Input: The substrates, which exhibited non-fluorescence or weak fluorescence in solution phase, were smoothly hydrolyzed by beta-d-galactosidase from Aspergillus oryzae and yielded a water-insoluble strong fluorescent pigment.


Input: The difference of fluorescent intensity exhibited a linear relationship with the amount of enzyme.


Input: Coenzyme Q10 protects Pc12 cells from cisplatin-induced DNA damage and neurotoxicity.

Coenzyme Q10

cisplatin


Input: The purpose of this study was to investigate the neuroprotective effect of a water-soluble formulation of coenzyme Q10 (WS-CoQ10) in PC12 cells exposed to cisplatin, a chemotherapeutic agent with a dose-limiting factor due to neurotoxicity.

coenzyme Q10

cisplatin


Input: In the cytokinesis-block micronucleus cytome assay (CBMN Cyt), WS-CoQ10 (at concentrations of 0. 1, 0. 5 and 1. 0 mu gmL (-1)) protected PC12 cells from cisplatin-induced DNA damage (0. 1 mu gmL (-1)), reducing the frequency of micronuclei (MNi) and nuclear buds (NBUDs).

cisplatin


Input: WS-CoQ10 did not alter the mRNA expression levels of Tp53 (at a concentration of 1. 0 mu gmL (-1)) and exhibited neuroprotective activity by stimulating cisplatin-inhibited neurite outgrowth in nerve growth factor (NGF)-differentiated PC12 cells (at a concentration of 0. 1 mu gmL (-1)).

cisplatin


Input: In conclusion, WS-CoQ10 protected the PC12 cells from cisplatin-induced DNA damage and neurotoxicity.

cisplatin


Input: Moreover, the neuroprotective effects of WS-CoQ10 suggest a possible application in chemotherapeutic protocols.


Input: Rapid and Sensitive Determination of Timosaponin AIII in Rat Plasma by LC-MS/MS and Its Pharmacokinetic Application.

Timosaponin AIII


Input: A rapid sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for determination of timosaponin AIII (TA-III) in rat plasma, using ginsenoside Re as an internal standard (IS).

timosaponin AIII

TA-III

ginsenoside Re


Input: TA-III and the IS were detected in MRM mode with a negative ionization electrospray mass spectrometer.

TA-III


Input: The calibration curves were linear over the concentration ranges from 11. 14 to 1114 ng/mL and the lower limit of quantification (LLOQ) was 11. 14 ng/mL.


Input: Intra-day and inter-day precisions (RSD) were within 10%, and accuracy ranged from 6. 4% to 9. 1%.


Input: The extraction recovery at three concentrations ranged from 92. 3% to 95. 5%.


Input: The validated method was successfully applied to monitor the concentrations of TA-III in rat plasma after intragastric administration.

TA-III


Input: The best fit pharmacokinetic model to estimate the pharmacokinetic parameters was a single compartment model with weight of 1/x2 for oral administration groups of rats for TA-III.

TA-III


Input: International journal of molecular science best paper award 2013.


Input: Since 2012, International Journal of Molecular Science has instituted an annual award to recognize outstanding papers in the area of chemistry, molecular physics and molecular biology that meet the aims, scope and high standards of this journal [1].


Input: We are pleased to announce the second " International Journal of Molecular Science Best Paper Award " for 2013.


Input: Nominations were made by the Section Editor-in-Chiefs of International Journal of Molecular Science, with all papers published in 2009 eligible for consideration.


Input: The awards are issued for reviews and articles separately.


Input: Upregulation of drug transporter expression by osteopontin in prostate cancer cells.


Input: Multidrug resistance is a major cause of chemotherapy failure.


Input: Recent studies indicate that drug resistance can be rapidly induced by some soluble factors, such as cytokines, chemokines, growth factors, and cell adhesion factors in the tumor microenvironment.


Input: Osteopontin (OPN), an extracellular matrix protein, has a functional arginine-glycine-aspartic acid (RGD) domain for binding to integrin.

arginine

glycine

aspartic acid


Input: Here we found OPN expression to be upregulated by hypoxic condition in PC-3 prostate tumor cells.


Input: OPN increased the mRNA and protein expression of p-glycoprotein (P-gp), a subfamily of ATP-binding cassette transporter in a concentration-and time-dependent manner.

ATP


Input: The increase in P-gp transporter by OPN was mediated by binding to alpha v beta 3 integrin.


Input: Daunomycin (DUN), a chemotherapeutic agent with autofluorescence, was used to evaluate the pump activity, and OPN increased the drug pumping-out activity.

Daunomycin

DUN


Input: OPN inhibited DUN-induced cell death, which was antagonized by alpha v beta 3 monoclonal antibody.

DUN


Input: Long-term treatment with DUN further enhanced the expression of OPN.

DUN


Input: Knockdown of endogenous OPN potentiated the DUN-induced apoptosis of PC-3 cells.

DUN


Input: Furthermore, knockdown of OPN enhanced cell death caused by other drugs, including paclitaxel, doxorubicin, actinomycin-D, and rapamycin, which are also P-gp substrates.

paclitaxel

doxorubicin

actinomycin-D

rapamycin


Input: The animal studies also showed that OPN knockdown enhanced the cytotoxic action of DUN.

DUN


Input: These results indicate that OPN is a potential therapeutic target for cancer therapy to reduce drug resistance in sensitive tumors.


Input: Asperolide A, a marine-derived tetranorditerpenoid, induces G2/M arrest in human NCI-H460 lung carcinoma cells, is mediated by p53-p21 stabilization and modulated by Ras/Raf/MEK/ERK signaling pathway.

Asperolide A

tetranorditerpenoid


Input: Here we first demonstrate that asperolide A, a very recently reported marine-derived tetranorditerpenoid, leads to the inhibition of NCI-H460 lung carcinoma cell proliferation by G2/M arrest with the activation of the Ras/Raf/MEK/ERK signaling and p53-dependent p21 pathway.

asperolide A

tetranorditerpenoid


Input: Treatment with 35 mu M asperolide A (2 x IC (50)) resulted in a significant increase in the proportion of G2/M phase cells, about a 2. 9-fold increase during 48 h.

asperolide A


Input: Immunoblot assays demonstrated time-dependent inhibition of G2/M regulatory proteins.


Input: Moreover, asperolide A significantly activated MAP kinases (ERK1/2, JNK and p38 MAP kinase) by phosphorylation, and only the inhibition of ERK activation by PD98059 reversed downregulation of G2/M regulatory proteins CDC2, and suppressed upregulation of p21 and p-p53 levels.

asperolide A


Input: Transfection of cells with dominant-negative Ras (RasN17) mutant genes up-regulated asperolide A-induced the decrease of cyclin B1 and CDC2, suppressed Raf, ERK activity and p53-p21 expression, and at last, abolished G2/M arrest.

asperolide A


Input: This study indicates that asperolide A-induced G2/M arrest in human NCI-H460 lung carcinoma cells relys on the participation of the Ras/Raf/MEK/ERK signaling pathway in p53-p21 stabilization.

asperolide A


Input: An in vivo study with asperolide A illustrated a marked inhibition of tumor growth, and little toxcity compared to Cisplatin therapy.

asperolide A

Cisplatin


Input: Overall, these findings provide potential effectiveness and a theoretical basis for the therapeutic use of asperolide A in the treatment of malignancies.

asperolide A


Input: Construction of monophosphoryl lipid A producing Escherichia coli mutants and comparison of immuno-stimulatory activities of their lipopolysaccharides.

monophosphoryl lipid A


Input: The lipid A moiety of Escherichia coli lipopolysaccharide is a hexaacylated disaccharide of glucosamine phosphorylated at the 1-and 4'-positions.

lipid A

hexaacylated disaccharide

glucosamine


Input: It can be recognized by the TLR4/MD-2 complex of mammalian immune cells, leading to release of proinflammatory cytokines.


Input: The toxicity of lipid A depends on its structure.

lipid A


Input: In this study, two E. coli mutants, HW001 and HW002, were constructed by deleting or integrating key genes related to lipid A biosynthesis in the chromosome of E. coli W3110.

lipid A


Input: HW001 was constructed by deleting lacI and replacing lacZ with the Francisella novicida lpxE gene in the chromosome and only synthesizes monophosphoryl lipid A.

monophosphoryl lipid A


Input: HW002 was constructed by deleting lpxM in HW001 and synthesizes only the pentaacylated monophosphoryl lipid A.

pentaacylated monophosphoryl lipid A


Input: The structures of lipid A made in HW001 and HW002 were confirmed by thin layer chromatography and electrospray ionization mass spectrometry.

lipid A


Input: HW001 and HW002 grew as well as the wild-type W3110.


Input: LPS purified from HW001 or HW002 was used to stimulate murine macrophage RAW264. 7 cells, and less TNF-alpha were released.


Input: This study provides a feasible way to produce interesting lipid A species in E. coli.

lipid A


Input: All-Cause and Cardiovascular Mortality in Middle-Aged People With Type 2 Diabetes Compared With People Without Diabetes in a Large U. K.


Input: Primary Care Database.


Input: OBJECTIVEMiddle-aged people with diabetes have been reported to have significantly higher risks of cardiovascular events than people without diabetes.


Input: However, recent falls in cardiovascular disease rates and more active management of risk factors may have abolished the increased risk.


Input: We aimed to provide an up-to-date assessment of the relative risks associated with type 2 diabetes of all-cause and cardiovascular mortality in middle-aged people in the U. K. RESEARCH DESIGN AND METHODSUsing data from the General Practice Research Database, from 2004 to 2010, we conducted a cohort study of 87, 098 people, 40-65 years of age at baseline, comparing 21, 798 with type 2 diabetes and 65, 300 without diabetes, matched on age, sex, and general practice.


Input: We produced hazard ratios (HRs) for mortality and compared rates of blood pressure testing, cholesterol monitoring, and use of aspirin, statins, and antihypertensive drugs. RESULTSPeople with type 2 diabetes, compared with people without diabetes, had a twofold increased risk of all-cause mortality (HR 2. 07 [95% CI 1. 95-2. 20], adjusted for smoking) and a threefold increased risk of cardiovascular mortality (3. 25 [2. 87-3. 68], adjusted for smoking).

cholesterol

aspirin


Input: Women had a higher relative risk than men, and people < 55 years of age had a higher relative risk than those > 55 years of age.


Input: Monitoring and medication rates were higher in those with diabetes (all P < 0. 001). CONCLUSIONSDespite efforts to manage risk factors, administer effective treatments, and develop new therapies, middle-aged people with type 2 diabetes remain at significantly increased risk of death.


Input: Reduced Heart Rate Variability Is Associated With Increased Arterial Stiffness in Youth With Type 1 Diabetes: The SEARCH Cardiovascular Disease Study.


Input: OBJECTIVEReduced heart rate variability (HRV) and increased arterial stiffness (AS) are both present in youth with type 1 diabetes.


Input: However, it is unclear whether they are associated and whether their association is independent of cardiovascular disease (CVD) risk factors. RESEARCH DESIGN AND METHODSThe SEARCH Cardiovascular Disease Study explored the cross-sectional relationships between HRV and several measures of AS in youth with (n = 344) and without (n = 171) type 1 diabetes.


Input: The SphygmoCor device (AtCor Medical, Sydney, Australia) was used to measure HRV using SD of normal R-R interval (SDNN), as well as AS, using pulse wave velocity in the carotid to femoral segment (PWV-trunk) and augmentation index adjusted to a heart rate of 75 bpm (AIx75).


