Input: The Ica (2) substitution resulted in two moderately potent and selective antioxytocic agents: [Mpa (1), Ica (2), D-Arg (8)] VP and [Mpa (1), Ica (2), Val (4), D-Arg (8)] VP (pA (2) = 7. 09 and 7. 50, respectively).

Ica

[Mpa (1), Ica (2), D-Arg (8)] VP

[Mpa (1), Ica (2), Val (4), D-Arg (8)] VP


Input: On the other hand, peptides modified with (2S, 4R)-4-(naphthalene-2-ylmethyl) pyrrolidine-2-carboxylic acid, apart from their moderate antioxytocic activity, turned out to be weak antagonists of the pressor response to arginine vasopressin.

(2S, 4R)-4-(naphthalene-2-ylmethyl) pyrrolidine-2-carboxylic acid

arginine vasopressin


Input: The results of this study provide useful information about the structure-activity relationship of arginine vasopressin analogues and can help to design compounds with desired biological properties.

arginine vasopressin


Input: Magnetic nanoclusters exhibiting protein-activated near-infrared fluorescence.


Input: Composite nanoclusters with chemical, magnetic, and biofunctionality offer broad opportunities for targeted cellular imaging.


Input: A key challenge is to load a high degree of targeting, imaging, and therapeutic functionality onto stable metal-oxide nanoparticles.

metal-oxide


Input: Here we report a route for producing magnetic nanoclusters (MNCs) with alkyne surface functionality that can be utilized as multimodal imaging probes.

alkyne


Input: We form MNCs composed of magnetic Fe (3) O (4) nanoparticles and poly (acrylic acid-co-propargyl acrylate) by the co-precipitation of iron salts in the presence of copolymer stabilizers.


Input: The MNCs were surface-modified with near-infrared (NIR) emitting fluorophore used in photodynamic therapy, an azide-modified indocyanine green.

azide

indocyanine green


Input: The fluorophores engaged and complexed with bovine serum albumin, forming an extended coverage of serum proteins on the MNCs.


Input: These proteins isolated indocyanine green fluorophores from the aqueous environment and induced an effective " turn-on " of NIR emission.

indocyanine green


Input: Transferable potentials for phase equilibria.


Input: Explicit-hydrogen description of substituted benzenes and polycyclic aromatic compounds.

hydrogen

benzenes

polycyclic aromatic


Input: The explicit-hydrogen version of the transferable potentials for phase equilibria (TraPPE-EH) force field is extended to various substituted benzenes through the parametrization of the exocyclic groups-F,-Cl,-Br,-C = N, and-OH and to polycyclic aromatic hydrocarbons through the parametrization of the aromatic linker carbon atom for multiple rings.

hydrogen

benzenes

F

Cl

Br

C = N

OH

polycyclic aromatic hydrocarbons

carbon


Input: The linker carbon together with the TraPPE-EH parameters for aromatic heterocycles constitutes a force field for fused-ring heterocycles.

carbon

aromatic heterocycles

fused-ring heterocycles


Input: Configurational-bias Monte Carlo simulations in the Gibbs ensemble were carried out to compute vapor-liquid coexistence curves for fluorobenzene; chlorobenzene; bromobenzene; di-, tri-, and hexachlorobenzene isomers; 2-chlorofuran; 2-chlorothiophene; benzonitrile; phenol; dihydroxybenzene isomers; 1, 4-benzoquinone; naphthalene; naphthalene-2-carbonitrile; naphthalen-2-ol; quinoline; benzo [b] thiophene; benzo [c] thiophene; benzoxazole; benzisoxazole; benzimidazole; benzothiazole; indole; isoindole; indazole; purine; anthracene; and phenanthrene.

fluorobenzene

chlorobenzene

bromobenzene

di-, tri-, and hexachlorobenzene

benzonitrile

phenol

dihydroxybenzene

1, 4-benzoquinone

naphthalene

quinoline

benzo [b] thiophene

benzo [c] thiophene

benzoxazole

benzisoxazole

benzimidazole

benzothiazole

indole

isoindole

indazole

purine

anthracene

phenanthrene


Input: The agreement with the limited experimental data is very satisfactory, with saturated liquid densities and vapor pressures reproduced to within 1. 5% and 15%, respectively.


Input: The mean unsigned percentage errors in the normal boiling points, critical temperatures, and critical densities are 0. 9%, 1. 2%, and 1. 4%, respectively.


Input: Additional simulations were carried out for binary systems of benzene/benzonitrile, benzene/phenol, and naphthalene/methanol to illustrate the transferability of the developed potentials to binary systems containing compounds of different polarity and hydrogen-bonding ability.

benzene

benzonitrile

benzene

phenol

naphthalene

methanol

hydrogen


Input: A detailed analysis of the liquid-phase structures is provided for selected neat systems and binary mixtures.


Input: Antiepileptic action of N-palmitoylethanolamine through CB1 and PPAR-alpha receptor activation in a genetic model of absence epilepsy.

N-palmitoylethanolamine


Input: N-palmitoylethanolamine (PEA), an endogenous fatty acid ethanolamide, plays a key role in the regulation of the inflammatory response and pain through, among others, activation of nuclear peroxisome proliferator-activated receptors (PPAR-alpha).

N-palmitoylethanolamine

PEA

fatty acid ethanolamide


Input: Endogenous cannabinoids play a protective role in several central nervous system (CNS) disorders, particularly those associated with neuronal hyperexcitability.

cannabinoids


Input: We investigated the effects of PEA and the role of PPAR-alpha in absence epilepsy using the WAG/Rij rat model.

PEA


Input: PEA, anandamide (AEA), a PPAR-alpha antagonist (GW6471) and a synthetic CB1 receptor antagonist/inverse agonist (SR141716) were administered to WAG/Rij rats in order to evaluate the effects on epileptic spike-wave discharges (SWDs) on EEG recordings.

PEA

anandamide

AEA


Input: We studied also the effects of PEA co-administration with SR141716 and GW6471 and compared these effects with those of AEA to evaluate PEA mechanism of action and focusing on CB1 receptors and PPAR-alpha.

PEA

AEA

PEA


Input: Both PEA and AEA administration significantly decreased SWDs parameters (absence seizures).

PEA

AEA


Input: In contrast, GW6471 was devoid of effects while SR141716 had pro-absence effects.


Input: The co-administration of SR141716 with PEA or AEA completely blocked the anti-absence effects of these compounds.

PEA

AEA


Input: GW6471 antagonized PEA' s effects whereas it did not modify AEA' s effects.

PEA

AEA


Input: Furthermore, we have also measured PEA, AEA and 2-AG (2-arachidonoylglycerol) brain levels identifying significant differences between epileptic and control rats such as decreased PEA levels in both thalamus and cortex that might contribute to absence epilepsy.

PEA

AEA

PEA


Input: Our data demonstrate that PEA has anti-absence properties in the WAG/Rij rat model and that such properties depend on PPAR-alpha and indirect activation of CB1 receptors.

PEA


Input: This article is part of the Special Issue entitled' New Targets and Approaches to the Treatment of Epilepsy'.


Input: Tetrahydro-beta-carboline derivatives targeting fatty acid amide hydrolase (FAAH) and transient receptor potential (TRP) channels.

Tetrahydro-beta-carboline

fatty acid amide


Input: A series of twenty-five derivatives of tetrahydro-beta-carbolines 1-3 was synthesized and assayed on FAAH and TRPV1 and TRPA1 channels.

tetrahydro-beta-carbolines


Input: Four carbamates, that is, 5a, c, e, and 9b inhibited FAAH with significant potency and interacted also effectively with TRPV1 and TRPA1 nociceptive receptors, while ureas 7b, d, f, and 8a, b were endowed with specific submicromolar TRPV1 modulating activities.

carbamates


Input: ESR1 polymorphisms, daily hassles, anger expression, and depressive symptoms in adolescent boys and girls.


Input: Studies reporting associations between genetic factors and mood-related traits have often been criticized (i) for failing to take into account the role of the social environment in which individuals act and (ii) for not maintaining a' transparent narrative connection' between genes and outcomes.


Input: In a sample of adolescents, we analyzed whether PvuII and XbaI, two polymorphisms on the ESR1 (Estrogen Receptor Gene alpha) were related to depressive symptoms, and considered whether daily hassles moderated this relationship and whether anger expression style mediated this relationship.

Estrogen


Input: Analyses suggested that ESR1 polymorphisms are relevant to the intra-sexual variability in depressive symptoms in boys and that the experience of daily hassles moderated this relationship.


Input: No such relationships were found in girls.


Input: Additionally, ESR1 polymorphisms are related to anger expression styles in girls.


Input: Anger-related variables, however, did not mediate the relationship between ESR1 polymorphisms and depressive symptoms, in boys nor in girls.


Input: Birth defects after exposure to misoprostol in the first trimester of pregnancy: prospective follow-up study.

misoprostol


Input: Misoprostol during the first trimester of pregnancy is associated with a specific malformative pattern (Moebius sequence and limb defects) whose incidence remains unknown.

Misoprostol


Input: Data originate mostly from illegal use for abortion and are mainly retrospective.


Input: The present prospective controlled study analyses outcomes of first trimester misoprostol exposures after medical prescriptions.

misoprostol


Input: Malformation rate was higher among 236 pregnancies exposed before 12 gestational weeks (4%) than in 255 controls (1. 8%), although not statistically significant (OR = 2. 2 [95% CI = 0. 6-7. 7]).


Input: Three malformations (2%) in the exposed group were consistent with the misoprostol malformative pattern.

misoprostol


Input: This is the largest prospective study on first trimester misoprostol exposure and the first one relying on prescriptions.

misoprostol


Input: A trend toward a doubling of the overall rate of malformations was observed and for the first time an estimation of the incidence of misoprostol specific spectrum is proposed (2%).

misoprostol


Input: Brainstem injuries including severe trismus might be added to this specific pattern.


Input: Effects of the herbal medicine composition " Saiko-ka-ryukotsu-borei-To " on the function of endothelial progenitor cells in hypertensive rats.


Input: Endothelial progenitor cells (EPCs) are known to repair vascular injuries.


Input: Recent studies suggest that Saiko-ka-ryukotsu-borei-To (SKRBT), a traditional herbal medicine that has been used to treat stress-related neuropsychiatric disorders, has protective effects on cardiovascular diseases such as hypertension and arteriosclerosis.


Input: Spontaneously hypertensive rats (SHRs) were fed diets containing lyophilized SKRBT extract for 6 weeks.


Input: Peripheral blood mononuclear cells (MNCs) were isolated and cultured to assay EPC colony formation.


Input: Oxidative stress in MNCs was evaluated by thiobarbituric acid reactive substance (TBARS) assay and flowcytometric analyses.

thiobarbituric acid


Input: Treatment with SKRBT increased EPC colony numbers significantly (p < 0. 05) with decrease in oxidative stress and without affecting blood pressure in SHRs.


