Input: The least susceptible cvs, above all Percoca Romagnola 7, contained the higher amounts of hexenyl, hexyl, 3-methylbutyl, butyl and 2-methylpropyl esters; among these, some C6 derivatives detected, such as (Z)-3-hexenyl acetate, are known to act as priming agents, enhancing plant defence response to insects.

hexenyl, hexyl, 3-methylbutyl, butyl and 2-methylpropyl esters

(Z)-3-hexenyl acetate


Input: Instead, a lower relative content of methyl esters, such as methyl hexanoate and methyl octanoate, known to act as medfly pheromone and attractant respectively, was found in the least susceptible cvs.

methyl esters

methyl hexanoate

methyl octanoate


Input: Comparison of spectrophotometric and HPLC methods for determination of carotenoids in foods.


Input: This report is aimed at intra-laboratory and inter-laboratory comparison of the results obtained during spectrophotometric and HPLC analyses of lycopene, beta-carotene and total carotenoids in tomato products and yellow maize flours/grits.

lycopene

beta-carotene


Input: Extensive statistical analyses are performed in order to identify the main sources of uncertainties which may occur when using: (i) different techniques/methods/approaches in the same/different laboratories, in various food samples, and (ii) to indicate the facts/conditions under which the biases between results may remain unidentified after applying statistical testing.


Input: Our data points to the inertness of t-test to detect significance of differences, particularly at low R values: in general, the higher correlation coefficient, the higher is sensitivity of statistical testing, especially of the paired t-test.


Input: Therefore, simple deviation of relationship line slope from unity could be used as additional evaluation parameter.


Input: This adds to reliable and objective quality assurance of foods in regard to carotenoids.


Input: Animal communication: sniffing is about more than just smell.


Input: A recent study shows that subordinate rats reduce their rate of sniffing while dominants explore their faces thus delaying dominants' subsequent aggression.


Input: Sniffing not only facilitates acquisition of olfactory information, but unexpectedly, also serves as a medium for communication.


Input: Irisin levels correlate with energy expenditure in a subgroup of humans with energy expenditure greater than predicted by fat free mass.


Input: OBJECTIVE: Obesity is a result of chronic overconsumption of calories relative to the amount of energy expended.


Input: While fat free mass can account for ~ 80% of the variance in energy expenditure, there is still considerable variability in energy requirements between individuals that cannot be explained.


Input: We hypothesized that responsiveness to the recently discovered myokine, irisin, which has been touted to increase energy expenditure via activation of brown adipocytes in rodents and possibly humans, may explain some of the variability in energy expenditure.


Input: MATERIALS/METHODS: Post-menopausal women (n = 17) spent 24-h in a whole room indirect calorimeter.


Input: During the study day, subjects remained sedentary and consumed meals tailored to their energy requirements.


Input: Plasma irisin, leptin and adiponectin were measured in samples taken from each subject.


Input: RESULTS: Our results suggest that in general, irisin levels do not correlate with 24-h energy expenditure, however, for a subpopulation irisin levels and energy expenditure are highly correlative.


Input: CONCLUSION: Irisin may help explain some of the observed variability in individual energy requirements that cannot be accounted for by fat free mass.


Input: Therefore, interventions designed to increase irisin action may prove to be promising avenues for the treatment of obesity.


Input: In vitro toxicological assessment of clays for their use in food packaging applications.


Input: Montmorillonite based clays have a wide range of applications that are going to contribute to increase human exposure to these materials.

Montmorillonite


Input: One of the most promising uses of clays is the development of reinforced food contact materials that results in nanocomposites with improved barrier properties.


Input: Different organoclays have been developed introducing modifiers in the natural clay which is commercially available.


Input: However, the toxicological aspects of these materials have been scarcely studied so far.


Input: In the present study, the cytotoxic effects of a non-modified clay (Cloisite (R) Na +) and an organoclay (Cloisite (R) 30B) have been investigated in the hepatic cell line HepG2.

Cloisite

Na +

Cloisite


Input: Only Cloisite (R) 30B showed cytotoxicity.

Cloisite


Input: In order to elucidate the toxic mechanisms underlying these effects, apoptosis, inflammation, oxidative stress and genotoxicity biomarkers were assayed.


Input: Moreover, a morphology study with light and electron microscopy was performed.


Input: Results showed genotoxic effects and glutathione decrease.

glutathione


Input: The most relevant ultraestructural alterations observed were mitochondrial degeneration, dilated endomembrane systems, heterophagosomes formation, fat droplets appearance and presence of nuclear lipid inclusions.


Input: Cloisite (R) 30B, therefore, induces toxic effects in HepG2 cells.

Cloisite


Input: Further research is needed to assess the risk of this clay on the human health.


Input: Sclerostin: how human mutations have helped reveal a new target for the treatment of osteoporosis.


Input: In the 1990s there was a tremendous mood of optimism among pharmaceutical scientists that identification of disease-associated variations in the human genome would result in a surge of new drug targets (the' gene-to-drug' mantra).


Input: To date the expected deluge of new drugs has not arrived.


Input: However, a small number of drugs arising directly from the study of rare human disorders showing Mendelian inheritance are now entering late stage clinical trials.


Input: Here we describe the advantages of this approach and discuss the background and early clinical trial findings with antibodies directed at a target identified in this way.


Input: Mechanisms of Glucose Lowering of Dipeptidyl Peptidase-4 Inhibitor Sitagliptin When Used Alone or With Metformin in Type 2 Diabetes: A double-tracer study.

Glucose

Sitagliptin

Metformin


Input: OBJECTIVETo assess glucose-lowering mechanisms of sitagliptin (S), metformin (M), and the two combined (M + S). RESEARCH DESIGN AND METHODSWe randomized 16 patients with type 2 diabetes mellitus (T2DM) to four 6-week treatments with placebo (P), M, S, and M + S.

glucose

sitagliptin

metformin


Input: After each period, subjects received a 6-h meal tolerance test (MTT) with [(14) C] glucose to calculate glucose kinetics.

MTT

[(14) C] glucose

glucose


Input: Fasting plasma glucose (FPG), fasting plasma insulin, C-peptide (insulin secretory rate [ISR]), fasting plasma glucagon, and bioactive glucagon-like peptide (GLP-1) and gastrointestinal insulinotropic peptide (GIP) was measured. RESULTSFPG decreased from P, 160 +/- 4 to M, 150 +/- 4; S, 154 +/- 4; and M + S, 125 +/- 3 mg/dL.

glucose

C


Input: Mean post-MTT PG decreased from P, 207 +/- 5 to M, 191 +/- 4; S, 195 +/- 4; and M + S, 161 +/- 3 mg/dL (P < 0. 01].

MTT


Input: The increase in mean post-MTT plasma insulin and in ISR was similar in P, M, and S and slightly greater in M + S.

MTT


Input: Fasting plasma glucagon was equal (~ 65-75 pg/mL) with all treatments, but there was a significant drop during the initial 120 min with S 24% and M + S 34% (both P < 0. 05) vs. P 17% and M 16%.


Input: Fasting and mean post-MTT plasma bioactive GLP-1 were higher (P < 0. 01) after S and M + S vs. M and P.

MTT


Input: Basal endogenous glucose production (EGP) fell from P 2. 0 +/- 0. 1 to S 1. 8 +/- 0. 1 mg/kg. min, M 1. 8 +/- 0. 2 mg/kg. min [both P < 0. 05 vs. P), and M + S 1. 5 +/- 0. 1 mg/kg. min (P < 0. 01 vs. P).

glucose


Input: Although the EGP slope of decline was faster in M and M + S vs. S, all had comparable greater post-MTT EGP inhibition vs. P (P < 0. 05). CONCLUSIONSM + S combined produce additive effects to 1) reduce FPG and postmeal PG, 2) augment GLP-1 secretion and beta-cell function, 3) decrease plasma glucagon, and 4) inhibit fasting and postmeal EGP compared with M or S monotherapy.


Input: Involvement of nNOS/NO/sGC/cGMP signaling pathway in cocaine sensitization and in the associated hippocampal alterations: does phosphodiesterase 5 inhibition help to drug vulnerability?

cocaine


Input: RATIONALE: Repeated cocaine administration induces behavioral sensitization in about 50% of treated animals.

cocaine


Input: Nitric oxide could be involved in the acquisition and maintenance of behavioral cocaine effects, probably by activation of neuronal nitric oxide synthase (nNOS)/NO/soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP) signaling pathway, since inhibition of the nNOS enzyme attenuates development of sensitization in rats.

Nitric oxide

cocaine

nitric oxide

guanylyl

cyclic guanosine monophosphate

cGMP


Input: On the other hand, increased cGMP availability by phosphodiesterase 5 inhibitors has been correlated to the misuse and recreational use of these agents and also to the concomitant use with illicit drugs in humans.

cGMP


Input: Hippocampus is an important brain region for conditioning to general context previously associated to drug availability, influencing drug-seeking behavior and sensitization.


Input: Moreover, cocaine and other drugs of abuse can affect the strength of glutamate synapses in this structure, lastly modifying neuronal activity in main regions of the reward circuitry.

cocaine

glutamate


Input: OBJECTIVE: The objective of this study is to determine whether the pharmacological manipulation of nNOS/NO/sGC/cGMP signaling pathway altered changes induced by repeated cocaine exposure.

cGMP

cocaine


Input: RESULTS: The present investigation showed a relationship between behavioral cocaine sensitization, reduced threshold to generate long-term potentiation (LTP) in hippocampal dentate gyrus, and increased nNOS activity in this structure.

cocaine


Input: However, when nNOS or sGC were inhibited, the number of sensitized animals was reduced, and the threshold to generate LTP was increased.


Input: The opposite occurred when cGMP availability was increased.

cGMP


Input: CONCLUSION: We demonstrate a key role of the nNOS activity and NO/sGC/cGMP signaling pathway in the development of cocaine sensitization and in the associated enhancement of hippocampal synaptic transmission.

cGMP

cocaine


Input: Plasmonic fluorescence enhancement by metal nanostructures: shaping the future of bionanotechnology.


Input: This review focuses on metal enhanced fluorescence (MEF) and its current and future applications in biotechnology.


Input: The mechanisms of MEF are discussed in terms of the additional radiative and nonradiative decay rates caused by the close proximity of the metal.


Input: We then review the current MEF materials and structures that show promise in bioapplications.


Input: The use of electromagnetic modelling to predict fluorescent rate enhancement is then considered.


Input: We then give particular focus to the recent work carried out in the homogeneous fabrication of metal nanoparticles using colloidal lithography.


Input: It is concluded that the use of computational electromagnetic modelling alongside homogeneous fabrication techniques will lead to predictable and controllable MEF, paving the way for increased applications in biotechnology.


Input: A statistical approach for analyzing the development of (1) H multiple-quantum coherence in solids.

(1) H


Input: A novel statistical approach for analyzing (1) H multiple-quantum (MQ) spin dynamics in so-called spin-counting solid-state NMR experiments is presented.

(1) H


Input: The statistical approach is based on the percolation theory with Monte Carlo methods and is examined by applying it to the experimental results of three solid samples having unique hydrogen arrangement for 1-3 dimensions: the n-alkane/d-urea inclusion complex as a one-dimensional (1D) system, whose (1) H nuclei align approximately in 1D, and magnesium hydroxide and adamantane as a two-dimensional (2D) and a three-dimensional (3D) system, respectively.

hydrogen

n-alkane

d-urea

(1) H

magnesium hydroxide

adamantane


Input: Four lattice models, linear, honeycomb, square and cubic, are used to represent the (1) H arrangement of the three samples.

