Input: Using in vitro single-cell recording techniques in mouse brain slices, we examined the physiological effects of KOR activation in CeA on GABAergic neurotransmission and its interaction with acute ethanol.

ethanol


Input: A selective KOR agonist (U69593, 1 mu M) diminished evoked GABAergic inhibitory postsynaptic currents (IPSCs) by 18% (n = 10) in the CeA, whereas blockade of KORs with a selective antagonist (nor-binaltorphimine, 1 mu M) augmented the baseline evoked GABAergic IPSCs by 14% (p < 0. 01; n = 34), suggesting that the KOR system contributes to tonic inhibition of GABAergic neurotransmission in the CeA.

nor-binaltorphimine


Input: In addition, the enhancement by acute ethanol of GABAergic IPSC amplitudes in the CeA was further augmented by pharmacological blockade of KORs, from 14% (n = 36) to 27% (n = 26; p < 0. 01), or by genetic deletion of KORs, from 14% in WT mice (n = 19) to 34% in KOR knockout (KO) mice (n = 13, p < 0. 01), suggesting that the KOR system regulates acute ethanol actions in the CeA.

ethanol

ethanol


Input: Subsequent experiments using tetrodotoxin to block activity-dependent neurotransmission suggest that KORs regulate GABA release at presynaptic sites.

GABA


Input: Thus, KOR activation modulates GABAergic neurotransmission and ethanol effects in CeA in a manner similar to other subtypes of opioid receptors, i. e., mu and delta opioid receptors (Kang-Park et al., 2007; Kang-Park et al., 2009).

ethanol


Input: Our data support the idea that KORs modulate GABAergic synaptic responses and ethanol effects as one of multiple opioid system-dependent actions of ethanol in the CeA, possibly in a circuit-specific manner.

ethanol

ethanol


Input: Application of the combinative particle size reduction technology H 42 to produce fast dissolving glibenclamide tablets.

glibenclamide


Input: Standard particle size reduction techniques such as high pressure homogenization or wet bead milling are frequently used in the production of nanosuspensions.


Input: The need for micronized starting material and long process times are their evident disadvantages.


Input: Combinative particle size reduction technologies have been developed to overcome the drawbacks of the standard techniques.


Input: The H 42 combinative technology consists of a drug pre-treatment by means of spray-drying followed by standard high pressure homogenization.


Input: In the present paper, spray-drying process parameters influencing the diminution effectiveness, such as drug and surfactant concentration, were systematically analyzed.


Input: Subsequently, the untreated and pre-treated drug powders were homogenized for 20 cycles at 1500bar.


Input: For untreated, micronized glibenclamide, the particle size analysis revealed a mean particle size of 772nm and volume-based size distribution values of 2. 686 mu m (d50%) and 14. 423 mu m (d90%).

glibenclamide


Input: The use of pre-treated material (10: 1 glibenclamide/docusate sodium salt ratio spray-dried as ethanolic solution) resulted in a mean particle size of 236nm and volume-based size distribution values of 0. 131 mu m (d50%) and 0. 285 mu m (d90%).

glibenclamide

docusate sodium


Input: These results were markedly improved compared to the standard process.


Input: The nanosuspensions were further transferred into tablet formulations.


Input: Wet granulation, freeze-drying and spray-drying were investigated as downstream methods to produce dry intermediates.


Input: Regarding the dissolution rate, the rank order of the downstream processes was as follows: Spray-drying > freeze-drying > wet granulation.


Input: The best drug release (90% within 10min) was obtained for tablets produced with spray-dried nanosuspension containing 2% mannitol as matrix former.

mannitol


Input: In comparison, the tablets processed with micronized glibenclamide showed a drug release of only 26% after 10min.

glibenclamide


Input: The H 42 combinative technology could be successfully applied in the production of small drug nanocrystals.


Input: A nanosuspension transfer to tablets that maintained the fast dissolution properties of the drug nanocrystals was successfully achieved.


Input: Regulation of connexin hemichannel activity by membrane potential and the extracellular calcium in health and disease.

calcium


Input: Connexins are thought to solely mediate cell-to-cell communication by forming gap junction channels composed of two membrane-spanning hemichannels positioned end-to-end.


Input: However, many if not all connexin isoforms also form functional hemichannels (i. e., the precursors of complete channels) that mediate the rapid exchange of ions, second messengers and metabolites between the cell interior and the interstitial space.


Input: Electrical and molecular signaling via connexin hemichannels is now widely recognized to be important in many physiological scenarios and pathological conditions.


Input: Indeed, mutations in connexins that alter hemichannel function have been implicated in several diseases.


Input: Here, we present a comprehensive overview of how hemichannel activity is tightly regulated by membrane potential and the external calcium concentration.

calcium


Input: In addition, we discuss the genetic mutations known to alter hemichannel function and their deleterious effects, of which a better understanding is necessary to develop novel therapeutic approaches for diseases caused by hemichannel dysfunction.


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


Input: Cyp1a reporter zebrafish reveals target tissues for dioxin.

dioxin


Input: 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD) is the unintentional byproduct of various industrial processes, is classified as human carcinogen and could disrupt reproductive, developmental and endocrine systems.

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

TCDD


Input: Induction of cyp1a1 is used as an indicator of TCDD exposure.

TCDD


Input: We sought to determine tissues that are vulnerable to TCDD toxicity using a transgenic zebrafish (Danio rerio) model.

TCDD


Input: We inserted a nuclear enhanced green fluorescent protein gene (EGFP) into the start codon of a zebrafish cyp1a gene in a fosmid clone using DNA recombineering.


Input: The resulting recombineered fosmid was then used to generate cyp1a reporter zebrafish, embryos of which were exposed to TCDD.

TCDD


Input: Expression pattern of EGFP in the reporter zebrafish mirrored that of endogenous cyp1a mRNA.


Input: In addition, exposure of the embryos to TCDD at as low as 10pM for 72h, which does not elicit morphological abnormalities of embryos, markedly increased GFP expression.

TCDD


Input: Furthermore, the reporter embryos responded to other AhR ligands as well.


Input: Exposure of the embryos to TCDD revealed previously reported (the cardiovascular system, liver, pancreas, kidney, swim bladder and skin) and unreported target tissues (retinal bipolar cells, otic vesicle, lateral line, cloaca and pectoral fin bud) for TCDD.

TCDD

TCDD


Input: Transgenic cyp1a reporter zebrafish we have developed can further understanding of ecotoxicological relevance and human health risks by TCDD.

TCDD


Input: In addition, they could be used to identify agonists of AhR and antidotes to TCDD toxicity.

TCDD


Input: Reduction of the enniatins A, A1, B, B1 by an in vitro degradation employing different strains of probiotic bacteria: Identification of degradation products by LC-MS-LIT.

enniatins A, A1, B, B1


Input: The degradation of the Fusarium mycotoxins ENs by 9 bacterial strains characteristic of the gastrointestinal tract like Bb. longum, Bb. bifidum, Bb. breve, Bb. adolescentes, Lb. rhamnosus, Lb. casei-casei, S. termofilus, Lb. ruminis, Lb. casei and twenty two strains of Saccharomyces cerevisiae was studied.

ENs


Input: The fermentations were carried out in the liquid medium of De Man Rogosa Sharpe (MRS) under anaerobic conditions for Bifidobacteria Streptococcus and Lactobacillus, and in Potato Dextrose Broth (PDB) for Saccharomyces strains, during 48 h.

Dextrose


Input: The degradation of the bioactive compounds ENs was also studied in a food system composed by wheat flour naturally contaminated by ENs through fermentation by a strain of Fusarium tricinctum.

ENs

ENs


Input: The determination of the ENs in the fermentation mediums was performed using the technique of the liquid chromatography coupled to the mass spectrometry detector in tandem (LC-MS/MS), whereas the identification of the degradation products produced by microbial fermentation was carried out using the technique of the LC coupled to the linear ion trap (LIT).

ENs


Input: All the bacteria analyzed in this study showed a significant ENs reduction in vitro during the fermentation processes, with degradation data ranging from 5 to the 99%.

ENs


Input: In the food system, the ENs degradation data evidenced ranged from 1. 3 to 49. 2%.

ENs


Input: Also three ENs degradation products were identified.

ENs


Input: Antimicrobial interactions of Khoi-San poly-herbal remedies with emphasis on the combination; Agathosma crenulata, Dodonaea viscosa and Eucalyptus globulus.


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Plants are often combined in traditional herbal remedies to increase medicinal efficacy, thus this investigation provides some insight into the antimicrobial efficacies of selected combinations.


Input: AIMS OF THE STUDY: The first aim was to scientifically validate antibacterial efficacy of plant mixtures that are traded within peri-urban centres of Cape Town (Western Cape, South Africa).


Input: This was followed by an in-depth evaluation of the most antimicrobially active mixture; Agathosma crenulata, Dodonaea viscosa with Eucalyptus globulus.


Input: MATERIALS AND METHODS: Methanol and aqueous extracts of six plant mixtures were screened for antibacterial properties against two Gram-negative and two Gram-positive bacteria using the minimum inhibitory microdilution method.

Methanol


Input: Thereafter, chloroform: methanol (1: 1; v/v) extracts, essential oils and aqueous extracts of Agathosma crenulata, Dodonaea viscosa and Eucalyptus globulus were assayed for antimicrobial activity independently and in various combinations.

chloroform

methanol


Input: The fractional inhibitory concentration indices (Esh FIC) were determined for double and triple plant combinations to establish antimicrobial interactions.


Input: RESULTS: From the six plant mixtures prepared by herbalists, a methanol extract derived from combining Agathosma crenulata, Dodonaea viscosa and Eucalyptus globulus showed the best antibacterial activity.

methanol


Input: The MIC values of 49 mu g/ml for Staphylococcus aureus and Bacillus subtilis, and 98 mu g/ml for Klebsiella pneumoniae and Escherichia coli were recorded.


Input: When Agathosma crenulata, Dodonaea viscosa and Eucalyptus globulus were mixed in various 1: 1 combinations, mostly additive and synergistic interactions were noted.


Input: The most noteworthy synergistic (Sigma FIC value 0. 07) 1: 1 combinations were observed for the chloroform: methanol extracts of Agathosma crenulata mixed with Eucalyptus globulus against Klebsiella pneumoniae, Staphylococcus aureus and Bacillus subtilis.

chloroform

methanol


Input: When combined in a mixture of three plants (1: 1: 1), enhanced efficacy was evident against most of the pathogens, for both organic and aqueous extracts.


Input: The triple combination against Bacillus subtilis demonstrated the greatest synergy (Sigma FIC values of 0. 03).


Input: CONCLUSIONS: The enhanced antimicrobial efficacy and synergistic interactions noted for some of the mixtures, particularly the combination of Agathosma crenulata, Dodonaea viscosa and Eucalyptus globulus support the Western Cape Khoi-San traditional medicinal practices of combining plants for enhanced efficacy.


Input: Changes in mRNA and protein expression in the renal cortex of male and female F344 rats treated with bromate.

bromate


Input: Bromate (BrO3 (-)), a by-product of ozonation of drinking water, induces nephrotoxicity in male rats at much lower doses than in female rats.

Bromate

BrO3 (-)


Input: This difference appears to be related to the development of alpha-2u-globulin nephropathy in males.


Input: To determine sex-dependent changes in mRNA and protein expression in the renal cortex attributable to alpha-2u-globulin nephropathy, we performed microarray and immunohistochemical analyses in proximal renal tubules of male and female F344 rats treated with KBrO3 for 28 days.