Input: Treatment with SKRBT did not reduce the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits in cardiovascular organs.

nicotinamide adenine dinucleotide phosphate

NADPH


Input: Serum IL-6 level was significantly reduced.


Input: SKRBT is a feasible herbal medicine that protects against cardiovascular diseases through an increase in EPC function along with anti-oxidative effects, and may affect the link between chronic inflammation and cardiovascular disease.


Input: Nasal administration of liquid crystal precursor mucoadhesive vehicle as an alternative antiretroviral therapy.


Input: The purpose of this study was to develop a mucoadhesive stimuli-sensitive drug delivery system for nasal administration of zidovudine (AZT).

zidovudine

AZT


Input: The system was prepared by formulating a low viscosity precursor of a liquid crystal phase, taking advantage of its lyotropic phase behavior.


Input: Flow rheology measurements showed that the formulation composed of PPG-5-CETETH-20, oleic acid and water (55, 30, 15% w/w), denominated P, has Newtonian flow behavior.

oleic acid


Input: Polarized light microscopy (PLM) revealed that formulation P is isotropic, whereas its 1: 1 (w/w) dilution with artificial nasal mucus (ANM) changed the system to an anisotropic lamellar phase (PD).


Input: Oscillatory frequency sweep analysis showed that PD has a high storage modulus (G') at nasal temperatures.


Input: Measurement of the mucoadhesive force against excised porcine nasal mucosa or a mucin disk proved that the transition to the lamellar phase tripled the work of mucoadhesion.


Input: Ex vivo permeation studies across porcine nasal mucosa exhibited an 18-fold rise in the permeability of AZT from the formulation.

AZT


Input: The Weibull mathematical model suggested that the AZT is released by Fickian diffusion mechanisms.

AZT


Input: Hence, the physicochemical characterization, combined with ex vivo studies, revealed that the PPG-5-CETETH-20, oleic acid, and water formulation could form a mucoadhesive matrix in contact with nasal mucus that promoted nasal absorption of the AZT.

oleic acid

AZT


Input: For an in vivo assessment, the plasma concentrations of AZT in rats were determined by HPLC method following intravenous and intranasal administration of AZT-loaded P formulation (PA) and AZT solution, respectively, at a dose of 8mg/kg.

AZT

AZT

AZT


Input: The intranasal administration of PA resulted in a fast absorption process (Tmax = 6. 7min).


Input: Therefore, a liquid crystal precursor formulation administered by the nasal route might represent a promising novel tool for the systemic delivery of AZT and other antiretroviral drugs.

AZT


Input: In the present study, the uptake of AZT absorption in the nasal mucosa was demonstrated, providing new foundations for clinical trials in patients with AIDS.

AZT


Input: Cobalt whole blood concentrations in healthy adult male volunteers following two-weeks of ingesting a cobalt supplement.

Cobalt

cobalt


Input: Recently, there has been an increase in the marketing and sales of dietary supplements, energy drinks, and other consumer products that may contain relatively high concentrations of essential elements.


Input: Cobalt-containing supplements are readily available in the U. S. and have been marketed to consumers as energy enhancers.

Cobalt


Input: However, little information is available regarding cobalt (Co) body burden and steady-state blood concentrations following the intake of Co dietary supplements.

cobalt

Co

Co


Input: We assessed Co whole blood concentrations in four healthy adult male volunteers who ingested a commercially available Co supplement (0. 4 mg Co/day) for 15 or 16 days.

Co

Co

Co


Input: Pre-supplementation blood Co concentrations were less than the reporting limit of 0. 5 mu g/L, consistent with background concentrations reported to range between 0. 1 and 0. 4 mu g/L.

Co


Input: The mean whole blood Co concentration in the volunteers after 15 or 16 days of dosing was 3. 6 mu g Co/L and ranged from 1. 8 to 5. 1 mu g Co/L.

Co

Co

Co


Input: The mean observed concentration in the study group was approximately 9-36 times greater than background concentrations.


Input: Further studies of Co whole blood concentrations following supplementation over longer time periods with additional monitoring of physiological parameters may provide useful information for evaluating the health of persons who take various doses of Co.

Co

Co


Input: Polysialic acid enhances the migration and invasion of human cytotrophoblasts.


Input: Polysialic acid (polySia) is a large, cell-surface linear homopolymer composed of alpha 2, 8-linked sialic acid residues.

acid


Input: Most extensively studied in the nervous system, this unique glycan modulates development by enhancing cell migration and regulating differentiation.


Input: PolySia also functions in developing and adult immune systems and is a signature of many cancers.


Input: In this study, we demonstrated that human placental trophoblasts, an epithelial lineage, also display this glycan.


Input: Cytotrophoblasts and syncytiotrophoblasts expressed polySia in the first trimester and downregulated it during the course of pregnancy.


Input: PolySia promoted cytotrophoblast migration in an explant model of chorionic villous growth.


Input: Removal of this glycan also reduced cytotrophoblast penetration of basement membranes in an in vitro model of invasion.


Input: Finally, we showed that polySia was overexpressed in biopsies from patients with gestational trophoblastic diseases, including benign molar pregnancies and malignant choriocarcinomas.


Input: These results demonstrated, for the first time, functional roles for polySia during normal human placental development and implicated these unusual oligosaccharides in the unrestrained invasion of trophoblast tumors.


Input: Endocrine-disrupting effects of thioxanthone photoinitiators.

thioxanthone


Input: Photoinitiators used in food packaging ink, such as 2-isopropylthioxanthone (2-ITX), have been shown to migrate into food and beverages.


Input: Recently, several studies indicated that 2-ITX might be an endocrine-disrupting chemical.


Input: In this work, the effects of 2-ITX, 4-isopropylthioxanthone (4-ITX), 2, 4-diethylthio xanthone (2, 4-diethyl-TX), 2-chlorothioxanthone (2-chloro-TX), and 1-chloro-4-propoxythioxanthone (1-chloro-4-propoxy-TX) on steroidogenesis and androgen and estrogen receptor-mediated transcription activation have been studied using human H295R adrenocarcinoma cells and yeast hormone bioassays, respectively.

2, 4-diethylthio xanthone

2, 4-diethyl-TX

androgen

estrogen


Input: None of the compounds showed androgenic or estrogenic activities, but clear antiandrogenic and antiestrogenic activities were observed for 2-ITX, 4-ITX, and 2, 4-diethyl-TX, whereas 2-chloro-TX showed only antiandrogenic activity.

2, 4-diethyl-TX


Input: In an adapted version of the H295R steroidogenesis assay, using gas chromatography-tandem mass spectrometry analysis of H295R media, all five compounds increased levels of 17 beta-estradiol and estrone.

17 beta-estradiol

estrone


Input: H295R cells incubated with 2-ITX also showed significantly reduced androgen and increased pregnenolone and progesterone levels.

androgen

pregnenolone

progesterone


Input: Expression of particular steroidogenic genes, including the one encoding for aromatase (CYP19A1), was significantly upregulated after incubation of H295R cells with 2-ITX, 4-ITX, and 2, 4-diethyl-TX.

2, 4-diethyl-TX


Input: In line with the increased CYP19A1 mRNA expression, 2-ITX increased catalytic activity of aromatase in H295R cells as measured by cognate aromatase assays.


Input: The results indicate that thioxanthone derivatives can act as potential endocrine disruptors both at the level of nuclear receptor signaling and steroid hormone production.

thioxanthone

steroid


Input: Poly (2-oxazoline)-derived contact biocides: contributions to the understanding of antimicrobial activity.

Poly (2-oxazoline)


Input: A set of poly (2-oxazoline)-derived (co-) polymers was prepared by microwave-assisted polymerizations and acid-mediated hydrolysis and tested for antimicrobial activity in 50 x 50 x 2 mm PP compound plates containing 5 wt% of the polymers.

poly (2-oxazoline)


Input: Antimicrobial activity against gram-negative E. coli and P. aeruginosa as well as C. albicans depended only on the degree of hydrolysis, while antimicrobial activity against gram-positive S. aureus was only observed for hydrolyzed poly (2-nonyl-2-oxazoline) s.

poly (2-nonyl-2-oxazoline) s


Input: The surface energies of the compound plates compared to pure PP were hardly altered, and the compounds can be considered as alternatives for PP.


Input: The presence of the biocide additives at the surface of the PP compound plates could be shown by combined ATR-IR, zeta potential, and SEM-EDX measurements.


Input: Antimicrobial activity was maintained during double incubation as well as for lowered amounts of the biocide additive of 1% in PP compound plates.


Input: Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.


Input: Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D).


Input: We conducted a two-stage genome-wide association study of T2D in 12, 535 Indians, a less explored but high-risk group.


Input: We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1. 31; P = 3. 32 x 10-9).


Input: Imputation analysis refined the signal to rs998451 (odds ratio 1. 56; P = 6. 3 x 10-(1) (2)) within TMEM163 that encodes a probable vesicular transporter in nerve terminals.


Input: TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion.


Input: The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders.


Input: Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0. 05).


Input: Known loci and the newly identified 2q21 locus altogether explained 7. 65% variance in the risk of T2D in Indians.


Input: Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.


Input: Cotinine in human placenta predicts induction of gene expression in fetal tissues.

Cotinine


Input: Maternal cigarette smoking during pregnancy is associated with increased risk of perinatal morbidity and mortality.


Input: However, the mechanisms underlying adverse birth outcomes following prenatal exposure to cigarette smoke remain unknown due, in part, to the absence or unreliability of information regarding maternal cigarette smoke exposure during pregnancy.


Input: Our goal was to determine if placental cotinine could be a reliable biomarker of fetal cigarette smoke exposure during pregnancy.

cotinine


Input: Cotinine levels were determined in placentas from 47 women who reported smoking during pregnancy and from 10 women who denied cigarette smoke exposure.

Cotinine


Input: Cotinine levels were significantly higher in placentas from women reporting cigarette smoking (median = 27. 2 ng/g) versus women who reported no smoke exposure (2. 3 ng/g, P < 0. 001).

Cotinine


Input: Receiver operating characteristic curve analysis identified an optimal cut point of 7. 5 ng/g (sensitivity = 78. 7%, specificity = 100%) to classify placenta samples from mothers who smoked versus those from mothers who did not.


