effect of miR-32 on PTEN expression was assessed in CRC cell lines with miR-32 mimics/inhibitor to increase/decrease miR-32 expression.


Input: Furthermore, the roles of miR-32 in regulating CRC cells biological properties were analyzed with miR-32 mimics/inhibitor-transfected cells.


Input: The 3 [prime]-untranslated region (3 [prime]-UTR) of PTEN combined with miR-32 was verified by dual-luciferase reporter assay.


Input: RESULTS: Gain-of-function and loss-of-function studies showed that overexpression of miR-32 promoted SW480 cell proliferation, migration, and invasion, reduced apoptosis, and resulted in downregulation of PTEN at a posttranscriptional level.


Input: However, miR-32 knock-down inhibited these processes in HCT-116 cells and enhanced the expression of PTEN protein.


Input: In addition, we further identified PTEN as the functional downstream target of miR-32 by directly targeting the 3 [prime]-UTR of PTEN.


Input: CONCLUSIONS: Our results demonstrated that miR-32 was involved in tumorigenesis of CRC at least in part by suppression of PTEN.


Input: Structure--activity relationships and in silico models of P-glycoprotein (ABCB1) inhibitors.


Input: Abstract 1.


Input: The efflux pump p-glycoprotein (P-gp/ABCB1) has received enormous attention in drug (xenobiotic) disposition due to its role in modulation of the drug availability and in protection of sensitive organs.


Input: P-gp mediated efflux is one of main mechanisms for multidrug resistance in cancer cells.


Input: A main approach to reverse the resistance and restore the drug efficacy is to use specific inhibitors of P-gp that suppress the efflux activity.


Input: This review summarizes the binding capabilities of known chemical inhibitors based on the analyses of structure-activity relationships, and computational modeling of the inhibitors as well as the binding site of P-gp protein.


Input: The molecular models will facilitate the design of lead inhibitors as drug candidates.


Input: Also, it helps scientists in early drug discovery phase to synthesize chemical series with better understanding of their P-gp binding liabilities.


Input: Nasal dosimetry of inspired naphthalene vapor in the male and female B6C3F1 mouse.

naphthalene


Input: Naphthalene vapor is a nasal cytotoxicant in the rat and mouse but is a nasal carcinogen in only the rat.

Naphthalene


Input: Inhalation dosimetry is a critical aspect of the inhalation toxicology of inspired vapors and may contribute to the species differences in the nasal response.


Input: To define the nasal dosimetry of naphthalene in the B6C3F1 male and female mouse, uptake of naphthalene vapor was measured in the surgically isolated upper respiratory tract (URT) at inspiratory flow rates of 25 or 50ml/min.

naphthalene

naphthalene


Input: Uptake was measured at multiple concentrations (0. 5, 3, 10, 30ppm) in controls and mice treated with the cytochrome P450 inhibitor 5-phenyl-1-pentyne.


Input: In both sexes, URT uptake efficiency was strongly concentration dependent averaging 90% at 0. 5ppm compared to 50% at 30ppm (25ml/min flow rate), indicating saturable processes were involved.


Input: Both uptake efficiency and the concentration dependence of uptake were significantly diminished by 5-phenyl-1-pentyne indicating inspired naphthalene vapor is extensively metabolized in the mouse nose with saturation of metabolism occurring at the higher concentrations.

naphthalene


Input: A hybrid computational fluid dynamic physiologically based pharmacokinetic model was developed for nasal dosimetry.


Input: This model accurately predicted the observed URT uptake efficiencies.


Input: Overall, the high URT uptake efficiency of naphthalene in the mouse nose indicates the absence of a tumorigenic response is not attributable to low delivered dose rates in this species.

naphthalene


Input: Exposure to DEHP decreased four fatty acid levels in plasma of prepartum mice.

DEHP

fatty acid


Input: Maternal exposure to di (2-ethylhexyl) phthalate (DEHP) decreased the plasma triglyceride in prepartum mice.

di (2-ethylhexyl) phthalate

DEHP

triglyceride


Input: To identify the fatty acid (FA) species involved and to understand the underlying mechanisms, pregnant Sv/129 wild-type (mPPAR alpha), peroxisome proliferator-activated receptor alpha-null (Ppar alpha-null) and humanized PPAR alpha (hPPAR alpha) mice were treated with diets containing 0%, 0. 01%, 0. 05% or 0. 1% DEHP.

fatty acid

DEHP


Input: Dams were dissected on gestational day 18 together with fetuses, and on postnatal day 2 together with newborns.


Input: n-3/n-6 polyunsaturated, saturated, and monounsaturated FAs in maternal plasma and in liver of wild-type offspring, and representative enzymes for FA desaturation and elongation in maternal liver, were measured.

n-3/n-6 polyunsaturated, saturated, and monounsaturated FAs


Input: The plasma levels of linoleic acid, alpha-linolenic acid, palmitic acid and oleic acid were higher in the pregnant control mPPARa mice than in Ppara-null and hPPARa mice.

linoleic acid

alpha-linolenic acid

palmitic acid

oleic acid


Input: DEHP exposure significantly decreased the levels of these four FAs only in pregnant mPPAR alpha mice.

DEHP


Input: Plasma levels of many FAs were higher in pregnant mice than in postpartum ones in a genotype-independent manner, while it was lower in the livers of fetuses than pups.


Input: DEHP exposure slightly increased hepatic arachidonic acid, alpha-linolenic acid, palmitoleic acid and oleic acid in fetuses, but not in pups.

DEHP

arachidonic acid

alpha-linolenic acid

palmitoleic acid

oleic acid


Input: However, DEHP exposure did not clearly influence FA desaturase 1 and 2 nor elongase 2 and 5 expressions in the liver of all maternal mice.

DEHP


Input: Taken together, the levels of plasma four FAs with shorter carbon chains were higher in pregnant mPPAR alpha mice than in other genotypes, and DEHP exposure decreased these specific FA concentrations only in mPPAR alpha mice, similarly to triglyceride levels.

carbon

DEHP

triglyceride


Input: The role of methyl-CpG binding protein 2 in liver fibrosis.

methyl

CpG


Input: Liver injure is induced by various insults such as alcohol abuse, if insults persistent, may result in the formation of liver fibrosis.

alcohol


Input: Hepatic stellate cell (HSC) activation and transdifferentiation into hepatic myofibroblast, accompanied with potent pro-inflammatory and pro-fibrogenic activities and the down-regulation of anti-inflammatory anti-fibrogenic in gene expression in coordination with epigenetic modifications at the level of the chromatin structure, are pivotal events in liver fibrogenesis.


Input: In this review we focus on the role of the methyl-CpG binding protein 2 (MeCP2) transcriptional regulation of different target genes and the interaction MeCP2 with microRNAs (miRNAs) during liver fibrosis.

methyl

CpG


Input: In addition, we address different signaling pathways interacted with MeCP2 regulated HSC activation.


Input: Such approaches provide valuable insights into the potential targets of liver fibrosis, and are useful pointers for the development of future therapeutic strategies.


Input: Dabigatran for the Prevention of Stroke and Systemic Embolism in Atrial Fibrillation: A NICE Single Technology Appraisal.

Dabigatran


Input: The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of dabigatran etexilate (Boehringer Ingelheim Ltd, UK) to submit evidence for the clinical and cost-effectiveness of this drug for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF) as part of the NICE single technology appraisal process.

dabigatran etexilate


Input: The Centre for Reviews and Dissemination and the Centre for Health Economics at the University of York were commissioned to act as the evidence review group (ERG).


Input: This article presents a summary of the manufacturer' s submission, the ERG report and the subsequent development of NICE guidance for the use of dabigatran within the UK National Health Service.

dabigatran


Input: Dabigatran was granted marketing authorisation by the European Medicines Agency for a sequential dosing regimen (DBG sequential), in which patients under 80 years are treated with dabigatran 150 mg twice daily (DBG150) and patients 80 years and over are given dabigatran 110 mg twice daily (DBG110).

Dabigatran

dabigatran

dabigatran


Input: NICE decisions are bound by the marketing authorisation; therefore, the decision problem faced by the committee was whether the DBG sequential regimen was effective and cost-effective compared with warfarin or aspirin for patients with non-valvular AF and one or more risk factors.

warfarin

aspirin


Input: The RE-LY trial, a large multi-centre non-inferiority randomised clinical trial, was the primary source of clinical evidence.


Input: DBG150 was shown to be non-inferior, and subsequently superior to warfarin, for the primary outcome of all stroke/systemic embolism.

warfarin


Input: DBG110 was found to be non-inferior to warfarin.

warfarin


Input: Results were presented for a post hoc subgroup analysis for patients under and over 80 years of age, where DBG110 showed a statistically significant reduction of haemorrhagic stroke and intracranial haemorrhage in comparison to warfarin in patients over 80 years of age.

warfarin


Input: This post hoc subgroup analysis by age was the basis for the licensed DBG sequential regimen.


Input: The economic evaluation compared the costs and outcomes of DBG110, DBG150 and DBG sequential against warfarin, aspirin, and aspirin plus clopidogrel.

warfarin

aspirin

aspirin

clopidogrel


Input: Across the three dosing regimens, dabigatran was associated with greater costs and better health outcomes than warfarin; however, DBG150 offered the most benefits and dominated DBG110 and DBG sequential (i. e. less costly and more effective).

dabigatran

warfarin


Input: The cost-effectiveness of DBG150 was less favourable for patients well controlled on warfarin.

warfarin


Input: In the first appraisal meeting, the committee issued a' minded no' decision until additional analyses on the licensed DBG sequential regimen were presented by the manufacturer.