(1) H


Input: It is shown that the MQ dynamics in adamantane is consistent with that calculated using the cubic lattice and that in Mg (OH) 2 with that calculated using the honeycomb and the square lattices.

adamantane

Mg (OH) 2


Input: For n-C20H42/d-urea, these 4 lattice models fail to express its result.

d-urea


Input: It is shown that a more realistic model representing the (1) H arrangement of n-C20H42/d-urea can describe the result.

(1) H

d-urea


Input: The present approach can thus be used to determine (1) H arrangement in solids.

(1) H


Input: Graphene sheets: gram-scale synthesis of graphene sheets by a catalytic arc-discharge method (small 8/2013).

Graphene

graphene


Input: Gram-scale amounts of high-quality graphene sheets are synthesized on page 1330 through an arc-discharge method.

graphene


Input: An arc, which is generated between two graphite rods when a high voltage is applied by Y.

graphite


Input: Liu and co-workers, can cause the graphite layers to separate into graphene sheets via a high-temperature exfoliation, or even broken into small clusters/atoms, which then form graphene sheets by catalytic growth, demonstrating that two mechanisms exist in an arc discharge process simultaneously.

graphite

graphene

graphene


Input: Free radicals: free radical reactions in two dimensions: a case study on photochlorination of graphene (small 8/2013).

graphene


Input: Graphene is a 2D giant polycyclic aromatic molecule that provides opportunities for studying chemical reactions in two dimensions.

Graphene


Input: H.


Input: Peng, Z.


Input: Liu, and co-workers have systematically investigated the influence of specific features of 2D molecules, such as their thickness, stacking order, single-and double-side upon graphene' s radical reactivity by utilizing a free radical photochlorination as a probe.

graphene


Input: The result, described on page 1388, can contribute to a deeper understanding of dimensionality effects for the chemistry of 2D graphene.

graphene


Input: Optoelectronic Processes in Squaraine Dye-Doped OLEDs for Emission in the Near-Infrared.

Squaraine Dye


Input: A novel all-organic host-guest system for emission in the NIR is introduced and investigated with respect to its opto-electronic processes.


Input: The good agreement between theoretical and experimental results highlights the model character of this system and its potential for electroluminescent application.


Input: Comparative measurements provide access to the recombination mechanisms on molecular length scale and show that the emission behavior of the device under operation is controlled by charge carrier dynamics.


Input: Small Molecule Inhibitors of ERCC1-XPF Protein-Protein Interaction Synergize Alkylating Agents in Cancer Cells.


Input: The benefit of cancer chemotherapy based on alkylating agents is limited due to the action of DNA repair enzymes which mitigate the damage induced by these agents.


Input: The interaction between the proteins ERCC1 and XPF, involves two major components of the nucleotide excision repair pathway.

nucleotide


Input: Here, novel inhibitors of this interaction were identified by virtual screening based on available structures using the National Cancer Institute (NCI) diversity set and a panel of DrugBank-small-molecules.


Input: Subsequently, experimental validation of the in silico screening was undertaken.


Input: Top hits were evaluated on A549 and HCT116 cancer cells.


Input: In particular, the compound labeled NSC130813 was shown to act synergistically with cisplatin and mitomycin C, to increase UVC mediated cytotoxicity, to modify DNA repair as indicated by the staining of phosphorylated H2AX and to disrupt interaction between ERCC1 and XPF in cells.

cisplatin

mitomycin C


Input: In addition, using the Biacore technique, we showed that this compound interacts with the domain of XPF responsible for interaction with ERCC1.


Input: This study shows that small molecules targeting the protein-protein interaction of ERCC1 and XPF can be developed in order to enhance the effects of alkylating agents on cancer cells.


Input: Magnetic Cooling at a Single Molecule Level: a Spectroscopic Investigation of Isolated Molecules on a Surface.


Input: A sub-monolayer distribution of isolated molecular Fe14 (bta) 6 nanomagnets is deposited intact on a Au (111) surface and investigated by X-ray magnetic circular dichroism spectroscopy.

Fe14 (bta) 6

Au (111)


Input: The entropy variation with respect to the applied magnetic field is extracted from the magnetization curves and evidences high magnetocaloric values at the single molecule level.


Input: Transgenic Mouse alpha-and beta-Cardiac Myosins Containing the R403Q Mutation Show Isoform Dependent Transient Kinetic Differences.


Input: Familial hypertrophic cardiomyopathy (FHC) is a major cause of sudden cardiac death in young athletes.


Input: The discovery in 1990 that a point mutation at residue 403 (R403Q) in the beta-myosin heavy chain (MHC) caused a severe form of FHC was the first of many demonstrations linking FHC to mutations in muscle proteins.


Input: A mouse model for FHC has been widely used to study the mechanochemical properties of mutated cardiac myosin, but mouse hearts express alpha-MHC, whereas the ventricles of larger mammals express predominantly beta-MHC.


Input: To address the role of the isoform backbone on function, we generated a transgenic mouse in which the endogenous alpha-MHC was partially replaced with transgenically encoded beta-MHC or alpha-MHC.


Input: A His-tag was cloned at the N-terminus, along with R403Q, to facilitate isolation of myosin subfragment-1 (S1).

His

N


Input: Stopped-flow kinetics were used to measure the equilibrium constants and rates of nucleotide binding and release for the mouse S1 isoforms bound to actin.

nucleotide


Input: For the wildtype isoforms, we found that the affinity of MgADP for alpha-S1 (100 mu M) is ~ 4-fold weaker than for beta-S1 (25 mu M).

MgADP


Input: Correspondingly, the MgADP release rate for alpha-S1 (350 s-1) is ~ 3-fold greater than for beta-S1 (120 s-1).

MgADP


Input: Introducing the R403Q mutation caused only a minor reduction in kinetics for beta-S1, but R403Q in alpha-S1 caused the ADP release rate to increase by 20% (430 s-1).

ADP


Input: These transient kinetic studies on mouse cardiac myosins provide strong evidence that the functional impact of an FHC mutation on myosin depends on the isoform backbone.


Input: A new isobenzofuranone from the mangrove endophytic fungus Penicillium sp.

isobenzofuranone


Input: A new isobenzofuranone, 4-(methoxymethyl)-7-methoxy-6-methyl-1 (3H)-isobenzofuranone (1), together with seven known compounds, dilation (2), lumichrome (3), curvulari (4), 5, 5'-oxy-dimethylene-bis (2-furaldehyde) (5), chromone (6), harman (1-methyl-beta-carboline) (7), N9-methyl-1methyl-beta-carboline (8), was isolated from the mangrove endophytic fungus, Penicillium sp.

isobenzofuranone

4-(methoxymethyl)-7-methoxy-6-methyl-1 (3H)-isobenzofuranone

dilation

lumichrome

curvulari

5, 5'-oxy-dimethylene-bis (2-furaldehyde)

chromone

harman (1-methyl-beta-carboline)


Input: ZH58 obtained from the South China Sea coast.


Input: Their structures were determined by analysis of spectroscopic data.


Input: Compound 1 exhibited cytotoxicity against KB and KBV200 cells with IC50 values of 6 and 10 mu g/mL, respectively.


Input: Design, Synthesis, and Structure-Activity Relationship Studies of Novel 3-Alkylindole Derivatives as Selective and Highly Potent Myeloperoxidase Inhibitors.


Input: Due to its production of potent antimicrobial oxidants including hypochlorous acid, human myeloperoxidase (MPO) plays a critical role in innate immunity and inflammatory diseases.

hypochlorous acid


Input: Thus MPO is an attractive target in drug design.


Input: (Aminoalkyl) fluoroindole derivatives were detected to be very potent MPO inhibitors; however, they also promote inhibition of the serotonin reuptake transporter (SERT) at the same concentration range.

(Aminoalkyl) fluoroindole

serotonin


Input: Via structure-based drug design, a new series of MPO inhibitors derived from 3-alkylindole were synthesized and their effects were assessed on MPO-mediated taurine chlorination and low-density lipoprotein oxidation as well as on inhibition of SERT.

taurine


Input: The fluoroindole compound with three carbons in the side chain and one amide group exhibited a selectivity index of 35 (Ki/IC50) with high inhibition of MPO activity (IC50 = 18 nM), whereas its effect on SERT was in the micromolar range.

fluoroindole

carbons

amide


Input: Structure-function relationships, mechanism of action, and safety of the molecule are discussed.


Input: Sacchathridine A, a Prostaglandin Release Inhibitor from Saccharothrix sp.

Sacchathridine A

Prostaglandin


Input: Sacchathridine A (1) was isolated from the fermentation broth of strain Saccharothrix sp.

Sacchathridine A


Input: The structure was determined as a new naphthoquinone derivative with an acetylhydrazino moiety by a combination of NMR, MS spectral analyses, and chemical degradation.

naphthoquinone

acetylhydrazino


Input: Compound 1 showed inhibitory activity of prostaglandin E2 release in a concentration-dependent manner from human synovial sarcoma cells, SW982, with an IC50 value of 1. 0 mu M, but had no effect on cell growth up to 30 mu M.

prostaglandin E2


Input: Design and synthesis of a tetrahydroisoquinoline-based hydroxamate derivative (ZYJ-34v), an oral active histone deacetylase inhibitor with potent antitumor activity.

tetrahydroisoquinoline

hydroxamate


Input: In our previous study we developed a novel series of tetrahydroisoquinoline-based hydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors (Bioorg. Med. Chem., 2010, 18, 1761-1772., J. Med. Chem., 2011, 54, 2823-2838.), among which compound ZYJ-34c (1) was identified and validated as the most potent one with marked in vitro and in vivo antitumor potency (J. Med. Chem., 2011, 54, 5532-5539.).

tetrahydroisoquinoline

hydroxamic acid


Input: Herein further modification of 1 afforded another oral active analogue ZYJ-34v (2) with simplified structure and lower molecular weight.


Input: Biological evaluation of compound 2 showed efficacious inhibition against HDAC1, 2, 3 and 6, which was confirmed by western blot analysis results.


Input: Most importantly, compound 2 exhibited similar even more potent in vitro and in vivo antitumor activities relative to the approved HDAC inhibitor SAHA This article is protected by copyright.

SAHA


Input: All rights reserved.


Input: Metabolism of 2, 2', 3, 3', 6, 6'-hexachlorobiphenyl (PCB 136) atropisomers in tissue slices from phenobarbital or dexamethasone-induced rats is sex-dependent.

2, 2', 3, 3', 6, 6'-hexachlorobiphenyl

PCB 136

phenobarbital

dexamethasone


Input: Abstract 1.


Input: Chiral polychlorinated biphenyls (PCBs) such as PCB 136 enantioselectively sensitize the ryanodine receptor (RyR).

polychlorinated biphenyls

PCBs

PCB 136

ryanodine


Input: In light of recent evidence that PCBs cause developmental neurotoxicity via RyR-dependent mechanisms, this suggests that enantioselective PCB metabolism may influence the developmental neurotoxicity of chiral PCBs.

PCBs

PCB

PCBs


Input: However, enantioselective disposition of PCBs has not been fully characterized.

PCBs


Input: The effect of sex and cytochrome P450 (P450) enzyme induction on the enantioselective metabolism of PCB 136 was studied using liver tissue slices prepared from na i ve control (CTL), phenobarbital (PB; CYP2B inducer) or dexamethasone (DEX; CYP3A inducer) pretreated adult Sprague-Dawley rats.

PCB 136

phenobarbital

dexamethasone

DEX


Input: PCB 136 metabolism was also examined in hippocampal slices derived from untreated rat pups.