Input: Brachial distensibility (BrachD), another index of AS, was measured with a DynaPulse instrument (Pulse Metric, San Diego, CA).


Input: Multiple linear regression analyses explored the associations between HRV and each of the three AS measures, after adjusting for demographic characteristics and traditional CVD risk factors (blood pressure, lipids, obesity, microalbuminuria, and smoking) separately, for youth with and without type 1 diabetes. RESULTSAmong youth with type 1 diabetes, lower SDNN was associated with peripheral AS (lower BrachD, P = 0. 01; r (2) = 0. 30) and central AS (higher PVW-trunk, P < 0. 0001; r (2) = 0. 37; and higher AIx75, P = 0. 007; r (2) = 0. 08).


Input: These associations were attenuated with adjustment for CVD risk factors, but remained statistically significant for BrachD and PWV-trunk.


Input: While a similar association between HRV and BrachD was present in control youth, lower HRV was not associated with increased central AS or with AIx75. CONCLUSIONSLongitudinal studies are needed to understand the pathways responsible for these associations.


Input: Changes in A1C Levels Are Significantly Associated With Changes in Levels of the Cardiovascular Risk Biomarker hs-CRP: Results from SteP Study.


Input: OBJECTIVEThe effect of therapeutic strategies on cardiovascular (CV) disease can be evaluated by monitoring changes in CV risk biomarkers.


Input: This study investigated the effect of a structured self-monitoring of blood glucose (SMBG) protocol and the resulting improvements in glycemic control on changes in high-sensitivity C-reactive protein (hs-CRP) in insulin-na i ve patients with type 2 diabetes. RESEARCH DESIGN AND METHODSThe Structured Testing Program (STeP) study was a prospective, cluster-randomized, multicenter trial in which 483 poorly controlled, insulin-na i ve patients with type 2 diabetes were randomized to active control (ACG) or structured testing (STG) that included quarterly structured SMBG.

glucose


Input: Changes in A1C, hs-CRP, and glycemic variability (STG subjects only) were measured at baseline and quarterly. RESULTSReductions in geometric mean hs-CRP values were significantly greater in the STG group at months 3 (P = 0. 005), 6 (P = 0. 0003), and 12 (P = 0. 04) than in the ACG group.


Input: STG patients at high CV risk (> 3 mg/L) showed significantly greater reductions in hs-CRP levels than ACG patients at high CV risk:-3. 64 mg/dL (95% CI-4. 21 to-3. 06) versus-2. 18 mg/dL (-2. 93 to-1. 43), respectively (P = 0. 002).


Input: There was a strong correlation between reductions in hs-CRP and A1C in both groups: standardized coefficient (beta) was 0. 25 for the entire cohort (P < 0. 0001), 0. 31 for STG (P < 0. 0001), and 0. 16 for ACG (P = 0. 02). CONCLUSIONSReductions in hs-CRP level are associated with reductions in A1C but not reductions in lipids or glycemic variability.


Input: Comprehensive structured SMBG-based interventions that lower A1C may translate into improvements in CV risk, as evidenced by levels of the biomarker hs-CRP.


Input: Rational development of novel leads from animal secretion based on coagulation and cell targets: 1.


Input: In silico analysis to explore a peptide derivative as lipocalins' signature.


Input: Animal venoms and secretions have been screened, in our research group, to discover, identify and isolate peptide molecules active in the mammalian haemostatic system.


Input: As result, this kind of research has provided a portfolio of promising drug candidates.


Input: These novel recombinant proteins have turned out to be multifunctional molecules, and are currently under different development phases.


Input: Lopap from bristles of the Lonomia obliqua moth caterpillar, for instance, is a prothrombin activator which belongs to the lipocalin family.


Input: It displays serine protease-like activity with procoagulant effect, and also induces cytokine secretion and antiapoptotic pathways in human cultured endothelial cells.

serine


Input: Furthermore, a Lopap-derived peptide has showed to induce collagen synthesis in fibroblast culture and in animal dermis.


Input: Here, the molecular properties (steric, electronic, hydrophobic, geometric), which are strongly dependent on chemical structure, were investigated by applying chemometric and computational chemistry methods.


Input: It was considered different patterns of amino acid substitution related to the lipocalins' motif 2, which was recently shown to modulate cell survival.

amino acid


Input: The calculated molecular properties were generally maintained in all investigated peptides extracted from three-dimensional structures of Protein Data Bank (1t0v, 1bbp, 1kxo, 2hzr, 1iiu, 1jyj, 1gka, 1s44, 3ebw) when compared to Lopap-derived peptide, specially the molecular shape and electronic density distribution, validating the lipocalin sequence signature previously reported.


Input: Indeed, those two properties are quite important for the molecular recognition process.


Input: Pro-inflammatory and pathogenic properties of Annexin-A1: The whole is greater than the sum of its parts.


Input: According to Aristotle, " The whole is greater than the sum of its parts " and yet, although a long time has passed still, we seem to struggle to accept this universal concept.


Input: Searching in the literature for the biological function of Annexin-A1, one would find a wealth of information on its homeostatic and protective anti-inflammatory effects.


Input: However, very little has been said on its emerging role in a wide variety of pathological conditions ranging from cancer to autoimmunity.


Input: In this commentary, we will focus our attention on this novel pro-inflammatory and pathogenic " dark side " of Annexin-A1.


Input: We will summarize our current understanding of the signaling pathways regulated by this protein and link it to clinical and experimental evidences.


Input: Finally we will discuss assets and limitations of Annexin-A1 therapeutic strategies.


Input: Most importantly, we hope that this commentary will provide scientific support to " controversial " findings one might encounter while studying this fascinating protein.


Input: Changes in morphometry and association between whole-body fatty acids and steroid hormone profiles in relation to bioaccumulation patterns in salmon larvae exposed to perfluorooctane sulfonic or perfluorooctane carboxylic acids.

fatty acids

steroid

perfluorooctane sulfonic or perfluorooctane carboxylic acids


Input: In the present study, we have used salmon embryos whose continuous exposure to waterborne PFOA or PFOS at 100 mu g/L started as freshly fertilized eggs, and lasted for a total of 52 days.

PFOA

PFOS


Input: PFOS and PFOA were dissolved in methanol (carrier vehicle) whose concentration never exceeded 0. 01% of total tank volume.

PFOS

PFOA

methanol


Input: Samples were collected at day 21, 28, 35, 52, 49 and 56 after the start of the exposure.


Input: Note that days 49 and 56 represent end of exposure and 1 week after a recovery period, respectively.


Input: Tissue bioaccumulations were determined by HPLC/MS/MS, steroid hormones, fatty acids (FAs) and lipids were determined by GC-MS, while mRNA expression levels of genes were determined by qPCR in whole body homogenate.

steroid

fatty acids

FAs


Input: We observed that PFOS and PFOA showed a steady increase in whole body burden during the exposure period, with a slight decrease after the recovery period.

PFOS

PFOA


Input: Calculated somatic indexes showed that PFOA produced increases in heart-, thymus-, liver-and kidney somatic indexes (HSI, TSI, LSI and KSI).

PFOA


Input: PFOA and PFOS exposure produced significant decreases in whole body dehydroepiandrosterone (DHEA), estrone and testosterone at sampling day 21 and a strong increase of cortisol and cholesterol at the end of recovery period (day 56).

PFOA

PFOS

dehydroepiandrosterone

DHEA

testosterone

cortisol

cholesterol


Input: PFOA and PFOS effects differed with DHEA and estrone.

PFOA

PFOS

DHEA

estrone


Input: While PFOS decreased DHEA levels, PFOA produced an increase at day 49, and while PFOS decreased estrone, PFOA produced a slight increase at day 56.

PFOS

DHEA

PFOA

PFOS

estrone

PFOA


Input: We observed changes in FA composition that predominantly involved increases in FA methyl esters (FAMEs), mono-and poly-unsaturated FA (MUFA and PUFA) and a decrease in n-3/n-6 PUFA ratio by both PFOA and PFOS.

FA methyl esters

FAMEs

mono-and poly-unsaturated FA

MUFA

PUFA

PUFA

PFOA

PFOS


Input: Particularly, an increase in-pentadecenoic MUFA (15: 1), two n-3 PUFAs alpha-linolenic acid [ALA: 18: 3 n3] and eicosapentaenoic acid [EPA: 20: 5 n-3] and n-6 PUFA: arachidonic acid [ARA: 20: 4 n6], docosapentaenoic acid (DPA) by PFOA and PFOS were observed.

pentadecenoic MUFA

PUFAs alpha-linolenic acid

ALA

eicosapentaenoic acid

EPA

PUFA

arachidonic acid

ARA

docosapentaenoic acid

DPA

PFOA

PFOS


Input: These effects were associated with changes in mRNA expression of FA elongase (FAE), Delta 5-desaturase (FAD5) and Delta 6-desaturase (FAD6) genes.


Input: In summary, the changes in hormonal and FA profiles may represent cellular and/or physiological adaptation to continuous PFOS and PFOA exposure by increasing membrane fluidity, and/or overt developmental effects.

PFOS

PFOA


Input: The present findings provide some potential insights and basis for a better understanding on the possible mechanisms of PFCs toxicity in fish.


Input: Transcriptional regulation of human ferredoxin 1 in ovarian granulosa cells.


Input: Ferredoxin 1 (FDX1; adrenodoxin) is an iron-sulfur protein that is involved in various metabolic processes, including steroid hormone synthesis in mammalian tissues.

iron

sulfur

steroid hormone


Input: We investigated the transcriptional regulation of FDX1 in ovarian granulosa cells.


Input: Previously, we reported that the NR5A family, including steroidogenic factor-1 (SF-1) and liver receptor homolog-1 could induce differentiation of human mesenchymal stem cells (hMSCs) into steroidogenic cells.


Input: A ChIP assay showed that SF-1 could bind to the FDX1 promoter in differentiated hMSCs.


Input: Luciferase reporter assays showed that transcription of FDX1 was synergistically activated by the NR5A family and 8Br-cAMP treatment through two SF-1 binding sites and a CRE-like sequence in a human ovarian granulosa cell line, KGN.


Input: Knockdown of FDX1 attenuated progesterone production in KGN cells.

progesterone


Input: These results indicate transcription of FDX1 is regulated by the NR5A family and cAMP signaling, and participates in steroid hormone production in ovarian granulosa cells.

cAMP

steroid hormone


Input: Attenuation by statins of membrane raft-redox signaling in coronary arterial endothelium.

statins


Input: Membrane raft (MR)-redox signaling platforms associated with NADPH oxidase are involved in coronary endothelial dysfunction.

NADPH


Input: Here, we studied whether statins interfere with the formation of MR-redox signaling platforms to protect the coronary arterial endothelium from oxidized low-density lipoprotein (OxLDL)-induced injury and from acute hypercholesterolemia.

statins


Input: In cultured human coronary arterial endothelial cells, confocal microscopy detected the formation of an MRs clustering when they were exposed to OxLDL, and such MR platform formation was inhibited markedly by statins, including pravastatin and simvastatin.

statins

pravastatin

simvastatin


Input: In these MR clusters, NADPH oxidase subunits gp91 (phox) and p47 (phox) were aggregated and were markedly blocked by both statins.