Input: Particular attention was paid to molecular biomarkers of renal tubular injury.


Input: Microarray analysis of male and female rats treated with BrO3 (-) at low doses (125 mg/L KBrO3) displayed marked sex-dependent changes in renal gene expression.

BrO3 (-)


Input: The greatest differences were seen in genes encoding for cellular differentiation, apoptosis, ion transport, and cell proliferation.


Input: Differences by sex were especially prominent for the cell cycle checkpoint gene p21, the renal injury protein Kim-1, and the kidney injury and cancer biomarker protein osteopontin.


Input: Dose-related nephrotoxicity, assessed by hematoxylin and eosin staining, was greater in males compared to female rats, as was cellular proliferation, assessed by bromodeoxyuridine staining.

hematoxylin

eosin

bromodeoxyuridine


Input: The fraction of proximal renal cells with elevated 8-oxodeoxyguanosine (8-OH-dG) was only increased at the high dose and did not differ by sex.


Input: Dose-dependent increases in the expression of osteopontin were detected immunohistochemically only in male rats and were localized in proximal tubule cells.


Input: Similarly, BrO3 (-) treatment increased clusterin and Kim-1 staining in the proximal tubules; however, staining for these proteins did not differ appreciably between males and females.

BrO3 (-)


Input: These data demonstrate both qualitative and quantitative differences in the response of male versus female kidneys to BrO3 (-)-treatment.

BrO3 (-)


Input: These sex-dependent effects likely contribute to renal carcinogenesis of BrO3 (-) in the male rat.

BrO3 (-)


Input: Why Clinical Inhibition of Efflux Transport at the Blood-Brain Barrier is Unlikely: The ITC Evidence-Based Position.


Input: Drug interactions due to efflux transporter inhibition at the blood-brain barrier have been receiving increasing scrutiny due to the theoretical possibility of adverse CNS effects based on findings from preclinical studies.


Input: In this commentary, evidence from pharmacokinetic, pharmacodynamic, imaging, pharmacogenetic, and pharmacovigilance studies, along with drug safety reports, is presented supporting a low probability of inhibiting efflux transporters at the human blood-brain barrier by currently marketed drugs. Clinical Pharmacology & Therapeutics (2013); accepted article preview 14 February 2013 doi: 10. 1038/clpt. 2013. 34.


Input: A Physiologically-Based Pharmacokinetic Modelling Approach to Predict Disease-Drug Interactions: Suppression of CYP3A by IL-6.


Input: Elevated cytokine levels can down-regulate expression of cytochrome P450 enzymes (CYPs) and suppress their activity.


Input: Treatment of inflammation or infection with cytokine-modulating therapeutic proteins (TP) could reverse suppression manifesting as therapeutic protein-drug drug interactions (TP-DDI).


Input: A physiologically-based pharmacokinetic model was used to quantitatively predict the impact of IL-6 on sensitive CYP3A4 substrates.


Input: Elevated simvastatin AUC in virtual rheumatoid arthritis patients, following 100 pg/mL of IL-6 was comparable to observed clinical data (59% versus 58%).

simvastatin


Input: In virtual bone marrow transplant (BMT) patients, 500 pg/ml of IL-6 resulted in increase in cyclosporine AUC that was in good agreement with the observed data (45% versus 39%).

cyclosporine


Input: In a different group of BMT patients treated with cyclosporine, the magnitude of interaction with IL-6 was under predicted ~ 3-fold.

cyclosporine


Input: The complexity of TP-DDI highlights underlying pathophysiological factors to be considered but these simulations provide valuable first steps towards predictions of TP-DDI risk. Clinical Pharmacology & Therapeutics (2013); accepted article preview online 10 April 2013 doi: 10. 1038/clpt. 2013. 79.


Input: Model-Based Drug Development: A Rational Approach to Efficiently Accelerate Drug Development.


Input: The pharmaceutical industry continues to face significant challenges.


Input: Very few compounds that enter development reach the marketplace, and the investment required for each success can surpass $1. 8 billion.


Input: Despite attempts to improve efficiency and increase productivity, total investment continues to rise whereas the output of new medicines declines.


Input: With costs increasing exponentially through each development phase, it is failure in phase II and phase III that is most wasteful.


Input: In today' s development paradigm, late-stage failure is principally a result of insufficient efficacy.


Input: This is manifested as either a failure to differentiate sufficiently from placebo (shown for both novel and precedented mechanisms) or a failure to demonstrate sufficient differentiation from existing compounds.


Input: Set in this context, this article will discuss the role model-based drug development (MBDD) approaches can and do play in accelerating and optimizing compound development strategies through a series of illustrative examples. Clinical Pharmacology & Therapeutics (2013); advance online publication 1 May 2013. doi: 10. 1038/clpt. 2013. 54.


Input: Aspects of physicians' attitudes towards the rational use of drugs at a training and research hospital: a survey study.


Input: PURPOSE: The rational use of drugs (RUD) is primarily the responsibility of physicians.


Input: The aim of this study was to investigate whether physicians are aware of RUD principles and how they apply them in daily medical practice.


Input: METHODS: A total 136 physicians working at the Kartal Training and Research Hospital in Istanbul were enrolled in the study between February and March 2012.


Input: A face-to-face interview was conducted with physicians to assess their knowledge and attitude regarding RUD.


Input: RESULTS: A large majority of the physicians declared that consultation time was insufficient (84%).


Input: The data obtained from the survey indicate that 54% of the enrolled physicians monitored the therapeutic outcome and that 27% found the information given to the patient to be sufficient.


Input: Participating physicians stated that the less known characteristics of the drugs they prescribed were drug interactions, traceability in market, and price.


Input: The most preferred reference source was Vademecum (a drug guideline prepared by the private sector).


Input: Two major factors contributing to prescribing patterns were " self study " and " observation of teachers " at clinical training.


Input: There was a significant difference between internists-surgeons and residents-specialists in the number of prescribed drugs per prescription (p < 0. 001) and in the information provided to the patient on the prescribed drugs (name, effect, dose, instructions, possible side effect) (p < 0. 05), respectively.


Input: CONCLUSIONS: Our findings overall show that the principles of RUD were not fully applied in daily medical practice by the participating physicians.


Input: One important reason for this is a heavy patient load, which requires a change in managerial practices within the healthcare system.


Input: The other, more essential explanation is education; consequently, serious consideration should be given to including effective clinical pharmacotherapy training and RUD courses in the medical education curriculum.


Input: Factors Influencing Magnitude and Duration of Target Inhibition Following Antibody Therapy: Implications in Drug Discovery and Development.


Input: Antibodies or antibody-related fusion proteins binding to soluble antigens in plasma form an important subclass of approved therapeutics.


Input: Pharmaceutical companies are constantly trying to accelerate the pace of drug discovery and development of these antibodies and identify superior candidates in face of significant attrition rates.


Input: Understanding the interplay between drug-and target-related factors on magnitude and duration of target inhibition is imperative for successful advancement of these therapeutics.


Input: Simulations using a target-mediated drug disposition model were performed to evaluate the influence of antibody-target binding affinity, baseline target concentration, and target turnover on magnitude and duration of soluble target inhibition.


Input: These simulations assumed intravenous dosing of the antibody and evaluated multiple parameters over a wide range.


Input: These simulations reveal that improvement in affinity reaches a point of diminishing returns following which further improvement in affinity does not alter the magnitude and more importantly the duration of target inhibition.


Input: Evaluation of unbound antibody and target kinetics indicated that point of diminishing returns in duration of inhibition was due to target-mediated binding and subsequent elimination of antibody at later time points.


Input: Similarly, influence of baseline target concentration and target turnover on magnitude and duration of target inhibition in plasma is shown.


Input: Additionally, the fraction of dose eliminated via target mediated elimination (Fel ((TM))) can be a useful tool to enable selection of strategies to increase duration of target inhibition.


Input: The implications of these simulations in drug discovery and development with regard to target identification, antibody optimization, and backup candidate selection are discussed.


Input: Molecular Mechanisms of Silibinin-Mediated Cancer Chemoprevention with Major Emphasis on Prostate Cancer.

Silibinin


Input: Despite advances in early detection, prostate cancer remains the second highest cancer mortality in American men, and even successful interventions are associated with enormous health care costs as well as prolonged deleterious effects on quality of patient life.


Input: Prostate cancer chemoprevention is one potential avenue to alleviate these burdens.


Input: It is a regime whereby long-term treatments are intended to prevent or arrest cancer development, in contrast to more direct intervention upon disease diagnosis.


Input: Based on this intention, cancer chemoprevention generally focuses on the use of nontoxic chemical agents which are well-tolerated for prolonged usage that is necessary to address prostate cancer' s multistage and lengthy period of progression.


Input: One such nontoxic natural agent is the flavonoid silibinin, derived from the milk thistle plant (Silybum marianum), which has ancient medicinal usage and potent antioxidant activity.

silibinin


Input: Based on these properties, silibinin has been investigated in a host of cancer models where it exhibits broad-spectrum efficacy against cancer progression both in vitro and in vivo without noticeable toxicity.

silibinin


Input: Specifically in prostate cancer models, silibinin has shown the ability to modulate cell signaling, proliferation, apoptosis, epithelial to mesenchymal transition, invasion, metastasis, and angiogenesis, which taken together provides strong support for silibinin as a candidate prostate cancer chemopreventive agent.

silibinin

silibinin


Input: The Fer tyrosine kinase is important for platelet-derived growth factor-BB-induced Stat3 phosphorylation, colony formation in soft agar and tumor growth in vivo.

tyrosine


Input: Fer is a cytoplasmic tyrosine kinase that is activated in response to platelet-derived growth factor (PDGF) stimulation.

tyrosine


Input: In the present report, we show that Fer associates with the activated PDGFbeta receptor (PDGFRbeta) through multiple autophosphorylation sites, i. e. Tyr579, Tyr581, Tyr740 and Tyr1021.


Input: Using low molecular weight inhibitors, we found that PDGF-BB-induced Fer activation is dependent on PDGFRbeta kinase activity, but not on the enzymatic activity of Src or Jak kinases.


Input: In cells in which Fer was downregulated using siRNA, PDGF-BB was unable to induce phosphorylation of Stat3, whereas phosphorylations of Stat5, Erk1/2 and Akt were unaffected.


Input: PDGF-BB-induced activation of Stat3 occurred also in cells expressing kinase-dead Fer, suggesting a kinase-independent adaptor role of Fer.


Input: Expression of Fer was dispensable for PDGF-BB-induced proliferation and migration, but essential for colony formation in soft agar.


Input: Tumor growth in vivo was delayed in cells depleted of Fer expression.


Input: Our data suggests a critical role of Fer in PDGF-BB-induced Stat3 activation and cell transformation.


Input: Exposure to mercury among dental health workers in Turkey: Correlation with amalgam work and own fillings.

mercury

amalgam


Input: PURPOSE: To investigate the current status of exposure to mercury (Hg) among dental health workers in Turkey.

mercury

Hg


Input: METHODS: A total of 115 persons working in the same hospital were included in the study and were divided into three groups.