PCB 136


Input: In liver tissue slices, hydroxylated PCB (OH-PCB) profiles depended on sex and inducer pretreatment, and OH-PCB levels followed the rank orders male > female and PB > DEX > CTL.

hydroxylated PCB

OH-PCB

OH-PCB

DEX


Input: In contrast, the enantiomeric enrichment of PCB 136 and its metabolites was independent of sex and inducer pretreatment.

PCB 136


Input: Only small amounts of PCB 136 partitioned into hippocampal tissue slices and no OH-PCB metabolites were detected.

PCB 136

OH-PCB


Input: Our results suggest that enantioselective metabolism, sex and induction status of P450 enzymes in the liver may modulate the neurotoxic outcomes of developmental exposure to chiral PCBs.

PCBs


Input: Self-Sorting Click Reactions That Generate Spatially Controlled Chemical Functionality on Surfaces.


Input: This Article describes the generation of a patterned surface that can be postpolymerization modified to incorporate fragile macromolecules or delicate biomolecules without the need for special equipment.


Input: Two monomers that undergo different click reactions, pentafluorophenyl acrylate (PFPA) and 4-(trimethylsilyl) ethynylstyrene (TMSES), were sequentially polymerized from a silicon surface in the presence of a shadowmask with UV light, generating 12. 5 and 62 mu m pitch patterns.

pentafluorophenyl acrylate

PFPA

4-(trimethylsilyl) ethynylstyrene

TMSES

silicon


Input: Two different dyes, 1-aminomethylpyrene (AMP) and 5-azidofluorescein (AF), were covalently attached to the polymer brushes through aminolysis and dual desilylation/copper (I)-catalyzed alkyne/azide cycloaddition (CuAAC) in one pot.

AMP

copper (I)

alkyne

azide


Input: Unlike most CuAAC reactions, the terminal alkyne of TMSES was not deprotected prior to functionalization.

TMSES


Input: Although a 2 nm thickness increase was observed for poly (PFPA) brushes after polymerization of TMSES, cross-contamination was not visible through fluorescence microscopy after functionalization.

poly (PFPA)

TMSES


Input: Agonism of human pregnane X receptor by rilpivirine and etravirine: Comparison with first generation non-nucleoside reverse transcriptase inhibitors.

pregnane

rilpivirine

etravirine

nucleoside


Input: Rilpivirine and etravirine are second generation non-nucleoside reverse transcriptase inhibitors approved recently by the United States Food and Drug Administration for the treatment of human immunodeficiency virus-1 infection.

Rilpivirine

etravirine

nucleoside


Input: Pregnane X receptor (PXR) is a member of the superfamily of nuclear receptors that regulate the expression of various genes controlling diverse biological functions.

Pregnane


Input: The present study investigated the effects of rilpivirine and etravirine on the activity of human PXR (hPXR), including the mode of activation, and compared them to those of efavirenz, nevirapine, and delavirdine, which are first generation non-nucleoside reverse transcriptase inhibitors.

rilpivirine

etravirine

efavirenz

nevirapine

delavirdine

nucleoside


Input: In transiently transfected HepG2 cells, rilpivirine, etravirine, and efavirenz, but not nevirapine or delavirdine, activated human, mouse, and rat PXR.

rilpivirine

etravirine

efavirenz

nevirapine

delavirdine


Input: Results from mechanistic studies indicated that rilpivirine, etravirine, and efavirenz, but not nevirapine or delavirdine, bound to the ligand-binding domain of hPXR, as assessed by a transactivation assay and by a competitive ligand-binding assay using time-resolved fluorescence resonance energy transfer; triggered nuclear translocation of a green fluorescence protein-tagged hPXR, as visualized by confocal imaging; and recruited steroid receptor coactivator-1 (SRC-1), SRC-2, and SRC-3 to hPXR, as demonstrated by mammalian two-hybrid assays.

rilpivirine

etravirine

efavirenz

nevirapine

delavirdine

steroid


Input: Rilpivirine, etravirine, and efavirenz, but not nevirapine or delavirdine, increased hPXR target gene (CYP3A4) expression in primary cultures of human hepatocytes.

Rilpivirine

etravirine

efavirenz

nevirapine

delavirdine


Input: In summary, select non-nucleoside reverse transcriptase inhibitors activated human and rodent PXR.

nucleoside


Input: Rilpivirine, etravirine, and efavirenz, but not nevirapine or delavirdine, were identified as agonists of hPXR, as assessed in mechanistic experiments, and inducers of CYP3A4, as determined in primary cultures of human hepatocytes.

Rilpivirine

etravirine

efavirenz

nevirapine

delavirdine


Input: Inhibitory effects of gypenosides on seven human cytochrome P450 enzymes in vitro.

gypenosides


Input: Among the various possible causes for drug interactions, pharmacokinetic factors such as inhibition of drug-metabolizing enzymes, especially cytochrome P450 (CYP) enzymes, are regarded as the most frequent and clinically important.


Input: Gypenosides is widely used as functional food and over-the-counter drug in East Asia.

Gypenosides


Input: In this study, the in vitro inhibitory effects of gypenosides on the major human CYP enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) activities in human liver microsomes were examined using liquid chromatography-tandem mass spectrometry.

gypenosides


Input: Gypenosides showed the strongest inhibition of CYP2D6, followed by CYP2C8, CYP3A4 and CYP2C9.

Gypenosides


Input: The IC50 values were 1. 61 mu g/mL, 20. 06 mu g/mL, 34. 76 mu g/mL (CYP3A4/midazolam), 46. 73 mu g/mL (CYP3A4/testosterone), and 54. 52 mu g/mL, respectively.

midazolam

testosterone


Input: Gypenosides exhibited competitive inhibition of CYP2D6 (Ki = 1. 18).

Gypenosides


Input: In conclusion, Gypenosides might cause herb-drug interactions via inhibition of CYP2D6.

Gypenosides


Input: An in vivo study is needed to examine this further.


Input: Novel racemic tetrahydrocurcuminoid dihydropyrimidinone analogues as potent acetylcholinesterase inhibitors.

tetrahydrocurcuminoid dihydropyrimidinone


Input: The synthesis of racemic tetrahydrocurcumin-(THC-), tetrahydrodemethoxycurcumin-(THDC-) and tetrahydrobisdemethoxycurcumin-(THBDC-) dihydropyrimidinone (DHPM) analogues was achieved by utilizing the multi-component Biginelli reaction in the presence of copper sulphate as a catalyst.

tetrahydrocurcumin

THC

tetrahydrodemethoxycurcumin

THDC

tetrahydrobisdemethoxycurcumin

THBDC

dihydropyrimidinone

DHPM

copper sulphate


Input: The evaluation of acetylcholinesterase inhibitors for Alzheimer' s disease of these compounds showed that they exhibited higher inhibitory activity than their parent analogues.


Input: THBDC-DHPM demonstrated the most potent inhibitory activity with an IC50 value of 1. 34 +/- 0. 03 mu M which was more active than the approved drug galanthamine (IC50 = 1. 45 +/- 0. 04 mu M).

THBDC-DHPM

galanthamine


Input: Design considerations for PAMAM dendrimer therapeutics.

PAMAM


Input: We have previously shown that methotrexate (MTX) conjugated to a cancer-specific poly amido amine (PAMAM) dendrimer has a higher therapeutic index than MTX alone.

methotrexate

MTX

poly amido amine

PAMAM

MTX


Input: Unfortunately, these therapeutics have been difficult to advance because of the complicated syntheses and an incomplete understanding of the dendrimer properties.


Input: We wished to address these obstacles by using copper-free click chemistry to functionalize the dendrimer scaffolds and to exploring the effects of two dendrimer properties (the targeting ligand and drug linkage) on cytotoxicity.

copper


Input: We conjugated either ester or amide-linker modified MTX to dendrimer scaffolds with or without folic acid (FA).

ester

amide

MTX

folic acid


Input: Because of multivalency, the FA and MTX functionalized dendrimers had similar capacities to target the folate receptor on cancer cells.

MTX

folate


Input: Additionally, we found that the ester-and amide-linker modified MTX compounds had similar cytotoxicity but the dendrimer-ester MTX conjugates were much more cytotoxic than the dendrimer-amide MTX conjugates.

ester

amide

MTX

ester MTX

amide MTX


Input: These results clarify the impact of these properties on therapeutic efficacy and will allow us to design more effective polymer therapeutics.


Input: A urinary metabonomics study on biochemical changes in yeast-induced pyrexia rats: a new approach to elucidating the biochemical basis of the febrile response.


Input: Fever is a prominent feature of many diseases, such as infection, inflammation and trauma.


Input: In the clinic, fever can be easily judged by measuring the body temperature; however, the pathogenesis of fever is still not fully understood.


Input: A febrile response is a systemic pathological process that can cause metabolic disorders.


Input: Metabonomics can provide powerful tools to reveal the pathological mechanisms for such a systemic disease.


Input: Thus, to reveal subtle metabolic changes under the condition of fever and to explore its mechanism, an ultra performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometry metabonomics approach was employed to investigate the urine biochemical characteristics of yeast-induced pyrexia rats.


Input: The acquired data were subjected to principal component analysis for differentiating the pyrexia rats from the control rats.


Input: Potential biomarkers were screened by using orthogonal partial least-squares-discriminant analysis and were identified by accurate mass, database, and MS/MS fragment information obtained from the MS (E) technique.


Input: Sixteen metabolites in rat urine were identified as potential biomarkers.


Input: The relative intensities of the 15 potential biomarkers were calculated.


Input: The thermoregulatory circuitry of " endogenous pyrogen (EP) ^-hypothalamus Na (+)/Ca (2 +)-cAMP ^ " was partially confirmed in this study.

Na (+)/Ca (2 +)-cAMP


Input: The results suggested that UPLC/MS-based metabolic profiling of rat urine identifies impaired tryptophan metabolism as the mechanism of yeast-induced fever.

tryptophan


Input: This research provided informative data that the impaired tryptophan metabolism might be one of the important reasons in elucidating the biochemical basis of the febrile response.

tryptophan


Input: Xiaoxuming decoction for acute ischemic stroke: A systematic review and meta-analysis.


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoxuming decoction (XXMD) is a well-known traditional Chinese herbal prescription in treatment of patients with stroke.


Input: The objective of this study is to assess the efficacy and safety of XXMD for acute ischemic stroke.


Input: MATERIALS AND METHODS: A systematic literature search was conducted in 6 databases until June 2012 to identify randomized controlled trials (RCTs) of XXMD for acute ischemic stroke compared with western conventional medicine (WCM).


Input: The primary outcome measures were National Institutes of Health Stroke Scale (NIHSS) scores and modified Rankin Scale (mRS) scores.


Input: The secondary outcome measures were the clinical effective rate and adverse events at the end of treatment course.


Input: The methodological quality of RCTs was assessed independently using 12-item criteria according to the Cochrane Back Review Group.


Input: All data were analyzed using Review Manager 5. 0 software.


Input: RESULTS: Eight RCTs with 601 individuals published from 1992 to 2012 were identified.


Input: The studies were deemed to have a high risk of bias.


Input: Compared with WCM, 1 RCT showed significant effects of XXMD for improving mRS after stroke (p < 0. 05); 3 RCTs for improving NIHSS scores [n = 186, weighted mean difference (WMD):-1. 86, 95% CI:-3. 25 to-0. 48, z = 2. 63, p < 0. 01]; 7 RCTs for improving the clinical effective rate [n = 531, risk ratio (RR) = 1. 17, 95% CI, 1. 09 to 1. 26, z = 4. 38, p < 0. 01].