NADPH

statins


Input: In addition, colocalization of acid sphingomyelinase (ASM) and ceramide was induced by OxLDL, which was blocked by statins.

ceramide

statins


Input: Electron spin resonance spectrometry showed that OxLDL-induced superoxide (O2 (.-)) production in the MR fractions was substantially reduced by statins.

superoxide

O2 (.-)

statins


Input: In coronary artery intima of mice with acute hypercholesterolemia, confocal microscopy revealed a colocalization of gp91 (phox), p47 (phox), ASM, or ceramide in MR clusters.

ceramide


Input: Such colocalization was rarely observed in the arteries of normal mice or significantly reduced by pretreatment of hypercholesterolemic mice with statins.

statins


Input: Furthermore, O2 (.-) production in situ was 3-fold higher in the coronary arteries from hypercholesterolemic mice than in those from normal mice, and such increase was inhibited by statins.

O2 (.-)

statins


Input: Our results indicate that blockade of MR-redox signaling platform formation in endothelial cell membrane may be another important therapeutic mechanism of statins in preventing endothelial injury and atherosclerosis and may be associated with their direct action on membrane cholesterol structure and function.

statins

cholesterol


Input: Pharmacogenomics of acetylsalicylic acid and other nonsteroidal anti-inflammatory agents: clinical implications.

acetylsalicylic acid


Input: PURPOSE: Pharmacogenomics investigates interindividual genetic variability in the DNA sequence of drug targets, drug-metabolizing enzymes or disease genes, RNA expression, or protein translation of genes affecting drug response and drug safety.


Input: Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed medications with well-documented variation in patient response in terms of efficacy and safety.

Aspirin


Input: This variation may in part be explained by pharmacogenomics.


Input: METHODS: In this paper I review data on the pharmacogenomics of aspirin and other NSAIDs focusing on clinical implications.


Input: RESULTS: Existing scientific evidence supports the pharmacogenomic basis of interindividual variation in treatment response to aspirin and NSAIDs, with clinical implications for antiplatelet action, cancer chemoprevention, and drug safety.


Input: However, further research efforts are needed before knowledge on the pharmacogenomics of aspirin and NSAIDs can be implemented in clinical practice.

aspirin


Input: CONCLUSION: The outcome of these research efforts would be anticipated to have added value for both science and society, contributing to the enhanced efficacy and safety of these agents through patient selection.


Input: Surface-enhanced Raman scattering spectra of adsorbates on Cu 2 O nanospheres: charge-transfer and electromagnetic enhancement.

Cu 2 O


Input: Surface-enhanced Raman scattering (SERS) spectra of 4-mercaptobenzoic acid (4-MBA) have been investigated on the surface of Cu2O nanospheres.

4-mercaptobenzoic acid


Input: The SERS signals were believed to originate from the static chemical enhancement, resonant chemical enhancement and electromagnetic enhancement.


Input: The coupling between the adsorbates and the semiconductor, evidenced by the shift in absorption spectrum of modified Cu2O and the enhancement of non-totally symmetric modes of the 4-MBA and 4-mercaptopyridine (4-MPY) molecules, were invoked to explain the experimental results.


Input: Furthermore, simulations were employed to investigate the nature of the enhancement mechanisms operative between the molecules and the semiconductor.


Input: Density functional theory (DFT) calculations suggested a charge transfer (CT) transition process between the molecules and the Cu2O nanospheres.


Input: Three-dimensional finite-difference time domain (3D-FDTD) simulations were conducted to map out the electromagnetic field around the Cu2O nanospheres.


Input: The experimental and simulation results have revealed the promise of the Cu2O nanospheres as a good SERS substrate and the prospect of using the SERS substrate as a valuable tool for in situ investigation and assay of the adsorption behavior on semiconductor surfaces.


Input: The characteristics of genistin-induced inhibitory effects on intestinal motility.

genistin


Input: Genistin belongs to isoflavones.

Genistin

isoflavones


Input: Based on the facts that genistin exerts inhibitory effects on the contractility of vascular smooth muscle, the present study was designed to characterize the effects of genistin on intestinal contractility and evaluate its potential clinical implication.

genistin

genistin


Input: Ex vivo [isolated jejunal segment (IJS) of rat], in vitro, and in vivo assays were used in the study.


Input: The results indicated that genistin (5-80 mu mol/L) inhibited the contraction of IJS in a dose-dependent manner and inhibited the increased-contractility of IJS induced by acetylcholine (ACh), histamine, high Ca (2 +), and erythromycin, respectively.

genistin

acetylcholine

ACh

histamine

Ca (2 +)

erythromycin


Input: The inhibitory effects of genistin were correlated with the stimulation of alpha adrenergic and beta adrenergic receptors since these inhibitory effects were significantly blocked in the presence of phentolamine and propranolol respectively.

genistin

phentolamine

propranolol


Input: No further inhibitory effects of genistin were observed in the presence of verapamil or in Ca (2 +)-free condition, indicating genistin-induced inhibitory effects are Ca (2 +)-dependent.

genistin

verapamil

Ca (2 +)

genistin

Ca (2 +)


Input: Genistin decreased myosin light chain kinase (MLCK) protein contents and MLCK mRNA expression in IJS, and inhibited both phosphorylation and Mg (2 +)-ATPase activity of purified myosin, implicating that the decrease of MLCK contents and inhibition of MLCK activity are involved in the genistin-induced inhibitory effects.

Genistin

Mg (2 +)

genistin


Input: The study suggests the potential clinical implications of genistin in relieving intestinal hypercontractility.

genistin


Input: The pharmacokinetics and pharmacodynamics of zaleplon delivered as a thermally generated aerosol in a single breath to volunteers.

zaleplon


Input: Pharmacokinetics, pharmacodynamics, safety, and tolerability of inhaled zaleplon were assessed in healthy volunteers.

zaleplon


Input: Forty participants received 0. 5, 1, 2, or 4 mg zaleplon or placebo as a thermally generated aerosol in a randomized, double-blind, parallel-group, dose escalation study.

zaleplon


Input: Blood was collected up to 24 hours after dosing, and sedation was assessed up to 8 hours.


Input: Following inhalation, the observed median time to maximum plasma concentrations (25%, 75%) was 1. 89 (1. 45, 3. 08) minutes and the mean (SD) elimination half-life was 1. 24 (0. 24) hours.


Input: The equilibration half-life for sedation (t (1/2) k (e0)) was 1. 16 (0. 62, 2. 17) minutes.


Input: The zaleplon AUC was dose proportional across doses, with a slope (90% confidence interval) of log-AUC versus log-dose of 0. 92 (0. 82, 1. 02).

zaleplon


Input: No clinically significant changes were noted in laboratory values, vital signs, or spirometry.


Input: The most common adverse events were dizziness, somnolence, euphoria, headache, and visual disturbance.


Input: Zaleplon inhalation represents a safe, well-tolerated means of rapidly achieving effective plasma concentrations.

Zaleplon


Input: The combination of exposure-response and case-control analyses in regulatory decision making.


Input: To reduce the bias introduced by confounding risk factors, a case-control comparison was incorporated in the exposure-response (ER) analysis to evaluate the recommended dosing regimen for trastuzumab in a pivotal trial.


Input: Results of Kaplan-Meier survival analysis suggest that patients with metastatic gastric cancer (mGC) in the lowest quartile trough concentrations of trastuzumab in cycle 1 (C (min 1)) had shorter overall survival (OS) than did those in other quartiles.


Input: The result of the case-matched control comparison suggests that adjusting for these risk factors, patients with the lowest quartile of trastuzumab exposure did not benefit from addition of trastuzumab treatment to chemotherapy.


Input: The identified subgroup without survival benefit and the ER relationship support the recommendation on conducting clinical trials to identify a treatment regimen with greater exposure and acceptable safety profiles and to prospectively evaluate whether this treatment regimen will result in survival benefit for the identified subgroup.


Input: Drug-induced liver injury: the role of drug metabolism and transport.


Input: Many studies have pinpointed the significant contribution of liver-mediated drug metabolism and transport to the complexity of drug-induced liver injury (DILI).


Input: Phase I cytochrome P450 (CYP450) enzymes can lead to altered drug metabolism and formation of toxic metabolites, whilst Phase II enzymes are also associated with DILI.


Input: The emerging role of hepatic transporters in regulating the movement of endogenous and exogenous chemicals (e. g., bile acids and drugs) across cellular and tissue membranes is critical in determining the pathophysiology of liver disease as well as drug toxicity and efficacy.

bile acids


Input: Genetic and environmental factors can have a significant impact on drug metabolism and transporter proteins, consequently increasing the risk of DILI in susceptible individuals.


Input: The assessment of these factors therefore represents an important approach for predicting and preventing DILI, by better understanding the pharmacological profile of a specific drug.


Input: This review focuses on the mechanisms of DILI associated with drug metabolism and hepatic transport, and how they can be influenced by underlying factors.


Input: Effect of excipients on acetaminophen metabolism and its implications for prevention of liver injury.

acetaminophen


Input: Acetaminophen poisoning is the most frequent cause of acute hepatic failure in the US.

Acetaminophen


Input: Toxicity requires reductive metabolism of acetaminophen, primarily via CYP2E1.

acetaminophen


Input: Liquid acetaminophen preparations contain propylene glycol, a common excipient that has been shown to reduce hepatocellular injury in vitro and in rodents.

acetaminophen

propylene glycol


Input: Children are less susceptible to acetaminophen toxicity for unclear reasons.

acetaminophen


Input: We conducted a pharmacokinetic single-blinded crossover study of 15 healthy adult volunteers comparing the CYP2E1 and conjugative metabolism of a 15 mg/kg dose of liquid versus solid preparations of acetaminophen.

acetaminophen


Input: Measured AUC' s for the CYP2E1 metabolites were 16-17% lower and extrapolated AUC' s were 25-28% lower in the liquid formulation arm while there was no difference in conjugative metabolite production.


Input: The formation rate constants for reductive metabolites were equivalent between solid and liquid formulations indicating that enzyme inhibition was competitive.


Input: Propylene glycol, an established CYP2E1 competitive antagonist, was detected in the liquid formulation but not solid formulation arm.

Propylene glycol


Input: Since children tend to ingest liquid preparations, the protective effect of this excipient could explain their decreased susceptibility to acetaminophen toxicity.

acetaminophen


Input: A less hepatotoxic formulation of acetaminophen could potentially be developed if co-formulated with a CYP2E1 inhibitor.

acetaminophen


Input: Addition of cilostazol to conventional dual antiplatelet therapy reduces the risk of cardiac events and restenosis after drug-eluting stent implantation: a meta-analysis.

cilostazol


Input: This meta-analysis was performed to compare the risk of cardiac events and restenosis between triple antiplatelet therapy (TAT, addition of cilostazol to aspirin and clopidogrel) and conventional dual antiplatelet therapy (DAT, aspirin and clopidogrel) in drug-eluting stents (DES) implantation patients.

cilostazol

aspirin

clopidogrel

aspirin

clopidogrel


Input: We performed PUBMED, MEDLINE, EMBASE, and Cochrane CENTRAL searches for randomized clinical trials of TAT versus DAT in patients after DES implantation.


Input: Five clinical trials were involved in the study.


Input: TAT was associated with a 36% reduction in major adverse cardiac events (MACE; odds ratio (OR) = 0. 64; 95% confidence interval (CI) = 0. 51-0. 81, P <. 01), a 40% reduction (OR = 0. 60, 95% CI = 0. 44-0. 80; P <. 01) in target vessel revascularization (TVR), a 44% reduction (OR = 0. 56, 95% CI = 0. 34-0. 91; P =. 02) in target lesion revascularization (TLR) and a 47%/44% reduction in in-segment/in-stent restenosis (P <. 01) and lower in-segment/in-stent late loss (P <. 01).