Input: Group 1 consisted of 67 dentists; group 2 consisted of 21 dental personnel who work with amalgam, and group 3 consisted of 27 control subjects who work in the same hospital but are non-dental personnel.

amalgam


Input: The number of amalgam fillings that have been made by the dentists and the number of own fillings of the subjects were recorded.

amalgam


Input: RESULTS: Plasma Hg levels were found to be 3. 76 +/- 1. 84, 3. 54 +/- 1. 83, and 2. 69 +/- 0. 97 micro g/L in groups 1, 2, and 3, respectively.

Hg


Input: Hg concentrations in group 1 were significantly higher than the control group.

Hg


Input: There was no significant difference between groups 1 and 2.


Input: The number of amalgam fillings made by the dentists in the previous year correlated significantly with plasma Hg levels (r = 0. 378, p < 0. 01).

amalgam

Hg


Input: There was no significant correlation between the own amalgam fillings in the teeth of the subjects and Hg levels.

amalgam

Hg


Input: CONCLUSION: Preventive measures for protection from exposure to Hg are necessary for occupational health in dentistry and proper industrial hygiene rules should be emphasized to avoid contamination during work.

Hg


Input: Amelioration of hepatotoxicity induced by aflatoxin using citrus fruit oil in broilers (Gallus domesticus).

aflatoxin


Input: This study was conducted to evaluate the efficacy of citrus fruit oil (CFO; 2. 5 g kg (-) (1)) on the clinicopathological changes in broilers fed with diets containing 1 ppm of aflatoxin (AF).

aflatoxin


Input: A total of 160 Ross 308 broiler chicks of 1-day-old were procured from a commercial hatchery, divided randomly on 7th day of age into four groups with two replicates of 20 birds each and fed with basal diet (group A), basal diet + CFO (group B), basal diet + AF (group C) and CFO + basal diet + AF (group D).


Input: The gross and histopathological changes in the liver, kidney, spleen, thymus and bursa of Fabricius were investigated and relative organ weights were calculated.


Input: Slight to moderate hydropic degeneration, fatty change with the formation of cyst in some cases, periportal necrosis, infiltration of heterophils and mononuclear cells and bile duct hyperplasia were observed in chicks fed with 1 ppm AF-containing diet.


Input: The addition of CFO to AF-containing diet moderately decreased the magnitude and severity of lesions (hydropic degeneration and bile duct hyperplasia) in the liver.


Input: The supplementation of CFO to the basal diet did not produce any adverse effects in birds.


Input: MAO Inhibitory Activity of 2-Arylbenzofurans versus 3-Arylcoumarins: Synthesis, in vitro Study, and Docking Calculations.


Input: Monoamine oxidase (MAO) is an important drug target for the treatment of neurological disorders.

Monoamine


Input: Several 3-arylcoumarin derivatives were previously described as interesting selective MAO-B inhibitors.


Input: Preserving the trans-stilbene structure, a series of 2-arylbenzofuran and corresponding 3-arylcoumarin derivatives were synthesized and evaluated as inhibitors of both MAO isoforms, MAO-A and MAO-B.

trans-stilbene


Input: In general, both types of derivatives were found to be selective MAO-B inhibitors, with IC50 values in the nano-to micromolar range.


Input: 5-Nitro-2-(4-methoxyphenyl) benzofuran (8) is the most active compound of the benzofuran series, presenting MAO-B selectivity and reversible inhibition (IC50 = 140 nM).

5-Nitro-2-(4-methoxyphenyl) benzofuran

benzofuran


Input: 3-(4'-Methoxyphenyl)-6-nitrocoumarin (15), with the same substitution pattern as that of compound 8, was found to be the most active MAO-B inhibitor of the coumarin series (IC50 = 3 nM).

coumarin


Input: However, 3-phenylcoumarin 14 showed activity in the same range (IC50 = 6 nM), is reversible, and also severalfold more selective than compound 15.


Input: Docking experiments for the most active compounds into the MAO-B and MAO-A binding pockets highlighted different interactions between the derivative classes (2-arylbenzofurans and 3-arylcoumarins), and provided new information about the enzyme-inhibitor interaction and the potential therapeutic application of these scaffolds.


Input: Direct Laser-Patterned Micro-Supercapacitors from Paintable MoS2 Films.


Input: Micrometer-sized electrochemical capacitors have recently attracted attention due to their possible applications in micro-electronic devices.


Input: Here, a new approach to large-scale fabrication of high-capacitance, two-dimensional MoS2 film-based micro-supercapacitors is demonstrated via simple and low-cost spray painting of MoS2 nanosheets on Si/SiO2 chip and subsequent laser patterning.

Si


Input: The obtained micro-supercapacitors are well defined by ten interdigitated electrodes (five electrodes per polarity) with 4. 5 mm length, 820 mu m wide for each electrode, 200 mu m spacing between two electrodes and the thickness of electrode is ~ 0. 45 mu m.


Input: The optimum MoS2-based micro-supercapacitor exhibits excellent electrochemical performance for energy storage with aqueous electrolytes, with a high area capacitance of 8 mF cm (-2) (volumetric capacitance of 178 F cm (-3)) and excellent cyclic performance, superior to reported graphene-based micro-supercapacitors.

graphene


Input: This strategy could provide a good opportunity to develop various micro-/nanosized energy storage devices to satisfy the requirements of portable, flexible, and transparent micro-electronic devices.


Input: Vortex-induced amyloid superstructures of insulin and its component a and B chains.


Input: Insulin is an amyloid-forming polypeptide built of two disulfide-linked chains (A and B), both themselves amyloidogenic.

disulfide


Input: An interesting property of insulin is that agitation strongly influences the course of its aggregation, resulting in characteristic chiral superstructures of amyloid fibrils.


Input: Here, we investigate the self-assembly of these superstructures by comparing the quiescent and vortex-assisted aggregation of insulin and its individual A and B chains in the presence or absence of reducing agent tris (2-carboxyethyl) phosphine (TCEP).

tris (2-carboxyethyl) phosphine

TCEP


Input: Our study shows that only the B chain in the presence of TCEP is converted into aggregates with morphology (according to atomic force microscopy) and optical activity (manifested as an extrinsic Cotton effect induced in bound thioflavin T) characteristic of amyloid superstructures that are normally formed by insulin in the absence of TCEP.

TCEP

thioflavin T

TCEP


Input: In contrast to more rigid B-peptide fibrils, elongated aggregates of the A peptide become amorphous upon agitation.


Input: Moreover, the aggregation of equimolar mixture of both peptides does not produce highly ordered entities.


Input: Our results suggest that the dynamics of the B chain are the driving force for the assembly of superstructures, with the A chain being complicit as long as its own dynamics are controlled by the firm attachment to the B chain provided by the intact covalent structure of insulin.


Input: Determination of urinary 6-mercaptopurine and three of its metabolites by HPLC-UV coupled with the iodine-azide reaction.

iodine

azide


Input: Background: The presented method is able to determine 6-mercaptopurine (6-MP), 6-thioguanine, 6-mercaptopurine riboside and 6-thioguanine riboside in urine, and is thereby dedicated to control of thiopurine therapy of children with acute lymphoblastic leukemia.

6-mercaptopurine riboside

6-thioguanine riboside

thiopurine


Input: Good separation of the mentioned compounds was achieved on a C18 stationary phase with a sodium azide and sodium heptane sulfonate solution, acetonitrile and water at ratio of 50: 1: 49 (v/v/v).

sodium azide

sodium heptane sulfonate

acetonitrile


Input: Results: Coefficient of regression is > 0. 99 for all linearity ranges.


Input: LOD and LOQ are 0. 3, 0. 4, 0. 3, 0. 8 and 0. 4, 0. 6, 0. 5 and 0. 9 nmol/ml of urine for 6-MP, 6-thioguanine, 6-mercaptopurine riboside and 6-thioguanine riboside, respectively.

6-mercaptopurine riboside

6-thioguanine riboside


Input: Intra-and inter-day recovery and RSD are close to 100% and less than 10%, respectively, for all investigated thiopurines.

thiopurines


Input: Conclusion: The elaborated method was successfully applied for detection and quantitation of 6-MP and its selected metabolites in patients' urine samples.


Input: A dried blood spot update: still an important bioanalytical technique?


Input: This article discusses the benefits of dried blood spot sampling and the recent issues that have emerged when this technique is used in the regulated quantitative bioanalytical environment.


Input: The author explores what the way forward might be for this important technique and what some of the unexpected benefits of this change in sampling methodologies have been.


Input: Use of Monte Carlo simulations in the assessment of calibration strategies-Part III: an evaluation of linear calibration.


Input: Background: The acceptance criteria for chromatographic bioassays are generally based upon the specifications found in the US FDA Guidance for Industry document, whereas regression analysis is a statistical process and, thus, most suited to large data populations, rather than the small populations used in assay calibration.


Input: Data that form part of the statistical population are often excluded in order that calibrations meet these acceptance criteria.


Input: Results/discussion: Monte Carlo simulations of various linear regression calibration strategies, which take into account guidance acceptance criteria, have been used to quantify calibration errors.


Input: Conclusion: It is concluded that 1/x (2) weighting generally produces results that meet both theoretical and regulatory requirements, and that use of single, rather than duplicate, calibrators can result in misleading statistics at the LLOQ.


Input: Polyelectrolyte-Surfactant Complexes of Poly [3, 5-bis (dimethylaminomethyl)-4-hydroxystyrene]-block-poly (ethylene oxide) and Sodium Dodecyl Sulfate: Anomalous Self-Assembly Behavior.

Poly [3, 5-bis (dimethylaminomethyl)-4-hydroxystyrene]-block-poly (ethylene oxide)

Sodium Dodecyl Sulfate


Input: Polyelectrolyte-surfactant complexes (PE-S) formed by double hydrophilic cationic polyelectrolyte poly [3, 5-bis (dimethylaminomethyl)-4-hydroxystyrene]-block-poly (ethylene oxide) (NPHOS-PEO) and anionic surfactant sodium dodecyl sulfate (SDS) in acidic aqueous solutions were studied by light scattering, SAXS, and scanning transmission electron microcopy in the environmental mode (wet-STEM) for various stoichiometric ratios between the numbers of SDS anions and dimethylaminomethyl groups of NPHOS in the complex.

poly [3, 5-bis (dimethylaminomethyl)-4-hydroxystyrene]-block-poly (ethylene oxide)

NPHOS-PEO

sodium dodecyl sulfate

SDS

dimethylaminomethyl

NPHOS


Input: The obtained results show that the NPHOS-PEO/SDS system behaves differently from other systems of double hydrophilic block polyelectrolyte and oppositely charged ionic surfactant because it forms water-insoluble PE-S for compositions close to the zero net charge of the complex.

NPHOS-PEO

SDS


Input: This phase separation occurs, instead of the PE-S rearrangement to core-shell particles, which is hindered due to conformational rigidity of the NPHOS blocks.

NPHOS


Input: For the surfactant amounts below and above the precipitation region, large spherical aggregates and their clusters are present in the solution.


Input: SAXS measurements indicate that although the NPHOS-PEO/SDS system does not form the core-shell particles with the NPHOS/SDS core and the PEO shell as other PE-S of double hydrophilic polyelectrolytes, the aggregates contain domains of closely packed surfactant micelles which bind to both NPHOS polyelectrolyte blocks and PEO blocks.

NPHOS-PEO

SDS

NPHOS

SDS

PEO

NPHOS

PEO


Input: Structure in the Visible Absorption Bands of Jet-Cooled Phenylperoxy Radicals.

Phenylperoxy


Input: The visible absorption bands of the phenylperoxy radical in the gas phase have been investigated using cavity ring-down spectroscopy.

phenylperoxy


Input: Jet-cooling was used to reduce the spectral congestion.