Input: Five trials contained safety assessments and stated that no adverse event was found, whereas the other 3 trials did not provide the information about adverse events.


Input: CONCLUSIONS: This systematic review showed positive but weak evidence of XXMD for acute ischemic stroke because of the poor methodological quality and the small quantity of the included trials.


Input: The difficulties of fitting Chinese herbal medicine (CHM) into the double blinded RCTs have raised as follows: (A) traditional Chinese medicine (TCM) as whole systems of healthcare offers unique methodological and theoretical challenges for RCTs; (B) suspicions against the placebo and unwillingness to stop taking other CHMs make recruitment more difficulty, time-consumption, and cost; (C) the shortcomings of the TCM diagnostic process includes the lack of standardization in terminology, disagreement of pattern differentiation (Bianzheng), and neglect of formula corresponding to syndrome (TCM Zheng); (D) It is difficult to design credible herbal placebos with similar appearance, smells and tastes to the experimental CHM and at the same time is absent of any pharmacological activity; (E) the achieving efficacy of CHM complex interventions is often nonspecific and the outcome measures is subjective using Chinese quantitative instrument.


Input: Insights into mast cell functions in asthma using mouse models.


Input: Therapeutics targeting specific mechanisms of asthma have shown promising results in mouse models of asthma.


Input: However, these successes have not transferred well to the clinic or to the treatment of asthma sufferers.


Input: We suggest a reason for this incongruity is that mast cell-dependent responses, which may play an important role in the pathogenesis of both atopic and non-atopic asthma, are not a key component in most of the current asthma mouse models.


Input: Two reasons for this are that wild type mice have, in contrast to humans, a negligible number of mast cells localized in the smaller airways and in the parenchyma, and that only specific protocols show mast cell-dependent reactions.


Input: The development of mast cell-deficient mice and the reconstitution of mast cells within these mice have opened up the possibility to generate mouse models of asthma with a marked role of mast cells.


Input: In addition, mast cell-deficient mice engrafted with mast cells have a distribution of mast cells more similar to humans.


Input: In this article we review and highlight the mast cell-dependent and-independent responses with respect to airway hyperresponsiveness and inflammation in asthma models using mast cell-deficient and mast cell-engrafted mice.


Input: Melanoidins isolated from heated potato fiber (Potex) affect human colon cancer cells growth via modulation of cell cycle and proliferation regulatory proteins.


Input: Melanoidins are brown, nitrogen containing, high molecular weight end products of Maillard reaction with poorly established activity towards tumor cells.

nitrogen


Input: The goal of present study was to verify whether both heated potato fiber Potex extract (180 degrees C for 2h) and melanoidins isolated from the extract exerts growth-inhibiting activity in human colon cancer cells in vitro.


Input: The cells of LS180 colon cancer cell line were tested upon treatment with roasted potato fiber extract (AM4) as well as with high (HMW) and low (LMW) molecular weight fractions isolated from the extract, since both may be regarded as/or contain melanoidins.


Input: The tested compounds at concentration of 1000 mu g/ml reduced cell growth down to 45%, 69% and 54%, respectively.


Input: Furthermore, deregulated ERK1/2 signaling was revealed upon treatment.


Input: Moreover, multiple alternations in cell cycle regulators activity were found (i. e. cyclinD1, cyclin-dependent kinase 4 and 6, p21, p27, p53, pRb) leading to cell cycle cessation in G0 phase.


Input: Importantly, LMW compounds revealed markedly stronger potential to alter specific molecular targets comparing to HMW compounds.


Input: Summarizing, the results emphasize that both high and low molecular weight melanoidins contribute to antiproliferative activity of heated potato fiber in LS180 colon cancer cells in vitro.


Input: Short-term heating reduces the anti-inflammatory effects of fresh raw garlic extracts on the LPS-induced production of NO and pro-inflammatory cytokines by downregulating allicin activity in RAW 264. 7 macrophages.

NO

allicin


Input: Garlic has a variety of biologic activities, including anti-inflammatory properties.


Input: Although garlic has several biologic activities, some people dislike eating fresh raw garlic because of its strong taste and smell.


Input: Therefore, garlic formulations involving heating procedures have been developed.


Input: In this study, we investigated whether short-term heating affects the anti-inflammatory properties of garlic.


Input: Fresh and heated raw garlic extracts (FRGE and HRGE) were prepared with incubation at 25 degrees C and 95 degrees C, respectively, for 2h.


Input: Treatment with FRGE and HRGE significantly reduced the LPS-induced increase in the pro-inflammatory cytokine concentration (TNF-alpha, IL-1 beta, and IL-6) and NO through HO-1 upregulation in RAW 264. 7 macrophages.

NO


Input: The anti-inflammatory effect was greater in FRGE than in HRGE.


Input: The allicin concentration was higher in FRGE than in HRGE.

allicin


Input: Allicin treatment showed reduced production of pro-inflammatory cytokines and NO and increased HO-1 activity.

Allicin

NO


Input: The results show that the decrease in LPS-induced NO and pro-inflammatory cytokines in RAW 264. 7 macrophages through HO-1 induction was greater for FRGE compared with HRGE.

NO


Input: Additionally, the results indicate that allicin is responsible for the anti-inflammatory effect of FRGE.

allicin


Input: Our results suggest a potential therapeutic use of allicin in the treatment of chronic inflammatory disease.

allicin


Input: Motor neuron dysfunction in a mouse model of ALS: Gender-dependent effect of P2X7 antagonism.


Input: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative progressive currently untreatable disease, characterized by selective motor neuron degeneration; the incidence and prevalence of ALS are greater in men than in women.


Input: Although some important mechanisms that might contribute to the death of motor neurons have been identified, the mechanisms underlying disease pathophysiology are still uncertain.


Input: In particular, the mechanisms underlying the role of gender in ALS and whether treatments should take into account sexual dimorphism remain only partially understood.


Input: Recently, the P2X7 receptor for ATP was reported to display neurotoxic potential in motor neuron disorders, and antagonism of the receptor has been suggested to be helpful in these disorders.

ATP


Input: Studying transgenic mice with superoxide dismutase 1 gene mutations, widely used as model for ALS, may provide a better understanding of pathogenic mechanisms and of toxicity towards motor neurons, also possibly helping to understand whether treatments for ALS should take into account sexual dimorphism.

superoxide


Input: The aim of the work was (1) investigating on gender-dependence of disease progression in the standard model for ALS-the transgenic mouse bearing superoxide dismutase 1 gene mutations-and (2) assessing if a P2X7 receptor antagonist treatment should take into account sexual dimorphism.

superoxide


Input: We evaluated if gender affect the disease course, the motor performance, the weight loss and the lifespan in mice overexpressing mutant superoxide dismutase 1.

superoxide


Input: We measured motor impairment, motor strength and coordination by rotarod and grip strength testing.


Input: Further, we assessed if a treatment with the P2X7 receptor antagonist Brilliant Blue G-a dye that can cross the blood-brain barrier, has low toxicity, and has exhibited therapeutic effects in animal models of neurodegenerative diseases-impact on the disease progression, in male and female ALS mice.

Brilliant Blue G


Input: We found that (1) the onset and the disease progression, and the survival were dependent on gender: male performed worst than female, lost body weight and died before; (2) treatment with the P2X7 receptor antagonist Brilliant Blue G ameliorated the disease progression.

Brilliant Blue G


Input: The treatment effect was gender-dependent: amelioration was greater in male than in female.


Input: In conclusions, we suggest that not only pathogenetic mechanism of motor neuron toxicity but also the drug treatment effectiveness may depend on gender; sexual dimorphism should be considered when investigating on ALS treatment efficacy in the ALS animal model.


Input: Our findings also point on the potential relevance of P2X7 receptor antagonism for ALS treatment, and highlight the importance of adopting a sex-specific approach to searching for treatment of ALS.


Input: 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin-induced inflammatory activation is mediated by intracellular free calcium in microglial cells.

2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin

calcium


Input: 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD) has been known to induce inflammatory signaling in a number of cell types and tissues.

2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin

TCDD


Input: However, the adverse effects of TCDD on the central nervous system (CNS) have not been entirely elucidated.

TCDD


Input: In this study, using reverse transcriptase PCR (RT-PCR) and ELISA, we showed that TCDD up-regulated the expression and secretion of tumor necrosis factor-alpha (TNF-alpha) in a time-dependent manner in cultured HAPI microglial cells.

TCDD


Input: TCDD also caused a fast (within 30min as judged by the increase in its mRNA level) activation of cytosolic phospholipase A2 (cPLA2).

TCDD


Input: This initial action was accompanied by up-regulation of cyclooxygenase-2 (COX-2), an important inflammation marker within 1h after TCDD treatment.

TCDD


Input: These pro-inflammatory responses were inhibited by two types of Ca (2 +) blockers, bis-(o-aminophenoxy) ethane-N, N, N', N'-tetra-acetic acid acetoxymethyl ester (BAPTA-AM) and nifedipine, thus, indicating that the effects are triggered by initial increase in the intracellular concentration of free Ca (2 +) ([Ca (2 +)] i).

Ca (2 +)

bis-(o-aminophenoxy) ethane-N, N, N', N'-tetra-acetic acid acetoxymethyl ester

BAPTA-AM

nifedipine

Ca (2 +)

Ca (2 +)


Input: Further, TCDD exposure could induce phosphorylation-and ubiquitination-dependent degradation of I k B alpha, and the translocation of NF-kappa B p65 from the cytosol to the nucleus in this microglial cell line.

TCDD


Input: Thus, the NF-kappa B signaling pathway can be activated after TCDD treatment.

TCDD


Input: However, Ca (2 +) blockers also obviously attenuated NF-kappa B activation and transnuclear transport induced by TCDD.

Ca (2 +)

TCDD


Input: In concert with these results, we highlighted that the secretion of pro-inflammatory cytokine and NF-kappa B activation induced by TCDD can be mediated by elevation of [Ca (2 +)] i in HAPI microglial cells.

TCDD

Ca (2 +)


Input: Extract from Mimosa pigra attenuates chronic experimental pulmonary hypertension.


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Different parts of Mimosa pigra (MPG) are used in traditional medicine in Madagascar, tropical Africa, South America and Indonesia for various troubles including cardiovascular disorders.


Input: AIM OF THE STUDY: To investigate the mechanisms underlying the vascular effects of MPG by assessing in vitro its antioxidant and anti-inflammatory properties, and its vascular relaxing effects, and in vivo, its action on hypoxic pulmonary hypertension (PAH) in rats.


Input: MATERIAL AND METHODS: The antioxidant activity of MPG leaf hydromethanolic extract was determined by using both the 1, 1-diphenyl-2-picrylhydrazyl radical scavenging and the oxygen radical absorbance capacity in vitro assays.

1, 1-diphenyl-2-picrylhydrazyl

oxygen


Input: Anti-inflammatory properties were assayed on TNF alpha-induced VCAM-1 expression in endothelial cells.


Input: The vasorelaxant effect of MPG extract was studied on rat arterial rings pre-contracted with phenylephrine (1 mu M) in the presence or absence of the endothelium.

phenylephrine


Input: In vivo MPG extract effects were analyzed in chronic hypoxic PAH, obtained by housing male Wistar rats, orally treated or not with MPG extract (400mg/kg/d), in a hypobaric chamber for 21 days.


Input: RESULTS: MPG leaf extract had antioxidant and anti-inflammatory properties.


Input: It induced endothelium-dependent, NO-mediated relaxation of rat aorta and pulmonary artery.