Input: As regards to the safety assessment, there was no significant difference about the risk of stent thrombosis and bleeding between TAT and DAT group, while the risk of gastrointestinal trouble was significantly higher in TAT group (OR = 2. 46, 95% CI = 1. 25-4. 86; P <. 01).


Input: Addition of cilostazol to DAT reduced the incidence of MACE, TVR, and TLR after DES implantation.

cilostazol


Input: TAT also reduced the risk of restenosis and late loss in patients after DES implantation.


Input: Blood Pressure Lowering Effect of Nigella sativa L.


Input: Seed Oil in Healthy Volunteers: A Randomized, Double-Blind, Placebo-controlled Clinical Trial.


Input: Nigella sativa L. seeds (N. sativa) have been used as a traditional remedy for a wide range of diseases including hypertension.


Input: The present study was performed to explore the effects of N. sativa oil on blood pressure (BP) in healthy volunteers.


Input: In a double-blind, randomized study, 70 healthy volunteers aged 34 to 63 years with systolic BP from 110 to 140 mmHg and diastolic BP from 60 to 90 mmHg were randomly allocated to receive 2. 5 mL N. sativa oil or placebo two times a day for 8 weeks.


Input: The systolic and diastolic BPs, body mass index and blood levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, creatinine and blood urea nitrogen were determined at baseline and endpoint.

aspartate

alanine

creatinine

urea nitrogen


Input: Results showed that in N. sativa oil treated group the systolic and diastolic BPs decreased significantly compared with baseline and placebo group at the endpoint.


Input: Other parameters did not significantly change in both groups at the endpoint.


Input: No adverse effects were reported.


Input: In conclusion, oral daily administration of 5 mL N. sativa oil to healthy volunteers for 8 weeks lowers systolic and diastolic BPs without any adverse effects.


Input: Copyright (c) 2013 John Wiley & Sons, Ltd.


Input: Readily accessible fluorescent probes for sensitive biological imaging of hydrogen peroxide.

hydrogen peroxide


Input: Hydrogen peroxide is a major component of oxygen metabolism in biological systems that, when present in high concentrations, can lead to oxidative stress in cells.

Hydrogen peroxide

oxygen


Input: Noninvasive molecular imaging of H (2) O (2) using fluorogenic systems represents an effective way to detect and measure the accumulation of this metabolite.

H (2) O (2)


Input: Herein, we detail the development of robust H (2) O (2)-sensitive fluorescent probes using a boronic ester trigger appended to the fluorophore through a benzyl ether linkage.

H (2) O (2)

boronic ester

benzyl ether


Input: A major advantage of the probes presented here is their synthetic accessibility, with only one step needed to generate the probes on the gram scale.


Input: The sensitivity of the probes was evaluated in simulated physiological conditions, showing micromolar sensitivity to H (2) O (2).

H (2) O (2)


Input: The probes were tested in biological model systems, demonstrating effective imaging of unstimulated, endogenous H (2) O (2) levels in RAW 264. 7 cells and murine brain tissue.

H (2) O (2)


Input: Mifepristone for management of Cushing' s syndrome.

Mifepristone


Input: Cushing' s syndrome is a debilitating endocrine disorder caused by elevated circulating glucocorticoid levels.


Input: Although uncommon, Cushing' s syndrome is associated with significant morbidity necessitating rapid reversal of hypercortisolemia.


Input: Primary therapy for most patients with Cushing' s syndrome is surgical, but many patients will require additional treatments with radiation or drugs.


Input: Although several options for drug therapy exist, few are readily available and all have dose-limiting adverse effects.


Input: Mifepristone (RU 486), a first-in-class glucocorticoid receptor antagonist, was approved by the United States Food and Drug Administration in 2012 for use in Cushing' s syndrome to control hyperglycemia in patients who are not surgical candidates or have not achieved remission from surgery.

Mifepristone

RU 486


Input: The drug is approved for oral once-daily administration.


Input: In its pivotal trial, 60% of patients responded to mifepristone with significant improvements in glycemic control and 38% had a reduction in diastolic blood pressure.

mifepristone


Input: The most common adverse events were nausea, fatigue, headache, endometrial hyperplasia, and hypokalemia.


Input: Adrenal insufficiency occurred in fewer than 5% of patients.


Input: The recommended starting dosage of mifepristone is 300 mg/day.

mifepristone


Input: The dosage may be increased every 2-4 weeks up to a maximum of 1200 mg/day, although it should not exceed 20 mg/kg/day.


Input: Significant drug-drug interactions exist due to mifepristone' s effects on a number of cytochrome P450 enzymes.

mifepristone


Input: Despite its limitations, mifepristone is a welcome addition and an appropriate alternative to the available drug therapy for Cushing' s syndrome.

mifepristone


Input: UV/Vis spectra of subporphyrazines and subphthalocyanines with aluminum and gallium: a time-dependent DFT study.

subporphyrazines

subphthalocyanines

aluminum

gallium


Input: The UV/Vis spectra of selected substituted subporphyrazines (SubPz) and subphthalocyanines (SubPc) with aluminum and gallium as central atoms are analyzed through time-dependent DFT calculations in chloroform.

subporphyrazines

SubPz

subphthalocyanines

SubPc

aluminum

gallium

chloroform


Input: The results are compared with previous results with boron as the central atom to analyze the photochemical properties of these two families of compounds on varying the metal along the same group.

boron


Input: The absorptions of SubPz (Al, Ga) are redshifted or blueshifted with respect to SubPz (B) depending on the nature of the R substituents of the molecule, whereas the absorptions of SubPc (Al, Ga) structures are redshifted and with smaller energy gaps with respect to SubPc (B) for all kinds of R substituents.

SubPz

Al

Ga

SubPz

SubPc

Al

Ga

SubPc


Input: Looking at their absorption spectra, these systems with aluminum and gallium may also have, as in the case of boron, promising photochemical properties.

aluminum

gallium

boron


Input: Pu-erh tea hot-water extract activates Akt and induces insulin-independent glucose transport in rat skeletal muscle.

glucose


Input: Skeletal muscle is a major organ that is important for whole-body glucose metabolism.

glucose


Input: We found that when isolated rat epitrochlearis muscle was incubated with a Pu-erh tea hot-water extract (PTE) for 30 min, the rate of 3-O-methyl-D-glucose (3MG) transport increased in the absence of insulin.


Input: This activation was associated with an increase in Ser (473) phosphorylation of Akt, a signaling intermediary leading to insulin-dependent glucose transport, but not Tyr (458) phosphorylation of phosphoinositide 3-kinase p85, an upstream molecule of Akt.

Ser

glucose

Tyr


Input: PTE-stimulated 3MG transport was also not accompanied by Thr (172) phosphorylation of the catalytic alpha-subunit of 5'-AMP-activated protein kinase (AMPK).

Thr

AMP


Input: Gallic acid, a water-soluble ingredient in Pu-erh tea, stimulated Akt phosphorylation, but not AMPK phosphorylation.

Gallic acid


Input: These results suggest that Pu-erh tea potentially promotes skeletal muscle glucose transport at least in part by activating Akt.

glucose


Input: Discovery, biological evaluation, and structure-activity and-selectivity relationships of 6'-substituted (E)-2-(benzofuran-3 (2H)-ylidene)-N-methylacetamides, a novel class of potent and selective monoamine oxidase inhibitors.

6'-substituted (E)-2-(benzofuran-3 (2H)-ylidene)-N-methylacetamides

monoamine


Input: The use of selective inhibitors of monoamine oxidase A (MAO-A) and B (MAO-B) holds a therapeutic relevance in the treatment of depressive disorders and Parkinson' s disease (PD), respectively.

monoamine


Input: Here, the discovery of a new class of compounds acting as monoamine oxidase inhibitors (MAO-Is) and bearing a 6'-substituted (E)-2-(benzofuran-3 (2H)-ylidene)-N-alkylacetamide skeleton is reported.

monoamine

6'-substituted (E)-2-(benzofuran-3 (2H)-ylidene)-N-alkylacetamide


Input: 6'-Sulfonyloxy derivatives exhibited outstanding affinities to MAO-A (7. 0 nM < IC50 < 49 nM, much higher than moclobemide) and a pronounced MAO-A/B selectivity.

moclobemide


Input: The corresponding 6'-benzyloxy derivatives showed potent MAO-B inhibition and inverted selectivity profile.


Input: The rigid E-geometry of the exocyclic double bond allowed a more efficient binding conformation compared to more flexible and less active 2-(1-benzofuran-3-yl)-N-methylacetamide isomers and 4-N-methylcarboxamidomethylcoumarin analogues.


Input: Focused structural modifications and docking simulations enabled the identification of key molecular determinants for high affinity toward both MAO isoforms.


Input: These novel MAO-Is may represent promising hits for the development of safer therapeutic agents with a potential against depression, PD, and other age-related neurodegenerative pathologies.


Input: From rings to crescents: a novel fabrication technique uncovers the transition details.


Input: A novel fabrication route is reported for the generation of substrate-supported symmetric and asymmetric metal nanostructures.


Input: We combine a colloidal template and angled evaporation to deposit in situ mask materials for subsequent lithographic pattern transfer.


Input: The technique is demonstrated for the fabrication of concentric and nonconcentric gold rings and crescents.


Input: Optical properties of localized plasmon resonances in such structures are studied by UV-vis-NIR spectroscopy and finite-difference time domain simulations during the transition from rings to crescents revealing the development of strong quadrupolar modes.


Input: Counterion Density Profile around Charged Cylinders: The Strong-Coupling Needle Limit.


Input: Charged rod-like polymers are not able to bind all their neutralizing counterions: a fraction of them evaporates, while the others are said to be condensed.


Input: We study here counterion condensation and its ramifications, both numerically by means of Monte Carlo simulations employing a previously introduced powerful logarithmic sampling of radial coordinates and analytically, with special emphasis on the strong-coupling regime.


Input: We focus on the thin rod or needle limit that is naturally reached under strong Coulombic couplings, where the typical intercounterion spacing a' along the rod is much larger than its radius R.


Input: This regime is complementary and opposite to the simpler thick rod case where a' << R.


Input: We show that due account of counterion evaporation, a universal phenomenon in the sense that it occurs in the same clothing for both weakly and strongly coupled systems, allows one to obtain excellent agreement between the numerical simulations and the strong-coupling calculations.


Input: pH-controlled nanoaggregation in amphiphilic polymer co-networks.


Input: Domain formation and control in pH-responsive amphiphilic polymer co-networks are studied theoretically.


Input: Two different molecular architectures of the polymer network are considered, depending on whether the pH-sensitive motif is borne by the hydrophobic or the hydrophilic monomer.


Input: When the hydrophobic polymer contains acidic groups, such chains form nanometric aggregates at acidic conditions, but they are found in a swollen state at alkaline pH.


Input: At intermediate pH, the nanoaggregation behavior of the hydrophobic polymer depends critically on the environment salt concentration.


Input: Moreover, our results indicate the presence of microphase separation into domains of swollen and aggregated hydrophobic chains.


Input: If the hydrophilic polymer is the ionizable component of the network, the nanoaggregation of hydrophobic monomers is weakly dependent on the pH and salt concentration, and except at very low volume fraction, the aggregate is the most probable conformation of the network in the entire range of pH and salt concentration studied.


Input: The two different hydrogels display quantitatively similar swelling transition and apparent pKa, but at the nanoscale, their behavior is qualitatively different.


Input: The spatial distribution of electric charge on the network as well as the local density of the different chemical species within the hydrogel can be controlled, as a function of pH and salt concentration, by the molecular architecture of the polymer network.