Input: Structured spectra spanning the range from 17 500 to 19 000 cm (-1) are reported for the first time.


Input: Analyses of these data have been guided by the results from time-dependent density functional calculations.


Input: The observed spectrum was found to be dominated by the bands of the B (2) A''-X (2) A'' transition.


Input: An analysis of the rotational contour for the origin band yielded a homogeneous line width of 2. 2 cm (-1), corresponding to a decay rate of 4. 1 x 10 (11) s (-1).


Input: The results provide a rationale for the lack of structure in room temperature spectra that have been previously attributed to phenylperoxy.

phenylperoxy


Input: They also indicate that the lower energy region of the spectrum may show resolvable structure at room temperature.


Input: If so, this would provide a more definitive signature for monitoring phenylperoxy in kinetic measurements.

phenylperoxy


Input: pH-Responsive Nanoparticle Vaccines for Dual-Delivery of Antigens and Immunostimulatory Oligonucleotides.


Input: Protein subunit vaccines offer important potential advantages over live vaccine vectors but generally elicit weaker and shorter-lived cellular immune responses.


Input: Here we investigate the use of pH-responsive, endosomolytic polymer nanoparticles that were originally developed for RNA delivery as vaccine delivery vehicles for enhancing cellular and humoral immune responses.


Input: Micellar nanoparticles were assembled from amphiphilic diblock copolymers composed of an ampholytic core-forming block and a redesigned polycationic corona block doped with thiol-reactive pyridyl disulfide groups to enable dual-delivery of antigens and immunostimulatory CpG oligodeoxynucleotide (CpG ODN) adjuvants.

thiol

pyridyl disulfide

CpG

CpG


Input: Polymers assembled into 23 nm particles with simultaneous packaging of CpG ODN and a thiolated protein antigen, ovalbumin (ova).

CpG


Input: Conjugation of ova to nanoparticles significantly enhanced antigen cross-presentation in vitro relative to free ova or an unconjugated, physical mixture of the parent compounds.


Input: Subcutaneous vaccination of mice with ova-nanoparticle conjugates elicited a significantly higher CD8 (+) T cell response (0. 5% IFN-gamma (+) of CD8 (+)) compared to mice vaccinated with free ova or a physical mixture of the two components.


Input: Significantly, immunization with ova-nanoparticle conjugates electrostatically complexed with CpG ODN (dual-delivery) enhanced CD8 (+) T cell responses (3. 4% IFN-gamma (+) of CD8 (+)) 7-, 18-, and 8-fold relative to immunization with conjugates, ova administered with free CpG, or a formulation containing free ova and CpG complexed to micelles, respectively.

CpG

CpG

CpG


Input: Similarly, dual-delivery carriers significantly increased CD4 (+) IFN-gamma (+) (Th1) responses and elicited a balanced IgG1/IgG2c antibody response.


Input: Intradermal administration further augmented cellular immune responses, with dual-delivery carriers inducing ~ 7% antigen-specific CD8 (+) T cells.


Input: This work demonstrates the ability of pH-responsive, endosomolytic nanoparticles to actively promote antigen cross-presentation and augment cellular and humoral immune responses via dual-delivery of protein antigens and CpG ODN.

CpG


Input: Hence, pH-responsive polymeric nanoparticles offer promise as a delivery platform for protein subunit vaccines.


Input: Improved Carrier Mobility in Few-Layer MoS2 Field-Effect Transistors with Ionic-Liquid Gating.


Input: We report the fabrication of ionic liquid (IL)-gated field-effect transistors (FETs) consisting of bilayer and few-layer MoS2.


Input: Our transport measurements indicate that the electron mobility mu =~ 60 cm (2) V (-1) s (-1) at 250 K in IL-gated devices exceeds significantly that of comparable back-gated devices.


Input: IL-FETs display a mobility increase from =~ 100 cm (2) V (-1) s (-1) at 180 K to =~ 220 cm (2) V (-1) s (-1) at 77 K in good agreement with the true channel mobility determined from four-terminal measurements, ambipolar behavior with a high ON/OFF ratio > 10 (7) (10 (4)) for electrons (holes), and a near ideal subthreshold swing of =~ 50 mV/dec at 250 K.


Input: We attribute the observed performance enhancement, specifically the increased carrier mobility that is limited by phonons, to the reduction of the Schottky barrier at the source and drain electrode by band bending caused by the ultrathin IL dielectric layer.


Input: pH-Responsive Aggregation States of Chiral Polymerizable Amphiphiles from l-Tyrosine and l-Phenyl Alanine in Water.

l-Tyrosine

l-Phenyl Alanine


Input: Sodium salts of maleamic acid derivatives of lauryl ester of tyrosine (MTNa) and phenyl alanine (MPNa) in water exhibited strong pH-responsive behaviors of viscosity and specific conductivity that originate from the concentration and pH dependence of their aggregation states.

Sodium

maleamic acid

lauryl ester

tyrosine

phenyl alanine


Input: The aggregates were characterized by a novel spin-probe-partitioning electron paramagnetic resonance (SPPEPR) method and dynamic light scattering (DLS).


Input: Results of high-precision fitting of the second-harmonic EPR spectra of the small spin probe di-tert-butyl nitroxide (DTBN) in these aggregates together with viscosity, conductivity, and DLS showed that, at pH ~ 7. 54, MTNa formed micelles and MPNa vesicles and MTNa exhibited a pH-induced micelle to vesicle transition as pH was lowered toward 6.

di-tert-butyl nitroxide

DTBN


Input: MTNa, at pH ~ 7. 54, formed small micelles at low concentrations that transformed to long worm-like micelles for concentrations >= 0. 05 M, accompanied by a 30-fold increase in solution viscosity.


Input: The hydrodynamic radii from DLS confirmed the presence of small micellar aggregates of radius ~ 2 nm in MTNa at pH ~ 7. 54 at the lower concentrations, with coexisting micelles (~ 2 nm) and vesicles (~ 50 nm) at pH near 6. 5, vesicles (radii ~ 70 nm) at pH near 6, and large vesicles (85 nm) in MPNa at pH ~ 7. 60.


Input: Both MTNa and MPNa precipitated upon reduction of pH below 6 and below 7, respectively.


Input: The rate of transfer of DTBN between the aqueous phase and the aggregate was calculated from the high-field Lorentzian linewidths of the electron paramagnetic resonance (EPR) spectra.

DTBN


Input: The activation energy for the transfer determined from the temperature dependence of the rate of transfer is 12. 7 kJ/mol for MTNa vesicles (pH ~ 6) and 20. 6 +/- 1. 3 kJ/mol for MPNa (pH ~ 7. 60).


Input: The pH-induced transformations were reversible.


Input: Discovery of aryl ureas and aryl amides as potent and selective histamine H3 receptor antagonists for the treatment of obesity (Part I).

aryl ureas

aryl amides

histamine


Input: A series of structurally novel aryl ureas was derived from optimization of the HTS lead as selective histamine H3 receptor (H3R) antagonists.

aryl ureas

histamine


Input: The SAR was explored and the data obtained set up the starting point and foundation for further optimization.


Input: The most potent tool compounds, as exemplified by compounds 2l, 5b, 5d, and 5e, displayed antagonism potencies in the subnanomolar range in in vitro human-H3R FLIPR assays and rhesus monkey H3R binding assays.


Input: Phenanthroimidazole-based thiobenzamide as an effective sensor for highly selective detection of mercury (II).

Phenanthroimidazole

thiobenzamide

mercury (II)


Input: Based on highly selective and irreversible Hg (2 +)-promoted desulfurization reaction, a new and simple phenanthroimidazole-type sensor was prepared and exhibited high selectivity towards Hg (2 +) ion over other metal ions, accompanied by transformation of a weakly fluorescent thioamide moiety (colorless) to a highly fluorescent amide one (blue), with a 136-fold increase in fluorescent intensity in aqueous solution with a pH span 2. 57-9. 12.

Hg (2 +)

phenanthroimidazole

Hg (2 +)

thioamide

amide


Input: Cerebral ischemia-induced difference in sensitivity to depression and potential therapeutics in rats.


Input: The' vascular depression' hypothesis has recently attracted significant research attention, although the causal relationship between vascular-related injuries and depression has not been established.


Input: Here, we show that one episode of cerebral ischemia was sufficient to greatly increase the sensitivity of rats to potentially depressogenic events, evaluated at below-threshold intensities in the open space swim test.


Input: The induced' ischemic depression' was lasting and sensitive to an acute administration of brain-derived neurotrophic factor or bryostatin-1, a relatively selective activator of protein kinase C epsilon, during the induction phase.


Input: Chronic treatment with bryostatin-1 (5 weeks) after the induction of depressive behavior reversed the depressive immobility and produced a lasting therapeutic effect, which remained effective 3 weeks after discontinuation of the treatment.


Input: Similar treatment with alaproclate, a selective serotonin reuptake inhibitor, in contrast, produced temporary relief from the depressive symptoms, with the therapeutic effect disappearing soon after the end of the treatment.

alaproclate

serotonin


Input: The results strongly suggest that cerebral ischemia has a direct role in shaping the sensitivity of an individual to depressogenic events and that bryostatin-1-like agents may be developed as therapeutics for treating ischemic depression in humans.


Input: Current status of liposomal porphyrinoid photosensitizers.

porphyrinoid


Input: The complete eradication of various targets, such as infectious agents or cancer cells, while leaving healthy host cells untouched, is still a great challenge faced in the field of medicine.


Input: Photodynamic therapy (PDT) seems to be a promising approach for anticancer treatment, as well as to combat various dermatologic and ophthalmic diseases and microbial infections.


Input: The application of liposomes as delivery systems for porphyrinoids has helped overcome many drawbacks of conventional photosensitizers and facilitated the development of novel effective photosensitizers that can be encapsulated in liposomes.

porphyrinoids


Input: The development, preclinical studies and future directions for liposomal delivery of conventional and novel photosensitizers are reviewed.


Input: Structure and energetics of gas phase halogen-bonding in mono-, bi-, and tri-dentate anion receptors as studied by BIRD.

halogen


Input: Complexes of mono-, bi-(RB), and tridentate (RT) receptors with a range of anions (Cl (-), Br (-), I (-), NO3 (-), H2PO4 (-), HSO4 (-), and tosylate (TsO (-))) have been studied in the gas phase by both experimental and theoretical methods.

Cl (-)

Br (-)

I (-)

NO3 (-)

H2PO4 (-)

HSO4 (-)

tosylate

TsO (-)


Input: Temperature dependent blackbody infrared radiative dissociation (BIRD) experiments were performed on complexes of C8F17I with Br (-) and I (-), RB with I (-), NO3 (-), HSO4 (-), H2PO4 (-), and TsO (-), and RT with I (-), HSO4 (-) and TsO (-) and the observed Arrhenius parameters are reported here.

Br (-)

I (-)

I (-)

NO3 (-)

HSO4 (-)

H2PO4 (-)

TsO (-)

I (-)

HSO4 (-)

TsO (-)


Input: Master equation modeling of the BIRD kinetics data was carried out to determine threshold dissociation energies.


Input: Geometry optimizations and thermochemistry calculations were performed using the B3LYP/6-31 + G (d, p) level of theory.


Input: Additional single point energies were calculated using MP2/6-311 + + G (2d, p).