NO


Input: In vivo, chronic MPG treatment reduced hypoxic PAH in rat by decreasing by 22. 3% the pulmonary arterial pressure and by 20. 0% and 23. 9% the pulmonary artery and cardiac remodelling, respectively.


Input: This effect was associated with a restoration of endothelium function and a 2. 3-fold increase in endothelial NO synthase phosphorylation.

NO


Input: MPG leaf hydromethanolic extract contained tryptophan and flavonoids, including quercetin glycosides.

tryptophan

flavonoids

quercetin glycosides


Input: Both compounds also efficiently limit hypoxia-induced PAH.


Input: CONCLUSIONS: Our results show endothelial protective action of MPG leaf hydromethanolic extract which is likely to be due to its antioxidant action.


Input: MPG successfully attenuated the development of PAH, thus demonstrating the protective effect of MPG on cardiovascular diseases.


Input: The ATP required for potentiation of skeletal muscle contraction is released via pannexin hemichannels.

ATP


Input: During repetitive stimulation of skeletal muscle, extracellular ATP levels raise, activating purinergic receptors, increasing Ca (2 +) influx, and enhancing contractile force, a response called potentiation.

ATP

Ca (2 +)


Input: We found that ATP appears to be released through pannexin1 hemichannels (Panx1 HCs).

ATP


Input: Immunocytochemical analyses and function were consistent with pannexin1 localization to T-tubules intercalated with dihydropyridine and ryanodine receptors in slow (soleus) and fast (extensor digitorum longus, EDL) muscles.

dihydropyridine

ryanodine


Input: Isolated myofibers took up ethidium (Etd (+)) and released small molecules (as ATP) during electrical stimulation.

ethidium

Etd (+)

ATP


Input: Consistent with two glucose uptake pathways, induced uptake of 2-NBDG, a fluorescent glucose derivative, was decreased by inhibition of HCs or glucose transporter (GLUT4), and blocked by dual blockade.

glucose

glucose

glucose


Input: Adult skeletal muscles apparently do not express connexins, making it unlikely that connexin hemichannels contribute to the uptake and release of small molecules.


Input: ATP release, Etd (+) uptake, and potentiation induced by repetitive electrical stimulation were blocked by HC blockers and did not occur in muscles of pannexin1 knockout mice.

ATP

Etd (+)


Input: MRS2179, a P2Y1R blocker, prevented potentiation in EDL, but not soleus muscles, suggesting that in fast muscles ATP activates P2Y1 but not P2X receptors.

ATP


Input: Phosphorylation on Ser and Thr residues of pannexin1 was increased during potentiation, possibly mediating HC opening.

Ser

Thr


Input: Opening of Panx1 HCs during repetitive activation allows efflux of ATP, influx of glucose and possibly Ca (2 +) too, which are required for potentiation of contraction.

ATP

glucose

Ca (2 +)


Input: This article is part of a Special Issue entitled' Connexin based channels'.


Input: Genetic deletion of the adenosine A2A receptor prevents nicotine-induced upregulation of alpha 7, but not alpha 4 beta 2 * nicotinic acetylcholine receptor binding in the brain.

adenosine

nicotine

acetylcholine


Input: Considerable evidence indicates that adenosine A2A receptors (A2ARs) modulate cholinergic neurotransmission, nicotinic acetylcholine receptor (nAChR) function, and nicotine-induced behavioural effects.

adenosine

acetylcholine

nicotine


Input: To explore the interaction between A2A and nAChRs, we examined if the complete genetic deletion of adenosine A2ARs in mice induces compensatory alterations in the binding of different nAChR subtypes, and whether the long-term effects of nicotine on nAChR regulation are altered in the absence of the A2AR gene.

adenosine

nicotine


Input: Quantitative autoradiography was used to measure cytisine-sensitive [(125) I] epibatidine and [(125) I] alpha-bungarotoxin binding to alpha 4 beta 2 * and alpha 7 nAChRs, respectively, in brain sections of drug-na i ve (n = 6) or nicotine treated (n = 5-7), wild-type and adenosine A2AR knockout mice.

cytisine

[(125) I] epibatidine

(125) I

nicotine

adenosine


Input: Saline or nicotine (7. 8 mg/kg/day; free-base weight) were administered to male CD1 mice via subcutaneous osmotic minipumps for a period of 14 days.

nicotine


Input: Blood plasma levels of nicotine and cotinine were measured at the end of treatment.

nicotine

cotinine


Input: There were no compensatory developmental alterations in nAChR subtype distribution or density in drug-na i ve A2AR knockout mice.


Input: In nicotine treated wild-type mice, both alpha 4 beta 2 * and alpha 7 nAChR binding sites were increased compared with saline treated controls.

nicotine


Input: The genetic ablation of adenosine A2ARs prevented nicotine-induced upregulation of alpha 7 nAChRs, without affecting alpha 4 beta 2 * receptor upregulation.

adenosine

nicotine


Input: This selective effect was observed at plasma levels of nicotine that were within the range reported for smokers (10-50 ng ml (-1)).

nicotine


Input: Our data highlight the involvement of adenosine A2ARs in the mechanisms of nicotine-induced alpha 7 nAChR upregulation, and identify A2ARs as novel pharmacological targets for modulating the long-term effects of nicotine on alpha 7 receptors.

adenosine

nicotine

nicotine


Input: Profiling the venom gland transcriptome of Tetramorium bicarinatum (Hymenoptera: Formicidae): The first transcriptome analysis of an ant species.


Input: Animal venoms are complex mixtures containing a range of bioactive elements with potential pharmacological and therapeutic use.


Input: Even though ants account among the most diverse zoological group, little information is available regarding their venom composition.


Input: To initiate the characterization of the transcriptomic venom gland expression of the ant species Tetramorium bicarinatum, 400 randomly selected clones from cDNA library were sequenced and a total of 364 high quality expressed sequence tags (ESTs) were generated.


Input: Based on the results of BLAST searches, these sequences were clustered and assembled into 83 contigs (22 multiple sequences) and 61 singletons.


Input: About 74% (267) of the contigs matched BLASTx hits with an interesting diversity together with an unusual abundance of cellular transcripts related to gene expression regulation (29% of the total library) reflecting the specialization of this tissue.


Input: About eighteen per cent of the ESTs were categorized as Hymenoptera venom compounds, the major part represented by allergens (62% of the total venom compounds).


Input: In addition, a high number of sequences (26%) had no similarity to any known sequences.


Input: This study provides a first insight of the gene expression scenario of the venom gland of T. bicarinatum which might contribute to acquiring a more comprehensive view on the origin and functional diversity of venom proteins among ants and more broadly among Hymenopteran insects.


Input: Simultaneous determination of methanol, acetaldehyde, acetone, and ethanol in human blood by gas chromatography with flame ionization detection.

methanol

acetaldehyde

acetone

ethanol


Input: Background: Methanol, acetaldehyde, acetone, and ethanol, which are commonly used as biomarkers of several diseases, in acute intoxications, and forensic settings, can be detected and quantified in biological fluids.

Methanol

acetaldehyde

acetone

ethanol


Input: Gas chromatography (GC)-mass spectrometry techniques are complex, require highly trained personnel and expensive materials.


Input: Gas chromatographic determinations of ethanol, methanol, and acetone have been reported in one study with suboptimal accuracy.

ethanol

methanol

acetone


Input: Our objective was to improve the assessment of these compounds in human blood using GC with flame ionization detection. Methods: An amount of 50 micro l of blood was diluted with 300 micro l of sterile water, 40 micro l of 10% sodium tungstate, and 20 micro l of 1% sulphuric acid.

sodium tungstate

sulphuric acid


Input: After centrifugation, 1 micro l of the supernatant was inje-cted into the gas chromatograph.


Input: We used a dimethylpolysiloxane capillary column of 30 m 0. 25 mm 0. 25 micro m. Results: We observed linear correlations from 7. 5 to 240 mg/l for methanol, acetaldehyde, and acetone and from 75 to 2400 mg/l for ethanol.

dimethylpolysiloxane

methanol

acetaldehyde

acetone

ethanol


Input: Precision at concentrations 15, 60, and 120 mg/l for methanol, acetaldehyde, and acetone and 150, 600, and 1200 mg/ml for ethanol were 0. 8-6. 9%.

methanol

acetaldehyde

acetone

ethanol


Input: Ranges of accuracy were 94. 7-98. 9% for methanol, 91. 2-97. 4% for acetaldehyde, 96. 1-98. 7% for acetone, and 105. 5-111. 6% for ethanol.

methanol

acetaldehyde

acetone

ethanol


Input: Limits of detection were 0. 80 mg/l for methanol, 0. 61 mg/l for acetaldehyde, 0. 58 mg/l for acetone, and 0. 53 mg/l for ethanol. Conclusion: This method is suitable for routine clinical and forensic practices.

methanol

acetaldehyde

acetone

ethanol


Input: Progression rates from HbA1c 6. 0-6. 4% and other prediabetes definitions to type 2 diabetes: a meta-analysis.


Input: AIMS/HYPOTHESIS: Precise estimates of progression rates from' prediabetes' to type 2 diabetes are needed to optimise prevention strategies for high-risk individuals.


Input: There is acceptance of prediabetes defined by impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), but there is some controversy surrounding HbA1c-defined prediabetes ranges, with some favouring 6. 0-6. 4% (42-46 mmol/mol).

glucose

glucose


Input: Comparing progression rates between groups might aid this issue, thus we aimed to accurately estimate progression rates to diabetes from different prediabetes categories.


Input: METHODS: Meta-analysis of prospective observational studies in which participants had prediabetes at baseline (ADA-defined IFG [5. 6-6. 9 mmol/l], WHO-defined IFG [6. 1-6. 9 mmol/l], IGT (7. 8-11. 0 mmol/l) or raised HbA1c [6. 0-6. 4%/42-46 mmol/mol]) and were followed up for incident diabetes.


Input: Incidence rates were combined using Bayesian random effects models.


Input: RESULTS: Overall, 70 studies met the inclusion criteria.


Input: In the six studies that used raised HbA1c, the pooled incidence rate (95% credible interval) of diabetes was 35. 6 (15. 1, 83. 0) per 1, 000 person-years.


Input: This rate was most similar to that for ADA-defined IFG (11 studies; 35. 5 [26. 6, 48. 0]) and was non-significantly lower than WHO-defined IFG (34 studies; 47. 4 [37. 4, 59. 8]), IGT (46 studies, 45. 5 [37. 8, 54. 5]) and IFG plus IGT (15 studies, 70. 4 [53. 8, 89. 7]).


Input: Similar results were seen when the data were analysed by the criteria used to diagnose diabetes.


Input: CONCLUSIONS/INTERPRETATION: This study provides evidence that progression rates differ by prediabetes definition, which has implications for the planning and implementation of diabetes prevention programmes.


Input: HbA1c 6. 0-6. 4% might identify people at a lower diabetes risk than other prediabetes definitions, but further research is needed.