Input: These additional analyses indicated that the incremental cost-effectiveness ratio (ICER) of the DBG sequential regimen compared with warfarin ranged from pound 8, 388 to pound 18, 987 per quality-adjusted life year (QALY) gained depending on the level of monitoring costs assumed for warfarin.

warfarin

warfarin


Input: Patients on warfarin would need to be within therapeutic range 83-85% of the time for the ICER to exceed pound 30, 000 per additional QALY.

warfarin


Input: Following consideration of the additional evidence and the responses from a large number of consultees and commentators, the committee recommended dabigatran as DBG sequential as an option for the prevention of stroke and systemic embolism in people with non-valvular AF with one or more risk factors for ischaemic stroke.

dabigatran


Input: Asymmetric zinc-catalyzed hydrosilylation of ketones and the effect of carboxylate on the enantioselectivity.

zinc

ketones

carboxylate


Input: Several chiral ligands containing (R, R)-diaminocyclohexane moieties and pyrrole, furan, or benzene have been synthesized.

(R, R)-diaminocyclohexane

pyrrole

furan

benzene


Input: These ligands were tested in enantioselective zinc-catalyzed hydrosilylation reactions; excellent enantioselectivities were obtained when the ligands containing (R, R)-diaminocyclohexane moieties and furan rings were used.

zinc

(R, R)-diaminocyclohexane

furan


Input: For comparison, zinc chloride combined with different potassium carboxylate salts and ligands were also tested for catalytic hydrosilylation reactions.

zinc chloride

potassium carboxylate


Input: Chirality 25: 275-280, 2013.


Input: (c) 2013 Wiley Periodicals, Inc.


Input: Variability in P-Glycoprotein Inhibitory Potency (IC50) Using Various In Vitro Experimental Systems: Implications for Universal Digoxin DDI Risk Assessment Decision Criteria.

Digoxin


Input: A P-glycoprotein (P-gp) IC50 working group was established with twenty-three participating pharmaceutical and contract research laboratories and one academic institution to assess inter-laboratory variability in P-gp IC50 determinations.


Input: Each lab followed their in-house protocol to determine in vitro IC50 values for sixteen inhibitors using four different test systems: Caco-2 (11 labs), MDCKII-MDR1 (6 labs) and LLC-PK1-MDR1 (4 labs) cells, and membrane vesicles containing human P-gp (5 labs).


Input: For cell models, various equations to calculate remaining transport activity (e. g. efflux ratio, unidirectional flux, net secretory flux) were also evaluated.


Input: The difference in IC50 values for each of the inhibitors across all test systems and equations ranged from a minimum of 20-and 24-fold between lowest and highest IC50 values for sertraline and isradipine, to a maximum of 407-and 796-fold for telmisartan and verapamil, respectively.

sertraline

isradipine

telmisartan

verapamil


Input: For telmisartan and verapamil, variability was greatly influenced by data from one laboratory in each case.

telmisartan

verapamil


Input: Excluding these two data sets brings the range in IC50 values for telmisartan and verapamil down to 69-and 159-fold.

telmisartan

verapamil


Input: The efflux ratio based-equation generally resulted in several fold lower IC50 values compared to unidirectional or net-secretory flux equations.


Input: Statistical analysis indicated that variability in IC50 values was mainly due to inter-laboratory variability, rather than an implicit systematic difference between test systems.


Input: Potential reasons for variability are discussed and the simplest, most robust experimental design for P-gp IC50 determination proposed.


Input: The impact of these findings on drug-drug interaction risk assessment is discussed in the companion paper and recommendations are provided.


Input: Mechanism of Fibrinogen Adsorption at Solid Substrates at lower pH.


Input: Adsorption of fibrinogen was theoretically studied using the three dimensional (3D) random sequential adsorption (RSA) model.


Input: Fibrinogen molecule shape was approximated by the bead model considering the presence of flexible side arms.


Input: Various cases were considered inter alia, the side-on adsorption mechanisms and the 3D side-on/end-on simultaneous adsorption mechanism.


Input: The latter mechanisms is pertinent to fibrinogen adsorption at lower pH where the entire molecule is positively charged.


Input: Extensive calculations enabled one to determine the jamming surface concentration (coverage) of molecules adsorbed under the side-on and end-on orientations as well as the total coverage.


Input: For the 3D model the maximum surface concentration was 7. 29x103 mu m-2 corresponding to the protein coverage of 4. 12 mg m-2 (without considering hydration).


Input: Additionally, the surface blocking functions for the side-on and the 3D adsorption regimes were determined and analytically approximated for the entire range of coverage by the interpolating polynomials.


Input: Using these blocking functions, fibrinogen adsorption kinetics for diffusion controlled transport conditions was evaluated.


Input: Comparison of these theoretical results with experimental data was made.


Input: It was demonstrated that the 3D model properly reflects the maximum coverage of fibrinogen adsorbed on latex particles determined via the electrokinetic (electrophoretic mobility) and AFM measurements.


Input: Also, streaming potential measurements of fibrinogen adsorption kinetics on mica were successfully interpreted in terms of the 3D adsorption model.

mica


Input: The theoretical results derived in this work have implications for basic science providing information on mechanisms of anisotropic protein adsorption.


Input: Key words: adsorption of fibrinogen, fibrinogen adsorption at lower pH, irreversible adsorption of fibrinogen, jamming coverage of fibrinogen, kinetics of fibrinogen adsorption, random sequential adsorption modeling of fibrinogen adsorption.


Input: Aggregation-Mediated Macromolecular Uptake by a Molecular Transporter.


Input: Endocytosis is a key process in cellular delivery of macromolecules by molecular transporters, although the mechanism of internalization remains unclear.


Input: Here, we probe the cellular uptake of streptavidin using biotinylated guanidinoneomycin (biotinGNeo), a low molecular weight guanidinium-rich molecular transporter.

biotinylated guanidinoneomycin

biotinGNeo

guanidinium


Input: Two distinct modes were explored: (i) incubation of cells with a preformed tetravalent streptavidin-(biotinGNeo) 4 conjugate and (ii) preincubation of cells with the biotinGNeo before exposure to streptavidin.

biotinGNeo

biotinGNeo


Input: A significant enhancement in uptake was observed after preincubation with biotinGNeo.

biotinGNeo


Input: FRET studies showed that the enhanced uptake was accompanied by extensive aggregation of streptavidin on the cell surface.


Input: Because guanidinylated neomycin was previously found to exclusively bind to heparan sulfate, our observations suggest that heparan sulfate proteoglycan aggregation is a pivotal step for endocytic entry into cells by guanidinoglycosides.

guanidinylated neomycin

guanidinoglycosides


Input: These observations put forward a practical and general pathway for the cellular delivery of diverse macromolecules.


Input: Study of Charge-Dependent Transport and Toxicity of Peptide-Functionalized Silver Nanoparticles Using Zebrafish Embryos and Single Nanoparticle Plasmonic Spectroscopy.

Silver


Input: Nanomaterials possess unusually high surface area-to-volume ratios, and surface-determined physicochemical properties.


Input: It is essential to understand their surface-dependent toxicity in order to rationally design biocompatible nanomaterials for a wide variety of applications.


Input: In this study, we have functionalized the surfaces of silver nanoparticles (Ag NPs, 11. 7 +/- 2. 7 nm in diameters) with three biocompatible peptides (CALNNK, CALNNS, CALNNE) to prepare positively (Ag-CALNNK NPs + zeta), negatively (Ag-CALNNS NPs-2 zeta), and more negatively charged NPs (Ag-CALNNE NPs-4 zeta), respectively.

silver

Ag

Ag

Ag

Ag


Input: Each peptide differs in a single amino acid at its C-terminus, which minimizes the effects of peptide sequences and serves as a model molecule to create positive, neutral and negative charges on the surface of the NPs at pH 4-10.

amino acid

C


Input: We have studied their charge-dependent transport into early-developing (cleavage-stage) zebrafish embryos and their effects on embryonic development using dark-field optical microscopy and spectroscopy (DFOMS).


Input: We found that all three Ag-peptide NPs passively diffused into the embryos via their chorionic pore canals, and stayed inside the embryos throughout their entire development (120 h), showing charge-independent diffusion modes and charge-dependent diffusion coefficients.

Ag


Input: Notably, the NPs create charge-dependent toxic effects on embryonic development, showing that the Ag-CALNNK NPs + zeta (positively charged) are the most biocompatible while the Ag-CALNNE NPs-4 zeta (more negatively charged) are the most toxic.

Ag

Ag


Input: By comparing with our previous studies of the same sized citrated Ag and Au NPs, the Ag-peptide NPs are much more biocompatible than the citrated Ag NPs, and nearly as biocompatible as the Au NPs, showing the dependence of nanotoxicity upon the surface charges, surface functional groups and chemical compositions of the NPs.

Ag

Au

Ag

Ag

Au


Input: This study also demonstrates powerful applications of single NP plasmonic spectroscopy for quantitative analysis of single NPs in vivo and in tissues, and reveals the possibility of rational design of biocompatible NPs.


Input: Small molecule mediated proliferation of primary retinal pigment epithelial cells.

retinal


Input: Retinal pigment epithelial (RPE) cells form a monolayer adjacent to the retina and play a critical role in the visual light cycle.

Retinal


Input: Degeneration of this layer results in vision loss, causing retinal disorders such as age-related macular degeneration.


Input: Cell transplant therapies exist to restore vision loss; however, risks associated with and an inadequate supply of donor cells have limited their therapeutic success.


Input: The identification of factors that proliferate RPE cells ex vivo could provide a renewable source of cells for the treatment of such disorders.


Input: We show that a small molecule (WS3) can reversibly proliferate primary RPE cells isolated from fetal and adult human donors.