Input: These findings have relevance for applications in biomaterials and nanotechnology, in particular, in the design of oral delivery devices for the administration of hydrophobic drugs.


Input: Isolation, characterization, cloning and expression of an alpha-neurotoxin from the venom of the Mexican coral snake Micrurus laticollaris (Squamata: Elapidae).


Input: A new member of short chain alpha-neurotoxic protein family from venom of the Mexican coral snake, Micrurus laticollaris, was characterized.


Input: This protein, named MlatA1, possesses 61 amino acids with 8 conserved cysteine residues, sharing 30-91% sequence identity with other fully sequenced Micrurus toxins.

amino acids

cysteine


Input: MlatA1 (LD50i. v. = 0. 064 mg/kg) antagonizes with both fetal and adult nicotinic acetylcholine receptor (nAChR) as well as alpha-7 neuronal nAChR in a dose-dependent way.

acetylcholine


Input: Specific rabbit anti-Mlat serum (titer higher than 18, 000) does not show any protective ability against this toxin, nevertheless it was able to recognize protein bands in six out of twelve Micrurus venoms showing the existence of two distinct antigenic groups for alpha-neurotoxins in North American coral snakes species.


Input: The MlatA1 gene was cloned and used to produce recombinant toxin (rMlatA1) that was recognized by rabbit anti-native toxin but was depleted of toxic activity.


Input: Rare-variant genome-wide association studies: a new frontier in genetic analysis of complex traits.


Input: Genome-wide association studies have, in the last few years, identified thousands of common genetic variants associated with common complex traits and diseases, implicating many genes not previously known to be involved in the biology of those traits.


Input: However, these variants have so far explained little of the population variance in trait values or disease susceptibility.


Input: As large-scale genome sequencing efforts have revealed the extent of genetic variation at the low end of the frequency range in human populations, the effects of rare variants have been proposed as an explanation of the' missing genetic variance.' Improved technologies for genotyping rare variants, including inexpensive whole-genome and whole-exome sequencing and rare-variant genotyping chips, coupled with novel analytical methods, are making genome-wide scans for the effects of rare variants possible, and seem likely to usher in a new era in the genetic analysis of complex traits.


Input: Does Microsecond Sugar Ring Flexing Encode 3D-Shape and Bioactivity in the Heparanome?

Sugar


Input: The biological information encoded in carbohydrate sequences dwarfs that of proteins and nucleic acids.

carbohydrate


Input: Deciphering structure-function relationships in heparin and heparan sulfate (the heparanome) is further compounded by extreme sequence diversity, experimental difficulties, and the computational cost of rigorous modeling.

sulfate


Input: Here we perform unbiased microsecond dynamics simulations of 11 heparanome oligosaccharides (55 microseconds total) to investigate the effect of sequence on 3D-structure and to underpin a coarse-grained model that is consistent with long-time scale experimentally validated atomic motions in water.


Input: Pyranose ring flexing (puckering) in 2-O-sulfo-alpha-l-iduronic acid, which underlies heparin-mediated anticoagulation, was modulated by polymerization (chain position and adjacent residues), which is supported by previous experiments.

Pyranose

2-O-sulfo-alpha-l-iduronic acid


Input: Furthermore, in coarse-grained simulations, inclusion of puckering was essential to predict macroscopic hydrodynamic properties of heparan sulfate chains containing hundreds of monosaccharaides.

sulfate

monosaccharaides


Input: Our structural findings and model enable rational molecular design, and we propose that, in the heparanome, puckering, polymer 3D-shape, and bioactivity are inextricably linked.


Input: Definition of formulation design space, in vitro bioactivity and in vivo biodistribution for hydrophilic drug loaded PLGA/PEO-PPO-PEO nanoparticles using OFAT experiments.

PLGA

PEO-PPO-PEO


Input: Modified nanoprecipitation method was used for improved incorporation of hydrophilic drug (irinotecan hydrochloride) into the PLGA/PEO-PPO-PEO blended and blended/adsorbed nanoparticles.

irinotecan hydrochloride

PLGA

PEO-PPO-PEO


Input: One factor at a time (OFAT) variation experiments were conducted in order to determine key formulation factors (concentration and volume of drug solution, evaporation rate and PLGA/PEO-PPO-PEO ratio) influencing nanoparticle properties (particle size and size distribution, encapsulation efficiency, drug content, zeta potential, drug dissolution rate, as well as protein binding capacity).

PLGA

PEO-PPO-PEO


Input: The insight into in vivo behavior of prepared nanoparticles and their potential for effective anticancer treatment was gained by performing biodistribution and cell culture studies as part of OFAT experiments.


Input: The mean particle size, mainly dependent upon PLGA/PEO-PPO-PEO ratio, was in the range of 112-125nm, with narrow unimodal distribution (PDI ~ 0. 1).

PLGA

PEO-PPO-PEO


Input: Encapsulation efficiency (32-63%) was impacted by evaporation rate and PLGA/PEO-PPO-PEO ratio.

PLGA

PEO-PPO-PEO


Input: Drug content (0. 2-1. 51%) and controlled release properties were related to the influence of all tested formulation factors.


Input: Structural information for the studied nanoparticles was obtained using DSC and FT-IR spectroscopy.


Input: Zeta potential values indicated that presence of PEO-PPO-PEO in the formulations shielded the high surface negative charge of PLGA.

PEO-PPO-PEO

PLGA


Input: PEO-PPO-PEO surface coverage of PLGA/PEO-PPO-PEO blended as well as blended/adsorbed nanoparticles depended upon amount of used PEO-PPO-PEO during preparation procedure and was related to the protein resistant characteristics of nanoparticles.

PEO-PPO-PEO

PLGA

PEO-PPO-PEO

PEO-PPO-PEO


Input: Results from in vivo studies evidenced prolonged blood circulation time of the prepared nanoparticles, while cell culture studies indicated higher in vitro bioefficacy compared to free drug.


Input: Performed experiments defined possible design space and justified further optimization of formulation using experimental design studies.


Input: Potential for preventive effects of cocoa and cocoa polyphenols in cancer.

polyphenols


Input: Prevention of cancer through the diet is receiving increasing interest, and cocoa because of its polyphenolic compounds has become an important potential chemopreventive and therapeutic natural agent.

polyphenolic


Input: Cocoa and its main polyphenols have been reported to interfere at the initiation, promotion and progression of cancer.

polyphenols


Input: Cocoa flavonoids have been demonstrated to influence several important biological functions in vitro and in vivo by their free radical scavenging ability or through the regulation of signal transduction pathways to stimulate apoptosis and to inhibit inflammation, cellular proliferation, apoptosis, angiogenesis and metastasis.

flavonoids


Input: Nevertheless, these molecular mechanisms of action are not completely characterized and many features remain to be elucidated.


Input: The aim of this review is to provide insights into the molecular basis of the potential chemopreventive activity of cocoa and its polyphenolic components by summarizing cell culture and animal models studies, as well as interventional and epidemiological studies on humans.

polyphenolic


Input: Biosafety and antioxidant effects of a beverage containing silymarin and arginine.

arginine


Input: A pilot, human intervention cross-over trial.


Input: The study objective was to investigate the potential of a beverage containing silymarin and l-arginine to alter basic physiological and urodynamic parameters in 22 normal healthy men aged 38-59years.

l-arginine


Input: The volunteers drank 500ml/day beverage without silymarin and l-arginine for 10days followed, after a 7-day washout period, by the beverage with 400mg silymarin and 295mg l-arginine for 10days.

l-arginine

l-arginine


Input: Blood and urine samples were collected on days 0, 10 and 27.


Input: The beverages were well-tolerated with no adverse effects.


Input: Most of the biochemical, hematological and urodynamic parameters remained unchanged.


Input: Total antioxidant capacity, total level of antioxidants, lipoperoxidation products (malondialdehyde), advanced oxidation products of proteins in plasma and glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase levels in erythrocytes were not influenced.

malondialdehyde

glutathione

glutathione

glutathione

superoxide


Input: Serum gamma-glutamyl transferase, malondialdehyde level and activity of glutathione S-transferase in erythrocytes were lowered at day 27 and the concentration of total plasma SH-groups was higher on day 10.

malondialdehyde

glutathione S

SH


Input: Using an ex vivo system, we found that silymarin/silybin at 10-100 mu M is able to adsorb onto human erythrocytes and the complexes displayed antioxidant properties as studied using ex situ square-wave voltammetry.

silybin


Input: The trial showed that silymarin in vivo may protect erythrocytes against oxidative damage.


Input: Ghrelin inhibits sodium metabisulfite induced oxidative stress and apoptosis in rat gastric mucosa.

sodium metabisulfite


Input: This study aimed to investigate the effect of ghrelin administration on sulfite induced oxidative and apoptotic changes in rat gastric mucosa.

sulfite


Input: Forty male albino Wistar rats were randomized into control (C), sodium metabisulfite (Na2S2O5) treated (S), ghrelin treated (G) and, Na2S2O5 + ghrelin treated (SG) groups.

sodium metabisulfite


Input: Sodium metabisulfite (100mg/kg/day) was given by gastric gavage and, ghrelin (20 mu g/kg/day) was given intraperitoneally for 5weeks.

Sodium metabisulfite


Input: Plasma-S-sulfonate level was increased in S and SG groups.

S

sulfonate


Input: Na2S2O5 administration significantly elevated total oxidant status (TOS) levels while depleting total antioxidant status (TAS) levels in gastric mucosa.


Input: Ghrelin significantly decreased gastric TOS levels in the SG group compared with the S group.


Input: Additionally, TAS levels were found to be higher in SG group in reference to S group.


Input: Na2S2O5 administration also markedly increased the number of apoptotic cells, cleaved caspase-3 and PAR expression (PARP activity indicator) and, decreased Ki67 expression (cell proliferation index) in gastric mucosal cells.


Input: Ghrelin treatment decreased the number apoptotic cells, cytochrome C release, PAR and, caspase-3 expressions while increasing Ki67 expression in gastric mucosa exposed to Na2S2O5.


Input: In conclusion, we suggest that ghrelin treatment might ameliorate ingested-Na2S2O5 induced gastric mucosal injury stemming from apoptosis and oxidative stress in rats.


Input: The development of synthetic antitumour vaccines from mucin glycopeptide antigens.


Input: Based on important cell-biological and biochemical results concerning the structural difference between membrane glycoproteins of normal epithelial cells and epithelial tumour cells, tumour-associated glycopeptide antigens have been chemically synthesised and structurally confirmed.


Input: Glycopeptide structures of the tandem repeat sequence of mucin MUC1 of epithelial tumour cells constitute the most promising tumour-associated antigens.


Input: In order to generate a sufficient immunogenicity of these endogenous structures, usually tolerated by the immune system, these synthetic glycopeptide antigens were conjugated to immune stimulating components: in fully synthetic two-component vaccines either with T-cell peptide epitopes or with Toll-like receptor2 lipopeptide ligands or in three-component vaccines with both these stimulants.


Input: Alternatively, the synthetic glycopeptide antigens were coupled to immune stimulating carrier proteins.


Input: In particular, MUC1 glycopeptide conjugates with Tetanus toxoid proved to be efficient vaccines inducing very strong immune responses in mice.


Input: The antibodies elicited with the fully synthetic vaccines showed selective recognition of the tumour-associated glycopeptides as was shown by neutralisation and micro-array binding experiments.


Input: After booster immunisations, most of the immune responses showed the installation of an immunological memory.