Input: Among 415 placentas for which maternal cigarette smoking status was unavailable, 167 had cotinine levels > 7. 5 ng/g and would be considered positive for cigarette smoke exposure.

cotinine


Input: Data from quantitative reverse-transcription polymerase chain reaction analyses demonstrated that in utero cigarette smoke exposure predicted by cotinine in placenta is associated with changes in the expression of xenobiotic-metabolizing enzymes in fetal tissues.

cotinine


Input: CYP1A1 mRNA in fetal lung and liver tissue and CYP1B1 mRNA in fetal lung tissue were significantly induced when cotinine was detected in placenta.

cotinine


Input: These findings indicate that cotinine in placenta is a reliable biomarker for fetal exposure and response to maternal cigarette smoking during pregnancy.

cotinine


Input: Development of vizantin, a safe immunostimulant, based on the structure-activity relationship of trehalose-6, 6'-dicorynomycolate.

vizantin

trehalose-6, 6'-dicorynomycolate


Input: Vizantin, 6, 6'-bis-O-(3-nonyldodecanoyl)-alpha, alpha'-trehalose, was developed as a safe immunostimulator on the basis of a structure-activity relationship (SAR) study with trehalose 6, 6'-dicorynomycolate (TDCM).

Vizantin

6, 6'-bis-O-(3-nonyldodecanoyl)-alpha, alpha'-trehalose

trehalose 6, 6'-dicorynomycolate

TDCM


Input: It was possible to synthesize vizantin on a large scale more easily than in the case of TDCM, and the compound exhibited more potent prophylactic effect on experimental lung metastasis of B16-F0 melanoma cells.

vizantin

TDCM


Input: Because vizantin stimulated human macrophages, it is a promising candidate for clinical application.

vizantin


Input: Qualitative studies among obese children and adolescents: a systematic review of the literature.


Input: Childhood obesity is a complex condition involving medical, social, moral and cultural issues.


Input: Qualitative approaches are of great value in understanding this complexity.


Input: This meta-synthesis of 45 qualitative studies deals specifically with the issue of obesity in children and adolescents from different perspectives-those of obese children and adolescents, of parents, and of health professionals providing support to the family.


Input: Our aim was to obtain a coherent view of child and adolescent obesity, focused on clinical and personal experience.


Input: The themes derived from the synthesis process fall under three main axes:' Seeing others, seeing oneself',' Understanding others, understanding oneself', and' Treating others, treating oneself'.


Input: It emerges that participants in all three groups had equal difficulty in perceiving and labelling obesity, mainly because of their lack of any real common ground.


Input: The insufficiency of shared representations destabilizes the therapeutic relationship and its construction: an important issue in the doctor-child-parent relationship in this context is the need to exchange their viewpoints of obesity.


Input: Health workers may also expand their understanding of obesity by incorporating the personal experiences of obese children and their parents in order to match treatment plans to their needs and expectations.


Input: An explicit formula for optical oscillator strength of excitons in semiconducting single-walled carbon nanotubes: family behavior.

carbon


Input: The sensitive structural dependence of the optical properties of single-walled carbon nanotubes, which are dominated by excitons and tunable by changing diameter and chirality, makes them excellent candidates for optical devices.

carbon


Input: Because of strong many-electron interaction effects, the detailed dependence of the optical oscillator strength f (s) of excitons on nanotube diameter d, chiral angle theta, and electronic subband index P (the so-called family behavior), however, has been unclear.


Input: In this study, based on results from an extended Hubbard Hamiltonian with parameters derived from ab initio GW plus Bethe-Salpeter equation (GW-BSE) calculations, we have obtained an explicit formula for the family behavior of the oscillator strengths of excitons in semiconducting single-walled carbon nanotubes (SWCNTs), incorporating environmental screening.

carbon


Input: The formula explains recent measurements well and is expected to be useful in the understanding and design of possible SWCNT optical and optoelectronic devices.


Input: Dendronized albumin core-shell transporters with high drug loading capacity.


Input: We describe the synthesis of a core-shell biohybrid consisting of a human serum albumin (HSA) core that serves as a reservoir for lipophilic molecules and a cationized shell region consisting of ethynyl-G2. 0-PAMAM or ethynyl-G3. 0-PAMAM dendrons.

ethynyl

PAMAM

ethynyl

PAMAM


Input: The binding capacity of lipophilic guests was quantified applying electron paramagnetic resonance (EPR) spectroscopy, and five to six out of seven pockets were still available compared with HSA.


Input: The attachment of ethynyl-G2. 0-PAMAM dendrons to HSA yielded a nontoxic core-shell macromolecule that was clearly uptaken by A549 human epithelial cells due to the presence of the dendritic PAMAM shell.

ethynyl

PAMAM

PAMAM


Input: Significantly higher loading of doxorubicin was observed for dendronized G2-DHSA compared with the native protein due to the availability of binding pockets of the HSA core, and interaction with the dendritic shell.

doxorubicin


Input: Dendronized G2-DHSA-doxorubicin displayed significant cytotoxicity resulting from high drug loading and high stability under different conditions, thus demonstrating its great potential as a transporter for drug molecules.

doxorubicin


Input: Natural cures for type 1 diabetes: a review of phytochemicals, biological actions, and clinical potential.


Input: Autoimmune diseases are the third largest category of illness in the industrialized world, following cardiovascular diseases and cancers.


Input: Among them, type 1 diabetes, also named autoimmune diabetes, afflicts 10 million people worldwide.


Input: This disease is caused by autoimmunity-mediated destruction of pancreatic beta-cells, leading to insulin deficiency, hyperglycemia and complications.


Input: Currently, there is no cure for type 1 diabetes.


Input: Insulin injection is the only medication; however, it accompanies serious medical complications.


Input: Current strategies to cure type 1 diabetes include immunotherapy, replacement therapy, and combination therapy.


Input: Despite recent advances in anti-diabetic strategies, no strategy is clinically successful.


Input: How to cure type 1 diabetes without undesirable side effects still remains a formidable challenge in drug research and development.


Input: Plants provide an extraordinary source of natural medicines for different diseases.


Input: Moreover, secondary metabolites of plant origin serve as an invaluable chemical library for drug discovery and current medicinal chemistry in the pharmaceutical industry.


Input: Over the past 25 years, 50% of prescription drugs have been developed from natural products and their derivatives.


Input: In this article, we review more than 20 plant compounds and extracts reported in the literature to prevent and treat type-1 diabetes.


Input: Emphasis is placed on their chemistry and biology in terms of regulation of immune cells and pancreatic beta-cells.


Input: We summarize recent progress in understanding the biological actions, mechanisms and therapeutic potential of the compounds and extracts of plant origin in type 1 diabetes.


Input: New views on phytocompound-based strategies for prevention and treatment of type 1 diabetes are also discussed.


Input: Green factories for biopharmaceuticals.


Input: Plants and plant cells have been used to produce many diverse and valuable recombinant proteins, including subunit vaccines, antibodies and antibody fragments, hormones, blood products, cytokines and enzymes.


Input: Different plant species and platforms have been explored as production hosts, each with unique properties in terms of production timescales, environmental containment, scalability, downstream processing strategy and overall costs.


Input: Whole plants are suitable for the economical and safe production of recombinant proteins on a large scale, providing unique advantages for pharmaceutical proteins that are required in large amounts and normally too expensive for conventional manufacturing processes.


Input: Seed-based systems have additional advantages because they exploit the natural storage properties of seeds to facilitate batch processing and distribution.


Input: The stabilizing effect of seeds after harvest allows recombinant subunit vaccines and antibodies to be delivered via the mucosal route as they are better able to withstand the harsh microenvironment when protected by the plant matrix.


Input: Although the differences between plant and human N-glycans were initially thought to limit the therapeutic potential of plant-derived glycoproteins, several such products have now been tested in the clinic and in some cases the presence of plant glycans has been turned into an advantage because they improve the performance of the protein or confer unique characteristics.


Input: In this review we discuss recent case studies of recombinant pharmaceuticals produced in plants to demonstrate the versatility and unique advantages of molecular farming and the bottlenecks that remain to be addressed.


Input: Plant metabolomics: from holistic data to relevant biomarkers.


Input: Metabolomics is playing an increasingly important role in plant science.


Input: It aims at the comprehensive analysis of the plant metabolome which consists both of primary and secondary metabolites.


Input: The goal of metabolomics is ultimately to identify and quantify this wide array of small molecules in biological samples.


Input: This new science is included in several systems biology approaches and is based primarily on the unbiased acquisition of mass spectrometric (MS) or nuclear magnetic resonance (NMR) data from carefully selected samples.


Input: This approach provides the most'' functional'' information of the' omics' technologies of a given organism since metabolites are the end products of the cellular regulatory processes.


Input: The application of state-of-the-art data mining, that includes various untargeted and targeted multivariate data analysis methods, to the vast amount of data generated by this data-driven approach leads to sample classification and the identification of relevant biomarkers.


Input: The biological areas that have been successfully studied by this holistic approach include global metabolite composition assessment, mutant and phenotype characterisation, taxonomy, developmental processes, stress response, interaction with the environment, quality control assessment, lead finding and mode of action of botanicals.


Input: This review summarises the main MS-and NMR-based approaches that are used to perform these studies and discusses the potential and current limitations of the various methods.


Input: The intent is not to provide an exhaustive overview of the field, which has grown considerably over the past decade, but to summarise the main strategies that are used and to discuss the potential and limitations of the different approaches as well as future trends.


Input: Recent advances in the development of catalytic inhibitors of human DNA topoisomerase II alpha as novel anticancer agents.


Input: DNA topoisomerases comprise an important family of enzymes that catalyse the induction of topological changes (e. g. relaxation/supercoiling, catenation/decatenation and knotting/unknotting) in the DNA molecule.


Input: These enzymes perform their functions by creating transient either single-stranded or double-stranded breaks in the DNA molecule.


Input: Due to their ability to modulate the topology of the DNA molecule, DNA topoisomerases play vital roles in replication, transcription, chromosome separation and segregation, and thus represent an important collection of design targets for novel anticancer drugs.


Input: The aim of this review is to provide an overview of the development of catalytic inhibitors of the human topoisomerase II alpha enzyme--an important member of the DNA topoisomerase family--as potential novel anticancer agents.


Input: The group of catalytic topoII inhibitors is classified into four types according to their molecular mechanism of action: inhibitors that bind to the ATP binding site, inhibitors that prevent the ATP hydrolysis step and trap the enzyme in a closed clamp, inhibitors that block the DNA cleavage and inhibitors that prevent the enzyme binding to the DNA.

ATP

ATP


Input: One of the important considerations highlighted throughout this review is the structure-based perspective of inhibitor design, giving the reader a medicinal chemist' s perspective on this vibrant and active field of drug design research.


Input: AT1 receptor antagonism is proangiogenic in the brain: BDNF a novel mediator.


Input: Candesartan is an angiotensin II type 1 receptor blocker (ARB) that has been to shown to limit ischemic stroke and improve stroke outcome.

Candesartan


Input: In experimental stroke, candesartan induces a proangiogenic effect that is partly attributable to vascular endothelial growth factor.

candesartan


Input: Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family that has been reported to have angiogenic effects and play an important role in recovery after stroke.