Input: Following withdrawal of WS3, RPE cells differentiate into a functional monolayer, as exhibited by their expression of mature RPE genes and phagocytosis of photoreceptor outer segments.


Input: Furthermore, chemically expanded RPE cells preserve vision when transplanted into dystrophic Royal College of Surgeons (RCS) rats, a well-established model of retinal degeneration.


Input: Two new vinblastine-type N-oxide alkaloids from Catharanthus roseus.

vinblastine

N-oxide alkaloids


Input: Two new vinblastine-type N-oxide alkaloids, 17-desacetoxyvinblastine [Formula: see text]-oxide (1) and 20'-deoxyvinblastine [Formula: see text]-oxide (2), were isolated from the leaves of Catharanthus roseus.

vinblastine

N-oxide alkaloids

oxide

oxide


Input: The structures of 1 and 2 were established by the analysis of their nuclear magnetic resonance and HR-ESI-MS spectroscopic data.


Input: All alkaloids were evaluated for their cytotoxic activities against the human hepatocellular carcinoma (HepG2) cell line, human colorectal carcinoma (Lovo) cell line and human breast carcinoma (MCF-7) cell line by the MTT method in vitro, respectively.

MTT


Input: The results showed that cytotoxic activities of alkaloids 1 and 2 exhibited moderate inhibitory activity on the proliferation of three cancer cells.


Input: Mechanism-based design of a photo-activatable firefly Luciferase.


Input: We developed a photo-activatable firefly luciferase (fLuc) whose activation can be controlled by light.


Input: A photocaged lysine analogue was site-specifically incorporated into fLuc to replace its key catalytic lysine residue-Lys529, rendering fLuc inactive until light-triggered removal of the caging group.

lysine

lysine


Input: This photo-induced gain-of-luminescence provides a facile approach for assessing the photolysis efficiency of this valuable photosensitive lysine analogue within the context of its carrier protein in vitro and in living cells.

lysine


Input: We further took advantage of the spatial and temporal activation feature of pfLuc for intracellular measurement of labile ATP levels without impairment of a cell' s physiology.

ATP


Input: The Histone Mark H3K36me3 Regulates Human DNA Mismatch Repair through Its Interaction with MutS alpha.


Input: DNA mismatch repair (MMR) ensures replication fidelity by correcting mismatches generated during DNA replication.


Input: Although human MMR has been reconstituted in vitro, how MMR occurs in vivo is unknown.


Input: Here, we show that an epigenetic histone mark, H3K36me3, is required in vivo to recruit the mismatch recognition protein hMutS alpha (hMSH2-hMSH6) onto chromatin through direct interactions with the hMSH6 PWWP domain.


Input: The abundance of H3K36me3 in G1 and early S phases ensures that hMutS alpha is enriched on chromatin before mispairs are introduced during DNA replication.


Input: Cells lacking the H3K36 trimethyltransferase SETD2 display microsatellite instability (MSI) and an elevated spontaneous mutation frequency, characteristic of MMR-deficient cells.


Input: This work reveals that a histone mark regulates MMR in human cells and explains the long-standing puzzle of MSI-positive cancer cells that lack detectable mutations in known MMR genes.


Input: Antiproliferative activity of 2, 3-disubstituted indoles toward apoptosis-resistant cancers cells.

2, 3-disubstituted indoles


Input: Many types of cancer, including glioma, melanoma, NSCLC, among others, are resistant to apoptosis induction and poorly responsive to current therapies with propaptotic agents.


Input: We describe a series of 2, 3-disubstituted indoles, which display cytostatic rather than cytotoxic effects in cancer cells, and serve as a new chemical scaffold to develop anticancer agents capable of combating apoptosis-resistant cancers associated with dismal prognoses.

2, 3-disubstituted indoles


Input: Synthesis and evaluation of Janus type nucleosides as potential HCV NS5B polymerase inhibitors.

Janus type nucleosides


Input: The synthesis of new ribo and 2'-beta-C-methyl ribo Janus type nucleosides J-AA, J-AG and J-AU is reported along with their ability to block HCV and HIV replication.

ribo and 2'-beta-C-methyl ribo Janus type nucleosides


Input: Their toxicity was also assessed in Huh7, human lymphocytes, CEM and Vero cells.


Input: The Demographic Transition Influences Variance in Fitness and Selection on Height and BMI in Rural Gambia.


Input: Recent human history is marked by demographic transitions characterized by declines in mortality and fertility [1].


Input: By influencing the variance in those fitness components, demographic transitions can affect selection on other traits [2].


Input: Parallel to changes in selection triggered by demography per se, relationships between fitness and anthropometric traits are also expected to change due to modification of the environment.


Input: Here we explore for the first time these two main evolutionary consequences of demographic transitions using a unique data set containing survival, fertility, and anthropometric data for thousands of women in rural Gambia from 1956-2010 [3].


Input: We show how the demographic transition influenced directional selection on height and body mass index (BMI).


Input: We observed a change in selection for both traits mediated by variation in fertility: selection initially favored short females with high BMI values but shifted across the demographic transition to favor tall females with low BMI values.


Input: We demonstrate that these differences resulted both from changes in fitness variance that shape the strength of selection and from shifts in selective pressures triggered by environmental changes.


Input: These results suggest that demographic and environmental trends encountered by current human populations worldwide are likely to modify, but not stop, natural selection in humans.


Input: First demonstration that brain CYP2D-mediated opiate metabolic activation alters analgesia in vivo.


Input: The response to centrally-acting drugs is highly variable between individuals and does not always correlate with plasma drug levels.


Input: Drug-metabolizing CYP enzymes in the brain may contribute to this variability by affecting local drug and metabolite concentrations.


Input: CYP2D metabolizes codeine to the active morphine metabolite.

codeine

morphine


Input: We investigate the effect of inhibiting brain, and not liver, CYP2D activity on codeine-induced analgesia.

codeine


Input: Rats received intracerebroventricular injections of CYP2D inhibitors (20 mu g propranolol or 40 mu g propafenone) or vehicle controls.

propranolol

propafenone


Input: Compared to vehicle-pretreated rats, inhibitor-pretreated rats had: a) lower analgesia in the tail-flick test (p < 0. 05) and lower areas under the analgesia-time curve (p < 0. 02) within the first hour after 30mg/kg subcutaneous codeine, b) lower morphine concentrations and morphine to codeine ratios in the brain (p < 0. 02 and p < 0. 05, respectively), but not in plasma (p > 0. 6 and p > 0. 7, respectively), tested at 30min after 30mg/kg subcutaneous codeine, and c) lower morphine formation from codeine ex vivo by brain membranes (p < 0. 04), but not by liver microsomes (p > 0. 9).

codeine

morphine

morphine

codeine

codeine

morphine

codeine


Input: Analgesia trended toward a correlation with brain morphine concentrations (p = 0. 07) and correlated with brain morphine to codeine ratios (p < 0. 005), but not with plasma morphine concentrations (p > 0. 8) or plasma morphine to codeine ratios (p > 0. 8).

morphine

morphine

codeine

morphine

morphine


Input: Our findings suggest that brain CYP2D affects brain morphine levels after peripheral codeine administration, and may thereby alter codeine' s therapeutic efficacy, side-effect profile and abuse liability.

morphine

codeine

codeine


Input: Brain CYPs are highly variable due to genetics, environmental factors and age, and may therefore contribute to interindividual variation in the response to centrally-acting drugs.


Input: Ethnopharmacological and bioactivity guided investigation of five TCM anticancer herbs.


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Five herbs, Curcuma longa L.


Input: (CL), Scutellaria baicalensis Georgi (SBC), Scutellaria barbata D.


Input: Don (SBB), Hedyotis diffusa Willd.


Input: (HD) and Solanum nigrum L.


Input: (SN), are often prescribed in the polyherbal formulas for cancer treatment by traditional Chinese medicine (TCM) practitioners.


Input: The purpose of the present study was to identify important anticancer herbs used in TCM and carry out bioactivity-directed fractionation and isolation (BDFI) using six cancer cell lines as well as peripheral blood mononuclear cells (PBMCs), to identify constituents with anticancer activity but devoid of toxic effects against healthy immune cells.


Input: MATERIALS AND METHODS: Of 243 document anticancer TCM treatments, 199 anticancer TCM herbs were ranked by the number of literature reports for each herb.


Input: Five herbs were identified from the top 50 ranked herbs by at least two out of three TCM practitioners as frequently used in the TCM treatment of cancer.


Input: BDFI using MTS assay was applied to determine the active anticancer extracts, fractions, and finally discrete compounds.

MTS


Input: RESULTS: Five herbs were selected for study of their anticancer activities.


Input: The extracts of Curcuma longa L., Scutellaria barbata D.


Input: Don, and Hedyotis diffusa showed antiproliferative activity to various extents, extracts of Scutellaria baicalensis Georgi and Solanum nigrum L. showed little anticancer activity.


Input: Seven out of the 21 fractions obtained from Hedyotis diffusa showed anticancer activity.


Input: One new compound, ethyl 13 (2) (S)-hydroxy-chlorophyllide a (1), along with 10 known compounds, i. e. 2-methyl-3-methoxyanthraquinone (2), 2-hydroxymethylanthraquinone (3), 2-hydroxy-3-methylanthraquinone (4), 2-hydroxymethy-1-hydroxyanthraquinone (5), 1-methoxy-2-hydroxyanthraquinone (6), 2-hydroxy-3-methyl-1-methoxyanthraquinone (7), oleanolic acid (8), ursolic acid (9), stigmasterol (10) and docosanoic acid (11), were isolated and identified.

ethyl 13 (2) (S)-hydroxy-chlorophyllide a

2-hydroxy-3-methyl-1-methoxyanthraquinone

oleanolic acid

ursolic acid

stigmasterol

docosanoic acid


Input: Compounds 2-6, 8 and 9 dose-dependently inhibited the cell viability of cancer cells within a concentration range of 1-200 micro M.