Input: Antibacterial oxazolidinone analogues having a N-hydroxyacetyl-substituted seven-membered [1, 2, 5] triazepane or [1, 2, 5] oxadiazepane C-ring unit.

oxazolidinone

N-hydroxyacetyl

[1, 2, 5] triazepane

[1, 2, 5] oxadiazepane C


Input: We synthesized a series of oxazolidinone analogues bearing a N-hydroxyacetyl-substituted [1, 2, 5] triazepane or [1, 2, 5] oxadiazepane C-ring unit as homologues of an earlier drug candidate, eperezolid.

oxazolidinone

N-hydroxyacetyl-substituted [1, 2, 5] triazepane or [1, 2, 5] oxadiazepane C

eperezolid


Input: Several of these compounds exhibited potent in vitro antibacterial activities towards not only Gram-positive, but also Gram-negative and linezolid-resistant pathogens.

linezolid


Input: Compounds 21a and 21b, bearing a thiocarbamate side chain, showed high in vivo activity against methicillin-resistant Staphylococcus aureus SR3637, together with a promising safety profile in terms of weak inhibition of monoamine oxidase and cytochrome P450 isozymes.

thiocarbamate

methicillin

monoamine


Input: Proteasomal cleavage site prediction of protein antigen using BP neural network based on a new set of amino acid descriptor.

amino acid


Input: The accurate identification of cytotoxic T lymphocyte epitopes is becoming increasingly important in peptide vaccine design.


Input: The ubiquitin-proteasome system plays a key role in processing and presenting major histocompatibility complex class I restricted epitopes by degrading the antigenic protein.


Input: To enhance the specificity and efficiency of epitope prediction and identification, the recognition mode between the ubiquitin-proteasome complex and the protein antigen must be considered.


Input: Hence, a model that accurately predicts proteasomal cleavage must be established.


Input: This study proposes a new set of parameters to characterize the cleavage window and uses a backpropagation neural network algorithm to build a model that accurately predicts proteasomal cleavage.


Input: The accuracy of the prediction model, which depends on the window sizes of the cleavage, reaches 95. 454% for the N-terminus and 95. 011% for the C-terminus.

N

C


Input: The results show that the identification of proteasomal cleavage sites depends on the sequence next to it and that the prediction performance of the C-terminus is better than that of the N-terminus on average.

C

N


Input: Thus, models based on the properties of amino acids can be highly reliable and reflect the structural features of interactions between proteasomes and peptide sequences.

amino acids


Input: Effects of Dietary Factors on the Pharmacokinetics of (58) Fe-labeled Hemin After Oral Administration in Normal Rats and the Iron-deficient Rats.

(58) Fe

Hemin

Iron


Input: Hemin, iron (III) protoporphyrin chloride (IX), as a stable form of heme iron, has been used in iron absorption studies.

Hemin

iron (III) protoporphyrin chloride (IX)

heme iron

iron


Input: The aim of the present study was to elucidate the influences of body iron status and three dietary factors (green tea extract, ascorbic acid, and calcium) on the pharmacokinetics of hemin using stable isotope labeling methods followed by ICP-MS measurement.

iron

ascorbic acid

calcium

hemin


Input: In this study, a rapid, sensitive, and specific ICP-MS method for the determination of (58) Fe originating from hemin in rat plasma was developed and a rat model of iron deficiency anemia was established.

(58) Fe

hemin

iron


Input: It was found that hemin iron absorption increased significantly under iron deficiency anemia status, with AUC0-t and AUC0-infinity showing significant increase in anemic rats compared to normal ones.

hemin iron

iron


Input: Green tea extract strongly inhibited hemin iron absorption in both normal rats and iron-deficient rats.

hemin iron

iron


Input: In normal rats administered with green tea extract, C max resulted significantly reduced, whereas in anemic rats administered with green tea extract both AUC0-t and AUC0-infinity were reduced.


Input: On the other hand, ascorbic acid significantly affected hemin iron absorption only in iron-deficient rats, in which C max showed a significant increase.

ascorbic acid

hemin iron

iron


Input: Interestingly, calcium slowed down the hemin iron absorption rate in normal rats, MRT0-t being significantly different in calcium-treated animals compared to untreated ones.

calcium

hemin iron

calcium


Input: This trend also appeared in the iron-deficient group but it did not reach statistical significance.

iron


Input: Our data suggest that the mechanism of hemin iron absorption is regulated by body iron status and dietary factors can influence hemin iron absorption to varying degrees.

hemin iron

iron

hemin iron


Input: Moreover, these results may also have general implication in the iron deficiency treatment with iron supplements and fortification of foods.

iron

iron


Input: Biocatalytic and structural properties of a highly engineered halohydrin dehalogenase.

halohydrin


Input: Two highly engineered halohydrin dehalogenase variants were characterized in terms of their performance in dehalogenation and epoxide cyanolysis reactions.

halohydrin

epoxide


Input: Both enzyme variants outperformed the wild-type enzyme in the cyanolysis of ethyl (S)-3, 4-epoxybutyrate, a conversion yielding ethyl (R)-4-cyano-3-hydroxybutyrate, an important chiral building block for statin synthesis.

ethyl (S)-3, 4-epoxybutyrate

ethyl (R)-4-cyano-3-hydroxybutyrate


Input: One of the enzyme variants, HheC2360, displayed catalytic rates for this cyanolysis reaction enhanced up to tenfold.


Input: Furthermore, the enantioselectivity of this variant was the opposite of that of the wild-type enzyme, both for dehalogenation and for cyanolysis reactions.


Input: The 37-fold mutant HheC2360 showed an increase in thermal stability of 8 degrees C relative to the wild-type enzyme.


Input: Crystal structures of this enzyme were elucidated with chloride and ethyl (S)-3, 4-epoxybutyrate or with ethyl (R)-4-cyano-3-hydroxybutyrate bound in the active site.

chloride

ethyl (S)-3, 4-epoxybutyrate

ethyl (R)-4-cyano-3-hydroxybutyrate


Input: The observed increase in temperature stability was explained in terms of a substantial increase in buried surface area relative to the wild-type HheC, together with enhanced interfacial interactions between the subunits that form the tetramer.


Input: The structures also revealed that the substrate binding pocket was modified both by substitutions and by backbone movements in loops surrounding the active site.


Input: The observed changes in the mutant structures are partly governed by coupled mutations, some of which are necessary to remove steric clashes or to allow backbone movements to occur.


Input: The importance of interactions between substitutions suggests that efficient directed evolution strategies should allow for compensating and synergistic mutations during library design.


Input: RNA global alignment in the joint sequence-structure space using elastic shape analysis.


Input: The functions of RNAs, like proteins, are determined by their structures, which, in turn, are determined by their sequences.


Input: Comparison/alignment of RNA molecules provides an effective means to predict their functions and understand their evolutionary relationships.


Input: For RNA sequence alignment, most methods developed for protein and DNA sequence alignment can be directly applied.


Input: RNA 3-dimensional structure alignment, on the other hand, tends to be more difficult than protein structure alignment due to the lack of regular secondary structures as observed in proteins.


Input: Most of the existing RNA 3D structure alignment methods use only the backbone geometry and ignore the sequence information.


Input: Using both the sequence and backbone geometry information in RNA alignment may not only produce more accurate classification, but also deepen our understanding of the sequence-structure-function relationship of RNA molecules.


Input: In this study, we developed a new RNA alignment method based on elastic shape analysis (ESA).


Input: ESA treats RNA structures as three dimensional curves with sequence information encoded on additional dimensions so that the alignment can be performed in the joint sequence-structure space.


Input: The similarity between two RNA molecules is quantified by a formal distance, geodesic distance.


Input: Based on ESA, a rigorous mathematical framework can be built for RNA structure comparison.


Input: Means and covariances of full structures can be defined and computed, and probability distributions on spaces of such structures can be constructed for a group of RNAs.


Input: Our method was further applied to predict functions of RNA molecules and showed superior performance compared with previous methods when tested on benchmark datasets.


Input: The programs are available at http://stat. fsu. edu/~ jinfeng/ESA. html.


Input: Fine Tuning of the Structure of Pt-Cu Alloy Nanocrystals by Glycine-Mediated Sequential Reduction Kinetics.

Pt-Cu

Glycine


Input: Uniform Pt-Cu alloy nanocrystals in the shape of dendrite,, yolk-cage, and box structures are prepared via a facile wet-chemical reduction route in which glycine is demonstrated to alter the reduction kinetics of metal cations, critical to the morphology of the obtained product.

Pt-Cu

glycine


Input: These alloy nanocrystals exhibit superior specific activity and stability in the electro-oxidation of methanol.

methanol


Input: Relationship between serum thyrotropin levels and intrarenal hemodynamic parameters in euthyroid subjects.


Input: OBJECTIVE: Low thyroid function may be associated with a reduced glomerular filtration rate (GFR) calculated on the basis of creatinine metabolism.

creatinine


Input: Thyroid hormone directly affects serum creatinine in muscle and low thyroid function might exert a similar direct effect in the kidney.

Thyroid hormone

creatinine


Input: The goal of the study was to evaluate this possibility by assessment of the inulin-based GFR and to examine the mechanism underlying the reduction of GFR.


Input: PATIENTS AND METHODS: Renal and glomerular hemodynamics were assessed by simultaneous measurements of plasma clearance of para-aminohippurate (CPAH) and inulin (Cin) in 26 patients with serum creatinine < 1. 00 mg/dl and without thyroid disease.

para-aminohippurate

creatinine


Input: All subjects were normotensive with or without antihypertensive treatment and were kept in a sodium-replete state.

sodium


Input: Renal and glomerular hemodynamics were calculated using Gomez `s formulae.


Input: RESULTS: Serum thyroid stimulating hormone (TSH), including within the normal range (0. 69-4. 30 mu IU/ml), was positively correlated with vascular resistance at the afferent arteriole (Ra) (r = 0. 609, p = 0. 0010), but not at the efferent arteriole (Re).


Input: Serum TSH was significantly and negatively correlated with renal plasma flow (RPF), renal blood flow (RBF), and glomerular filtration rate (GFR) (r =-0. 456, p = 0. 0192; r =-0. 438, p = 0. 0252; r =-0. 505, p = 0. 0086, respectively).


Input: In multiple regression analysis, serum TSH was significantly positively associated with Ra after adjustment for age and mean blood pressure.


Input: CONCLUSIONS: These findings suggest that low thyroid function, even within the normal range, is associated with reduced RPF, RBF and GFR, which might be caused by a preferential increase of Ra.


Input: Deformation of an elastic capsule in a rectangular microfluidic channel.


Input: In the present study we investigate computationally the deformation of an elastic capsule in a rectangular microfluidic channel and compare it with that of a droplet.


Input: In contrast to the bullet or parachute shape in a square or cylindrical channel where the capsule extends along the flow direction, in a rectangular channel the capsule extends mainly along the less-confined lateral direction of the channel cross-section (i. e. the channel width), obtaining a pebble-like shape.


Input: The different shape evolution in these two types of solid channels results from the different tension development on the capsule membrane required for interfacial stability.


Input: Furthermore, in asymmetric channel flows, capsules show a different deformation compared to droplets with constant surface tension (which extend mainly along the flow direction) and to vesicles which extend along the more-confined channel height.


Input: Therefore, our study highlights the different stability dynamics associated with these three types of interfaces.


Input: Our findings suggest that the erythrocyte deformation in asymmetric vessels (which is similar to that of capsules) results from the erythrocyte' s inner spectrin skeleton rather than from its outer lipid bilayer.


Input: Molecular-Beam Optical Stark and Zeeman Study of the [17. 8] 0 (+)-X (1) Sigma (+) (0, 0) Band System of AuF.

AuF


Input: The [17. 8] 0 (+)-X (1) Sigma (+) (0, 0) band of gold monofluoride, AuF, has been recorded at a resolution of 40 MHz both field free and in the presence of a static electric and magnetic field.

gold monofluoride

AuF


Input: The observed Stark shifts were analyzed to determine the permanent electric dipole moment, mu el, of 2. 03 +/- 0. 05 D and 4. 13 +/- 0. 02 D, for the [17. 8] 0 (+) (v = 0) and X (1) Sigma (+) (v = 0) states, respectively.