Input: The purpose of this investigation was to determine the role of BDNF in the proangiogenic effect of candesartan in the brain under hypertensive conditions.


Input: Accordingly, spontaneously hypertensive rats were treated with candesartan, and brain tissue samples were collected for quantification of BDNF expression.

candesartan


Input: In addition, human cerebromicrovascular endothelial cells were treated with either low-dose (1 f M) or high-dose (1 micro M) angiotensin II alone or in combination with candesartan (0. 16 micro M) to assess the effect of candesartan treatment and BDNF involvement in the behavior of endothelial cells.

candesartan

candesartan


Input: Candesartan significantly increased the expression of BDNF in the SHR (P < 0. 05).

Candesartan


Input: In addition, candesartan reversed the antiangiogenic effect of the 1-micro M dose of AngII (P = 0. 0001).

candesartan


Input: The observed effects of candesartan were ablated by neutralizing the effects of BDNF.

candesartan


Input: Treatment with the AT2 antagonist PD-123319 significantly reduced tube-like formation in endothelial cells.


Input: AT2 stimulation induced the BDNF expression and migration (P < 0. 05).


Input: In conclusion, candesartan exerts a proangiogenic effect on brain microvascular endothelial cells treated with angiotensin II.

candesartan


Input: This response is attributable to increased BDNF expression and is mediated through stimulation of the AT2 receptor.


Input: Regulation of the human hydroxysteroid sulfotransferase (SULT2A1) by ROR alpha and ROR gamma and its potential relevance to human liver diseases.

hydroxysteroid


Input: The retinoid-related orphan receptors (RORs) were postulated to have functions in tissue development and circadian rhythm.

retinoid


Input: In this study, we revealed a novel function of ROR alpha (NR1F1) and ROR gamma (NR1F3) in regulating the human hydroxysteroid sulfotransferase (SULT2A1), a phase II conjugating enzyme known to sulfonate bile acids, hydroxysteroid dehydroepiandrosterone, and related androgens.

hydroxysteroid

sulfonate bile acids

hydroxysteroid dehydroepiandrosterone

androgens


Input: A combination of promoter reporter gene assay and EMSA and chromatin immunoprecipitation (ChIP) assays showed that both ROR alpha and ROR gamma transactivated the SULT2A1 gene promoter through their binding to a ROR response element found in the SULT2A1 gene promoter.


Input: Interestingly, this ROR response element overlaps with a previously reported constitutive androstane receptor response element on the same promoter.


Input: Down-regulation of ROR alpha and/or ROR gamma by small interfering RNA inhibited the expression of endogenous SULT2A1.


Input: In primary human hepatocytes and human livers, we found a positive correlation between the expression of SULT2A1 and RORs, which further supported the regulation of SULT2A1 by RORs.


Input: We also found that the expression of ROR alpha and ROR gamma was impaired in several liver disease conditions, such as steatosis/steatohepatitis, fibrosis, and hepatocellular carcinoma.


Input: The positive regulation of human SULT2A1 by RORs is opposite to the negative regulation of Sult2a1 by RORs in rodents.


Input: In summary, our results established SULT2A1 as a novel ROR target gene.


Input: The expression of RORs is a potential predictor for the expression of SULT2A1 as well as disease conditions.


Input: Clinical applications for microRNAs in cancer.


Input: The discovery that noncoding components of the genome, including microRNA (miRNA or miR), can contribute to the pathogenesis of cancer has led investigators to contemplate using these molecules to guide clinical decision making.


Input: Currently, miRNA signatures are being applied in human clinical trials and miRNA-directed therapy is under way, with miR-122 targeting in hepatitis C (HCV) being the most developed therapy thus far.


Input: miRNA-based targeting in cancer is not far behind, with several private companies developing therapeutics.


Input: We are recognizing the potential for miRNA biology to clarify both the molecular pathogenesis of cancer and the inherent complexities in translating its biology to clinics.


Input: An increased understanding of fundamental miRNA biology, improved bioinformatics, and directed in vivo targeting while minimizing off-target effects and toxicity will be required for successful translational application.


Input: Here, we provide an overview of miRNAs, with a focus on aspects of translating bench-based discoveries to the clinic.


Input: Fast screening of authentic ginseng products by surface desorption atmospheric pressure chemical ionization mass spectrometry.


Input: Surface desorption atmospheric pressure chemical ionization mass spectrometry was developed as a rapid online detection technology for the chemical fingerprints of ginseng products without any sample pretreatment.


Input: More than 20 ginsenosides were detected in the ginseng tissue and identified by their tandem mass spectrometry.

ginsenosides


Input: Data were well matched with their reference compounds.


Input: Herein, surface desorption atmospheric pressure chemical ionization mass spectrometry was first applied to study the nonvolatile compounds in ginseng.


Input: White and red ginseng have been successfully differentiated from their counterfeits using some ginsenosides as chemical markers.

ginsenosides


Input: Ginsenoside can be used to differentiate between white ginseng, red ginseng, unboiled ginseng, and their counterfeits.

Ginsenoside


Input: Ginsenosides Ra1-3, Rb2-3, and Rc might be used to differentiate between white ginseng and boiled ginseng.

Ginsenosides Ra1-3, Rb2-3, and Rc


Input: Our result showed that surface desorption atmospheric pressure chemical ionization mass spectrometry not only could be used for fast screening authentic ginseng products but also might become a useful promising technique for the characterization of nonvolatile compounds in medicinal herbs to save researchers the laborious effort of sample pretreatment.


Input: Bio-based biodegradable and biocompatible hyperbranched polyurethane: a scaffold for tissue engineering.

polyurethane


Input: Hyperbranched polyurethanes are synthesized using TDI, PCL diol, butanediol, and pentaerythritol (1-5 wt%) as the B (4) reactant with and without the monoglyceride of sunflower oil.

polyurethanes

TDI

PCL diol

butanediol

pentaerythritol

monoglyceride


Input: The biodegradation, physico-mechanical, and thermal properties are found to be tailored by varying the percentage weight of the branching unit.


Input: An MTT/hemolytic assay and subcutaneous implantation in Wistar rats followed by cytokine/ALP assay and histopathology studies confirm a better biocompatibility of HBPU with MG than without MG.

MTT


Input: HBPU supports the proliferation of dermatocytes with no toxic effect in major organs, in addition the in vitro degraded products are non-toxic.


Input: Cell adherence and proliferation endorse the bio-based HBPU as a prospective scaffold material in the niche of tissue engineering.


Input: Poly (N-vinylpyrrolidone)-modified surfaces for biomedical applications.

Poly (N-vinylpyrrolidone)


Input: Poly (N-vinylpyrrolidone) (PVP), an important water soluble synthetic polymer, has many desirable properties including low toxicity, chemical stability, and good biocompatibility.

Poly (N-vinylpyrrolidone)

PVP


Input: Since PVP is hemocompatible and physiologically inactive, it has been used as a blood plasma substitute.

PVP


Input: Surface modification with PVP has been investigated extensively over the past few years as a means of preventing nonspecific protein adsorption.

PVP


Input: PVP may therefore be seen as a promising antifouling surface modifier comparable to poly (ethylene glycol) (PEG).

PVP

poly (ethylene glycol)

PEG


Input: In this review, various approaches for the design and preparation of PVP-modified surfaces are summarized and potential biomedical applications of these PVP-modified materials are indicated.

PVP

PVP


Input: Finally, some perspectives on future research on PVP for surface modification are discussed.

PVP


Input: Design of mixed PEO/PAA brushes with switchable properties toward protein adsorption.

PEO

PAA


Input: Adsorption of proteins at interfaces is an ubiquitous phenomenon of prime importance.


Input: Layers of poly (ethylene oxide) (PEO) are widely used to repel proteins.

poly (ethylene oxide)

PEO


Input: Conversely, proteins were shown to adsorb deeply into brushes of poly (acrylic acid) (PAA), and their subsequent partial release could be triggered by a change of pH and/or ionic strength (I).

poly (acrylic acid)

PAA


Input: Mixed brushes of these polymers are thus promising candidates to tune protein adsorption onto new smart surfaces.


Input: In this work, the synthesis of such mixed brushes was performed based on a " grafting to " approach, the two polymers being either grafted sequentially or simultaneously.


Input: Detailed characterization of the obtained brushes using static water contact angle measurements, X-ray photoelectron spectroscopy, electrochemical impedance spectroscopy, and polarization-modulation reflection-absorption infrared spectroscopy is presented.


Input: While sequential grafting of the two polymers for different reactions times did not give rise to a broad range of composition of mixed brushes, simultaneous grafting of the polymers from solutions with different compositions allows for the synthesis of a range of mixed brushes (mass fraction of PEO in the mixed brushes from 0. 35 to 0. 65).

PEO


Input: A key example is then chosen to illustrate the switchable behavior of a selected mixed PEO/PAA brush toward albumin adsorption.

PEO

PAA


Input: The adsorption behavior was monitored with a quartz crystal microbalance.


Input: The mixed brush could adsorb high amounts of albumin, but 86% of the adsorbed protein could then be desorbed upon pH and I change.


Input: The obtained properties are thus a combination of the ones of PEO and PAA, and a highly switchable behavior is observed toward protein adsorption.

PEO

PAA


Input: Anisotropy of chemical bonding in semifluorinated graphite C2F revealed with angle-resolved X-ray absorption spectroscopy.

graphite C2F


Input: Highly oriented pyrolytic graphite characterized by a low misorientation of crystallites is fluorinated using a gaseous mixture of BrF (3) with Br (2) at room temperature.

graphite

BrF (3)

Br (2)


Input: The golden-colored product, easily delaminating into micrometer-size transparent flakes, is an intercalation compound where Br (2) molecules are hosted between fluorinated graphene layers of approximate C (2) F composition.

Br (2)

graphene

C (2) F


Input: To unravel the chemical bonding in semifluorinated graphite, we apply angle-resolved near-edge X-ray absorption fine structure (NEXAFS) spectroscopy and quantum-chemical modeling.

graphite


Input: The strong angular dependence of the CK and FK edge NEXAFS spectra on the incident radiation indicates that room-temperature-produced graphite fluoride is a highly anisotropic material, where half of the carbon atoms are covalently bonded with fluorine, while the rest of the carbon atoms preserve pi electrons.

graphite fluoride

carbon

fluorine


Input: Comparison of the experimental CK edge spectrum with theoretical spectra plotted for C (2) F models reveals that fluorine atoms are more likely to form chains.

C (2) F

fluorine


Input: This conclusion agrees with the atomic force microscopy observation of a chain-like pattern on the surface of graphite fluoride layers.

graphite fluoride


Input: Structure enhancement factor relationships in single gold nanoantennas by surface-enhanced Raman excitation spectroscopy.