Input: Results were examined in terms of the binding order of various anions as well as the added binding strength from additional halogen bonding (XB) interactions.

halogen


Input: The relative binding energies of ions were generally consistent with the ordering previously reported from solution phase experiments; however, the relatively strong binding of H2PO4 (-) to the bidentate receptor contrasted the solution phase observation of oxoanions having weaker interactions when compared to halides.

H2PO4 (-)

oxoanions

halides


Input: An increase in the energy required to remove the same anion from the tridentate receptor when compared to the bidentate and monodentate receptors is explained as being due to the increase in halogen bonding interactions.

halogen


Input: The possibility of mixed halogen and hydrogen bonded complexes were considered.

halogen

hydrogen


Input: A new potential nano-oncological therapy based on polyamino acid nanocapsules.

polyamino acid


Input: A critical objective in cancer therapy is to reduce the systemic toxicity through the modification of the biodistribution of anticancer drugs.


Input: Herein, we disclose a new biodegradable nanocarrier, polyglutamic acid (PGA) nanocapsules, and present the in vivo pharmacokinetics/toxicity proof-of-concept for the anticancer drug plitidepsin.

polyglutamic acid

PGA

plitidepsin


Input: These novel nanocapsules were prepared using a modified solvent displacement technique where the polyamino acid was electrostatically deposited onto the lipid core.

polyamino acid


Input: The nanocapsules exhibited an average size of 200nm, a negative zeta potential and a great capacity for the encapsulation of plitidepsin (encapsulation efficiency above 90%).

plitidepsin


Input: In addition, the nanocapsules could be freeze-dried and showed an adequate stability profile upon storage.


Input: Finally, the in vivo proof-of-concept studies performed in mice indicated that the encapsulation provided the drug with a prolonged blood circulation and a significantly reduced toxicity.


Input: In fact, the maximum tolerated dose of the nanoencapsulated drug was more than 3 times that of the reference formulation (Cremophor (R) EL plitidepsin solution).

Cremophor

plitidepsin


Input: Overall, beyond the value of this specific formulation, the work reported here represents the evidence of the potential of polyamino acid nanocapsules in nano-oncological therapy.

polyamino acid


Input: Effects of Selenium Intervention on Chronic Fluorosis-Induced Renal Cell Apoptosis in Rats.

Selenium


Input: This study aims to explore the effect of selenium in fluoride-induced renal cell apoptosis in rats and determine the optimal level of selenium in drinking water to prevent fluorosis.

selenium

fluoride

selenium


Input: Experimental animals were divided into a control group, a sodium fluoride-treated group (NaF, 50 mg/L), three sodium selenite-treated groups (Na2SeO3, 0. 375, 0. 75, and 1. 5 mg/L), and three selenium + NaF-treated groups (Na2SeO3, 0. 375, 0. 75, and 1. 5 mg/L; NaF, 50 mg/L).

sodium fluoride

NaF

sodium selenite

selenium

NaF

NaF


Input: Ultrastructural changes in the kidney tissues of each group were observed by transmission electron microscopy.


Input: Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and the expressions of Bcl-2 and Bax proteins were detected by immunohistochemical methods.

dUTP


Input: The expressions of Bcl-2 and Bax mRNA were detected by reverse transcription-polymerase chain reaction.


Input: The results showed that Bcl-2, Bax, and Bax/Bcl-2 protein expressions in the fluoride and high selenium groups were highly elevated compared with the control group (P < 0. 01).

fluoride

selenium


Input: Bax expression in the low selenium group and Bcl-2, Bax, and Bax/Bcl-2 protein expressions in the moderate selenium groups were observably elevated (P < 0. 05).

selenium

selenium


Input: Bax and Bax/Bcl-2 expressions in the fluoride group and Bax mRNA expression in the high selenium group were highly elevated (P < 0. 01).

fluoride

selenium


Input: Bax/Bcl-2 mRNA expression in the high selenium group was also highly elevated (P < 0. 05).

selenium


Input: Compared with the fluoride group, the group treated with low selenium has Bax protein expression that was observably reduced (P < 0. 05); the group treated with moderate selenium has Bcl-2 protein expression that was observably elevated (P < 0. 05), Bax protein expression that was highly reduced (P < 0. 01), and Bax/Bcl-2 protein expression that was observably reduced (P < 0. 05); the group treated with high selenium has Bcl-2 protein expression that was highly elevated (P < 0. 01), Bax protein expression that was highly elevated (P < 0. 01), and Bax/Bcl-2 protein expression that was highly reduced (P < 0. 01); the groups treated with moderate selenium and high selenium have Bax mRNA expression that was highly reduced (P < 0. 01), and the groups treated with high selenium have Bax/Bcl-2 mRNA expression that was observably reduced (P < 0. 05).

fluoride

selenium

selenium

selenium

selenium

selenium

selenium


Input: Selenium may inhibit the apoptosis of renal cells in fluorosis rats by regulating the expressions of Bcl-2 and Bax.

Selenium


Input: The optimal dose of Na2SeO3 to protect against fluoride-induced renal cell apoptosis was determined to be 1. 5 mg/L.

fluoride


Input: Melatonin and its analogue 5-MCA-NAT potentiate adrenergic receptor-mediated ocular hypotensive effects in rabbits: Significance for combination therapy in glaucoma.

Melatonin


Input: Melatonin is currently considered as a promising drug for glaucoma treatment due to its ocular hypotensive and neuroprotective effects.

Melatonin


Input: We have investigated the effect of melatonin and its analogue 5-methoxycarbonylamino-N-acetyltryptamine, 5-MCA-NAT, on beta 2/alpha 2A-adrenergic receptor mRNA as well as protein expression in cultured rabbit non-pigmented ciliary epithelial cells.

melatonin

5-methoxycarbonylamino-N-acetyltryptamine


Input: Quantitative PCR and immunocytochemical assays revealed a significant beta 2-adrenergic receptor down-regulation as well as alpha 2A-adrenergic receptor up-regulation of treated cells (p < 0. 001, maximal significant effect).


Input: In addition, we have studied the effect of these drugs upon the ocular hypotensive action of a non-selective beta-adrenergic receptor (timolol) and a selective alpha 2-adrenergic receptor agonist (brimonidine) in normotensive rabbits.

timolol

brimonidine


Input: IOP experiments showed that the administration of timolol in rabbits pre-treated with melatonin or 5-MCA-NAT evoked an additional IOP reduction of 14. 02 +/- 5. 8% or 16. 75 +/- 5. 48% (p < 0. 01) in comparison with rabbits treated with timolol alone for 24 hours.

timolol

melatonin

timolol


Input: Concerning brimonidine hypotensive action, an additional IOP reduction of 29. 26 +/- 5. 21% or 39. 07 +/- 5. 81% (p < 0. 001) was observed in rabbits pretreated with melatonin or 5-MCA-NAT when compared with animals treated with brimonidine alone for 24 hours.

brimonidine

melatonin

brimonidine


Input: Additionally, a sustained potentiating effect of a single dose of 5-MCA-NAT was seen in rabbits treated with brimonidine once daily for up four days (extra IOP decrease of 15. 57 +/- 5. 15%, p < 0. 05, compared to brimonidine alone).

brimonidine

brimonidine


Input: These data confirm the indirect action of melatoninergic compounds on adrenergic receptors and their remarkable effect upon the ocular hypotensive action mainly of alpha 2-adrenergic receptor agonists but also of beta-adrenergic antagonists.


Input: Focal adhesion kinase regulates collagen I-induced airway smooth muscle phenotype switching.


Input: Increased extracellular matrix (ECM) deposition and airway smooth muscle (ASM) mass are major contributors to airway remodeling in asthma.


Input: Recently, we have demonstrated that the ECM protein collagen I, which is increased surrounding asthmatic ASM, induces a proliferative, hypocontractile ASM phenotype.


Input: Little is known, however, on the signaling pathways involved.


Input: Using bovine tracheal smooth muscle, we investigated the role of focal adhesion kinase (FAK) and downstream signaling pathways in collagen I-induced ASM phenotype modulation.


Input: Phosphorylation of FAK was increased during adhesion to both uncoated and collagen I-coated culture dishes, without differences between these matrices.


Input: No differences in cellular adhesion were found either.


Input: Inhibition of FAK activity by overexpression of the FAK deletion mutants FAT (focal adhesion targeting domain) and FRNK (FAK-related non-kinase) attenuated adhesion.


Input: After attachment, FAK phosphorylation was time-dependently increased in cells cultured on collagen I, whereas no activation was found on an uncoated plastic matrix.


Input: In addition, collagen I time-and concentration-dependently increased cell proliferation, which was fully inhibited by FAT and FRNK.


Input: Similarly, the specific pharmacological FAK inhibitor PF-573, 228 as well as specific inhibitors of p38 MAPK and Src also fully inhibited collagen I-induced proliferation, whereas partial inhibition was observed by inhibition of PI3-kinase and MEK.

PF-573, 228


Input: The inhibition of cell proliferation by these inhibitors was associated with attenuation of the collagen I-induced hypocontractility.


Input: Collectively, the results indicate that induction of a proliferative, hypocontractile ASM phenotype by collagen I is mediated by FAK and downstream signaling pathways.


Input: Selective Smad4 Knockout in Ovarian Preovulatory Follicles Results in Multiple Defects in Ovulation.


Input: The TGF-beta signaling pathway is involved with multiple processes in the mammalian ovary, including primordial follicle formation, granulosa cell (GC) proliferation, follicle atresia, ovulation, and feedback regulation between the pituitary and ovary.


Input: The transcriptional factor SMAD4 is the central component of the canonical TGF-beta signaling pathway.


Input: Smad4 knockout using Amhr2-Cre, which is expressed in GCs of immature developing follicles, causes premature luteinization.


Input: In this study, we specifically depleted Smad4 in GCs of preovulatory follicles using Cyp19-Cre mice.


Input: As different from results with Smad4 (fl/fl); Amhr2-Cre mice, Smad4 depletion in preovulatory follicles did not cause premature luteinization or suppress GC proliferation; rather, it increased follicle atresia.


Input: In addition, Nppc and Npr2 expressions were reduced by Smad4 depletion; thus, their effect of maintaining oocyte meiotic arrest was weakened in Smad4 conditional knockout mice.


Input: Smad4 (fl/fl); Cyp19-Cre female mice were subfertile and had irregular estrous cycles and ovulation defects.


Input: Smad4 knockout also blocked luteinizing hormone (LH)-induced cumulus expansion and follicle rupture, but not oocyte meiotic resumption.


Input: Our results also indicated that SMAD4 was required for LH-stimulated activation of ERK1/2 and the expressions of ovulation-related genes.


Input: The defects arising from SMAD4 depletion could not be rescued by intra-ovarian mediators of LH actions, such as EGF-like factors and prostaglandin E2.

prostaglandin E2


Input: Furthermore, corpus lutea did not form in Smad4 (fl/fl); Cyp19-Cre female mice, indicating that SMAD4 was crucial for GCs terminal differentiation.


Input: Thus, by characterizing the ovarian phenotypes of preovulatory follicle-specific Smad4 knockout mice, we identified the developmental stage-specific functions of the canonical TGF-beta signaling pathway in ovulation and luteinization.


Input: Charge-Transfer Interaction between Few-Layer MoS2 and Tetrathiafulvalene.

Tetrathiafulvalene


Input: Graphene look-alike: MoS2 has a layered structure similar to graphene.