Input: The small magnetic tuning observed for the [17. 8] 0 (+) (v = 0) state is attributed to rotational and magnetic field mixing with the [17. 7] 1 state and has been successfully modeled using an effective Hamiltonian for the (3) Pi state.


Input: A comparison with the numerous published theoretical predictions is made.


Input: Dynamic and Electronic Transport Properties of DNA Translocation through Graphene Nanopores.

Graphene


Input: Graphene layers have been targeted in the last years as excellent host materials for sensing a remarkable variety of gases and molecules.

Graphene


Input: Such sensing abilities can also benefit other important scientific fields such as medicine and biology.


Input: This has automatically led scientists to probe graphene as a potential platform for sequencing DNA strands.

graphene


Input: In this work, we use robust numerical tools to model the dynamic and electronic properties of molecular sensor devices composed of a graphene nanopore through which DNA molecules are driven by external electric fields.

graphene


Input: We performed molecular dynamic simulations to determine the relation between the intensity of the electric field and the translocation time spent by the DNA to pass through the pore.


Input: Our results reveal that one can have extra control on the DNA passage when four additional graphene layers are deposited on the top of the main graphene platform containing the pore in a 2 x 2 grid arrangement.

graphene

graphene


Input: In addition to the dynamic analysis, we carried electronic transport calculations on realistic pore structures with diameters reaching nanometer scales.


Input: The transmission obtained along the graphene sensor at the Fermi level is affected by the presence of the DNA.

graphene


Input: However, it is rather hard to distinguish the respective nucleobases.

nucleobases


Input: This scenario can be significantly altered when the transport is conducted away from the Fermi level of the graphene platform.

graphene


Input: Under an energy shift, we observed that the graphene pore manifests selectiveness toward DNA nucleobases.

graphene

nucleobases


Input: The tail wagging the dog-regulation of lipid metabolism by protein kinase C.


Input: Upon their discovery almost 40 years ago, isoforms of the lipid-activated protein kinase C (PKC) family were initially regarded only as downstream effectors of the second messengers calcium and diacylglycerol, undergoing activation upon phospholipid hydrolysis in response to acute stimuli.

calcium

diacylglycerol


Input: Subsequently, several isoforms were found to be associated with the inhibitory effects of lipid over-supply on glucose homeostasis, especially the negative cross-talk with insulin signal transduction, observed upon accumulation of diacylglycerol in insulin target tissues.

glucose

diacylglycerol


Input: The PKC family has therefore attracted much attention in diabetes and obesity research, because intracellular lipid accumulation is strongly correlated with defective insulin action and the development of type 2 diabetes.


Input: Causal roles for various isoforms in the generation of insulin resistance have more recently been confirmed using PKC-deficient mice.


Input: However, during characterization of these animals, it became increasingly evident that the enzymes play key roles in the modulation of lipid metabolism itself, and may control the supply of lipids between tissues such as adipose and liver.


Input: Molecular studies have also demonstrated roles for PKC isoforms in several aspects of lipid metabolism, such as adipocyte differentiation and hepatic lipogenesis.


Input: While the precise mechanisms involved, especially the identities of protein substrates, are still unclear, the emerging picture suggests that the currently held view of the contribution of PKC isoforms to metabolism is an over-simplification.


Input: Although PKCs may inhibit insulin signal transduction, these enzymes are not merely downstream effectors of lipid accumulation, but in fact control the fate of fatty acids, thus the tail wags the dog.

fatty acids


Input: Kappa-opioid receptor-selective dicarboxylic ester-derived salvinorin A ligands.

dicarboxylic ester

salvinorin A


Input: Salvinorin A, the active ingredient of the hallucinogenic plant Salvia divinorum is the most potent known naturally occurring hallucinogen and is a selective kappa-opioid receptor agonist.

Salvinorin A


Input: To better understand the ligand-receptor interactions, a series of dicarboxylic ester-type of salvinorin A derivatives were synthesized and evaluated for their binding affinity at kappa-, delta-and mu-opioid receptors.

dicarboxylic ester

salvinorin A


Input: Most of the analogues show high affinity to the kappa-opioid receptor.


Input: Methyl malonyl derivative 4 shows the highest binding affinity (Ki = 2nM), analogues 5, 7, and 14 exhibit significant affinity for the kappa-receptor (Ki = 21, 36 and 39nM).

Methyl malonyl


Input: Acute and chronic interference with BDNF/TrkB-signaling impair LTP selectively at mossy fiber synapses in the CA3 region of mouse hippocampus.


Input: Brain-derived neurotrophic factor (BDNF) signaling via TrkB crucially regulates synaptic plasticity in the brain.


Input: Although BDNF is abundant at hippocampal mossy fiber (MF) synapses, which critically contribute to hippocampus dependent memory, its role in MF synaptic plasticity (long-term potentiation, LTP) remained largely unclear.


Input: Using field potential recordings in CA3 of adult heterozygous BDNF knockout (ko, BDNF +/-) mice we observed impaired (~ 50%) NMDAR-independent MF-LTP.


Input: In contrast to MF synapses, LTP at neighboring associative/commissural (A/C) fiber synapses remained unaffected.


Input: To exclude that impaired MF-LTP in BDNF +/-mice was due to developmental changes in response to chronically reduced BDNF levels, and to prove the importance of acute availability of BDNF in MF-LTP, we also tested effects of acute interference with BDNF/TrkB signaling.


Input: Inhibition of TrkB tyrosine kinase signaling with k252a, or with the selective BDNF scavenger TrkB-Fc, both inhibited MF-LTP to the same extent as observed in BDNF +/-mice.

tyrosine


Input: Basal synaptic transmission, short-term plasticity, and synaptic fatigue during LTP induction were not significantly altered by treatment with k252a or TrkB-Fc, or by chronic BDNF reduction in BDNF +/-mice.


Input: Since the acute interference with BDNF-signaling did not completely block MF-LTP, our results provide evidence that an additional mechanism besides BDNF induced TrkB signaling contributes to this type of LTP.


Input: Our results prove for the first time a mechanistic action of acute BDNF/TrkB signaling in presynaptic expression of MF-LTP in adult hippocampus.


Input: Genetics of diabetes-Are we missing the genes or the disease?


Input: Diabetes is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both.


Input: The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of different organs, especially the eyes, kidneys, nerves, heart, and blood vessels.


Input: Several pathogenic processes are involved in the development of diabetes.


Input: These range from autoimmune destruction of the beta-cells of the pancreas with consequent insulin deficiency to abnormalities that result in resistance to insulin action (American Diabetes Association, 2011).


Input: The vast majority of cases of diabetes fall into two broad categories.


Input: In type 1 diabetes (T1D), the cause is an absolute deficiency of insulin secretion, whereas in type 2 diabetes (T2D), the cause is a combination of resistance to insulin action and an inadequate compensatory insulin secretory response.


Input: However, the subdivision into two main categories represents a simplification of the real situation, and research during the recent years has shown that the disease is much more heterogeneous than a simple subdivision into two major subtypes assumes.


Input: Worldwide prevalence figures estimate that there are 280 million diabetic patients in 2011 and more than 500 million in 2030 (http://www. diabetesatlas. org/).


Input: In Europe, about 6-8% of the population suffer from diabetes, of them about 90% has T2D and 10% T1D, thereby making T2D to the fastest increasing disease in Europe and worldwide.


Input: This epidemic has been ascribed to a collision between the genes and the environment.


Input: While our knowledge about the genes is clearly better for T1D than for T2D given the strong contribution of variation in the HLA region to the risk of T1D, the opposite is the case for T2D, where our knowledge about the environmental triggers (obesity, lack of exercise) is much better than the understanding of the underlying genetic causes.


Input: This lack of knowledge about the underlying genetic causes of diabetes is often referred to as missing heritability (Manolio et al., 2009) which exceeds 80% for T2D but less than 25% for T1D.


Input: In the following review, we will discuss potential sources of this missing heritability which also includes the possibility that our definition of diabetes and its subgroups is imprecise and thereby making the identification of genetic causes difficult.


Input: Structure-activity relationships of hybrid annonaceous acetogenins: Powerful growth inhibitory effects of their connecting groups between heterocycle and hydrophobic carbon chain bearing THF ring on human cancer cell lines.

annonaceous acetogenins

carbon

THF


Input: Five novel hybrid molecules of annonaceous acetogenins and insecticides targeting mitochondrial complex I were synthesized and their growth inhibitory activities against 39 human cancer cell lines were investigated.

annonaceous acetogenins


Input: It was revealed that the connecting group between the N-methylpyrazole part and the hydrophobic alkyl chain bearing the THF ring influenced their biological activities significantly.

N-methylpyrazole

alkyl

THF


Input: Amide-connected analog 2, in particular, showed selective and very potent activity (< 10 nM) against some cancer cell lines.

Amide


Input: Prevalence and natural history of Graves' orbitopathy in the XXI century.


Input: Graves' orbitopathy (GO) is an autoimmune disorder and the main extrathyroidal expression of Graves' disease.


Input: There is a spectrum of ocular involvement in Graves' disease, from complete absence of symptoms and signs to sight-threatening conditions.


Input: The prevalence of GO varies in different published series of Graves' patients, due to confounding factors (new diagnosis vs. long-lasting disease, way of defining and assessing ocular involvement, treatment of hyperthyroidism with potentially GO-modifying treatments, such as radioiodine).

radioiodine


Input: Recent studies, however, suggest that most Graves' patients have mild or no GO at presentation, while moderate-to-severe GO is rare, and sight-threatening GO (mostly due to dysthyroid optic neuropathy) is exceptional in non-tertiary referral centers.


Input: The natural course of GO is incompletely defined, particularly in patients with moderate-to12 severe GO, because these patients require prompt and disease-modifying therapies for orbital disease.


Input: In patients with mild GO at presentation, progression to severe forms is rare, while partial or complete remission is frequent.


Input: Progression of preexisting GO or de novo occurrence of GO is more likely in smokers.


Input: There seems to be a trend towards a decline in progression of GO, possibly due to a better control of risk factors (cigarette smoking, thyroid dysfunction, etc.) and a closer interaction between endocrinologists and ophthalmologists allowing an improved integrated management of thyroid and orbital disease.


Input: Antiulcer and gastric antisecretory effects of dichloromethane fraction and piplartine obtained from fruits of Piper tuberculatum Jacq. in rats.

dichloromethane

piplartine


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Piper tuberculatum Jacq.


Input: (Piperaceae) is medicinally used as an analgesic and as a treatment for gastric complaints.


Input: Thus, the current study aimed to investigate the gastroprotective and antisecretory properties of the dichloromethane fraction of the fruit of Piper tuberculatum (DFPT) and piplartine, a compound isolated from the DFPT, in rats.

dichloromethane

piplartine


Input: MATERIALS AND METHODS: Gastric ulcers were induced in fasted rats by oral administration of absolute ethanol and then mucus content and glutathione (GSH) levels were measured.

ethanol

glutathione

GSH


Input: Mechanisms underlying the antisecretory action were studied through gastric H (+), K (+)-ATPase activity of highly purified rabbit gastric microsomes and pylorus ligature method in rats.

H (+)

K (+)


Input: RESULTS: In the acute toxicity test the values of estimated LD50 for oral and intraperitoneal administration of DFPT were 1. 6266 and 0. 2684g/kg, respectively.


Input: The DFPT (ED50 = 29mg/kg, p. o.) and piplartine (4. 5mg/kg, p. o.) promoted gastroprotection against acute lesions induced by ethanol, effect that could be related with the maintenance of GSH levels in the gastric mucosa.

piplartine

ethanol

GSH


Input: However, only DFPT stimulated gastric mucus secretion.