Input: Determining the existence of any direct spectral relationship between the far-field scattering properties and the near-field Raman-enhancing properties of surface-enhanced Raman spectroscopy (SERS) substrates has been a challenging task with only a few significant results to date.


Input: Here, we prove that hot spot dominated systems show little dependence on the far-field scattering properties because of differences between near-and far-field localized surface plasmon resonance (LSPR) effects as well as excitation of new plasmon modes via a localized emitter.


Input: We directly probe the relationship between the near-and far-field light interactions using a correlated LSPR-transmission electron microscopy (TEM) surface-enhanced Raman excitation spectroscopy (SERES) technique.


Input: Fourteen individual SERS nanoantennas, Au nanoparticle aggregates ranging from dimers to undecamers, coated in a reporter molecule and encased in a protective silica shell, were excited using eight laser wavelengths.

Au

silica


Input: We observed no correlation between the spectral position of the LSPR maxima and the maximum enhancement factor (EF).


Input: The single nanoantenna data reveal EFs ranging from (2. 5 +/- 0. 6) x 10 (4) to (4. 5 +/- 0. 6) x 10 (8) with maximum enhancement for excitation wavelengths of 785 nm and lower energy.


Input: The magnitude of maximum EF was not correlated to the number of cores in the nanoantenna or the spectral position of the LSPR, suggesting a separation between near-field SERS enhancement and far-field Rayleigh scattering.


Input: Computational electrodynamics confirms the decoupling of maximum SERS enhancement from the peak of the scattering spectrum.


Input: It also points to the importance of a localized emitter for radiating Raman photons to the far-field which, in nonsymmetric systems, allows for the excitation of radiative plasmon modes that are difficult to excite with plane waves.


Input: Once these effects are considered, we are able to fully explain the hot spot dominated SERS response of the nanoantennas.


Input: Fibril formation by pH and temperature responsive silk-elastin block copolymers.


Input: In this report, we study the self-assembly of two silk-elastin-like proteins: one is a diblock S (24) E (40) composed of 24 silk-like (S) repeats and 40 elastin-like (E) repeats; the other is a triblock S (12) C (4) E (40), in which the S and E blocks are separated by a random coil block (C (4)).


Input: Upon lowering the pH, the acidic silk-like blocks fold and self-assemble into fibrils by a nucleation-and-growth process.


Input: While silk-like polymers without elastin-like blocks form fibrils by heterogeneous nucleation, leading to monodisperse populations, the elastin-like blocks allow for homogeneous nucleation, which gives rise to polydisperse length distributions, as well as a concentration-dependent fibril length.


Input: Moreover, the elastin-like blocks introduce temperature sensitivity: at high temperature, the fibrils become sticky and tend to bundle and aggregate in an irreversible manner.


Input: Concentrated solutions of S (12) C (4) E (40) form weak gels at low pH that irreversibly lose elasticity in temperature cycling; this is also attributed to fibril aggregation.


Input: Mechanism of homogeneous reduction of CO2 by pyridine: proton relay in aqueous solvent and aromatic stabilization.

pyridine


Input: We employ quantum chemical calculations to investigate the mechanism of homogeneous CO (2) reduction by pyridine (Py) in the Py/p-GaP system.

CO (2)

pyridine


Input: We find that CO (2) reduction by Py commences with PyCOOH (0) formation where: (a) protonated Py (PyH (+)) is reduced to PyH (0), (b) PyH (0) then reduces CO (2) by one electron transfer (ET) via nucleophilic attack by its N lone pair on the C of CO (2), and finally (c) proton transfer (PT) from PyH (0) to CO (2) produces PyCOOH (0).

CO (2)

PyCOOH (0)

PyH (+)

PyH (0)

PyH (0)

CO (2)

N

C

CO (2)

PyH (0)

CO (2)

PyCOOH (0)


Input: The predicted enthalpic barrier for this proton-coupled ET (PCET) reaction is 45. 7 kcal/mol for direct PT from PyH (0) to CO (2).

PyH (0)

CO (2)


Input: However, when PT is mediated by one to three water molecules acting as a proton relay, the barrier decreases to 29. 5, 20. 4, and 18. 5 kcal/mol, respectively.


Input: The water proton relay reduces strain in the transition state (TS) and facilitates more complete ET.


Input: For PT mediated by a three water molecule proton relay, adding water molecules to explicitly solvate the core reaction system reduces the barrier to 13. 6-16. 5 kcal/mol, depending on the number and configuration of the solvating waters.


Input: This agrees with the experimentally determined barrier of 16. 5 +/- 2. 4 kcal/mol.


Input: We calculate a pK (a) for PyH (0) of 31 indicating that PT preceding ET is highly unfavorable.

PyH (0)


Input: Moreover, we demonstrate that ET precedes PT in PyCOOH (0) formation, confirming PyH (0)' s pK (a) as irrelevant for predicting PT from PyH (0) to CO (2).

PyCOOH (0)

PyH (0)

PyH (0)

CO (2)


Input: Furthermore, we calculate adiabatic electron affinities in aqueous solvent for CO (2), Py, and Py. CO (2) of 47. 4, 37. 9, and 66. 3 kcal/mol respectively, indicating that the anionic complex PyCOO (-) stabilizes the anionic radicals CO (2) (-) and Py (-) to facilitate low barrier ET.

CO (2)

Py. CO (2)

PyCOO (-)

CO (2) (-)

Py (-)


Input: As the reduction of CO (2) proceeds through ET and then PT, the pyridine ring becomes aromatic, and thus Py catalyzes CO (2) reduction by stabilizing the PCET TS and the PyCOOH (0) product through aromatic resonance stabilization.

CO (2)

pyridine

CO (2)

PyCOOH (0)


Input: Our results suggest that Py catalyzes the homogeneous reductions of formic acid and formaldehyde en route to formation of CH (3) OH through a series of one-electron reductions analogous to the PCET reduction of CO (2) examined here, where the electrode only acts to reduce PyH (+) to PyH (0).

formic acid

formaldehyde

CH (3) OH

CO (2)

PyH (+)

PyH (0)


Input: Total synthesis of AMF-26, an antitumor agent for inhibition of the Golgi system, targeting ADP-ribosylation factor 1.

ADP


Input: An effective method for the total synthesis of 1 (AMF-26), a potentially promising new anticancer drug that disrupts the Golgi system by inhibiting the ADP-ribosylation factor 1 (Arf1) activation, has been developed for the first time.

ADP


Input: The construction of the chiral linear precursor (a key to the synthesis) was achieved by the asymmetric aldol reaction followed by the computer-assisted predictive stereoselective intramolecular Diels-Alder reaction.


Input: The global antitumor activity of the totally synthetic 1 against a variety of human cancer cells was assessed using a panel of 39 human cancer cell lines (JFCR39), and it was shown that the synthetic 1 strongly inhibited the growth of several cancer cell lines at concentrations of less than 0. 04 mu M.


Input: Biological assays of novel derivatives, 26 and 31, which have different side-chains at the C-4 positions in the Delta (1), (2)-octalin backbone, disclosed the importance of the suitable structure of the side-chain containing conjugated multidouble bonds.

Delta (1), (2)-octalin


Input: 3-Amido pyrrolopyrazine JAK kinase inhibitors: development of a JAK3 vs JAK1 selective inhibitor and evaluation in cellular and in vivo models.

3-Amido pyrrolopyrazine


Input: The Janus kinases (JAKs) are involved in multiple signaling networks relevant to inflammatory diseases, and inhibition of one or more members of this class may modulate disease activity or progression.


Input: We optimized a new inhibitor scaffold, 3-amido-5-cyclopropylpyrrolopyrazines, to a potent example with reasonable kinome selectivity, including selectivity for JAK3 versus JAK1, and good biopharmaceutical properties.


Input: Evaluation of this analogue in cellular and in vivo models confirmed functional selectivity for modulation of a JAK3/JAK1-dependent IL-2 stimulated pathway over a JAK1/JAK2/Tyk2-dependent IL-6 stimulated pathway.


Input: Protein adsorption mechanisms determine the efficiency of thermally controlled cell adhesion on poly (N-isopropyl acrylamide) brushes.

poly (N-isopropyl acrylamide)


Input: This study investigated the impact of the protein adsorption mechanism (s) on the efficiency of thermally controlled cell adhesion and release from poly (N-isopropyl acrylamide) brushes.

poly (N-isopropyl acrylamide)


Input: Large format polymer gradients were used to screen for grafting densities and substrate chemistries that alter both cell adhesion at 37 degrees C and rapid cell release at 25 degrees C.


Input: In particular, the grafting conditions investigated allowed protein adsorption to the underlying substrate, penetration of the brush only, or adsorption to the outer edge of the film.


Input: At an average molecular weight of 30 kDa (degree of polymerization N ~ 270), the results show that robust protein adsorption to polymer brushes impairs rapid cell release below the lower critical solution temperature.


Input: Conversely, grafting conditions that permit protein penetration of the brush but block strong adsorption to the underlying substrate support cell adhesion above the transition temperature and ensure efficient cell recovery at lower temperature.


Input: These findings demonstrate the impact of protein adsorption mechanisms, surface chemistry, and polymer properties on thermally controlled cell capture and release.


Input: Thermochemistry of uracils.

uracils


Input: Experimental and computational enthalpies of formation of 5, 6-dimethyl-, 1, 3, 5-trimethyl-, and 1, 3, 5, 6-tetramethyluracils.

5, 6-dimethyl-, 1, 3, 5-trimethyl-, and 1, 3, 5, 6-tetramethyluracils


Input: We describe in the current paper an experimental and computational study of three methylated uracils, in particular, the 5, 6-dimethyl-, 1, 3, 5-trimethyl-, and 1, 3, 5, 6-tetramethyl derivatives.

5, 6-dimethyl-, 1, 3, 5-trimethyl-, and 1, 3, 5, 6-tetramethyl


Input: The values of the standard (p (0) = 0. 1 MPa) molar enthalpies of formation in the gas phase at T = 298. 15 K have been determined.


Input: The energies of combustion were measured by static bomb combustion calorimetry, and from the results obtained, the standard molar enthalpies of formation in the crystalline state at T = 298. 15 K were calculated.


Input: The enthalpies of sublimation were determined using the transpiration method in a saturated N (2) stream.

N (2)


Input: Values of-(376. 2 +/- 2. 6),-(355. 9 +/- 3. 0), and-(381. 7 +/- 2. 8) kJ. mol (-1) for the gas-phase enthalpies of formation at T = 298. 15 K of 5, 6-dimethyluracil, 1, 3, 5-trimethyluracil, and 1, 3, 5, 6-tetramethyluracil, respectively, were obtained from the experimental thermochemical study.