Input: Furthermore, compounds 2, 3, 5 and 9 showed significantly stronger inhibition of tested cancer cell lines than on that of PBMCs.


Input: CONCLUSION: This study identified anticancer herbs, extracts, fractions and eventually compounds from the documented anticancer TCM herbs by using BDFI.


Input: It also determined the antiproliferative activity in cancer and healthy immune cells of the isolated compounds from Hedyotis diffusa.


Input: The results will be useful in the validation of the clinical application of these herbs and the development of novel anticancer therapeutics.


Input: Production of Cyr61 protein is modulated by extracellular acidification and PI3K/Akt signaling in prostate carcinoma PC-3 cells.


Input: High expression of Cyr61, an extracellular cysteine-rich heparin-binding protein, has been associated with a malignant cell phenotype and poor outcome in prostate cancers.

cysteine


Input: Although Cyr61 was found by us to be overproduced in androgen-independent PC-3 cells treated with N-acetylcysteine (NAC), its significance is still unclear.

androgen

N-acetylcysteine

NAC


Input: We therefore aimed to determine how and why Cyr61 protein is overexpressed in NAC-treated cells.

NAC


Input: Here, we found that Cyr61 protein level markedly increased in cells treated with NAC at high cell seeding density.

NAC


Input: Silencing of Cyr61 by siRNA induced enhanced activity of caspase-3/7, upregulation of the proapototic Bok, BimL and BimS, cleavage of apoptosis hallmarkers such as Bax, PARP and caspase-3, and downregulation of antiapoptotic Bcl2, Bcl-xL and Mcl-1 proteins.


Input: NAC treatment caused a reduction of extracellular medium pH to acidic and an increase in Akt phosphorylation, after which the replacement with NAC-free medium returned them to control levels within 24h.

NAC

NAC


Input: Acid stimulation increased the levels of Cyr61 and p-Akt proteins, whereas it suppressed the induction of proapoptotic and antiapoptotic proteins.


Input: Overall, our data indicate that PC-3 cells overproduce Cyr61 protein via activation of the PI3K/Akt signaling as a part of the survival mechanisms under the conditions causing extracellular acidity and further cytotoxicity.


Input: Comparative evaluation of oral and dermal cypermethrin exposure on antioxidant profile in Bubalus bubalis.

cypermethrin


Input: Cypermethrin, a type II synthetic pyrethroid insecticide, @0. 5mg/kg/day for 14 consecutive weeks produced mild signs of toxicity in buffalo calves.

Cypermethrin

pyrethroid


Input: Significant changes were observed in various antioxidant parameters in blood.


Input: There was a marked increase in the extent of lipid peroxidation (33. 9%) and enzymic activity of glutathione peroxidase (6. 7%), superoxide dismutase (35. 0%), catalase (43. 7%), glutathione-S-transferase (64. 4%), glutathione reductase (36. 7%) and glucose-6-phosphate dehydrogenase (32. 1%).

glutathione

superoxide

glutathione

glutathione


Input: A significant decrease in blood glutathione (16. 7%), total antioxidant activity (45. 4%) and vitamin E (40. 8%) was observed and no significant effect was found on blood selenium levels.

glutathione

vitamin E

selenium


Input: However, the extent of lipid peroxidation (42%) and the depletion of glutathione (28. 8%) was greater after dermal sub-acute toxicity of cypermethrin (0. 25%) for 14 consecutive days.

glutathione

cypermethrin


Input: Similarly, it was observed that the incline in the enzymic activity of glutathione peroxidase (29. 7%), superoxide dismutase (38. 3%) and glutathione reductase (38. 3%) was higher in dermally cypermethrin exposed animals.

glutathione

superoxide

glutathione

cypermethrin


Input: Thus, the present investigation contemplates that oxidative stress is the important mechanisms involved in cypermethrin-induced toxicity and the oxidative insult produced by dermal route is more severe as compared to oral intoxication.

cypermethrin


Input: Biological effects induced by BSA-stabilized silica nanoparticles in mammalian cell lines.

silica


Input: Much of the concerns regarding engineered nanoparticle (NP) toxicity are based on knowledge from previous studies on particles in ambient air or occupational situations.


Input: E. g., the effects of exposure to silica dust particles have been studied intensely due to the carcinogenicity of crystalline silica.

silica

silica


Input: However, the increasing usage of engineered amorphous silica NPs has emphasized the need for further mechanistic insight to predict the consequences of exposure to the amorphous type of silica NPs.

silica

silica


Input: The present study focused on the in vitro biological effects following exposure to well-dispersed, BSA-stabilized, amorphous silica NPs whereas unmodified silica NPs where included for reasons of comparison.

silica

silica


Input: The cytotoxicity of the silica NPs was investigated in six different cell lines (A549, THP-1, CaCo-2, ASB-XIV, J-774A. 1, and Colon-26) selected to explore the significance of organ and species sensitivity in vitro.

silica


Input: Viability data demonstrated that macrophages were most sensitive to silica NP and interestingly, murine cell lines were generally found to be more sensitive than comparable human cell lines.

silica


Input: Further studies were conducted in the human epithelial lung cell line, A549, to explore the molecular mechanism of silica toxicity.

silica


Input: Generation of reactive oxygen species, one of the proposed toxicological mechanisms of NPs, was investigated in A549 cells by the dichlorofluorescin (DCF) assay to be significantly induced at NP concentrations above 113 mu g/mL.

oxygen

dichlorofluorescin

DCF


Input: However, induction of oxidative stress related pathways was not found after silica NP exposure for 24h in gene array studies conducted in A549 cells at a relatively low NP concentration (EC20).

silica


Input: Up-regulated genes (more than 2-fold) were primarily related to lipid metabolism and biosynthesis whereas down-regulated genes included several processes such as transcription, cell junction, extra cellular matrix (ECM)-receptor interaction and others.


Input: Thus, gene expression data proposes that several cellular processes other than oxidative stress could be affected by exposure to silica NPs.

silica


Input: Anthelmintic activity of Arisaema franchetianum and Arisaema lobatum essential oils against Haemonchus contortus.


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Arisaema franchetianum and Arisaema lobatum are two perennial plants native to China.


Input: Arisaema franchetianum is universally used to promote the subsidence of induration and swelling, quicken blood and relieve pains, and kill intestinal parasites in humans and animals.


Input: Arisaema lobatum is used to treat malaria, intestinal parasites, and snake and insect bites in humans and animals.


Input: The aim of this study was to determine the composition of the essential oils from Arisaema franchetianum and Arisaema lobatum and evaluate the anthelmintic effect against Haemonchus contortus.


Input: MATERIALS AND METHODS: Two oils were investigated by GC and GC-MS.


Input: The anthelmintic bioassay tests of Arisaema franchetianum and Arisaema lobatum essential oil, linalool and carvacrol were performed using egg hatch assay (EHA), larval development assay (LDA) and larval migration inhibition assay (LMIA).

linalool

carvacrol


Input: RESULTS: Fifty six components representing 96. 88% of the Arisaema franchetianum oil and 64 components representing 96. 88% of the Arisaema lobatum oil were identified.


Input: Carvacrol and linalool were found to be the major constituents of two oils.

Carvacrol

linalool


Input: In the EHA, greater than 99% inhibition were observed with Arisaema franchetianum oil at 10mg/mL (CE50 1. 63mg/mL) and Arisaema lobatum oil at 5 and 10mg/mL (CE50 0. 48mg/mL).


Input: In the LDA, both oils induced complete inhibition at 10mg/mL, with the CE50 being 1. 10mg/mL for Arisaema franchetianum oil and 0. 73mg/mL for Arisaema lobatum oil.


Input: In the LMIA, the Arisaema franchetianum oil and Arisaema lobatum oil at best inhibited 74. 1% and 95. 6% of larval migration at 10mg/mL, respectively.


Input: Carvacrol exhibited similar activity to Arisaema lobatum essential oil and linalool did not show high activity in every assay.

Carvacrol

linalool


Input: CONCLUSIONS: These data show for the first time that the essential oils obtained from Arisaema franchetianum or Arisaema lobatum had promising anthelmintic activity against Haemonchus contortus.


Input: Arisaema plant may offer an alternative source for the control of gastrointestinal nematodes of sheep and goats.


Input: Sciadopitysin protects osteoblast function via its antioxidant activity in MC3T3-E1 cells.

Sciadopitysin


Input: Age-related osteoblast dysfunction is the main cause of age-related bone loss in both men and women.


Input: In the present study, the effect of sciadopitysin, a type of biflavonoids, on osteoblast function was investigated in osteoblastic MC3T3-E1 cells.

sciadopitysin

biflavonoids


Input: Sciadopitysin caused a significant elevation of alkaline phosphatase activity, collagen synthesis, osteocalcin production, mineralization, and glutathione content in the cells (P < 0. 05).

Sciadopitysin

glutathione


Input: Sciadopitysin also decreased the production of tumor necrosis factor-a (TNF-alpha) induced by antimycin A, a mitochondrial electron transport inhibitor.