Input: In vitro, the DFPT and piplartine inhibited the H (+), K (+)-ATPase activity and, in vivo DFPT and piplartine also reduced basal gastric acid secretion, as well as that stimulated by pentagastrin.

piplartine

H (+)

K (+)

piplartine

pentagastrin


Input: CONCLUSIONS: These results demonstrate that DFPT and piplatine cause marked gastroprotective effects accompanied by the increase and maintenance of gastric mucus and GSH levels, as well as a reduction in gastric acid secretion through the gastrinergic pathway.

piplatine

GSH


Input: Emerging Transporters of Clinical Importance: An Update from the International Transporter Consortium.


Input: The International Transporter Consortium (ITC) has described recently seven transporters of particular relevance for drug development (Giacomini et al., Nat. Rev. Drug Discov. 9: 215-236, 2010).


Input: Based on the second ITC transporter workshop in 2012, we have identified additional transporters of emerging importance in pharmacokinetics, interference of drugs with transport of endogenous compounds and drug-drug interactions in humans.


Input: The multidrug and toxin extrusion proteins (MATEs, gene symbol SLC47A) mediate excretion of organic cations into bile and urine.


Input: MATEs are important in renal drug-drug interactions.


Input: Multidrug resistance proteins (MRPs or ABCCs) are drug and conjugate efflux pumps, and impaired activity of MRP2 results in conjugated hyperbilirubinemia.


Input: The bile salt export pump (BSEP or ABCB11) prevents accumulation of toxic bile salt concentrations in hepatocytes, and BSEP inhibition or deficiency may cause cholestasis and liver injury.

bile salt

bile salt


Input: Additionally, examples are presented on the roles of nucleoside and peptide transporters in drug targeting and disposition. Clinical Pharmacology & Therapeutics (2013); accepted article preview online 8 April 2013 doi: 10. 1038/clpt. 2013. 74.

nucleoside


Input: Biomarkers for Smoking Cessation.


Input: One way to enhance therapeutic development is through the identification and development of evaluative tools such as biomarkers.


Input: This review focuses on putative diagnostic, pharmacodynamic, and predictive biomarkers for smoking cessation.


Input: These types of biomarkers may be used to more accurately diagnose a disease, personalize treatment, identify novel targets for drug discovery, and enhance the efficiency of drug development.


Input: Promising biomarkers are presented across a range of approaches including metabolism, genetics, and neuroimaging.


Input: A preclinical viewpoint is also offered, as are analytical considerations and a regulatory perspective summarizing a pathway toward biomarker qualification. Clinical Pharmacology & Therapeutics (2013); advance online publication 8 May 2013. doi: 10. 1038/clpt. 2013. 57.


Input: The effects of water molecules on the electronic and structural properties of peptide nanotubes.


Input: The self-assembly of short amino acid chains appears to be one of the most promising strategies for the fabrication of nanostructures.

amino acid


Input: Their solubility in water and the possibility of chemical modification by targeting the amino or carboxyl terminus give peptide-based nanostructures several advantages over carbon nanotube nanostructures.

amino

carboxyl

carbon


Input: However, because these systems are synthesized in aqueous solution, a deeper understanding is needed on the effects of water especially with respect to the electronic, structural and transport properties.


Input: In this work, the electronic properties of l-diphenylalanine nanotubes (FF-NTs) have been studied using the Self-Consistent Charge Density-Functional-based Tight-Binding method augmented with dispersion interaction.

l-diphenylalanine


Input: The presence of water molecules in the central hydrophilic channel and their interaction with the nanostructures are addressed.


Input: We demonstrate that the presence of water leads to significant changes in the electronic properties of these systems decreasing the band gap which can lead to an increase in the hopping probability and the conductivity.


Input: Low allopurinol doses are sufficient to optimize azathioprine therapy in inflammatory bowel disease patients with inadequate thiopurine metabolite concentrations.

allopurinol

azathioprine

thiopurine


Input: PURPOSE: Recent studies in patients with inflammatory bowel diseases (IBD) on thiopurine therapy suggest that too low 6-thioguanine nucleotide concentrations (6-TGN) and too high methylmercaptopurine nucleotide concentrations (MMPN) can be reversed by a combination therapy of allopurinol and low-dose thiopurines.

thiopurine

6-thioguanine nucleotide

methylmercaptopurine nucleotide

MMPN

allopurinol

thiopurines


Input: To date, however, optimal dosing has not been established.


Input: The aim of this study was to evaluate the minimal allopurinol doses necessary to achieve adequate 6-TGN concentrations in combination with low-dose azathioprine.

allopurinol

azathioprine


Input: METHODS: A stepwise dose-escalation of allopurinol was performed in 11 azathioprine-pretreated IBD patients with inadequately low 6-TGN concentrations (< 235 pmol/8 x 10 (8) erythrocytes) and/or elevated MMPN concentrations (> 5, 000 pmol/8 x 10 (8) erythrocytes) and/or elevated liver enzymes (alanine aminotransferase and/or aspartate aminotransferase levels one-to threefold the upper limit of normal).

allopurinol

azathioprine

MMPN

alanine

aspartate


Input: Six patients were recruited into an open study, and five were treated in the context of an individualized therapeutic approach.


Input: Adverse effects, azathioprine metabolites, liver enzymes and whole blood counts were monitored two to three times per month.

azathioprine


Input: RESULTS: Adequate 6-TGN concentrations were achieved with a combination of 25 mg allopurinol and 50 mg azathioprine in one patient and with 50 mg allopurinol and 50 mg azathioprine in nine patients.

allopurinol

azathioprine

allopurinol

azathioprine


Input: Median 6-TGN concentrations (range) were 336 (290-488) pmol/8 x 10 (8) erythrocytes after an 8-week-long intake of the final dose combination.


Input: One patient dropped out due to nausea after the first intake.


Input: MMPN concentrations and liver enzymes normalized immediately in all affected patients.

MMPN


Input: All patients finishing the dose-escalation regimen tolerated the treatment without toxicity.


Input: CONCLUSIONS: Combination therapy with only 50 mg allopurinol and 50 mg azathioprine daily is sufficient, efficacious and safe in most IBD patients with inadequate thiopurine metabolite concentrations to optimize azathioprine-based IBD therapy.

allopurinol

azathioprine

thiopurine

azathioprine


Input: Population pharmacokinetics analysis of cyclophosphamide with genetic effects in patients undergoing hematopoietic stem cell transplantation.

cyclophosphamide


Input: PURPOSE: To build a population pharmacokinetic (PK) model of cyclophosphamide (CY) and its metabolite, 4-hydroxycyclophosphamide (HCY), in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) and to identify covariates, including genetic polymorphisms, which affect CY and HCY PK parameters.

cyclophosphamide

HCY

HCY


Input: METHOD: The study cohort comprised 21 patients undergoing HSCT who received CY intravenously between 2009 and 2011.


Input: Clinical characteristics and CY and HCY concentration data were collected for all patients, and ABCB1, ABCC2, GSTA1, GSTM1, GSTP1, GSTT1, CYP2B6, CYP2C19, and CYP3A5 genotyping was performed.

HCY


Input: A hypothetical enzyme compartment was conducted using the NONMEM program.


Input: RESULTS: A population PK analysis showed that the ABCC2 1249 genotype and aspartate aminotransferase levels significantly affected non-induced clearance (CL UI) and induced clearance (CL I) of CY, respectively.

aspartate


Input: The final estimate of the mean CL UI and CL I of CY was 15. 5 and 0. 683 L/h, respectively, and the mean volume of distribution (V 1) of CY was 88. 0 L.


Input: The inter-individual variability for CL UI, CL I, and V 1 of CY was 52. 8, 200, and 18. 0%, respectively.


Input: Additionally, the CL UI of CY was significantly decreased to approximately 51% in patients with the 1249 GA heterozygous genotype compared to those with the 1249 GG wild-type genotype (p < 0. 05).


Input: There were only three heterozygous GA variants of ABCC2 1249 in the study patients.


Input: CONCLUSIONS: The population PK model developed in this study implies an influence of genetic factors on the clearance of CY.


Input: Clearance was moderately reduced in patients with the ABCC2 1249GA heterozygous genotype.


Input: Synthesis, characterization and organic field effect transistor performance of a diketopyrrolopyrrole-fluorenone copolymer.

diketopyrrolopyrrole

fluorenone


Input: A diketopyrrolopyrrole (DPP) with fluorenone (FN) based low band gap alternating copolymer (PDPPT-alt-FN) has been synthesized via Suzuki coupling.

diketopyrrolopyrrole

DPP

fluorenone

PDPPT-alt-FN


Input: PDPPT-alt-FN exhibits a deep HOMO level with a lower band gap.

PDPPT-alt-FN


Input: Fabricated organic thin film transistors using PDPPT-alt-FN as a channel semiconductor show p-channel behaviour with the highest hole mobility of 0. 083 cm (2) V (-1) s (-1) measured in air.

PDPPT-alt-FN


Input: Dermatoprotective effects of some plant extracts (genus Ficus) against experimentally induced toxicological insults in rabbits.


Input: Aim: Present study was conducted to evaluate the dermatoprotective effects of plant extracts (Ficus religiosa, Ficus benghalensis, and Ficus racemosa) against known irritants such as sodium dodecyl sulfate (SDS), atrazine, and petrol.

sodium dodecyl sulfate

SDS

atrazine


Input: METHODS: The study was conducted in adult male rabbits.


Input: Ethanol extracts of plants were obtained through Soxhlet.

Ethanol


Input: All irritants and Ficus extracts were topically applied to the backs of rabbits daily for 4 days, while pure ethanol served as control.

ethanol


Input: Skin was examined after 24, 48, and 96 h for erythema.


Input: Skin biopsies were taken on 5th day for microscopic examination.


Input: RESULTS: Erythema produced by irritants reduced significantly with the simultaneous application of Ficus extracts.


Input: The mean +/- SEM epidermal thickness (micrometer) with SDS was 45. 40 +/- 1. 89, F. religiosa + SDS was 18. 60 +/- 0. 51, F. benghalensis + SDS was 18. 40 +/- 0. 25, F. racemosa + SDS was 18. 80 +/- 0. 37, and mixture of three Ficus species + SDS was 16. 80 +/- 0. 37.

SDS

SDS

SDS

SDS

SDS


Input: Similar findings were revealed after using plant extracts with atrazine and petrol.

atrazine


Input: The mean +/- SEM epidermal layer count for SDS was 3. 60 +/- 0. 25, atrazine was 3. 40 +/- 0. 25, petrol was 3. 40 +/- 0. 25, and ethanol (control) was 1. 00 +/- 0. 20.

SDS

atrazine

ethanol


Input: This count reduced to 1. 20 +/- 0. 20 for three Ficus species + SDS, 1. 40 +/- 0. 25 for Ficus species + atrazine, and 1. 40 +/- 0. 25 for Ficus species + petrol.

SDS

atrazine


Input: CONCLUSION: Ficus species demonstrated the potential to block the dermatotoxic effects of topical irritants and could be used successfully to prevent skin toxicity.


Input: Protective effects of caffeic acid phenethyl ester on dose-dependent intoxication of rats with paraquat.

caffeic acid phenethyl ester

paraquat


Input: PURPOSE: Paraquat (PQ; 1, 1' dimethyl-bipyridilium 4, 4'-dichloride), which is used extensively throughout the world, is highly toxic to humans.

Paraquat

1, 1' dimethyl-bipyridilium 4, 4'-dichloride