Graphene

graphene


Input: Tetrathiafulvalene (TTF) interacts with thin, few-layer MoS2 material by donating an electron, resulting in the formation of TTF radical cation and n-type doping of MoS2.

Tetrathiafulvalene

TTF

TTF


Input: Electron-withdrawing tetracyanoethylene, in contrast, does not cause p-type doping in MoS2.

tetracyanoethylene


Input: Protective effect of wogonin on proinflammatory cytokine generation via Jak1/3-STAT1/3 pathway in lipopolysaccharide stimulated BV2 microglial cells.

wogonin


Input: Wogonin is a flavonoid compound which exhibits antioxidation, anti-inflammation, neuroprotection, and antitumorgenesis functions.

Wogonin

flavonoid


Input: However, the mechanism of how wogonin reduces proinflammatory cytokine generation in activated microglia is unclear.

wogonin


Input: At present, we found wogonin inhibited lipopolysaccharide (LPS)-/interferon-gamma (INF-gamma)-induced generation of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha).

wogonin


Input: Wogonin exhibited parallel inhibition on LPS-/INF-gamma-induced expression of IL-6 and TNF-alpha messenger RNA at the same concentration range.

Wogonin


Input: LPS-/INF-gamma-induced phosphorylation of signal transduction and transcription 1 and 3 (STAT1/3) were also inhibited by wogonin.

wogonin


Input: Although wogonin expressed only weak inhibitory effect on LPS-/INF-gamma-induced phosphorylation of Janus kinase-2 (Jak-2) and tyrosine kinase (Tyk)-2, it significantly attenuated the phosphorylation of Jak-1 and Jak-3.

wogonin

tyrosine


Input: These results indicated that the blockade of IL-6 and TNF-alpha production by wogonin in LPS-/INF-gamma-stimulated BV2 microglial cells was attributed mainly to the interference in Jak-1/-3-STAT1/3 signaling pathway.

wogonin


Input: Structural mechanism of ring opening reaction of glucose by human serum albumin.

glucose


Input: Glucose reacts with proteins non-enzymatically under physiological conditions.

Glucose


Input: Such glycation is exacerbated in diabetic patients with high level of blood sugar, and induces various complications.

sugar


Input: Human albumin serum (HSA) is the most abundant protein in plasma and is glycated by glucose.

glucose


Input: The glycation sites on HSA remain controversial among different studies.


Input: Here, we report two protein crystal structures of HSA in complex with either glucose or fructose.

glucose

fructose


Input: These crystal structures reveal that the presence of linear forms of sugar for both monosaccharides.

sugar

monosaccharides


Input: The linear form of glucose forms a covalent bond to Lys195 of HSA, but not the case for fructose.

glucose

fructose


Input: Based on these structures, we propose a mechanism for glucose ring opening involving both residues Lys195 and Lys199.

glucose


Input: These results provide mechanistic insights to understand the glucose ring opening reaction and the glycation of proteins by monosaccharides.

glucose

monosaccharides


Input: AP-1/Fos-TGase2 axis mediates wounding-induced Plasmodium falciparum killing in Anopheles gambiae.


Input: Anopheline mosquitoes are the only vectors of human malaria worldwide.


Input: It is now widely accepted that mosquito immune responses play a crucial role in restricting Plasmodium development within the vector, therefore further dissection of the molecular mechanisms underlying these processes should inform new vector control strategies urgently needed to roll back the disease.


Input: Here, using genome-wide transcriptional profiling, bioinformatics and functional gene analysis we identify a new axis of mosquito resistance to monoclonal P. falciparum infections that includes the AP-1 transcription factor Fos and the transglutaminase 2 (TGase2), a cross-linking enzyme with known roles in wound responses.


Input: We demonstrate that Fos regulates induction of TGase2 expression after wounding but does not affect expression of the components of the well-characterized complement-like system.


Input: Silencing of Fos or of TGase2 aborts the wounding-induced mosquito killing of P. falciparum.


Input: These results reveal multiple signaling pathways that are required for efficient Plasmodium killing in A. gambiae.


Input: Nutrient signaling in protein homeostasis: an increase in quantity at the expense of quality.


Input: The discovery that rapamycin extends the life span of diverse organisms has triggered many studies aimed at identifying the underlying molecular mechanisms.

rapamycin


Input: Mammalian target of rapamycin complex 1 (mTORC1) regulates cell growth and may regulate organismal aging by controlling mRNA translation.

rapamycin


Input: However, how inhibiting mTORC1 and decreasing protein synthesis can extend life span remains an unresolved issue.


Input: We showed that constitutively active mTORC1 signaling increased general protein synthesis but unexpectedly reduced the quality of newly synthesized polypeptides.


Input: We demonstrated that constitutively active mTORC1 decreased translation fidelity by increasing the speed of ribosomal elongation.


Input: Conversely, rapamycin treatment restored the quality of newly synthesized polypeptides mainly by slowing the rate of ribosomal elongation.

rapamycin


Input: We also found distinct roles for mTORC1 downstream targets in maintaining protein homeostasis.


Input: Loss of S6 kinases, but not 4E-BP family proteins, which are both involved in regulation of translation, attenuated the effects of rapamycin on the quality of newly translated proteins.

rapamycin


Input: Our results reveal a mechanistic connection between mTORC1 and protein quality, highlighting the central role of nutrient signaling in growth and aging.


Input: DFT Modeling of 45S5 and 77S Soda-Lime Phospho-Silicate Glass Surfaces: Clues on Different Bioactivity Mechanism.


Input: The reactivity of bioglasses, which is related to the dissolution of cations and orthosilicate groups in the physiological fluid, strongly depends on the key structural features present at the glass surfaces.

orthosilicate


Input: On the basis of the composition and the synthetic routes employed to make the glass, surfaces with very different characteristics and thus presenting different mechanisms of dissolution can be observed.


Input: In this paper, the surface structures of two very different bioglass compositions, namely 45S5 (46. 1 SiO2, 24. 4 Na2O, 26. 9 CaO, and 2. 6 P2O5 mol%) and 77S (80. 0 SiO2, 16. 0 CaO, and 4. 0 P2O5 mol%), have been investigated by means of periodic DFT calculations based on a PBE functional and localized Gaussian basis set as encoded in the CRYSTAL code.

CaO

CaO


Input: Our calculations show that the two glass surfaces differ by the relative amount of key structural sites such as NBOs, exposed ions, orthosilicate units, and small rings.

orthosilicate


Input: We have demonstrated how the number of these sites affects the surface stability and reactivity (bioactivity).


Input: Formation Mechanism of TiO 2 Nanotubes and Their Applications in Photoelectrochemical Water Splitting and Supercapacitors.

TiO 2


Input: Structural observations of the transition of TiO 2 nanopores into nanotubes by increasing the OH (-) concentration in the electrolyte challenge the validity of existing formation mechanisms of anodic TiO 2 nanotubes.

TiO 2

OH (-)

TiO 2


Input: In this study, dehydration of titanium hydroxide in the cell wall is proposed as the mechanism that leads to the separation of neighboring nanotubes.

titanium hydroxide


Input: Based on this understanding, bamboo-type TiO 2 nanotubes with large surface area and excellent interconnectivity are achieved by cycling high and low applied potentials.

TiO 2


Input: After thermal treatment in a H 2 atmosphere, the bamboo-type TiO 2 nanotubes show large photoelectrochemical water splitting efficiency and supercapacitors performace.

H 2

TiO 2


Input: Ultralow Thermal Conductivity in Organoclay Nanolaminates Synthesized via Simple Self-Assembly.


Input: Because interfaces impede phonon transport of thermal energy, nanostructuring can transform fully dense solids into ultralow thermal conductivity materials.


Input: Here we report a simple self-assembly approach to synthesizing organoclay nanolaminates with cross-planar thermal conductivities below 0. 10 W m (-1) K (-1)-a 5-fold decrease compared to unmodified clay.


Input: These organoclays are produced via alkylammonium cation exchange with colloidally dispersed montmorillonite clay sheets followed by solvent casting.

alkylammonium

montmorillonite


Input: Time-domain thermoreflectance (TDTR) is used to evaluate the thermal conductivity of the organoclay nanolaminates.


Input: Variations in both organic layer thickness and cation chemistry are investigated.


Input: At these interface densities (1. 0-1. 5 interfaces/nm), we demonstrate that thermal conductivity is relatively independent of nanolaminate spacing.


Input: A simple series resistance model describes the behavior and gives an interfacial thermal conductance value of =~ 150 MW m (-2) K (-1) for the organic/clay interface, consistent with similar organic-inorganic interfaces.


Input: The wide range of compositional substitutions and structural variations possible in these materials, make organoclays a versatile new platform for investigating the underlying physics of nanolaminate structures.


Input: Matrix Isolation Spectroscopy and Nuclear Spin Conversion of NH3 and ND3 in Solid Parahydrogen.

Parahydrogen


Input: We present matrix isolation infrared absorption spectra of NH3 and ND3 trapped in solid parahydrogen (pH2) at temperatures around 1. 8 K.

parahydrogen


Input: We used the relatively slow nuclear spin conversion (NSC) of NH3 and ND3 in freshly deposited pH2 samples as a tool to assign the sparse vibration-inversion-rotation (VIR) spectra of NH3 in the regions of the nu 2, nu 4, 2 nu 4, nu 1, and nu 3 bands and ND3 in the regions of the nu 2, nu 4, nu 1, and nu 3 fundamentals.


Input: Partial assignments are also presented for various combination bands of NH3.


Input: Detailed analysis of the nu 2 bands of NH3 and ND3 indicates that both isotopomers are nearly free rotors; that the vibrational energy is blue-shifted by 1-2%; and that the rotational constants and inversion tunneling splitting are 91-94% and 67-75%, respectively, of the gas-phase values.


Input: The line shapes of the VIR absorptions are narrow (0. 2-0. 4 cm (-1)) for upper states that cannot rotationally relax and broad (> 1 cm (-1)) for upper states that can rotationally relax.


Input: We report and assign a number of NH3-induced infrared absorption features of the pH2 host near 4150 cm (-1), along with a cooperative transition that involves simultaneous vibrational excitation of a pH2 molecule and rotation-inversion excitation of NH3.


Input: The NSCs of NH3 and ND3 were found to follow first-order kinetics with rate constants at 1. 8 K of k = 1. 88 (16) x 10 (-3) s (-1) and k = 1. 08 (8) x 10 (-3) s (-1), respectively.


Input: These measured rate constants are compared to previous measurements for NH3 in an Ar matrix and with the rate constants measured for other dopant molecules isolated in solid pH2.


Input: Development and validation of NIR-chemometric methods for chemical and pharmaceutical characterization of meloxicam tablets.

meloxicam


Input: Abstract Context: Near-Infrared (NIR) spectroscopy is an important component of a Process Analytical Technology (PAT) toolbox and is a key technology for enabling the rapid analysis of pharmaceutical tablets.