Sciadopitysin

antimycin A


Input: We investigated the protective effects of sciadopitysin on antimycin A-induced toxicity in osteoblastic MC3T3-E1 cells.

sciadopitysin

antimycin A


Input: Exposure of MC3T3-E1 cells to antimycin A caused a significant reduction in osteoblast dysfunction.

antimycin A


Input: However, pretreatment with sciadopitysin prior to antimycin A exposure significantly reduced antimycin A-induced cell damage by preventing mitochondrial membrane potential dissipation, adenosine triphosphate (ATP) loss, reactive oxygen species (ROS) release, and nitrotyrosine increase, suggesting that sciadopitysin may be useful for protecting mitochondria against a burst of oxidative stress.

sciadopitysin

antimycin A

antimycin A

adenosine triphosphate

ATP

oxygen

nitrotyrosine

sciadopitysin


Input: Moreover, sciadopitysin increased phosphorylation of cAMP-response element-binding protein (CREB) inhibited by antimycin A.

sciadopitysin

cAMP

antimycin A


Input: Our results demonstrate that sciadopitysin may reduce or prevent osteoblasts degeneration.

sciadopitysin


Input: In vitro binding affinities of a series of flavonoids for mu-opioid receptors.

flavonoids


Input: Antinociceptive effect of the synthetic flavonoid 3, 3-dibromoflavanone in mice.

flavonoid 3, 3-dibromoflavanone


Input: The pharmacotherapy for the treatment of pain is an active area of investigation.


Input: There are effective drugs to treat this problem, but there is also a need to find alternative treatments free of undesirable side effects.


Input: In the present work the capacity of a series of flavonoids to bind to the mu opioid receptor was evaluated.

flavonoids


Input: The most active compound, 3, 3-dibromoflavanone (31), a synthetic flavonoid, presented a significant inhibition of the binding of the selective mu opioid ligand [(3) H] DAMGO, with a Ki of 0. 846 +/- 0. 263 mu M.

3, 3-dibromoflavanone

flavonoid

[(3) H] DAMGO


Input: Flavanone 31 was further synthesized using a simple and cheap procedure with good yield.

Flavanone


Input: Its in vivo effects in mice, after acute treatments, were studied using antinociceptive and behavioral assays.


Input: It showed no sedative, anxiolytic, motor incoordination effects or inhibition of the gastrointestinal transit in mice at the doses tested.


Input: It evidenced antinociceptive activity on the acetic acid-induced nociception, hot plate and formalin tests (at 10 mg/kg and 30 mg/kg).

acetic acid

formalin


Input: The results showed that the 5-HT2 receptor and the adrenoceptors seem unlikely to be involved in its antinociceptive effects.


Input: Naltrexone, a nonselective opioid receptors antagonist, totally blocked compound 31 antinociceptive effects on the hot plate test, but naltrindole (delta opioid antagonist) and nor-binaltorphimine (kappa opioid antagonist) did not.

Naltrexone

naltrindole

nor-binaltorphimine


Input: These findings demonstrated that 3, 3-dibromoflavanone (31), at doses that did not interfere with the motor performance, exerted clear dose dependent antinociception when assessed in the chemical and thermal models of nociception in mice and it seems that its action is related to the activation of the mu opioid receptor.

3, 3-dibromoflavanone


Input: Trabecular bone adapts to long-term cyclic loading by increasing stiffness and normalization of dynamic morphometric rates.


Input: Bone has the ability to adapt to external loading conditions.


Input: Especially the beneficial effect of short-term cyclic loading has been investigated in a number of in vivo animal studies.


Input: The aim of this study was to assess the long-term effect (> 10weeks) of cyclic mechanical loading on the bone microstructure, bone stiffness, and bone remodeling rates.


Input: Mice were subjected to cyclic mechanical loading at the sixth caudal vertebra with 8N or 0N (control) three times per week for a total period of 14weeks.


Input: Structural bone parameters were determined from in vivo micro-computed tomography (micro-CT) scans performed at week 0, 4, 6, 8, 10, 12, and 14.


Input: Mechanical parameters were derived from micro-finite element analysis.


Input: Dynamic bone morphometry was calculated using registration of serial micro-CT scans.


Input: Bone volume fraction and trabecular thickness increased significantly more for the loaded group than for the control group (p = 0. 006 and p = 0. 002 respectively).


Input: The trabecular bone microstructure adapted to the load of 8N in approximately ten weeks, indicated by the trabecular bone volume fraction, which increased from 16. 7% at 0weeks to 21. 6% at week 10 and only showed little change afterwards (bone volume fraction of 21. 5% at 14weeks).


Input: Similarly bone stiffness-at the start of the experiment 649N/mm-reached 846N/mm at 10weeks in the loaded group and was maintained to the end of the experiment (850N/mm).


Input: At 4weeks the bone formation rate was 32% greater and the bone resorption rate 22% less for 8N compared to 0N.


Input: This difference was significantly reduced as the bone adapted to 8N, with 8N remodeling rates returning to the values of the 0N group at approximately 10weeks.


Input: Together these data suggest that once bone has adapted to a new loading state, the remodeling rates reduce gradually while maintaining bone volume fraction and stiffness.


Input: The extraction and analysis of cylindrospermopsin from human serum and urine.

cylindrospermopsin


Input: The naturally derived cyanotoxin, cylindrospermopsin (CYN), has been detected in freshwater systems worldwide and poses a threat to human health.

cylindrospermopsin

CYN


Input: The methods for the extraction and detection of this toxin in source water are well documented, but methods for CYN determination in exposed individuals have not been investigated.

CYN


Input: In this study, the extraction and detection of CYN from two different matrices, serum and urine, was explored.

CYN


Input: Both serum and urine matrices inherently produce interference with analytical analyses and require extensive clean-up.


Input: Methods for extraction of CYN from both matrices were developed and validated using fortified samples.

CYN


Input: Serum extraction included homogenization followed by protein precipitation and solid phase extraction (SPE).


Input: Urine samples were processed using filtration, pH manipulation, and SPE.


Input: Analyses using a commercially available enzyme-linked immunosorbent assay (ELISA) and liquid chromatography coupled with mass spectrometry (LC/MS/MS) were assessed.


Input: Matrix effects inhibited ELISA' s use as a quantitative tool for both matrices.


Input: LC/MS/MS was determined to be the most effective and reproducible means to detect and quantify CYN.

CYN


Input: The method detection limits determined in this study using LC/MS/MS were 0. 25 and 0. 50 ng mL (-1) for serum and urine, respectively.


Input: This method can be used to test individuals exposed to blooms of cyanobacteria producing CYN.

CYN


Input: Developmental toxicity and estrogenic potency of zearalenone in zebrafish (Danio rerio).

zearalenone


Input: Zearalenone (ZEA, F2) is one of the most common mycotoxins and the only known mycoestrogen.

Zearalenone

ZEA

mycoestrogen


Input: It enters the food and feed chain from contaminated cereals and infiltrates into sewage or natural waters posing potential threat to exposed livestock, wildlife and humans.


Input: Therefore evaluation of its biological effects is of international importance.


Input: We performed toxicological tests on zebrafish (Danio rerio) larvae and adults.


Input: Developmental toxicity was assessed by an extended (5 days) fish embryo toxicity test (FET).


Input: Effects of early ZEA exposure were concentration-dependent with LC50 and LC10 values of 893 and 335 mu g/L.

ZEA


Input: In larvae exposed to 500 mu g/L and above, ZEA induced similar phenotype to has (heart-and soul) showing defects in heart and eye development and upward curvature of the body axis.

ZEA


Input: From 250 mu g/L at 72hpf the gap in the melanophore streak at the base of the tail fin was missing and the fin fold was abnormal, suggesting disturbance in the development of the adult tail fin primordium.


Input: Estrogenic potency was measured on the basis of Vitellogenin (Vtg) protein (adults) levels and relative abundance of vitellogenin-1 mRNA (vtg-1) (larvae and adults).


Input: qRT-PCR in larvae proved to be sufficient substitute to adult tests and sensitive enough to detect ZEA in 0. 1 mu g/L concentrations, that is close to levels observed in wastewaters.

ZEA


Input: Developmental defects reveal that besides direct estrogenic effects, zearalenone might interact with other ontogenic pathways.

zearalenone


Input: Controlled electrochemical deposition and transformation of hetero-nanoarchitectured electrodes for energy storage.


Input: A review of electrochemically synthesized nanomaterials with different controllable architectures for electrochemical energy storage devices is shown.


Input: It is demonstrated that these nano-architectures can be created either by electrodeposition or by the electrochemical transformation of materials.


Input: Electrochemical synthesis is presented here as it provides intimate contact between the electrode and current collector and also promotes an electronic pathway for all materials to be connected to the circuit.


Input: Although still in their infancy, electrosynthesized nano-architectures show promise to be used in future electrochemical energy storage devices as utilization of this method bypasses the need for bulky conductive additives and electrochemically inactive binders.


Input: Furthermore, electrochemical transformations can be used to create additional architectural features or change the chemical make-up of the electrode.


Input: This review is meant to show the creativity of current science when it comes to these nano-architectured electrodes.


Input: It is organized by technique used for synthesis including hard template, soft template, and template-free synthesis along with electrochemical transformation techniques.


Input: Effects of intravenous nicotine on prepulse inhibition in smokers and non-smokers: relationship with familial smoking.

nicotine


Input: RATIONALE: The reinforcing properties of nicotine may be, in part, derived from its ability to enhance certain forms of cognitive processing.

nicotine


Input: Several animal and human studies have shown that nicotine increases prepulse inhibition (PPI) of the startle reflex.

nicotine


Input: However, it remains unclear whether these effects are related to smoking susceptibility.


Input: OBJECTIVES: The current study examined the effects of intravenously delivered nicotine on PPI in smokers and non-smokers, as well as its association with a quantitative index of familial smoking.

nicotine


Input: METHODS: The sample consisted of 30 non-smokers and 16 smokers, who completed an initial assessment, followed on a separate day by a laboratory assessment of PPI prior to and following each of two intravenous nicotine infusions.

nicotine


Input: Separate doses were used in smoker and non-smoker samples.