5, 6-dimethyluracil

1, 3, 5-trimethyluracil

1, 3, 5, 6-tetramethyluracil


Input: An extended theoretical study with the G3 and the G4 quantum-chemical methods has been carried out for all the possible methylated uracils.

methylated uracils


Input: There is a very good agreement between experimental and calculated enthalpies of formation for the three derivatives studied.


Input: A Free-Wilson analysis on G4-calculated enthalpies of formation has been carried out, and the contribution of methylation in the different positions of the uracil ring has been estimated.


Input: Lipid reassembly in asymmetric Langmuir-Blodgett/Langmuir-Schaeffer bilayers.


Input: Molecular-reorganization-induced morphology alteration in asymmetric substrate-supported lipid bilayers (SLBs) was directly visualized by means of atomic force microscopy (AFM) and total internal reflection fluorescence (TIRF) microscopy.


Input: SLB samples were fabricated on mica-on-glass and glass substrates by Langmuir-Blodgett (LB)/Langmuir-Schaeffer (LS) using binary lipid mixtures, namely, 1, 2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/1, 2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and ternary mixtures DOPC/DPPC/1, 2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS), labeled with 0. 2 mol% Texas Red 1, 2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine triethylammonium salt (TR-DHPE) dye.

1, 2-dioleoyl-sn-glycero-3-phosphocholine

DOPC

1, 2-dipalmitoyl-sn-glycero-3-phosphocholine

DPPC

DOPC

DPPC

1, 2-dioleoyl-sn-glycero-3-phospho-L-serine

DOPS

Texas Red 1, 2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine triethylammonium

TR-DHPE


Input: Phase segregations were characterized by TIRF imaging, and DPPC-enriched domain structures were also observed.

DPPC


Input: Interestingly for ~ 40% (n = 6) of the samples with binary mixtures in the LB leaflet and a single component in the LS leaflet, that is, (DOPC/DPPC) (LB) + DOPC (LS), the contrast of the DPPC domains changed from the original dark (without dye) to bright (more TR dye partitioning) on TIRF images, returning to dark again.

DOPC

DPPC

DOPC

DPPC


Input: This contrast reverse was also correlated to AFM height images, where a DPPC-DPPC gel phase was spotted after the TIRF image contrast returned to dark.

DPPC

DPPC


Input: The rupture force mapping results measured on these binary mixture samples also confirmed unambiguously the formation of DPPC-DPPC gel domain components during the contrast change.

DPPC

DPPC


Input: The samples were tracked over 48 h to investigate the lipid molecule movements in both the DPPC domains and the DOPC fluid phase.

DPPC

DOPC


Input: The fluorescence contrast changes from bright to dark in SLBs indicate that the movement of dye molecules was independent of the movement of lipid molecules.


Input: In addition, correlated multimodal imaging using AFM, force mapping, and fluorescence provides a novel route to uncover the reorganization of lipid molecules at the solid-liquid interface, suggesting that the dynamics of dye molecules is highly structure dependent.


Input: Chemically tailored dielectric-to-metal transition for the design of metamaterials from nanoimprinted colloidal nanocrystals.


Input: We demonstrate optical metamaterial design using colloidal gold nanocrystal building blocks.


Input: In the solid state, chemically exchanging the nanocrystals' surface-capping molecules provides a tailorable dielectric-to-metal transition exhibiting a 10 (10) range in DC conductivity and dielectric permittivity ranging from everywhere positive to everywhere negative throughout the visible-to-near-IR.


Input: Direct, wide-area nanoimprinting of subwavelength superstructures at room temperature, on plastic and glass substrates, affords plasmonic resonances ranging from 660 to 1070 nm, in agreement with numerical simulations.


Input: Encapsulation of living E. coli cells in hollow polymer microspheres of highly defined size.


Input: Here, we report the preparation and characterization of hollow polymer microspheres based on the preprecipitation of porous calcium carbonate cores with an average size of 5 mu m and their use for encapsulation of living microorganisms.

calcium carbonate


Input: The microspheres filled with individual living E. coli cells were prepared by layer-by-layer (LbL) deposition of different polyelectrolytes and proteins onto the porous calcium carbonate cores leading to the formation of matrix-like complexes of the compounds followed by calcium carbonate core dissolution using EDTA.

calcium carbonate

calcium carbonate

EDTA


Input: Both the influence of the encapsulation process as well as of the used polyelectrolytes on the survival rate of the cells were determined by confocal laser scanning microscopy (CLSM) and microtiter plate fluorescence tests.


Input: After the encapsulation process ~ 40% of the cells were alive.


Input: Cultivation tests indicated that the lag phase of cells treated with polyelectrolytes increases and the encapsulated E. coli cells were able to produce green fluorescent protein inside the microcapsules.


Input: Recombinant human fibrinogen that produces thick fibrin fibers with increased wound adhesion and clot density.


Input: Human fibrinogen is a biomaterial used in surgical tissue sealants, scaffolding for tissue engineering, and wound healing.


Input: Here we report on the post-translational structure and functionality of recombinant human FI (rFI) made at commodity levels in the milk of transgenic dairy cows.


Input: Relative to plasma-derived fibrinogen (pdFI), rFI predominately contained a simplified, neutral carbohydrate structure and > 4-fold higher levels of the gamma'-chain transcriptional variant that has been reported to bind thrombin and Factor XIII.

carbohydrate


Input: In spite of these differences, rFI and pdFI were kinetically similar with respect to the thrombin-catalyzed formation of protofibrils and Factor XIIIa-mediated formation of cross-linked fibrin polymer.


Input: However, electron microscopy showed rFI produced fibrin with much thicker fibers with less branching than pdFI.


Input: In vivo studies in a swine liver transection model showed that, relative to pdFI, rFI made a denser, more strongly wound-adherent fibrin clot that more rapidly established hemostasis.


Input: Platelet-derived microparticles in overweight/obese women with the polycystic ovary syndrome.


Input: A substantial proportion of women with the polycystic ovary syndrome (PCOS) are obese and obesity is considered as a prothrombotic state.


Input: Platelet-derived microparticles (PMPs) might be implicated in the activation of the coagulation cascade.


Input: We aimed to assess plasma PMPs in overweight/obese women with PCOS.


Input: We measured plasma PMPs and determined anthropometric, metabolic, hormonal and ultrasonographic features of PCOS in 67 overweight/obese women with PCOS (with body mass index [BMI] > 25. 0 kg/m (2)) and in 21 BMI-matched healthy women.


Input: Circulating androgens and markers of insulin resistance (IR) were higher in women with PCOS than in controls.

androgens


Input: Plasma PMPs were also higher in women with PCOS than in controls (p = 0. 046).


Input: In women with PCOS, plasma PMPs correlated with the mean number of follicles in the ovaries (r = 0. 343; p = 0. 006).


Input: In controls, plasma PMPs did not correlate with any of the studied parameters.


Input: In conclusion, plasma PMPs are elevated in overweight/obese women with PCOS compared with BMI-matched controls.


Input: The cause of this increase is unclear but both IR and hyperandrogenemia might be implicated.


Input: More studies are required to elucidate the pathogenesis of the elevation of PMPs in PCOS and to assess its implications on the cardiovascular risk of these patients.


Input: Structure-activity relationship study on benzoic acid part of diphenylamine-based retinoids.

benzoic acid

diphenylamine

retinoids


Input: Based on structure-activity relationship studies of the benzoic acid part of diphenylamine-based retinoids, the potent RXR agonist 4 was derivatized to obtain retinoid agonists, synergists, and an antagonist.

benzoic acid

diphenylamine

retinoids

retinoid


Input: Cinnamic acid derivatives 5 and phenylpropionic acid derivatives 6 showed retinoid agonistic and synergistic activities, respectively.

Cinnamic acid

phenylpropionic acid

retinoid


Input: The difference of the activities is considered to be due to differences in the flexibility of the carboxylic acid-containing substituent on the diphenylamine skeleton.

carboxylic acid

diphenylamine


Input: Compound 7, bearing a methyl group at the meta position to the carboxyl group, was an antagonist, dose-dependently inhibiting HL-60 cell differentiation induced by 3. 3 x 10 (-10) M Am80.

methyl

carboxyl


Input: Discovery of a novel phenylethyl benzamide glucokinase activator for the treatment of type 2 diabetes mellitus.

phenylethyl benzamide


Input: Novel benzamide derivatives were synthesized and tested at in vitro assay by measuring fold increase of glucokinase activity at 5. 0 mM glucose concentration.

benzamide

glucose


Input: Among the prepared compounds, YH-GKA was found to be an active glucokinase activator with EC (50) of 70 nM.

YH-GKA


Input: YH-GKA showed similar glucose AUC reduction of 29. 6% (50 mg/kg) in an OGTT study with C57BL/J6 mice compared to 29. 9% for metformin (300 mg/kg).

YH-GKA

glucose


Input: Acute treatment of the compound in C57BL/J6 and ob/ob mice elicited basal glucose lowering activity.

glucose


Input: In subchronic study with ob/ob mice, YH-GKA showed significant decrease in blood glucose levels and no adverse effects on serum lipids or body weight.

YH-GKA

glucose


Input: In addition, YH-GKA exhibited high bioavailability and moderate elimination in preclinical species.

YH-GKA


Input: Inhibition of norovirus 3CL protease by bisulfite adducts of transition state inhibitors.

bisulfite


Input: Noroviruses are the most common cause of acute viral gastroenteritis, accounting for > 21 million cases annually in the US alone.


Input: Norovirus infections constitute an important health problem for which there are no specific antiviral therapeutics or vaccines.


Input: In this study, a series of bisulfite adducts derived from representative transition state inhibitors (dipeptidyl aldehydes and alpha-ketoamides) was synthesized and shown to exhibit anti-norovirus activity in a cell-based replicon system.

bisulfite

dipeptidyl aldehydes

alpha-ketoamides


Input: The ED (50) of the most effective inhibitor was 60 nM.


Input: This study demonstrates for the first time the utilization of bisulfite adducts of transition state inhibitors in the inhibition of norovirus 3C-like protease in vitro and in a cell-based replicon system.

bisulfite


Input: The approach described herein can be extended to the synthesis of the bisulfite adducts of other classes of transition state inhibitors of serine and cysteine proteases, such as alpha-ketoheterocycles and alpha-ketoesters.

bisulfite

serine

cysteine

alpha-ketoheterocycles

alpha-ketoesters


Input: Indoleamine 2, 3-dioxygenase inhibitory activity of derivatives of marine alkaloid tsitsikammamine A.

Indoleamine

tsitsikammamine A


Input: Tsitsikammamines are marine alkaloids whose structure is based on the pyrroloiminoquinone scaffold.