Input: Immunisation with fully synthetic three-component vaccines induced immune reactions with therapeutic effects in terms of reduction of the tumour burden in mice or in killing of tumour cells in culture, while MUC1 glycopeptide-Tetanus toxoid vaccines elicited antibodies in mice which recognised tumour cells in human tumour tissues.


Input: The results achieved so far are considered to be promising for the development of an active immunisation against tumours.


Input: Lab-on-DVD: standard DVD drives as a novel laser scanning microscope for image based point of care diagnostics.


Input: We present a novel " Lab-on-DVD " system and demonstrate its capability for rapid and low-cost HIV diagnostics by counting CD4 + cells isolated from whole blood.


Input: We show that a commercial DVD drive can, with certain modifications, be turned into an improved DVD-based laser scanning microscope (DVD-LSM).


Input: The system consists of a multi-layered disposable polymer disc and a modified commercial DVD reader with rotational control for sample handling, temperature control for optimized bioassay, a photodiode array for detection, and software for signal processing and user interface-all the necessary components required for a truly integrated lab-on-a-chip system, with the capability to deliver high-resolution images down to 1 mu m in size.


Input: Using discs modified with antibodies, we specifically captured CD4 + cells from whole blood, demonstrating single cell resolution imaging.


Input: The novel integrated DVD platform with sub-micron image resolution brings, for the first time, affordable cellular diagnostic testing to the point-of-care and should be readily applicable at resource-limited settings.


Input: Vitamin A and retinoid signaling: genomic and non-genomic effects.

Vitamin A

retinoid


Input: Vitamin A or retinol is arguably the most multifunctional vitamin in the human body as it is essential from embryogenesis to adulthood.

Vitamin A

retinol

vitamin


Input: The pleiotropic effects of vitamin A are exerted mainly by one active metabolite, all-trans retinoic acid (atRA), which regulates the expression of a battery of target genes through several families of nuclear receptors (RARs, RXRs and PPAR beta/delta), polymorphic retinoic acid (RA) response elements and multiple coregulators.

vitamin A

all-trans retinoic acid

atRA

retinoic acid


Input: It also involves extra nuclear and non-transcriptional effects such as the activation of kinase cascades, which are integrated in the nucleus via the phosphorylation of several actors of RA signaling.


Input: However, vitamin A itself proved recently to be active and RARs to be present in the cytosol to regulate translation and cell plasticity.

vitamin A


Input: All these new concepts expand the scope of the biologic functions of vitamin A and RA.

vitamin A


Input: Synthesis and antiproliferative activity evaluation of imidazole-based indeno [1, 2-b] quinoline-9, 11-dione derivatives.

imidazole

indeno [1, 2-b] quinoline-9, 11-dione


Input: A series of new imidazole substituted indeno [1, 2-b] quinoline-9, 11-dione derivatives were synthesized and evaluated for their antiproliferative effects on HeLa, LS180, MCF-7 and Jurkat human cancer cell lines.

imidazole

indeno [1, 2-b] quinoline-9, 11-dione


Input: Antiproliferative effects were evaluated using MTT assay.

MTT


Input: Prepared compounds exhibited weak to good antiproliferative activity in evaluated cell lines.


Input: Prepared compounds were more potent in Jurkat cell line when compared to LS180, HeLa and MCF-7 cell lines.


Input: Compounds 29 (IC16 = 0. 7 mu M) and 31 (IC16 = 1. 7 mu M) and 33 (IC16 = 1. 7 mu M) were found to be the most potent molecules on Jurkat cell lines.


Input: Moreover; it was found that some of the tested compounds bearing imidazole-2-yl moiety on the C11-position of dihydropyridine ring exhibited superior antiproliferative activity in comparison to cis-platin especially in Jurkat cell line (compounds 29, 31, and 33).

dihydropyridine

cis-platin


Input: It seemed that the introduction of electron-withdrawing groups on the imidazole ring enhanced the antiproliferative potential of these compounds (compounds 27, 29 and 31).

imidazole


Input: The results of this study proposed that some of the imidazole substituted indeno [1, 2-b] quinoline-9, 11-dione compounds may act as efficient anticancer agents in vitro, emphasizing their potential role as a source for rational design of potent antiproliferative agents.

imidazole

indeno [1, 2-b] quinoline-9, 11-dione


Input: Epigenetic regulation of hypoxia inducible factor in diseases and therapeutics.


Input: Hypoxia-inducible factors (HIFs) are master regulators of angiogenesis and cellular adaptation in hypoxic microenvironments.


Input: Accumulating evidence indicates that HIFs also regulate cell survival, glucose metabolism, microenvironmental remodeling, cancer metastasis, and tumor progression, and thus, HIFs are viewed as therapeutic targets in many diseases.

glucose


Input: Epigenetic changes are involved in the switching' on' and' off' of many genes, and it has been suggested that the DNA hypermethylation of specific gene promoters, histone modifications (acetylation, phosphorylation, and methylation) and small interfering or micro RNAs be regarded epigenetic gene targets for the regulation of disease-associated cellular changes.


Input: Furthermore, the hypoxic microenvironment is one of the most important cellular stress stimuli in terms of the regulation of cellular epigenetic status via histone modification.


Input: Therefore, drug development and therapeutic approaches to ischemic diseases or cancer for targeting HIFs by modulation of epigenetic status become an attractive area.


Input: Here, the authors provide a review of the literature regarding the targeting of HIF, a key modulator of hypoxic-cell response under various disease conditions, by modulating histone or DNA using endogenous small RNAs or exogenous chemicals.


Input: Unraveling a municipal effluent' s toxicity to Tripneustes gratilla sperm fertilization.


Input: A tiered investigative approach was employed to characterize and identify substances responsible for the persistent toxicity of a primary-treated municipal effluent to gametes of the Hawaiian sea urchin, Tripneustes gratilla.


Input: Toxicity identification evaluation (TIE) procedures from the US Environmental Protection Agency were modified to account for the tolerance of T. gratilla gametes to various sample manipulations.


Input: Microtox rapid toxicity screening was applied in some aspects of the study after verifying a correlation between the pattern of toxic responses of T. gratilla gametes and that of the bioluminescent bacteria Vibrio fischeri.


Input: Toxicity identification evaluation phase I manipulations revealed a toxicity profile implicating surfactants as possible toxicants, and TIE phase II toxicity assessment of isolated fractions coupled with colorimetric surfactant analyses confirmed the possible role of surfactants in effluent toxicity.


Input: The toxic effects of standard reference surfactants on T. gratilla fertilization indicated a concordance with the effects of the more nonpolar effluent fractions.


Input: Treatability studies showed that biodegradation by activated sludge eliminated effluent toxicity to urchin gametes.


Input: Environ Toxicol Chem 2013; 32: 1382-1387.


Input: (c) 2013 SETAC.


Input: Phase stability and elastic properties of chromium borides with various stoichiometries.

chromium borides


Input: Phase stability is important to the application of materials.


Input: By first-principles calculations, we establish the phase stability of chromium borides with various stoichiometries.

chromium borides


Input: Moreover, the phases of CrB3 and CrB4 have been predicted by using a newly developed particle swarm optimization (PSO) algorithm.


Input: Formation enthalpy-pressure diagrams reveal that the MoB-type structure is more energetically favorable than the TiI-type structure for CrB.

MoB

TiI

CrB


Input: For CrB2, the WB2-type structure is preferred at zero pressure.


Input: The predicted new phase of CrB3 belongs to the hexagonal P-6m2 space group and it transforms into an orthorhombic phase as the pressure exceeds 93 GPa.


Input: The predicted CrB4 (space group: Pnnm) phase is more energetically favorable than the previously proposed Immm structure.


Input: The mechanical and thermodynamic stabilities of predicted CrB3 and CrB4 are verified by the calculated elastic constants and formation enthalpies.


Input: The full phonon dispersion calculations confirm the dynamic stability of WB2-type CrB2 and predicted CrB3.


Input: The large shear moduli, large Young' s moduli, low Poisson ratios, and low bulk and shear modulus ratios of CrB4 <F8FF> PSC and CrB4 <F8FF> PSD indicate that they are potential hard materials.


Input: Analyses of Debye temperature, electronic localization function, and electronic structure provide further understanding of the chemical and physical properties of these borides.


Input: Mussel-inspired histidine-based transient network metal coordination hydrogels.

histidine


Input: Transient network hydrogels cross-linked through histidine-divalent cation coordination bonds were studied by conventional rheologic methods using histidine-modified star poly (ethylene glycol) (PEG) polymers.

histidine

histidine

poly (ethylene glycol)

PEG


Input: These materials were inspired by the mussel, which is thought to use histidine-metal coordination bonds to impart self-healing properties in the mussel byssal thread.

histidine


Input: Hydrogel viscoelastic mechanical properties were studied as a function of metal, pH, concentration, and ionic strength.


Input: The equilibrium metal-binding constants were determined by dilute solution potentiometric titration of monofunctional histidine-modified methoxy-PEG and were found to be consistent with binding constants of small molecule analogs previously studied.

histidine

methoxy-PEG


Input: pH-dependent speciation curves were then calculated using the equilibrium constants determined by potentiometric titration, providing insight into the pH dependence of histidine-metal ion coordination and guiding the design of metal coordination hydrogels.

histidine


Input: Gel relaxation dynamics were found to be uncorrelated with the equilibrium constants measured, but were correlated to the expected coordination bond dissociation rate constants.


Input: Comparative Study of Chromatographic Medium-Associated Mass and Potential Antitumor Activity Loss with Bioactive Extracts.


Input: Natural product drug discovery programs often rely on the use of silica (Si) gel, reversed-phase media, or size-exclusion resins (e. g., RP-C (18), Sephadex LH-20) for compound purification.

silica

Si


Input: The synthetic polymer-based sorbent Diaion HP20SS (cross-linked polystyrene matrix) is used as an alternative to prepare purified natural product libraries.

Diaion HP20SS

polystyrene


Input: To evaluate the impact of chromatographic media on the isolation of biologically active, yet chromatographically unstable natural products, Diaion HP20SS was evaluated side-by-side with normal-phase sorbents for irreversible binding of extract constituents and their effects on bioactivity.

Diaion HP20SS


Input: An array of chemically diverse natural product-rich extracts was selected as a test panel, and a cell-based reporter assay for hypoxia-inducible factor-1 (HIF-1) was employed to monitor potential change (s) in bioactivity.


Input: Silica gel caused significant irreversible binding of three out of 10 extracts.


Input: Curcuma longa, Saururus cernuus, and Citrus reticulata extracts showed decreased HIF-1 inhibitory activity after elution through Si gel.

Si


Input: An additional nonpolar column wash of HP20SS with EtOAc retained considerable bioactivities of active extracts.

EtOAc


Input: In general, Si gel produced the greatest loss of bioactivity.

Si


Input: However, HP20SS elution reduced significantly HIF-1 inhibitory activity of certain extracts (e. g., Asimina triloba).


Input: A new pentacyclic phenol and other constituents from the root bark of Bauhinia racemosa Lamk.

pentacyclic phenol


Input: This work reported the isolation of one unknown (1) and 10 known compounds (2-11) from the root bark of Bauhinia racemosa Lamk.


Input: (family: Caesalpiniaceae).


Input: Racemosolone (1) was characterised as a pentacyclic phenolic compound possessing an unusual skeleton with a cycloheptane ring and a rare furopyran moiety.

Racemosolone

pentacyclic phenolic

cycloheptane

furopyran


Input: The structure elucidation was carried out on the basis of UV, infrared (IR), HR-ESI-MS, 1D and 2D NMR spectra and finally confirmed by the single crystal X-ray analysis.