Input: RESULTS: Analyses indicated that both nicotine infusions acutely enhanced PPI among non-smokers, and this enhancement was positively related to the degree of smoking among first and second-degree relatives.

nicotine


Input: Smokers also displayed PPI enhancement after receiving the first infusion, but this effect was unrelated to familial smoking.


Input: CONCLUSIONS: These data suggest that the PPI paradigm may have utility as an endophenotype for cognitive processes which contribute to smoking risk.


Input: Ventral tegmental area alpha 6 beta 2 nicotinic acetylcholine receptors modulate phasic dopamine release in the nucleus accumbens core.

acetylcholine

dopamine


Input: RATIONALE: Phasic dopamine (DA) signaling underlies reward learning.

dopamine


Input: Cholinergic and glutamatergic inputs into the ventral tegmental area (VTA) are crucial for modulating burst firing activity and subsequent phasic DA release in the nucleus accumbens (NAc), but the specific VTA nicotinic receptor subtypes that regulate phasic DA release have not been identified.


Input: OBJECTIVE: The goal was to determine the role of VTA N-methyl-D-aspartate receptors (NMDARs) and specific subtypes of nicotinic acetylcholine receptors (nAChRs) in regulating phasic DA release in the NAc core.

N-methyl-D-aspartate

acetylcholine


Input: METHODS: Fast-scan cyclic voltammetry in anesthetized rats was combined with intra-VTA micro-infusion to evaluate the ability of glutamatergic and cholinergic drugs to modulate stimulated phasic DA release in the NAc core.


Input: RESULTS: VTA NMDAR blockade with AP-5 decreased, while VTA NMDAR activation with NMDA increased NAc peak phasic DA release.

NMDAR


Input: Intra-VTA administration of the nonspecific nAChR antagonist mecamylamine produced a persistent decrease in phasic DA release.

mecamylamine


Input: Infusion of the alpha 6-selective antagonist alpha-conotoxin MII (alpha-ctx MII) produced a robust, but transient decrease in phasic DA, whereas infusion of selective doses of either the alpha 4 beta 2-selective antagonist, dihydro-beta-erythroidine, or the alpha 7 antagonist, methyllycaconitine, had no effect.

dihydro-beta-erythroidine

methyllycaconitine


Input: Co-infusion of AP-5 and alpha-ctx MII produced a similar phasic DA decrease as either drug alone, with no additive effect.


Input: CONCLUSIONS: The results suggest that VTA alpha 6 beta 2 nAChRs, but not alpha 4 beta 2 or alpha 7 nAChRs, regulate phasic DA release in the NAc core and that VTA alpha 6 beta 2 nAChRs and NMDA receptors act at a common site or target to regulate NAc phasic DA signaling.

NMDA


Input: The Value of Expression of M2-PK and VEGF in Patients with Advanced Gastric Cancer.


Input: Glycolytic pyruvate kinase isoenzyme type M2 (M2-PK) plays a key role in tumor metabolism and energy production.

pyruvate


Input: Vascular endothelial growth factor (VEGF) is critical in regulating angiogenesis which is an essential process required for tumor growth and metastasis.


Input: These two genes may function in accordance with tumor development.


Input: The purpose of this study was to investigate the relationship between the expression of M2-PK and VEGF, and their association with clinicopathological features in patients with advanced gastric cancer.


Input: Expression of M2-PK and VEGF were examined in 142 cases of paraffin-embedded tissue blocks from patients with advanced gastric cancer.


Input: M2-PK expression was found to strongly correlate with that of VEGF (r = 0. 718).


Input: In addition, expression of M2-PK and VEGF correlates with tumor size (p = 0. 0001, and p = 0. 0017, respectively), depth of invasion (p = 0. 0024, and p = 0. 0261, respectively), and lymph node metastasis (p = 0. 036, and p = 0. 028, respectively).


Input: The high expression levels of M2-PK and VEGF may indicate poor prognosis in patients with advanced gastric cancer.


Input: Effects of Soil Trace Elements on Longevity Population in China.


Input: Based on background concentrations of elements in soils and the sixth population census data of China, this study discussed the distribution characteristics of soil elements and longevity population at province level in China.


Input: Percentages of the aging population are high in Southwest China and the eastern coastal region but low in western and northwestern regions.


Input: Provinces in South and Southwest China gain a high level of longevity, while the northern part of China has a low level of longevity.


Input: The background concentration of Se in soil has a significant positive correlation with longevity index, while Ba and Ni have a significant negative correlation with longevity indexes.

Se

Ba

Ni


Input: By regression analysis, longevity index C/100, 000 can be expressed as C/100, 000 = 1. 679-0. 205 Ni + 0. 413 Co + 0. 006 Se (with R (2) = 0. 402 and p < 0. 01), C/65 + can be expressed as C/65 + = 3. 425-0. 262 Ni + 0. 435 Co + 0. 006 Se (with R (2) = 0. 369 and p < 0. 01).

Ni

Co

Se

Ni

Co

Se


Input: Glomerular Filtration Rate Equations Overestimate Creatinine Clearance in Older Individuals Enrolled in the Baltimore Longitudinal Study on Aging: Impact on Renal Drug Dosing.

Creatinine


Input: OBJECTIVES: To evaluate the performance of kidney function estimation equations and to determine the frequency of drug dose discordance in an older population.


Input: DESIGN: Cross-sectional analysis of data from community-dwelling volunteers randomly selected from the Baltimore Longitudinal Study of Aging from January 1, 2005, to December 31, 2010.


Input: SUBJECTS: A total of 269 men and women with a mean +/- SD age of 81 +/- 6 years, mean serum creatinine concentration (Scr) of 1. 1 +/- 0. 4 mg/dl, and mean 24-hour measured creatinine clearance (mClcr) of 53 +/- 13 ml/minute.

creatinine

creatinine


Input: MEASUREMENTS AND MAIN RESULTS: Kidney function was estimated by using the following equations: Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).


Input: The performance of each equation was assessed by measuring bias and precision relative to mClcr.


Input: Dose calculation errors (discordance) were determined for 10 drugs requiring renal dosage adjustments to avoid toxicity when compared with the dosages approved by the Food and Drug Administration.


Input: The CG equation was the least biased estimate of mClcr.


Input: The MDRD and CKD-EPI equations were significantly positively biased compared with CG (mean +/- SD 34 +/- 20% and 22 +/- 15%, respectively, p < 0. 001) and mClcr (29 +/- 47% and 18 +/- 40%, respectively, p < 0. 001).


Input: Rounding low Scr values (less than 1. 0 mg/dl) up to an arbitrary value of 1. 0 mg/dl resulted in CG values (44 +/- 10 ml/minute) that were significantly lower than mClcr (56 +/- 12 ml/minute, p < 0. 001) and CG (56 +/- 15 ml/minute, p < 0. 001).


Input: The MDRD and CKD-EPI equations had median dose discordance rates of 28. 6% and 22. 9%, respectively.


Input: CONCLUSION: The MDRD and CKD-EPI equations significantly overestimated creatinine clearance (mClcr and CG) in elderly individuals.

creatinine


Input: This leads to dose calculation errors for many drugs, particularly in individuals with severe renal impairment.


Input: Thus equations estimating glomerular filtration rate should not be substituted in place of the CG equation in older adults for the purpose of renal dosage adjustments.


Input: In addition, the common practice of rounding or replacing low Scr values with an arbitrary value of 1. 0 mg/dl for use in the CG equation should be avoided.


Input: Additional studies that evaluate alternative eGFR equations in the older populations that incorporate pharmacokinetic and pharmacodynamic outcomes measures are needed.


Input: Multiple Site-Selective Insertions of Noncanonical Amino Acids into Sequence-Repetitive Polypeptides.

Amino Acids


Input: A simple and efficient method is described for the introduction of noncanonical amino acids at multiple, defined sites within recombinant polypeptide sequences.

amino acids


Input: Escherichia coli MRA30, a bacterial host strain with attenuated activity of release factor 1 (RF1), was assessed for its ability to support incorporation of a diverse range of noncanonical amino acids in response to multiple encoded amber (TAG) codons within genes derived from superfolder GFP and an elastin-mimetic protein polymer.

amino acids


Input: Suppression efficiency and protein yield depended on the identity of the orthogonal aminoacyl-tRNA synthetase/tRNA (CUA) pair and the noncanonical amino acid.

aminoacyl

amino acid


Input: Elastin-mimetic protein polymers were prepared in which noncanonical amino acid derivatives were incorporated at up to 22 specific sites within the polypeptide sequence with high substitution efficiency.

amino acid


Input: The identities and positions of the variant residues were confirmed by mass spectrometric analysis of the full-length polypeptides and proteolytic cleavage fragments from thermolysin digestion.


Input: The data suggest that this multisite suppression approach permits the preparation of protein-based materials in which novel chemical functionalities can be introduced at precisely defined positions within the polypeptide sequence.


Input: Studying the effect of antioxidants on cytogenetic manifestations of solvent exposure in paint industry.


Input: OBJECTIVE: To investigate the antioxidant role in reversing cytogenetic changes caused by solvent exposure in paint industry. Subjects and METHODS: A prospective controlled clinical trial was performed on 39 workers exposed to solvents and 39 workers not exposed to solvents by supplying a mixture of antioxidant vitamins (A, C, E and selenium) and the after effects of such regimen were analyzed.

vitamins (A, C, E

selenium


Input: Environmental monitoring was carried out for air concentrations of different solvents at workplace.


Input: Exposed group was cytogenetically tested before and after giving the mixture of antioxidant vitamins for 1 month duration.


Input: RESULTS: Frequency of chromosomal aberrations (CAs) and the mean of sister chromatid exchanges (SCEs) were statistically significantly higher among exposed workers than among controls.