Tsitsikammamines

pyrroloiminoquinone


Input: These and related compounds have attracted attention due to various interesting biological properties, including cytotoxicity, topoisomerase inhibition, antimicrobial, antifungal and antimalarial activity.


Input: Indoleamine 2, 3-dioxygenase (IDO1) is a well-established therapeutic target as an important factor in the tumor immune evasion mechanism.

Indoleamine


Input: In this preliminary communication, we report the inhibitory activity of tsitsikammamine derivatives against IDO1.

tsitsikammamine


Input: Tsitsikammamine A analogue 11b displays submicromolar potency in an enzymatic assay.

Tsitsikammamine A


Input: A number of derivatives are also active in a cellular assay while showing little or no activity towards tryptophan 2, 3-dioxygenase (TDO), a functionally related enzyme.

tryptophan


Input: This IDO1 inhibitory activity is rationalized by molecular modeling studies.


Input: An interest is thus established in this class of compounds as a potential source of lead compounds for the development of new pharmaceutically useful IDO1 inhibitors.


Input: Synthesis and insecticidal evaluation of novel N-pyridylpyrazolecarboxamides containing cyano substituent in the ortho-position.

N-pyridylpyrazolecarboxamides

cyano


Input: In an attempt to search for potent insecticides targeting the ryanodine receptor (RyR), a series of novel N-pyridylpyrazolecarboxamides containing cyano substituent in the ortho-position were designed and synthesized.

ryanodine

N-pyridylpyrazolecarboxamides

cyano


Input: Their insecticidal activities of target compounds against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella) indicated that most of the compounds showed moderate to high activities at the tested concentrations.


Input: In particular, compound 6l and 6o showed 86% larvicidal activities against Plutella xylostella at the concentration of 0. 1mg/L, while the activity of compound 6h against Mythimna separate was 80% at 1mg/L.


Input: The calcium imaging technique was applied to investigate the effects of some title compounds on the intracellular calcium ion concentration ([Ca (2 +)] (i)), experimental results demonstrated that compound 6h stimulates a transient elevation in [Ca (2 +)] (i) in the absence of external calcium after the central neurons dye loading with fluo-3 AM.

calcium

calcium

Ca (2 +)

Ca (2 +)

calcium

fluo-3 AM


Input: However, when the central neurons were dyed with fluo-5N and incubated with 2-APB, [Ca (2 +)] i decreased transiently by treated of compound 6h.

Ca (2 +)


Input: All of the calcium imaging technique experiments demonstrated that these novel compounds deliver calcium from endoplasmic reticulum to cytoplasm, which proved that the title compounds were the possible activators of insect RyR.

calcium

calcium


Input: DNA polymerase POLQ and cellular defense against DNA damage.


Input: In mammalian cells, POLQ (pol theta) is an unusual specialized DNA polymerase whose in vivo function is under active investigation.


Input: POLQ has been implicated by different experiments to play a role in resistance to ionizing radiation and defense against genomic instability, in base excision repair, and in immunological diversification.


Input: The protein is formed by an N-terminal helicase-like domain, a C-terminal DNA polymerase domain, and a large central domain that spans between the two.

N

C


Input: This arrangement is also found in the Drosophila Mus308 protein, which functions in resistance to DNA interstrand crosslinking agents.


Input: Homologs of POLQ and Mus308 are found in multicellular eukaryotes, including plants, but a comparison of phenotypes suggests that not all of these genes are functional orthologs.


Input: Flies defective in Mus308 are sensitive to DNA interstrand crosslinking agents, while mammalian cells defective in POLQ are primarily sensitive to DNA double-strand breaking agents.


Input: Cells from Polq (-/-) mice are hypersensitive to radiation and peripheral blood cells display increased spontaneous and ionizing radiation-induced levels of micronuclei (a hallmark of gross chromosomal aberrations), though mice apparently develop normally.


Input: Loss of POLQ in human and mouse cells causes sensitivity to ionizing radiation and other double strand breaking agents and increased DNA damage signaling.


Input: Retrospective studies of clinical samples show that higher levels of POLQ gene expression in breast and colorectal cancer are correlated with poorer outcomes for patients.


Input: A clear understanding of the mechanism of action and physiologic function of POLQ in the cell is likely to bear clinical relevance.


Input: Novel cinnoline-based inhibitors of LRRK2 kinase activity.

cinnoline


Input: Leucine rich repeat kinase 2 (LRRK2) has been implicated in the pathogenesis of Parkinson' s disease (PD).

Leucine


Input: Inhibition of LRRK2 kinase activity is a therapeutic approach that may lead to new treatments for PD.


Input: Herein we report the discovery of a series of cinnoline-3-carboxamides that are potent against both wild-type and mutant LRRK2 kinase activity in biochemical assays.


Input: These compounds are also shown to be potent inhibitors in a cellular assay and to have good to excellent CNS penetration.


Input: Neuroprotective effects of oxymatrine against excitotoxicity partially through down-regulation of NR2B-containing NMDA receptors.

oxymatrine

NMDA


Input: Oxymatrine (OMT) is a major bioactive component derived from Sophora flavescens Ait (kushen), which is widely used in Chinese medicine.

Oxymatrine

OMT


Input: Recent studies have shown that it has neuroprotective effects; however, its underlying mechanisms remain unclear.


Input: We focus on the mechanisms of pharmacologic action in OMT by detecting its pharmacological properties against focal cerebral ischemia in vivo and NMDA-induced neurotoxicity in vitro.

OMT

NMDA


Input: OMT prevented cerebral ischemic injury in mice induced via a 2 h middle cerebral artery occlusion and a 24 h reperfusion, in vivo.

OMT


Input: In vitro cultured neurons challenged with N-methyl-D-aspartate (NMDA, 200 mu M) for 30 min showed significant decrease in the viability of neurons; however, OMT was able to protect neurons against induced neurotoxicity via NMDA exposure.

N-methyl-D-aspartate

NMDA

OMT

NMDA


Input: Western blot analysis revealed that OMT decreased the expression of Bax and repaired the balance of pro-and anti-apoptotic proteins.

OMT


Input: Furthermore, OMT significantly reversed the up-regulation of NR2B and inhibited the calcium overload in the cultured neurons after challenging the NMDA.

OMT

calcium

NMDA


Input: OMT showed partial protection in the cortical neurons via down-regulation of NR2B containing NMDA receptors and up-regulation of Bcl-2 family.

OMT

NMDA


Input: Our results provide new insights into the development of natural therapeutic anti-oxidants against ischemia.


Input: Direct transmembrane interaction between actin and the pore-competent, cholesterol-dependent cytolysin pneumolysin.

cholesterol


Input: The eukaryotic actin cytoskeleton is an evolutionarily well-established pathogen target, as a large number of bacterial factors disturb its dynamics to alter the function of the host cells.


Input: These pathogenic factors modulate or mimic actin effector proteins or they modify actin directly, leading to an imbalance of the precisely regulated actin turnover.


Input: Here, we show that the pore-forming, cholesterol-dependent cytolysin pneumolysin (PLY), a major neurotoxin of Streptococcus pneumoniae, has the capacity to bind actin directly and to enhance actin polymerisation in vitro.

cholesterol


Input: In cells, the toxin co-localised with F-actin shortly after exposure, and this direct interaction was verified by F o rster resonance energy transfer.


Input: PLY was capable of exerting its effect on actin through the lipid bilayer of giant unilamellar vesicles, but only when its pore competence was preserved.


Input: The dissociation constant of G-actin binding to PLY in a biochemical environment was 170-190 nM, which is indicative of a high-affinity interaction, comparable to the affinity of other intracellular actin-binding factors.


Input: Our results demonstrate the first example of a direct interaction of a pore-forming toxin with cytoskeletal components, suggesting that the cross talk between pore-forming cytolysins and cells is more complex than previously thought.


Input: Influence of sildenafil and tadalafil on the enzyme-and transporter-inducing effects of bosentan and ambrisentan in LS180 cells.

sildenafil

bosentan

ambrisentan


Input: The combinations of the endothelin-1 receptor antagonists bosentan or ambrisentan with the phosphodiesterase 5 inhibitors sildenafil or tadalafil are current standard therapies of advanced pulmonary arterial hypertension.

bosentan

ambrisentan

sildenafil

tadalafil


Input: However, these drugs have a number of drug interactions.


Input: Changes of bosentan pharmacokinetics by sildenafil are attributed to reduced hepatic uptake as a consequence of inhibition of organic anion transporting polypeptides.

bosentan

sildenafil


Input: We therefore tested in vitro the hypothesis that sildenafil and tadalafil reduce the enzyme-and transporter-inducing effects of bosentan or ambrisentan by preventing cellular access.

sildenafil

tadalafil

bosentan

ambrisentan


Input: Although intracellular concentrations of bosentan and ambrisentan (measured by high pressure liquid chromatography coupled with tandem mass-spectrometry) after four days of incubation of LS180 cells were lower when sildenafil or tadalafil were present, quantification of mRNA expression in these cells by real-time reverse transcription polymerase chain reaction revealed that bosentan and ambrisentan-mediated induction was stable or even increased in combination with sildenafil or tadalafil.

bosentan

ambrisentan

sildenafil

tadalafil

bosentan

ambrisentan

sildenafil

tadalafil


Input: For the drug transporter P-glycoprotein this was confirmed at the protein and functional level with highly significant correlations between P-gp mRNA, protein, and function.


Input: Moreover, using a reporter gene assay in LS180 cells, our study demonstrates for the first time that tadalafil is a potent, ambrisentan a weak, and sildenafil no activator of pregnane X receptor.

tadalafil

ambrisentan

sildenafil

pregnane


Input: In conclusion, our study demonstrates that although sildenafil and tadalafil indeed reduce intracellular concentrations of bosentan and ambrisentan in LS180 cells, they do not mitigate the inducing effects of these endothelin-1 receptor antagonists.

sildenafil

tadalafil

bosentan

ambrisentan


Input: Mechanism of maprotiline-induced apoptosis: role of [Ca2 +] (i), ERK, JNK and caspase-3 signaling pathways.

maprotiline

Ca2 +


Input: Antidepressants are generally used for treatment of various mood and anxiety disorders.


Input: Several studies have shown the anti-tumor and cytotoxic activities of some antidepressants, but the underlying mechanisms were unclear.


Input: Maprotiline is a tetracyclic antidepressant and possesses a highly selective norepinephrine reuptake ability.

Maprotiline

norepinephrine


Input: We found that maprotiline decreased cell viability in a concentration-and time-dependent manner in Neuro-2a cells.

maprotiline


Input: Maprotiline induced apoptosis and increased caspase-3 activation.

Maprotiline


Input: The activation of caspase-3 by maprotiline appears to depend on the activation of JNK and the inactivation of ERK.

maprotiline


Input: Maprotiline also induced [Ca (2 +)] (i) increases which involved the mobilization of intracellular Ca (2 +) stored in the endoplasmic reticulum.