Input: The known compounds were characterised as n-tetracosane, beta-sitosteryl stearate, eicosanoic acid, stigmasterol, beta-sitosterol, racemosol, octacosyl ferulate, de-O-methyl racemosol, lupeol and 1, 7, 8, 12b-tetrahydro-2, 2, 4-trimethyl-2H-benzo [6, 7] cyclohepta [1, 2, 3-de] [1] benzopyran-5, 10, 11 triol on the basis of spectroscopic data comparison with the literature value.

n-tetracosane

beta-sitosteryl stearate

eicosanoic acid

stigmasterol

beta-sitosterol

racemosol

octacosyl ferulate

de-O-methyl racemosol

lupeol

1, 7, 8, 12b-tetrahydro-2, 2, 4-trimethyl-2H-benzo [6, 7] cyclohepta [1, 2, 3-de] [1] benzopyran-5, 10, 11 triol


Input: Compounds with skeleton similar to 1 have never been reported from any natural or other source.


Input: Spur reactions observed by picosecond pulse radiolysis in highly concentrated bromide aqueous solutions.

bromide


Input: The formation of the well-known product Br3 (-), observed in the steady-state radiolysis of highly concentrated Br (-) aqueous solutions, has now been directly observed at ultrashort times corresponding to the relaxation of the spur.

Br3 (-)

Br (-)


Input: The transient absorption induced by picosecond pulse radiolysis of 6 M Br (-) aqueous solution was probed simultaneously at 260 nm with the third harmonic laser wave and from 350 to 750 nm with a supercontinuum generated by the fundamental laser wave.

Br (-)


Input: This approach allows several transient radiolytic species to be followed in parallel, particularly the solvated electron, BrOH (-*), Br2 (-*), and Br3 (-).

BrOH (-*)

Br2 (-*)

Br3 (-)


Input: The kinetics measured within 4 ns at 260 and 370 nm clearly exhibit that the decay of Br2 (*-) is correlated with the formation of Br3 (-).

Br2 (*-)

Br3 (-)


Input: In highly concentrated Br (-) solutions, the OH (*) radical is fully replaced by Br2 (*-), and the spur kinetics of OH (*) radical in pure water is comparable with that of Br2 (-*).

Br (-)

OH (*)

Br2 (*-)

OH (*)

Br2 (-*)


Input: Model calculations indicate that the main OH (*) radical combination product H2O2 in pure water has formation kinetics similar to that of Br3 (-) in 6 M Br (-) solutions.

OH (*)

Br3 (-)

Br (-)


Input: Moreover, they point out that oxidation of Br (-) occurs within the electron pulse both by direct energy absorption and by scavenging of the water radical cation, H2O (* +).

Br (-)

H2O (* +)


Input: Nanomechanical properties of proteins and membranes depend on loading rate and electrostatic interactions.


Input: Knowing the dynamic mechanical response of tissue, cells, membranes, proteins, nucleic acids, and carbohydrates to external perturbations is important to understand various biological and biotechnological problems.

carbohydrates


Input: Atomic force microscopy (AFM)-based approaches are the most frequently used nanotechnologies to determine the mechanical properties of biological samples that range in size from microscopic to (sub) nanoscopic.


Input: However, the dynamic nature of biomechanical properties has barely been addressed by AFM imaging.


Input: In this work, we characterizethe viscoelastic properties of the native light-driven proton pump bacteriorhodopsin of the purple membrane of Halobacterium salinarum.


Input: Using force-distance curve (F-D)-based AFM we imaged purple membranes while force probing their mechanical response over a wide range of loading rates (from ~ 0. 5 to 100 mu N/s).


Input: Our results show that the mechanical stiffness of protein and membrane increases with the loading rate up to a factor of 10 (from ~ 0. 3 to 3. 2 N/m).


Input: In addition, the electrostatic repulsion between AFM tip and sample can alter the mechanical stiffness measured by AFM up to ~ 60% (from ~ 0. 8 to 1. 3 N/m). These findings indicate that the mechanical response of membranes and proteins and probably of other biomolecular systems should be determined at different loading rates to fully understand their properties.


Input: Through the looking glass: adventures in kinase inhibitor design and optimization.


Input: Developing a viable new drug candidate is difficult.


Input: Developing one that is a small molecule kinase inhibitor that binds competitively with respect to ATP with superb selectivity is even more difficult, which makes the design and optimization work described by Jimenez et al.

ATP


Input: (J. Med. Chem., DOI: 10. 1021/jm301465a) particularly remarkable.


Input: They took a lead from a high-throughput screen against protein kinase C theta (PKC theta) through a series of optimization steps, culminating in the demonstration of in vivo activity in mice.


Input: Having identified and improved the hinge-binding " warhead " at one end of their lead molecule, they proceeded to use structure-based design tools to guide modification of the other end to enhance selectivity over a closely related isoform of the kinase.


Input: With that accomplished, they used a series of protection and deprotection maneuvers to modify the central portion of the series scaffold to further enhance potency against the target while also improving pharmacokinetic properties.


Input: The project was a success at the preclinical level: oral administration of the ultimate analogue obtained was effective at suppressing interleukin-2 induction in mice.


Input: Characterization of Palytoxin Binding to HaCaT Cells Using a Monoclonal Anti-Palytoxin Antibody.

Palytoxin

Palytoxin


Input: Palytoxin (PLTX) is the reference compound for a group of potent marine biotoxins, for which the molecular target is Na +/K +-ATPase.

Palytoxin

PLTX

Na +

K +


Input: Indeed, ouabain (OUA), a potent blocker of the pump, is used to inhibit some PLTX effects in vitro.

ouabain

OUA

PLTX


Input: However, in an effort to explain incomplete inhibition of PLTX cytotoxicity, some studies suggest the possibility of two different binding sites on Na +/K +-ATPase.

PLTX

Na +

K +


Input: Hence, this study was performed to characterize PLTX binding to intact HaCaT keratinocytes and to investigate the ability of OUA to compete for this binding.

PLTX

OUA


Input: PLTX binding to HaCaT cells was demonstrated by immunocytochemical analysis after 10 min exposure.

PLTX


Input: An anti-PLTX monoclonal antibody-based ELISA showed that the binding was saturable and reversible, with a K (d) of 3 x 10-10 M.

PLTX


Input: However, kinetic experiments revealed that PLTX binding dissociation was incomplete, suggesting an additional, OUA-insensitive, PLTX binding site.

PLTX

OUA

PLTX


Input: Competitive experiments suggested that OUA acts as a negative allosteric modulator against high PLTX concentrations (0. 3-1. 0 x 10-7 M) and possibly as a non-competitive antagonist against low PLTX concentrations (0. 1-3. 0 x 10-9 M).

OUA

PLTX

PLTX


Input: Antagonism was supported by PLTX cytotoxicity inhibition at OUA concentrations that displaced PLTX binding (1 x 10-5 M).

PLTX

OUA

PLTX


Input: However, this inhibition was incomplete, supporting the existence of both OUA-sensitive and-insensitive PLTX binding sites.

OUA

PLTX


Input: Correlation of photobleaching, oxidation and metal induced fluorescence quenching of DNA-templated silver nanoclusters.

silver


Input: Few-atom noble metal nanoclusters have attracted a lot of interest due to their potential applications in biosensor development, imaging and catalysis.


Input: DNA-templated silver nanoclusters (AgNCs) are of particular interest as different emission colors can be obtained by changing the DNA sequence.

silver


Input: A popular analytical application is fluorescence quenching by Hg (2 +), where d (10)-d (10) metallophilic interaction has often been proposed for associating Hg (2 +) with nanoclusters.

Hg (2 +)

Hg (2 +)


Input: However, it cannot explain the lack of response to other d (10) ions such as Zn (2 +) and Cd (2 +).

Zn (2 +)

Cd (2 +)


Input: In our effort to elucidate the quenching mechanism, we studied a total of eight AgNCs prepared by different hairpin DNA sequences; they showed different sensitivity to Hg (2 +), and DNA with a larger cytosine loop size produced more sensitive AgNCs.

Hg (2 +)

cytosine


Input: In all the cases, samples strongly quenched by Hg (2 +) were also more easily photobleached.

Hg (2 +)


Input: Light of shorter wavelengths bleached AgNCs more potently, and photobleached samples can be recovered by NaBH4.


Input: Strong fluorescence quenching was also observed with high redox potential metal ions such as Ag (+), Au (3 +), Cu (2 +) and Hg (2 +), but not with low redox potential ions.

Ag (+)

Au (3 +)

Cu (2 +)

Hg (2 +)


Input: Such metal induced quenching cannot be recovered by NaBH4.


Input: Electronic absorption and mass spectrometry studies offered further insights into the oxidation reaction.


Input: Our results correlate many important experimental observations and will fuel the further growth of this field.


Input: Computational drug repositioning: from data to therapeutics.


Input: Traditionally, most drugs have been discovered using phenotypic or target-based screens.


Input: Subsequently, their indications are often expanded on the basis of clinical observations, providing additional benefit to patients.


Input: This review highlights computational techniques for systematic analysis of transcriptomics (Connectivity Map, CMap), side effects, and genetics (genome-wide association study, GWAS) data to generate new hypotheses for additional indications.


Input: We also discuss data domains such as electronic health records (EHRs) and phenotypic screening that we consider promising for novel computational repositioning methods.


Input: On the accuracy of explicitly correlated methods to generate potential energy surfaces for scattering calculations and clustering: application to the HCl-He complex.

HCl

He


Input: We closely compare the accuracy of multidimensional potential energy surfaces (PESs) generated by the recently developed explicitly correlated coupled cluster (CCSD (T)-F12) methods in connection with the cc-pVXZ-F12 (X = D, T) and aug-cc-pVTZ basis sets and those deduced using the well-established orbital-based coupled cluster techniques employing correlation consistent atomic basis sets (aug-cc-pVXZ, X = T, Q, 5) and extrapolated to the complete basis set (CBS) limit.


Input: This work is performed on the benchmark rare gas-hydrogen halide interaction (HCl-He) system.

hydrogen halide

HCl

He


Input: These PESs are then incorporated into quantum close-coupling scattering dynamical calculations in order to check the impact of the accuracy of the PES on the scattering calculations.


Input: For this system, we deduced inelastic collisional data including (de-) excitation collisional and pressure broadening cross sections.


Input: Our work shows that the CCSD (T)-F12/aug-cc-pVTZ PES describes correctly the repulsive wall, the van der Waals minimum and long range internuclear distances whereas cc-pVXZ-F12 (X = D, T) basis sets are not diffuse enough for that purposes.


Input: Interestingly, the collision cross sections deduced from the CCSD (T)-F12/aug-cc-pVTZ PES are in excellent agreement with those obtained with CCSD (T)/CBS methodology.


Input: The position of the resonances and the general shape of these cross sections almost coincide.


Input: Since the cost of the electronic structure computations is reduced by several orders of magnitude when using CCSD (T)-F12/aug-cc-pVTZ compared to CCSD (T)/CBS methodology, this approach can be recommended as an alternative for generation of PESs of molecular clusters and for the interpretation of accurate scattering experiments as well as for a wide production of collisional data to be included in astrophysical and atmospherical models.


Input: Eugenol alters the integrity of cell membrane and acts against the nosocomial pathogen Proteus mirabilis.

Eugenol


Input: Eugenol, a member of the phenylpropanoids class of chemical compounds, is a clear to pale yellow oily liquid extracted from certain essential oils especially from clove oil, nutmeg, cinnamon, and bay leaf.