Input: After the supplementation of antioxidants, there was a statistically significant decrease in the frequency of CAs, and 88% abnormal levels of SCEs were back to normal levels.


Input: CONCLUSION: Antioxidant supplementation decreases the frequency of CAs and SCEs among exposed workers.


Input: Pirimicarb-based formulation-induced genotoxicity and cytotoxicity in the fresh water fish Cnesterodon decemmaculatus (Jenyns, 1842) (Pisces, Poeciliidae).

Pirimicarb


Input: We analyzed the aspects of lethality, genotoxicity, and cytotoxicity in the ten spotted live-bearer exposed under laboratory conditions to the pirimicarb-based formulation Patton Flow ((R)) (50% active ingredient (a. i.)).

pirimicarb


Input: Acute effects were evaluated using different end points for lethality, genotoxicity, and cytotoxicity.


Input: Median lethal concentration (LC50) estimation was employed as a bioassay for lethality, whereas micronucleus (MN) induction and alterations in erythrocyte/erythroblast frequency were used as end points for genotoxicity and cytotoxicity, respectively.


Input: Results demonstrated an LC5096h value of 88 mg/L.


Input: Patton Flow ((R)) increased the MN frequency in fish erythrocytes after 48 h of exposure at a concentration of 66 mg/L, whereas a concentration range of 22-66 mg/L was able to exert the same genotoxic effect at 96 h of treatment.


Input: Furthermore, cytotoxicity was also observed by alterations in erythrocyte/erythroblast frequencies within the concentration range of 22-66 mg/L, regardless of the exposure time.


Input: Our current observations provide evidence that Patton Flow ((R)) (50% a. i.) should be considered a clear lethal, cytotoxic, and genotoxic agent on Cnesterodon decemmaculatus.


Input: Thus, repeated applications of this carbamic insecticide can enter the aquatic environment and exert deleterious effects on aquatic organisms other than the evaluated species C. decemmaculatus.

carbamic


Input: 1, 1-Diphenyl, 2-picrylhydrazyl free radical scavenging, bactericidal, fungicidal and leishmanicidal properties of Teucrium stocksianum.

1, 1-Diphenyl, 2-picrylhydrazyl


Input: In the present study, we evaluated the pharmacological and toxicological effects of Teucrium stocksianum.


Input: The crude extract of T. stocksianum (Ts. Cr) and its subsequent organic fractions: n-hexane (Ts. Hex), chloroform (Ts. CHCl3) and ethyl acetate (Ts. EtAc) exhibited 1, 1-diphenyl, 2-picrylhydrazyl free radical scavenging activity with different potencies.

n-hexane

Hex

chloroform

ethyl acetate

EtAc

1, 1-diphenyl, 2-picrylhydrazyl


Input: Ts. EtAc was found to be most potent.

EtAc


Input: Ts. Cr, Ts. Hex, Ts. CHCl3 and Ts. EtAc showed significant bactericidal activity against Escherichia coli, Staphylococcus aureus, Salmonella typhi, Shigella flexneri and Bacillus subtilis at their extent.

Hex

EtAc


Input: Ts. Cr, Ts. Hex, Ts. CHCl3 and Ts. EtAc displayed fungicidal action against Aspergillus niger, Aspergillus flavus, Aspergillus fumigatus and Fusarium solani at various minimum inhibitory concentrations.

Hex

EtAc


Input: Ts. Cr and Ts. EtAc exhibited marked inhibition of Leishmania tropica growth, observed after 48 and 96 hrs of treatment.

EtAc


Input: These data indicate that the T. stocksianum methanolic extract and its resultant fractions possess antioxidant, antibacterial, antifungal and antileishmanial activities.


Input: Thus, the present research unearths the scientific base for T. stocksianum medicinal application as antioxidant and antimicrobial agents.


Input: Effect of paraoxonase 1 192 Q/R polymorphism on paraoxonase and acetylcholinesterase enzyme activities in Turkish population exposed to organophosphate.

organophosphate


Input: Organophosphate (OP) compounds are the most commonly used pesticide groups and they are commercially used in the market for local and industrial purposes.

Organophosphate


Input: Paraoxonase 1 (PON1) enzyme plays an important role in biotransformation of OP compounds, which shows toxic effects via inhibiting the acetylcholinesterase (AChE).


Input: The aim of this study was to determine the effects of PON1 gene polymorphism and its effects on PON and AChE enzyme activities in individuals who were exposed to organophosphorus insecticides due to occupational reasons, and to profile the probability of susceptibility to organophosphorus compounds.

organophosphorus

organophosphorus


Input: For this purpose, 54 individuals who were exposed to OPs and 54 healthy unrelated controls were studied.


Input: First, PON1 and AChE enzyme activities were measured.


Input: Second, PON1 192 Q/R polymorphism was determined by standard polymerase chain reaction-restriction fragment length polymorphism technique.


Input: When the PON1 192 Q/R polymorphism was compared with PON1 enzyme activities, statistically significant association was found in both OP-exposed and control groups (p < 0. 05).


Input: PON1 192 R (+) (QR + RR genotypes) genotype carriers had higher PON1 activities than 192 R (-) (QQ) genotype carriers.


Input: On the other hand, results were statistically analyzed in terms of AChE enzyme activities and there were statistically significant differences only in the OP-exposed group (p < 0. 05).


Input: The mean AChE concentration in the OP-exposed group was determined as 33. 79 +/- 6. 84 U/g haemoglobin (Hb) for PON1 192 R (+) carriers and 30. 37 +/- 7. 62 U/g Hb for PON1 192 R (+) carriers.


Input: As a conclusion, PON1 and AChE activities were increasing according to the genotypes found in individuals having been exposed to OPs at a chronic level; 192 R (+) > 192 R (-), respectively.


Input: Structural Determinants of Agonist Efficacy at the Glutamate Binding Site of NMDA Receptors.

Glutamate

NMDA


Input: NMDA receptors are ligand-gated ion channels assembled from GluN1 and GluN2 subunits.

NMDA


Input: We utilized a series of N-hydroxypyrazole-5-glycine (NHP5G) partial agonists at the GluN2 glutamate binding site as tools to study activation of GluN1/GluN2A and GluN1/GluN2D NMDA receptor subtypes.

glutamate

NMDA


Input: We show using two-electrode voltage-clamp electrophysiology, fast-application patch-clamp, and single channel recordings that propyl-and ethyl-substituted NHP5G agonists have a broad range of agonist efficacies relative to the full agonist glutamate (< 1%-72%).

propyl-and ethyl-substituted NHP5G

glutamate


Input: Crystal structures of the agonist binding domains (ABDs) of GluN2A and GluN2D do not reveal any differences in the overall domain conformation induced by binding of the full agonist glutamate or the partial agonist propyl-NHP5G, which is strikingly different from ABD structures of AMPA and kainate receptors bound to full and partial agonists.

glutamate

AMPA

kainate


Input: Subsequent evaluation of relative NHP5G agonist efficacy at GluN2A-GluN2D chimeric subunits implicates the amino-terminal domain (ATD) as a strong determinant of agonist efficacy, suggesting that interdomain interactions between the ABD and the ATD may be a central element in controlling the manner by which agonist binding leads to channel opening.

amino


Input: We propose that variation in the overall receptor conformation, which is strongly influenced by the nature of interdomain interactions in resting and active states, mediates differences in agonist efficacy and partial agonism at the GluN2 subunits.


Input: Microfluidic affinity and ChIP-seq analyses converge on a conserved FOXP2-binding motif in chimp and human, which enables the detection of evolutionarily novel targets.


Input: The transcription factor forkhead box P2 (FOXP2) is believed to be important in the evolution of human speech.


Input: A mutation in its DNA-binding domain causes severe speech impairment.


Input: Humans have acquired two coding changes relative to the conserved mammalian sequence.


Input: Despite intense interest in FOXP2, it has remained an open question whether the human protein' s DNA-binding specificity and chromatin localization are conserved.


Input: Previous in vitro and ChIP-chip studies have provided conflicting consensus sequences for the FOXP2-binding site.


Input: Using MITOMI 2. 0 microfluidic affinity assays, we describe the binding site of FOXP2 and its affinity profile in base-specific detail for all substitutions of the strongest binding site.


Input: We find that human and chimp FOXP2 have similar binding sites that are distinct from previously suggested consensus binding sites.


Input: Additionally, through analysis of FOXP2 ChIP-seq data from cultured neurons, we find strong overrepresentation of a motif that matches our in vitro results and identifies a set of genes with FOXP2 binding sites.


Input: The FOXP2-binding sites tend to be conserved, yet we identified 38 instances of evolutionarily novel sites in humans.


Input: Combined, these data present a comprehensive portrait of FOXP2' s-binding properties and imply that although its sequence specificity has been conserved, some of its genomic binding sites are newly evolved.


Input: Self-Assembly and Near Perfect Macroscopic Alignment of Fluorescent Triangulenium Salt in Spin Cast Thin Films on PTFE.

Triangulenium

PTFE


Input: Highly fluorescent, discotic trioxatriangulenium dyes were aligned by simple spin casting on substrates with friction transferred PTFE layers.

trioxatriangulenium

PTFE


Input: The fluorescent crystalline thin films show near perfect macroscopic alignment on centimeter large areas directly from spin casting.


Input: Gracing Incidence X-ray Diffraction (GIXD) unambiguously allowed to determine a long range order unit cell as well as its orientation with respect to the PTFE fibers.

PTFE


Input: Further analysis of the X-ray data, in conjunction with polarized absorption spectroscopy, suggest a lamellar packing model with alternating layers of alkyl chains and ionic dyes oriented parallel to the substrate.

alkyl


Input: This structure results in a highly anisotropic electrostatic potential around the cationic chromophore, causing significant shifts in energy and orientation of the optical transitions.