Input: Objective: The aim of this research work was to develop and validate NIR-chemometric methods not only for the determination of active pharmaceutical ingredients content but also pharmaceutical properties (crushing strength, disintegration time) of meloxicam tablets.

meloxicam


Input: Materials and methods: The development of the method for active content assay was performed on samples corresponding to 80%, 90%, 100%, 110% and 120% of meloxicam content and the development of the methods for pharmaceutical characterization was performed on samples prepared at seven different compression forces (ranging from 7 to 45 kN) using NIR transmission spectra of intact tablets and PLS as a regression method.

meloxicam


Input: Results: The results show that the developed methods have good trueness, precision and accuracy and are appropriate for direct active content assay in tablets (ranging from 12 to 18 mg/tablet) and also for predicting crushing strength and disintegration time of intact meloxicam tablets.

meloxicam


Input: Discussion: The comparative data show that the proposed methods are in good agreement with the reference methods currently used for the characterization of meloxicam tablets (HPLC-UV methods for the assay and European Pharmacopeia methods for determining the crushing strength and disintegration time).

meloxicam


Input: Conclusion: The results show the possibility to predict both chemical properties (active content) and physical/pharmaceutical properties (crushing strength and disintegration time) directly, without any sample preparation, from the same NIR transmission spectrum of meloxicam tablets.

meloxicam


Input: Physicochemical characterization of phyllanthin from Phyllanthus amarus Schum.

phyllanthin


Input: et Thonn.


Input: Abstract Phyllanthin is a major bioactive lignan component of Phyllanthus amarus, with several known biological activities.

Phyllanthin

lignan


Input: This study dealt with the isolation and physicochemical characterization of phyllanthin.

phyllanthin


Input: Phyllanthin was isolated from P. amarus leaves by column chromatography and purified by recrystallization to obtain phyllanthin crystals with a purity of more than 98%.

Phyllanthin

phyllanthin


Input: UV, IR, MS, (1) H NMR and (13) C NMR spectra were employed to identify phyllanthin.

(1) H

(13) C

phyllanthin


Input: The physicochemical properties of phyllanthin were characterized using differential scanning calorimetry, thermogravimetric analysis, X-ray diffraction, pH-solubility, ionization property and lipophilicity.

phyllanthin


Input: The results indicated that phyllanthin crystals had the melting point and melting enthalpy range of 96. 67-97. 03 degrees C and 109. 61-116. 34 J/g, respectively.

phyllanthin


Input: Three kinds of phyllanthin crystals, recrystallized by petroleum ether, absolute ethanol and 25% ethanol solution, showed only one polymorph and no polymorphic impurity.

phyllanthin

petroleum ether

ethanol

ethanol


Input: Phyllanthin in a solid state was found to undergo significant thermal decomposition above 200 degrees C.

Phyllanthin


Input: The compound demonstrated good stability in aqueous solution over a pH range of 1. 07-10. 02 for at least 4 h.


Input: The solubility of phyllanthin appeared to be pH-independent of pH range from 1. 07 to 10. 26.

phyllanthin


Input: Ionization property studied by absorbance spectroscopy method was in agreement with the result of pH-solubility study, showing that phyllanthin has no pKa over a pH range of 1. 12-10. 02.

phyllanthin


Input: The log Pow value of phyllanthin was found to be 3. 30 +/- 0. 05 at pH 7. 48, suggesting that phyllanthin may have good permeability through biological membranes.

phyllanthin

phyllanthin


Input: The findings could be useful tools for the development of stable and bioavailable oral dosage forms of phyllanthin.

phyllanthin


Input: Genistein-Modified Poly (ethylene oxide)/Poly (d, l-lactic acid) Electrospun Mats with Improved Antioxidant and Anti-inflammatory Properties.

Poly (ethylene oxide)

Poly (d, l-lactic acid)


Input: Genistein is a phytochemical with a broad range of desirable biological activity for wound healing.

Genistein


Input: However, its poor bioavailability requires developing a new method for fabricating an appropriate carrier vehicle to deliver genistein in a sustained manner.

genistein


Input: Based on the guidance afforded by the ternary phase diagram of poly (d, l-lactic acid) (PDLLA), poly (ethylene oxide) (PEO), and genistein blends, certain selective compositions were electrospun.

poly (d, l-lactic acid)

PDLLA

poly (ethylene oxide)

PEO

genistein


Input: We obtained a uniformly smooth surface morphology in unmodified and genistein-modified PEO/PDLLA fibers, documented by scanning electron microscopy.

genistein

PEO

PDLLA


Input: Moreover, wide-angle X-ray diffraction and (1) H NMR studies revealed that the genistein molecules, successfully incorporated in the blends, remained chemically stable after electrospinning.

(1) H

genistein


Input: Besides surface wettability and dimensional stability of the electrospun mats, the released genistein amount has been evaluated as a function of PEO concentration.

genistein

PEO


Input: Our biocompatibility investigations suggest that genistein-modified PEO/PDLLA electrospun mats exhibit strong antioxidant and anti-inflammatory activities which indicate they have potential applications for wound dressings.

genistein

PEO

PDLLA


Input: Selective Permeation of Hydrogen Gas Using Cellulose Nanofibril Film.

Hydrogen


Input: Biobased membranes that can selectively permeate hydrogen gas have been developed from aqueous dispersions of 2, 2, 6, 6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidized cellulose nanofibrils (TOCN) prepared from wood cellulose: TOCN-coated plastic films and self-standing TOCN films.

hydrogen

2, 2, 6, 6-tetramethylpiperidine-1-oxyl

TEMPO


Input: Compared with TOCNs with sodium, lithium, potassium, and cesium carboxylate groups, TOCN with free carboxyl groups (TOCN-COOH) had much high and selective H2 gas permeation performance.

sodium

lithium

potassium

cesium carboxylate

carboxyl

COOH


Input: Because permeabilities of H2, N2, O2, and CO2 gases through the membranes primarily depended on their kinetic diameters, the gas permeation behavior of the various TOCNs can be explained in terms of a diffusion mechanism.


Input: Thus, the selective H2 gas permeability for TOCN-COOH was probably due to a larger average size in free volume holes present between nanofibrils in the layer and film than those of other TOCNs with metal carboxylate groups.

COOH

metal carboxylate


Input: The obtained results indicate that TOCN-COOH membranes are applicable as biobased H2 gas separation membranes in fuel cell electric power generation systems.

COOH


Input: Antimalarial Activity of Axidjiferosides, New beta-Galactosylceramides from the African Sponge Axinyssa djiferi.

Axidjiferosides

beta-Galactosylceramides


Input: The marine sponge, Axinyssa djiferi, collected on mangrove tree roots in Senegal, was investigated for glycolipids.


Input: A mixture containing new glycosphingolipids, named axidjiferoside-A,-B and-C, accounted for 0. 07% of sponge biomass (dry weight) and for 2. 16% of total lipids.

glycosphingolipids

axidjiferoside-A,-B and-C


Input: It showed a significant antimalarial activity, with a 50% inhibitory concentration (IC50) of 0. 53 +/- 0. 2 mu M against a chloroquine-resistant strain of Plasmodium falciparum.

chloroquine


Input: They were identified as homologous beta-galactopyranosylceramides composed of 2-amino-(6E)-octadec-6-en-1, 3, 4-triol, and the major one, axidjiferoside-A (around 60%), contained 2-hydroxytetracosanoic acid.

beta-galactopyranosylceramides

2-amino-(6E)-octadec-6-en-1, 3, 4-triol

axidjiferoside-A

2-hydroxytetracosanoic acid


Input: Cytotoxicity was studied in vitro on human cancer cell lines (multiple myeloma, colorectal adenocarcinoma, glioblastoma and two lung cancer NSCLC-N6 and A549).


Input: Results of this investigation showed that axidjiferosides are of interest, because they proved a good antiplasmodial activity, with only a low cytotoxicity against various human cell lines and no significant antitrypanosomal and antileishmanial activity.

axidjiferosides


Input: Thus, it seems that galactosylceramides with a beta anomeric configuration may be suitable in searching for new antimalarial drugs.

galactosylceramides


Input: Cannabis intoxication inhibits avoidance action tendencies: a field study in the Amsterdam coffee shops.


Input: RATIONALE: Experimental laboratory studies suggest that the approach bias (relatively fast approach responses) toward substance-related materials plays an important role in problematic substance use.


Input: How this bias is moderated by intention to use versus recent use remains unknown.


Input: Moreover, the relationship between approach bias and other motivational processes (satiation and craving) and executive functioning remains unclear.


Input: OBJECTIVES: The aim of this study was to investigate the cannabis approach bias before and after cannabis use in real-life setting (Amsterdam coffee shops) and to assess the relationship between approach bias, craving, satiation, cannabis use, and response inhibition.


Input: METHODS: Cannabis, tobacco, and neutral approach and avoidance action tendencies were measured with the Approach Avoidance Task and compared between 42 heavy cannabis users with the intention to use and 45 heavy cannabis users shortly after cannabis use.


Input: The classical Stroop was used to measure response inhibition.


Input: Multiple regression analyses were conducted to investigate relationships between approach bias, satiation, craving, cannabis use, and response inhibition.


Input: RESULTS: In contrast to the hypotheses, heavy cannabis users with the intention to use did not show a cannabis approach bias, whereas intoxicated cannabis users did show an approach bias regardless of image category.


Input: This could be attributed to a general slowing of avoidance action tendencies.


Input: Moreover, craving was negatively associated with the approach bias, and no relationships were observed between the cannabis approach bias, satiation, prior cannabis use, and response inhibition.


Input: CONCLUSION: Cannabis intoxication in a real-life setting inhibited general avoidance.


Input: Expression of the cannabis approach bias appeared not to be modulated by satiation or response inhibition.


Input: Unraveling the Reaction Mechanisms Governing Methanol-to-Olefins Catalysis by Theory and Experiment.

Methanol

Olefins


Input: The conversion of methanol to olefins (MTO) over a heterogeneous nanoporous catalyst material is a highly complex process involving a cascade of elementary reactions.

methanol

olefins


Input: The elucidation of the reaction mechanisms leading to either the desired production of ethene and/or propene or undesired deactivation has challenged researchers for many decades.

ethene

propene


Input: Clearly, catalyst choice, in particular topology and acidity, as well as the specific process conditions determine the overall MTO activity and selectivity; however, the subtle balances between these factors remain not fully understood.


Input: In this review, an overview of proposed reaction mechanisms for the MTO process is given, focusing on the archetypal MTO catalysts, H-ZSM-5 and H-SAPO-34.


Input: The presence of organic species, that is, the so-called hydrocarbon pool, in the inorganic framework forms the starting point for the majority of the mechanistic routes.


Input: The combination of theory and experiment enables a detailed description of reaction mechanisms and corresponding reaction intermediates.


Input: The identification of such intermediates occurs by different spectroscopic techniques, for which theory and experiment also complement each other.


Input: Depending on the catalyst topology, reaction mechanisms proposed thus far involve aromatic or aliphatic intermediates.


Input: Ab initio simulations taking into account the zeolitic environment can nowadays be used to obtain reliable reaction barriers and chemical kinetics of individual reactions.


Input: As a result, computational chemistry and by extension computational spectroscopy have matured to the level at which reliable theoretical data can be obtained, supplying information that is very hard to acquire experimentally.


Input: Special emphasis is given to theoretical developments that open new perspectives and possibilities that aid to unravel a process as complex as methanol conversion over an acidic porous material.

methanol


Input: Metabolism and pathways for denitration of organic nitrates in the human liver.

nitrates


Input: Liver first-pass metabolism differs considerably among organic nitrates but little information exists on the mechanism of denitration of these compounds in hepatic tissue.

nitrates


Input: The metabolism of nitrooxybutyl-esters of flurbiprofen and ferulic-acid, a class of organic nitrates with potential therapeutic implication in variety of different conditions, was investigated in comparison with glyceryl trinitrate (GTN) in human liver by a multiple approach, using a spontaneous metabolism-independent NO donor (NOC-5) as a reference tool.

nitrooxybutyl-esters

flurbiprofen

ferulic-acid

nitrates

glyceryl trinitrate

GTN

NO


Input: Nitrooxybutyl-esters were rapidly and quantitatively metabolized to their respective parent compounds and the organic nitrate moiety nitrooxybutyl-alcohol (NOBA).