Eugenol


Input: The antibacterial activity of eugenol and its mechanism of bactericidal action against Proteus mirabilis were evaluated.

eugenol


Input: Treatment with eugenol at their minimum inhibitory concentration [0. 125% (v/v)] and minimum bactericidal concentration [0. 25% (v/v)] reduced the viability and resulted in complete inhibition of P. mirabilis.

eugenol


Input: A strong bactericidal effect on P. mirabilis was also evident, as eugenol inactivated the bacterial population within 30 min exposure.

eugenol


Input: Chemo-attractant property and the observance of highest antibacterial activity at alkaline pH suggest that eugenol can work more effectively when given in vivo.

eugenol


Input: Eugenol inhibits the virulence factors produced by P. mirabilis as observed by swimming motility, swarming behavior and urease activity.

Eugenol


Input: It interacts with cellular membrane of P. mirabilis and makes it highly permeable, forming nonspecific pores on plasma membrane, which in turn directs the release of 260 nm absorbing materials and uptake of more crystal violet from the medium into the cells.

crystal violet


Input: SDS-polyacrylamide gel, scanning electron microscopy and Fourier transform infrared analysis further proves the disruptive action of eugenol on the plasma membrane of P. mirabilis.

SDS

polyacrylamide

eugenol


Input: The findings reveal that eugenol shows an excellent bactericidal activity against P. mirabilis by altering the integrity of cell membrane.

eugenol


Input: miR-7641 modulates the expression of CXCL1 during endothelial differentiation derived from human embryonic stem cells.


Input: MicroRNAs (miRNAs) are a class of small noncoding RNAs that negatively regulate gene expression through binding to 3' untranslated region.


Input: We identified and characterized the novel miRNA, miR-7641, in human mesenchymal stem cells.


Input: The expression of miR-7641 was downregulated during differentiation from human embryonic stem cells to endothelial cells.


Input: The CXCL1, a member of the CXC chemokine family, is known as promoting neovascularization by binding G-protein coupled receptors and is related to endothelial cells biogenesis such as angiogenesis, and it was predicted as target gene of miR-7641 by computerized analysis and the luciferase reporter assay.


Input: The miR-7641 significantly suppressed CXCL1 of transcriptional and post-translational levels.


Input: These data suggest that miR-7641 might be related with differentiation of human endothelial cells.


Input: Phenolic constituents from Parakmeria yunnanensis and their anti-HIV-1 activity.

Phenolic


Input: Three new phenolic compounds, yunnanensins A-C (1-3), together with fourteen known ones (4-17), were isolated from the leaves and stems of Parakmeria yunnanensis.

phenolic

yunnanensins A-C


Input: The structures of new compounds were established on the basis of extensive spectroscopic analyses.


Input: Several compounds showed weak anti-HIV-1 activity.


Input: Selective inhibition of an apicoplastic aminoacyl-tRNA synthetase from Plasmodium falciparum.

aminoacyl


Input: The resistance of malaria parasites to available drugs continues to grow, and this makes the need for new antimalarial therapies pressing.


Input: Aminoacyl-tRNA synthetases (ARSs) are essential enzymes and well-established antibacterial targets and so constitute a promising set of targets for the development of new antimalarials.

Aminoacyl


Input: Despite their potential as drug targets, apicoplastic ARSs remain unexplored.


Input: We have characterized the lysylation system of Plasmodium falciparum, and designed, synthesized, and tested a set of inhibitors based on the structure of the natural substrate intermediate: lysyl-adenylate.

lysyl-adenylate


Input: Here we demonstrate that selective inhibition of apicoplastic ARSs is feasible and describe new compounds that that specifically inhibit Plasmodium apicoplastic lysyl-tRNA synthetase and show antimalarial activities in the micromolar range.

lysyl


Input: Pseudo-complementary PNA actuators as reversible switches in dynamic DNA nanotechnology.


Input: The structural reorganization of nanoscale DNA architectures is a fundamental aspect in dynamic DNA nanotechnology.


Input: Commonly, DNA nanoarchitectures are reorganized by means of toehold-expanded DNA sequences in a strand exchange process.


Input: Here we describe an unprecedented, toehold-free switching process that relies on pseudo-complementary peptide nucleic acid (pcPNA) by using a mechanism that involves double-strand invasion.


Input: The usefulness of this approach is demonstrated by application of these peptide nucleic acids (PNAs) as switches in a DNA rotaxane architecture.


Input: The monomers required for generating the pcPNA were obtained by an improved synthesis strategy and were incorporated into a PNA actuator sequence as well as into a short DNA strand that subsequently was integrated into the rotaxane architecture.


Input: Alternate addition of a DNA and PNA actuator sequence allowed the multiple reversible switching between a mobile rotaxane macrocycle and a stationary pseudorotaxane state.


Input: The switching occurs in an isothermal process at room temperature and is nearly quantitative in each switching step.


Input: pcPNAs can potentially be combined with light-and toehold-based switches, thus broadening the toolbox of orthogonal switching approaches for DNA architectures that open up new avenues in dynamic DNA nanotechnology.


Input: The neonicotinoid imidacloprid shows high chronic toxicity to mayfly nymphs.

imidacloprid


Input: The present study evaluated the acute and chronic toxicity of imidacloprid to a range of freshwater arthropods.

imidacloprid


Input: Mayfly and caddisfly species were most sensitive to short-term imidacloprid exposures (10 tests), whereas the mayflies showed by far the most sensitive response to long-term exposure of all seven arthropod species tested (28-d EC10 values of approximately 0. 03 micro g/L).

imidacloprid


Input: The results indicated a high aquatic risk of chronic exposure of imidacloprid to mayflies.

imidacloprid


Input: Environ.


Input: Toxicol.


Input: Chem.


Input: 2013; 32: 1096-1100.


Input: (c) 2013 SETAC.


Input: Pharmacokinetics of modified-release prednisone tablets in healthy subjects and patients with rheumatoid arthritis.

prednisone


Input: In rheumatoid arthritis (RA), nocturnal release of proinflammatory cytokines is not adequately counteracted by endogenous glucocorticoid and is associated with symptoms of morning stiffness and pain.


Input: Taking exogenous glucocorticoid during the night reduces morning stiffness significantly more than treatment at the conventional time in the morning, although waking to take tablets is unacceptable for patients.


Input: Modified-release prednisone tablets were developed to allow administration at bedtime for programmed delivery of glucocorticoid during the night.

prednisone


Input: Single-center crossover studies were conducted, each in <= 24 healthy subjects, to compare the pharmacokinetics of a single 5-mg oral dose of modified-release prednisone and conventional prednisone, as well as the effect of food on bioavailability.

prednisone

prednisone


Input: There was no substantial difference in pharmacokinetic parameters of the formulations apart from the programmed delay in release of glucocorticoid from the modified-release tablets (C (max) 97%, AUC (0-infinity) 101%, 90% confidence intervals within the requisite range for bioequivalence).


Input: Administration after a full or light meal did not affect pharmacokinetic characteristics, but bioavailability was reduced under fasted conditions.


Input: Pharmacokinetic evaluation in 9 patients with RA confirmed that modified-release prednisone tablets taken at bedtime (around 22: 00 h) with or after an evening meal result in programmed release of glucocorticoid 4 to 6 hours after intake.

prednisone


Input: Modification of the Catalytic Function of Human Hydroxysteroid Sulfotransferase hSULT2A1 by Formation of Disulfide Bonds.

Hydroxysteroid

Disulfide


Input: The human cytosolic sulfotransferase hSULT2A1 catalyzes the sulfation of a broad range of xenobiotics, as well as endogenous hydroxysteroids and bile acids.

hydroxysteroids

bile acids


Input: Reversible modulation of the catalytic activity of this enzyme could play important roles in its physiologic functions.


Input: Whereas other mammalian sulfotransferases are known to be reversibly altered by changes in their redox environment, this has not been previously shown for hSULT2A1.


Input: We have examined the hypothesis that the formation of disulfide bonds in hSULT2A1 can reversibly regulate the catalytic function of the enzyme.

disulfide


Input: Three thiol oxidants were used as model compounds to investigate their effects on homogeneous preparations of hSULT2A1: glutathione disulfide, 5, 5'-dithiobis (2-nitrobenzoic acid), and 1, 1'-azobis (N, N-dimethylformamide) (diamide).

thiol

glutathione disulfide

5, 5'-dithiobis (2-nitrobenzoic acid)

1, 1'-azobis (N, N-dimethylformamide

diamide


Input: Examination of the effects of disulfide bond formation with these agents indicated that the activity of the enzyme is reversibly altered.

disulfide


Input: Studies on the kinetics of the hSULT2A1-catalyzed sulfation of dehydroepiandrosterone (DHEA) showed the effects of disulfide bond formation on the substrate inhibition characteristics of the enzyme.

dehydroepiandrosterone

DHEA

disulfide


Input: The effects of these agents on the binding of substrates and products, liquid chromatography-mass spectrometry identification of the disulfides formed, and structural modeling of the modified enzyme were examined.

disulfides


Input: Our results indicate that conformational changes at cysteines near the nucleotide binding site affect the binding of both the nucleotide and DHEA to the enzyme, with the specific effects dependent on the structure of the resulting disulfide.

cysteines

nucleotide

nucleotide

DHEA

disulfide


Input: Thus, the formation of disulfide bonds in hSULT2A1 is a potentially important reversible mechanism for alterations in the rates of sulfation of both endogenous and xenobiotic substrates.

disulfide


Input: Prokaryotic multicellularity: a nanopore array for bacterial cell communication.


Input: The transition from unicellular to multicellular life, which occurred several times during evolution, requires tight interaction and communication of neighboring cells.


Input: The multicellular cyanobacterium Nostoc punctiforme ATCC 29133 forms filaments of hundreds of interacting cells exchanging metabolites and signal molecules and is able to differentiate specialized cells in response to environmental stimuli.


Input: Mutation of cell wall amidase AmiC2 leads to a severe phenotype with formation of aberrant septa in the distorted filaments, which completely lack cell communication and potential for cell differentiation.


Input: Here we demonstrate the function of the amidase AmiC2 in formation of cell-joining structures.


Input: The AmiC2 protein localizes to the young septum between cells and shows bona fide amidase activity in vivo and in vitro.


Input: Vancomycin staining identified the overall septum morphology in living cells.

Vancomycin


Input: By electron microscopy of isolated peptidoglycan sacculi, the submicroscopic structure of the cell junctions could be visualized, revealing a novel function for a cell wall amidase: AmiC2 drills holes into the cross-walls, forming an array of ~ 155 nanopores with a diameter of ~ 20 nm each.


Input: These nanopores seem to constitute a framework for cell-joining proteins, penetrating the cell wall.


Input: The entire array of junctional nanopores appears as a novel bacterial organelle, establishing multicellularity in a filamentous prokaryote.-Lehner, J., Berendt, S., D o rsam, B., P e rez, R., Forchhammer, K., Maldener, I.


Input: Prokaryotic multicellularity: a nanopore array for bacterial cell communication.


Input: Characterization, pharmacokinetics, tissue distribution and antitumor activity of honokiol submicron lipid emulsions in tumor-burdened mice.

honokiol


Input: Honokiol, isolated from the Chinese traditional herb magnolia, is a poorly water-soluble component and has been found to have anti-tumor properties.

Honokiol


Input: In the current study, honokiol submicron lipid emulsions (HK-SLEs) were prepared by high pressure homogenization technology.

honokiol