Input: Thus, the optical properties of the material are, to a large extent, controlled by the position of the otherwise inert PF6-counter ions.


Input: The bright fluorescence from the films is also polarized parallel to the PTFE alignment layer.

PTFE


Input: Doping of the thin films with fluorescent energy acceptor traps shows that efficient exciton migration takes place in the thin films.


Input: The excellent exciton transfer capabilities, in conjunction with the perfect alignment, might be of interest in future applications in solar energy harvesting or as thin film sensors.


Input: How Selective Are the New Guidelines for Treatment of Subclinical Hypothyroidism for Patients with Thyrotropin Levels At or Below 10 mIU/L?


Input: Background: By consensus, a thyrotropin (TSH) level persistently > 10 mIU/L is an indication for the treatment of subclinical hypothyroidism (SCH).


Input: Controversy exists regarding patients whose TSH level is elevated but < 10 mIU/L.


Input: Recently, the American Thyroid Association (ATA) and the American Association of Clinical Endocrinologists (AACE) published their position about factors that should be considered in the decision on treating SCH.


Input: This study evaluated the frequency of these factors among adult (non-pregnant) women with SCH whose TSH levels are <= 10 mIU/L.


Input: Methods: The presence of the conditions that should be considered for the treatment of SCH according to ATA and AACE was evaluated in 252 women who were diagnosed with SCH and had TSH levels <= 10 mIU/L.


Input: Pregnant women were excluded.


Input: Results: Antithyroperoxidase antibodies (TPOAbs) were detected in 137 (54. 3%) women.


Input: A high cardiovascular risk was observed in 43 (17%) women.


Input: Eighty (31. 7%) women who were not at high cardiovascular risk presented at least one classical risk factor (arterial hypertension, elevated level of low-density lipoprotein-cholesterol or low level of high-density lipoprotein-cholesterol, smoking, or first-degree family history of premature coronary artery disease).

cholesterol

cholesterol


Input: At least one symptom or sign of hypothyroidism that could not be explained by another condition was observed in 180 (71. 4%) women.


Input: Two hundred thirty-two (92%) women had positive TPOAbs, or at least one classical cardiovascular risk factor, or at least one symptom or sign of hypothyroidism.


Input: Conclusions: According to the new ATA and AACE guidelines, L-T4 therapy would be considered for 92% of women with SCH and TSH <= 10 mIU/L.


Input: NMDA receptors and memory encoding.

NMDA


Input: It is humbling to think that 30 years have passed since the paper by Collingridge, Kehl and McLennan showing that one of Jeff Watkins most interesting compounds, R-2-amino-5-phosphonopentanoate (d-AP5), blocked the induction of long-term potentiation in vitro at synapses from area CA3 of the hippocampus to CA1 without apparent effect on baseline synaptic transmission (Collingridge et al., 1983).


Input: This dissociation was one of the key triggers for an explosion of interest in glutamate receptors, and much has been discovered since that collectively contributes to our contemporary understanding of glutamatergic synapses-their biophysics and subunit composition, of the agonists and antagonists acting on them, and their diverse functions in different networks of the brain and spinal cord.

glutamate


Input: It can be fairly said that Collingridge et al.' s (1983) observation was the stimulus that has led, on the one hand, to structural biological work at the atomic scale describing the key features of NMDA receptors that enables their coincidence function to happen; and, on the other, to work with whole animals investigating the contributions that calcium signalling via this receptor can have on rhythmical activities controlled by spinal circuits, memory encoding in the hippocampus (the topic of this article), visual cortical plasticity, sensitization in pain, and other functions.

NMDA

calcium


Input: In this article, I lay out how my then interest in long-term potentiation (LTP) as a model of memory enabled me to recognise the importance of Collingridge et al.' s discovery-and how I and my colleagues endeavoured to take things forward in the area of learning and memory.


Input: This is in some respects a personal story, and I tell it as such.


Input: The idea that NMDA receptor activation is essential for memory encoding, though not for storage, took time to develop and to be accepted.

NMDA


Input: Along the way, there have been confusions, challenges, and surprises surrounding the idea that activation of NMDA receptors can trigger memory.

NMDA


Input: Some of these are described and how they have been addressed and resolved.


Input: Last, I touch on some new directions of interest with respect to the functional role of the NMDA receptor in cognition.

NMDA


Input: This article is part of a Special Issue entitled' GluR-dep synaptic plasticity'.


Input: Scientific evidence for traditional claim of antiobesity activity of Tecomella undulata bark.


Input: ETHNOPHARMACOLOGICAL RELEVANCE: The bark of Tecomella undulata is traditionally claimed in the treatment of various disease ailments including obesity and cancer.


Input: Till now there are no studies about anti obesity activity of Tecomella undulata bark.


Input: AIM OF THE STUDY: The present study was aimed to establish a scientific evidence for anti obesity efficiency of ethyl acetate extract of Tecomella undulata bark (EATUB).

ethyl acetate


Input: Further to standardize the active fractions of EATUB using different biomarkers.


Input: MATERIALS AND METHODS: We investigated activity of EATUB fractions (F1-F7) using 3T3-L1 fibroblasts.


Input: Further, F1-mediated effects were characterized by determining mRNA and protein levels of SIRT1, one of the key targets for the treatment of obesity, using semi quantitative RT-PCR (sqRT-PCR) and western blot analysis.


Input: The consequences of modulation of SIRT1 on mRNA and protein levels of various adipogenesis mediators like PPAR gamma, C/EBP alpha, E2F1, leptin, adiponectin and LPL were also studied.


Input: In-vivo studies were performed using High Fat Diet (HFD) obese mice.


Input: RESULTS: Our data showed that compared to controls, preadipocytes and adipocytes incubated with F1 exhibited a significant decrease in adipogenesis and lipogenesis.


Input: In addition, sqRT-PCR and western blot analysis showed significant increase in SIRT1 and adiponectin levels and decrease in PPAR gamma, C/EBP alpha, E2F1, leptin and LPL levels in preadipocytes and adipocytes.


Input: In-vivo studies of F1 in HFD induced obese mice showed significant improvement in lipid profile and glucose levels.

glucose


Input: The bioactive fraction (F1) was determined to possess 4. 95% of ferulic acid.

ferulic acid


Input: CONCLUSION: Thus, our findings signified the beneficial effects of Tecomella undulata bark in pharmacologic interventions related to obesity and metabolic disorders.


Input: Ferulic acid and rutin are being reported and quantified for the first time from the bark of Tecomella undulata.

Ferulic acid

rutin


Input: Cytotoxic effects of amphetamine mixtures in primary hepatocytes are severely aggravated under hyperthermic conditions.

amphetamine


Input: Amphetamine consumers are often, deliberately or not, polydrug abusers.

Amphetamine


Input: Predicting combination effects based on concentration-response analysis of individual components is a valid strategy for accurate toxicological assessment of mixtures.


Input: We previously reported that joint effects of 3, 4-methylenedioxymethamphetamine (MDMA, ecstasy) and three other often co-ingested amphetamines (methamphetamine, 4-methylthyoamphetamine and D-amphetamine) could be predicted by the concentration addition (CA) model in HepG2 cells.

3, 4-methylenedioxymethamphetamine

MDMA

ecstasy

amphetamines

methamphetamine

D-amphetamine


Input: We sought to further evaluate the relevance of these findings by extending these studies to a cell model that more closely mimics the in vivo situation.


Input: Detailed cytotoxic information of the four individual amphetamines on primary rat hepatocytes was recorded by the MTT assay, at 37 degrees C and 40. 5 degrees C, simulating the rise in body temperature that could be induced following amphetamine intake.

amphetamines

MTT

amphetamine


Input: Mixture expectations were calculated using CA and independent action (IA) models.


Input: At 37 degrees C, concentration-dependent cytotoxicity occurred for the drugs individually and combined.


Input: Mixture effects were accurately predicted by the CA model, while the IA model underestimated cytotoxicity.


Input: At 40. 5 degrees C these cytotoxic effects were aggravated.


Input: Our findings provide evidence of the increased risks associated with the abuse of amphetamine mixtures, especially during hyperthermia, emphasising the need to increase awareness of misinformed users who believe these drugs are safe.

amphetamine


Input: Receiver Operating Characteristic Analysis of HLA, CTLA4, and Insulin Genotypes for Type 1 Diabetes.


Input: OBJECTIVEThis study assessed the ability to distinguish between type 1 diabetes-affected individuals and their unaffected relatives using HLA and single nucleotide polymorphism (SNP) genotypes. RESEARCH DESIGN AND METHODSEight models, ranging from only the high-risk DR3/DR4 genotype to all significantly associated HLA genotypes and two SNPs mapping to the cytotoxic T-cell-associated antigen-4 gene (CTLA4) and insulin (INS) genes, were fitted to high-resolution class I and class II HLA genotyping data for patients from the Type 1 Diabetes Genetics Consortium collection.


Input: Pairs of affected individuals and their unaffected siblings were divided into a " discovery " (n = 1, 015 pairs) and a " validation " set (n = 318 pairs).


Input: The discriminating performance of various combinations of genetic information was estimated using receiver operating characteristic (ROC) curve analysis. RESULTSThe use of only the presence or absence of the high-risk DR3/DR4 genotype achieved very modest discriminating ability, yielding an area under the curve (AUC) of 0. 62 in the discovery set and 0. 59 in the validation set.


Input: The full model, which included HLA information from the class II loci DPB1, DRB1, DQB1, selected alleles from HLA class I loci A and B, and SNPs from the CTLA4 and INS genes, increased the AUC to 0. 74 in the discovery set and to 0. 71 in the validation set.