Nitrooxybutyl-esters

nitrate

nitrooxybutyl-alcohol

NOBA


Input: Differently from GTN which was rapidly and completely metabolized to nitrite, NOBA was slowly metabolized to nitrate.

GTN

nitrite

NOBA

nitrate


Input: In contrast to the spontaneous NO donor NOC-5, NOBA and GTN did not generate detectable NO and failed to suppress the activity of cytochromeP450; an enzyme known to be inhibited by NO.

NO

NOBA

GTN

NO

NO


Input: The direct identification of NOBA following liver metabolism targets this compound as the functional organic nitrate metabolite of nitrooxybutyl-esters.

NOBA

nitrate

nitrooxybutyl-esters


Input: Moreover the investigation of the pathways for denitration of NOBA and GTN suggests that organic nitrates are not primarily metabolized to NO in the liver but to different extents of nitrite or nitrate depending from their different chemical structure.

NOBA

GTN

nitrates

NO

nitrite

nitrate


Input: It follows that cytochromeP450-dependent metabolism of concomitant drugs is not likely to be affected by oral co-administration of organic nitrates.

nitrates


Input: However the first-pass may differently affect the pharmacological profile of organic nitrates in connection with the different extent of denitration and the distinct bioactive species generated and exported from the liver (nitrate or nitrite).

nitrates

nitrate

nitrite


Input: From a Multipotent Stilbene to Soluble Epoxide Hydrolase Inhibitors with Antiproliferative Properties.

Stilbene

Epoxide


Input: Inspired by nature: Natural product isopropylstilbene was identified as an inhibitor of soluble epoxide hydrolase exhibiting antiproliferative properties.

isopropylstilbene

epoxide


Input: Following the natural product inspired design approach, a library of (E)-styryl-1H-benzo [d] imidazoles was synthesized and evaluated with recombinant enzyme and on several cancer cell lines.

(E)-styryl-1H-benzo [d] imidazoles


Input: Temporal Concordance between Apical and Transcriptional Points-of-Departure for Chemical Risk Assessment.


Input: The number of legacy chemicals without toxicity reference values combined with the rate of new chemical development are overwhelming the capacity of the traditional risk assessment paradigm.


Input: More efficient approaches are needed to quantitatively estimate chemical risks.


Input: In this study, rats were dosed orally with multiple doses of six chemicals for 5 days, 2, 4, and 13 weeks.


Input: Target organs were analyzed for traditional histological and organ weight changes and transcriptional changes using microarrays.


Input: Histological and organ weight changes in this study and the tumor incidences in the original cancer bioassays were analyzed using benchmark dose (BMD) methods to identify noncancer and cancer points-of-departure.


Input: The dose-response changes in gene expression were also analyzed using BMD methods and the responses grouped based on signaling pathways.


Input: A comparison of transcriptional BMD values for the most sensitive pathway with BMD values for the noncancer and cancer apical endpoints showed a high degree of correlation at all time points.


Input: When the analysis included data from an earlier study with 8 additional chemicals, transcriptional BMD values for the most sensitive pathway were significantly correlated with noncancer (r = 0. 830, p = 0. 0016) and cancer-related (r = 0. 943, p = 0. 0001) BMD values at 13 weeks.


Input: The average ratio of apical-to-transcriptional BMD values was less than two suggesting that for the current chemicals, transcriptional perturbation did not occur at significantly lower doses than apical responses.


Input: Based on our results, we propose a practical framework for application of transcriptomic data to chemical risk assessment.


Input: Methamidophos exposure during the early postnatal period of mice: Immediate and late-emergent effects on the cholinergic and serotonergic systems and on behavior.

Methamidophos


Input: Organophosphates (OPs) are among the most used pesticides.

Organophosphates

OPs


Input: While some OPs have had their use progressively more restricted, other OPs are being used without sufficient investigation of their effects.

OPs

OPs


Input: Here, we investigated the immediate neurochemical and delayed neurochemical and behavioral actions of the OP methamidophos to verify whether there are concerns regarding exposure during early postnatal development.

methamidophos


Input: From the 3 (rd) to the 9 (th) postnatal day (PN), Swiss mice were subcutaneously injected with methamidophos (1 mg/kg).

methamidophos


Input: At PN10, we assessed cholinergic and serotonergic biomarkers in the cerebral cortex and brainstem.


Input: From PN60 to PN63, mice were submitted to a battery of behavioral tests and subsequently to biochemical analyses.


Input: At PN10, the effects were restricted to females and to the cholinergic system: Methamidophos promoted increased choline transporter binding in the brainstem.

Methamidophos

choline


Input: At PN63, in the brainstem, there was a decrease in choline transporter, a female-only decrease in 5HT1A and a male-only increase in 5HT2 receptor binding.

choline


Input: In the cortex, choline acetyltransferase activity was decreased and 5HT2 receptor binding was increased both in males and females.

choline


Input: Methamidophos elicited behavioral alterations suggestive of increased depressive-like behavior and impaired decision-making.

Methamidophos


Input: There were no significant alterations on anxiety-related measures and on memory/learning.


Input: Methamidophos elicited cholinergic and serotonergic alterations that depended on brain region, sex and age of the animals.

Methamidophos


Input: These outcomes, together with the behavioral effects, indicate that this OP is deleterious to the developing brain and that alterations are indeed identified long after the end of exposure.


Input: Pheromone evolution, reproductive genes, and comparative transcriptomics in Mediterranean earthworms (Annelida, Oligochaeta, Hormogastridae).


Input: Animals inhabiting cryptic environments are often subjected to morphological stasis due to the lack of obvious agents driving selection, and hence chemical cues may be important drivers of sexual selection and individual recognition.


Input: Here we provide a comparative analysis of de novo assembled transcriptomes in two Mediterranean earthworm species with the objective to detect pheromone proteins and other reproductive genes that could be involved in cryptic speciation processes, as recently characterized in other earthworm species.


Input: cDNA libraries of unspecific tissue of Hormogaster samnitica and three different tissues of Hormogaster elisae were sequenced in an Illumina Genome Analyzer II or Hi-Seq.


Input: Two pheromones, Attractin and Temptin were detected in all tissue samples and both species.


Input: Attractin resulted in a reliable marker for phylogenetic inference.


Input: Temptin contained multiple paralogues and was slightly overexpressed in the digestive tissue, suggesting that these pheromones could be released with the casts.


Input: Genes involved in sexual determination and fertilization were highly expressed in reproductive tissue.


Input: This is thus the first detailed analysis of the molecular machinery of sexual reproduction in earthworms.


Input: Determining osmotic pressure of drug solutions by air humidity in equilibrium method.


Input: Abstract Objective: To establish a new osmotic pressure measuring method with a wide measuring range.


Input: Method: The osmotic pressure of drug solutions is determined by measuring the relative air humidity in equilibrium with the solution.


Input: The freezing point osmometry is used as a control.


Input: Results: The data obtained by the proposed method are comparable to those by the control method, and the measuring range of the proposed method is significantly wider than that of the control method.


Input: Conclusion: The proposed method is performed in an isothermal and equilibrium state, so it overcomes the defects of the freezing point and dew point osmometries which result from the heterothermal process in the measurement, and therefore is not limited to diluted solutions.


Input: Enhanced Triboelectric Nanogenerators and Triboelectric Nanosensor Using Chemically Modified TiO2 Nanomaterials.


Input: Mechanical energy harvesting based on triboelectric effect has been proven to be a simple, cost-effective, and robust method for electricity generation.


Input: In this study, we developed a rationally designed triboelectric nanogenerator (TENG) by utilizing the contact electrification between a polytetrafluoroethylene (PTFE) thin film and a layer of TiO2 nanomaterial (nanowire and nanosheet) array.

polytetrafluoroethylene

PTFE


Input: The as-developed TENG was systematically studied and demonstrated as a self-powered nanosensor toward catechin detection.

catechin


Input: The high sensitivity (detection limit of 5 mu M) and selectivity are achieved through a strong interaction between Ti atoms of TiO2 nanomaterial and enediol group of catechin.

Ti

catechin


Input: The output voltage and current density were increased by a factor of 5. 0 and 2. 9, respectively, when adsorbed with catechin of a saturated concentration, because of the charge transfer from catechin to TiO2.

catechin

catechin


Input: This study demonstrates the possibility of improving the electrical output of TENG through chemical modification.


Input: Investigation of Protein Detection Parameters Using Nanofunctionalized Organic Field-Effect Transistors.


Input: Biodetection using organic field-effect transistors (OFETs) is gaining increasing interest for applications as diverse as food security, environmental monitoring, and medical diagnostics.


Input: However, there still lacks a comprehensive, empirical study on the fundamental limits of OFET sensors.


Input: In this paper, we present a thorough study of the various parameters affecting biosensing using an OFET decorated with gold nanoparticle (AuNP) binding sites.


Input: These parameters include the spacing between receptors, pH of the buffer, and ionic strength of the buffer.


Input: To this end, we employed the thrombin protein and its corresponding DNA binding aptamer to form our model detection system.


Input: We demonstrate a detection limit of 100 pM for this protein with high selectivity over other proteases in situ.


Input: We describe herein a feasible approach for protein detection with OFETs and a thorough investigation of parameters governing biodetection events using OFETs.


Input: Our obtained results should provide important guidelines to tailor the sensor' s dynamic range to suit other desired OFET-based biodetection applications.


Input: Magnetic-Nanoparticle-Decorated Polypyrrole Microvessels: Toward Encapsulation of mRNA Cap Analogues.

Polypyrrole


Input: Many phosphorylated nucleoside derivatives have therapeutic potential, but their application is limited by problems with membrane permeability and with intracellular delivery.

nucleoside


Input: Here, we prepared polypyrrole microvessel structures modified with superparamagnetic nanoparticles for use as potential carriers of nucleotides.

polypyrrole

nucleotides


Input: The microvessels were prepared via the photochemical polymerization of the monomer onto the surface of aqueous ferrofluidic droplets.


Input: A complementary physicochemical analysis revealed that a fraction of the nanoparticles was embedded in the microvessel walls, while the other nanoparticles were in the core of the vessel.


Input: SQUID (superconducting quantum interference device) measurements indicated that the incorporated nanoparticles retained their superparamagnetic properties; thus, the resulting nanoparticle-modified microvessels can be directed by an external magnetic field.


Input: As a result of these features, these microvessels may be useful as drug carriers in biomedical applications.


Input: To demonstrate the encapsulation of drug molecules, two labeled mRNA cap analogues, nucleotide-derived potential anticancer agents, were used.

nucleotide


Input: It was shown that the cap analogues are located in the aqueous core of the microvessels and can be released to the external solution by spontaneous permeation through the polymer walls.


Input: Mass spectrometry analysis confirmed that the cap analogues were preserved during encapsulation, storage, and release.


Input: This finding provides a foundation for the future development of anticancer therapies and for the delivery of nucleotide-based therapeutics.

nucleotide


Input: Enantioselective thiourea-catalyzed intramolecular cope-type hydroamination.

thiourea