Maprotiline

Ca (2 +)

Ca (2 +)


Input: Pretreatment with BAPTA/AM, a Ca (2 +) chelator, suppressed maprotiline-induced ERK phosphorylation, enhanced caspase-3 activation and increased maprotiline-induced apoptosis.

BAPTA

Ca (2 +)

maprotiline

maprotiline


Input: In conclusion, maprotiline induced apoptosis in Neuro-2a cells through activation of JNK-associated caspase-3 pathways.

maprotiline


Input: Maprotiline also evoked an anti-apoptotic response that was both Ca (2 +)-and ERK-dependent.

Maprotiline

Ca (2 +)


Input: Immunotherapy blocking the tissue plasminogen activator-dependent activation of N-methyl-d-aspartate glutamate receptors improves hemorrhagic stroke outcome.

N-methyl-d-aspartate glutamate


Input: Ischemic and hemorrhagic strokes have different etiologies, but share some pathogenic mechanisms, including a pro-neurotoxic effect of endogenous tissue plasminogen activator (tPA) via N-methyl-d-Aspartate (NMDA) receptors.

N-methyl-d-Aspartate

NMDA


Input: Thus, in a model of intracerebral hemorrhage in rats, we investigated the therapeutic value of a strategy of immunotherapy (alpha ATD-GluN1 antibody) preventing the interaction of tPA with NMDA receptors.

NMDA


Input: We found that a single intravenous injection of alpha ATD-GluN1 reduced brain edema, neuronal death, microglial activation and functional deficits following intracerebral hemorrhage, without affecting the hematoma volume.


Input: Do mollusks use vertebrate sex steroids as reproductive hormones?

steroids


Input: II.


Input: Critical review of the evidence that steroids have biological effects.

steroids


Input: In assessing the evidence as to whether vertebrate sex steroids (e. g. testosterone, estradiol, progesterone) have hormonal actions in mollusks, ca.

steroids

testosterone

estradiol

progesterone


Input: 85% of research papers report at least one biological effect; and 18 out of 21 review papers (published between 1970 and 2012) express a positive view.


Input: However, just under half of the research studies can be rejected on the grounds that they did not actually test steroids, but compounds or mixtures that were only presumed to behave as steroids (or modulators of steroids) on the basis of their effects in vertebrates (e. g. Bisphenol-A, nonylphenol and sewage treatment effluents).

steroids

steroids

steroids

Bisphenol-A

nonylphenol


Input: Of the remaining 55 papers, some can be criticized for having no statistical analysis; some for using only a single dose of steroid; others for having irregular dose-response curves; 40 out of the 55 for not replicating the treatments; and 50 out of 55 for having no within-study repetition.

steroid


Input: Furthermore, most studies had very low effect sizes in comparison to fish-based bioassays for steroids (i. e. they had a very weak' signal-to-noise' ratio).

steroids


Input: When these facts are combined with the fact that none of the studies were conducted with rigorous randomization or' blinding' procedures (implying the possibility of' operator bias') one must conclude that there is no indisputable bioassay evidence that vertebrate sex steroids have endocrinological or reproductive roles in mollusks.

steroids


Input: The only observation that has been independently validated is the ability of estradiol to trigger rapid (1-5 min) lysosomal membrane breakdown in hemocytes of Mytilus spp.

estradiol


Input: This is a typical' inflammatory' response, however, and is not proof that estradiol is a hormone-especially when taken in conjunction with the evidence (discussed in a previous review) that mollusks have neither the enzymes necessary to synthesize vertebrate steroids nor nuclear receptors with which to respond to them.

estradiol

steroids


Input: Budding yeast Wapl controls sister chromatid cohesion maintenance and chromosome condensation.


Input: The establishment of stable sister chromatid cohesion during DNA replication requires acetylation of the chromosomal cohesin complex by the replication fork-associated acetyltransferase Eco1.


Input: Cohesin acetylation is thought to facilitate replication fork progression by counteracting an as yet ill-defined cohesion " antiestablishment " activity imposed by the Wapl protein.


Input: Here, using budding yeast, we find no evidence that cohesin acetylation must overcome Wapl during replication fork progression.


Input: Instead, Wapl emerges as a negative regulator of cohesion maintenance in G2, a function that it likely exerts through its role as destabilizer of unacetylated, chromosome-bound cohesin.


Input: Our results suggest that acetylation renders cohesin Wapl-resistant from S phase onward until mitosis.


Input: In the absence of Wapl, sister chromatid cohesion functions well, suggesting that Wapl partakes in a cohesin function outside of sister chromatid cohesion.


Input: We find that Wapl is not required for cohesin' s known role in transcriptional regulation.


Input: Rather, cells lacking Wapl display increased chromosome condensation in both interphase and mitosis.


Input: Thus, as a conserved regulator of cohesin dynamics on chromosomes, Wapl controls cohesion maintenance after its establishment in S phase and adjusts the chromosome condensation status.


Input: Tartary buckwheat improves cognition and memory function in an in vivo amyloid-beta-induced Alzheimer model.


Input: Protective effects of Tartary buckwheat (TB) and common buckwheat (CB) on amyloid beta (A beta)-induced impairment of cognition and memory function were investigated in vivo in order to identify potential therapeutic agents against Alzheimer' s disease (AD) and its associated progressive memory deficits, cognitive impairment, and personality changes.


Input: An in vivo mouse model of AD was created by injecting the brains of ICR mice with A beta (25-35), a fragment of the full-length A beta protein.


Input: Damage of mice recognition ability through following A beta (25-35) brain injections was confirmed using the T-maze test, the object recognition test, and the Morris water maze test.


Input: Results of behavior tests in AD model showed that oral administration of the methanol (MeOH) extracts of TB and CB improved cognition and memory function following A beta (25-35) injections.

methanol

MeOH


Input: Furthermore, in groups receiving the MeOH extracts of TB and CB, lipid peroxidation was significantly inhibited, and nitric oxide levels in tissue, which are elevated by injection of A beta (25-35), were also decrease.

MeOH

nitric oxide


Input: In particular, the MeOH extract of TB exerted a stronger protective activity than CB against A beta (25-35)-induced memory and cognition impairment.

MeOH


Input: The results indicate that TB may play a promising role in preventing or reversing memory and cognition loss associated with A beta (25-35)-induced AD.


Input: Progressive post-yield behavior of human cortical bone in shear.


Input: Bone fragility depends on its post-yield behavior since most energy dissipation in bone occurs during the post-yield deformation.


Input: Previous studies have investigated the progressive changes in the post-yield behavior of human cortical bone in tension and compression using a novel progressive loading scheme.


Input: However, little is known regarding the progressive changes in the post-yield behavior of bone in shear.


Input: The objective of this short study was to address this issue by testing bone specimens in an inclined double notch shear configuration using the progressive loading protocol.


Input: The results of this study indicated that the shear modulus of bone decreased with respect to the applied strain, but the rate of degradation was about 50% less than those previously observed in compression and tension tests.


Input: In addition, a quasi-linear relationship between the plastic and applied strains was observed in shear mode, which is similar to those previously reported in tension and compression tests.


Input: However, the viscous responses of bone (i. e. relaxation time constants and stress magnitude) demonstrated slight differences in shear compared with those observed in tension and compression tests.


Input: Nonetheless, the results of this study suggest that the intrinsic mechanism of plastic deformation of human cortical bone may be independent of loading modes.


Input: Bioactive cis-stilbenoids from the tubers of Scirpus yagara.

cis-stilbenoids


Input: Two new cis-stilbenoids, sciryagarol I (1) and II (2) were isolated from the EtOAc extract of the tubers of Scirpus yagara, together with four known compounds.

cis-stilbenoids

sciryagarol I (1) and II

EtOAc


Input: The structures of all compounds were determined by comprehensive analyses of their spectroscopic data and comparison with literature information.


Input: The compounds 3, 4 and 6 were isolated for the first time from this genus.


Input: Some compounds were tested for their cytotoxicity against human tumor cell lines and antimicrobial activity.


Input: Compounds 1-4 showed significant cytotoxicity against the Hela cell lines with IC (50) values ranging from 7. 21 to 61. 21 mu M.


Input: 1 and 2 exhibited some antimicrobial activity against Staphylococcus aureus and Candida albicans with uniform MICs of 79. 3 mu l/ml for 2, and 152 mu l/ml for 1, respectively.


Input: Neuropathy target esterase (NTE): overview and future.


Input: Neuropathy target esterase (NTE) was discovered by M. K.


Input: Johnson in his quest for the entity responsible for the striking and mysterious paralysis brought about by certain organophosphorus (OP) esters.

organophosphorus

esters


Input: His pioneering work on OP neuropathy led to the view that the biochemical lesion consisted of NTE that had undergone OP inhibition and aging.


Input: Indeed, nonaging NTE inhibitors failed to produce disease but protected against neuropathy from subsequently administered aging inhibitors.


Input: Thus, inhibition of NTE activity was not the culprit; rather, formation of an abnormal protein was the agent of the disorder.


Input: More recently, however, Paul Glynn and colleagues showed that whereas conventional knockout of the NTE gene was embryonic lethal, conditional knockout of central nervous system NTE produced neurodegeneration, suggesting to these authors that the absence of NTE rather than its presence in some altered form caused disease.


Input: We now know that NTE is the 6th member of a 9-protein family called patatin-like phospholipase domain-containing proteins, PNPLA1-9.


Input: Mutations in the catalytic domain of NTE (PNPLA6) are associated with a slowly developing disease akin to OP neuropathy and hereditary spastic paraplegia called NTE-related motor neuron disorder (NTE-MND).


Input: Furthermore, the NTE protein from affected individuals has altered enzymological characteristics.


Input: Moreover, closely related PNPLA7 is regulated by insulin and glucose.

glucose


Input: These seemingly disparate findings are not necessarily mutually exclusive, but we need to reconcile recent genetic findings with the historical body of toxicological data indicating that inhibition and aging of NTE are both necessary in order to produce neuropathy from exposure to certain OP compounds.


Input: Solving this mystery will be satisfying in itself, but it is also an enterprise likely to pay dividends by enhancing our understanding of the physiological and pathogenic roles of the PNPLA family of proteins in neurological health and disease, including a potential role for NTE in diabetic neuropathy.


Input: Glyoxal and methylglyoxal: autoxidation from dihydroxyacetone and polyphenol cytoprotective antioxidant mechanisms.

Glyoxal

methylglyoxal

dihydroxyacetone

polyphenol


Input: Previously, this laboratory had shown that fructose and its downstream metabolites can be enzymatically metabolized to form glyoxal and methylglyoxal.

fructose

glyoxal

methylglyoxal


Input: Fructose metabolites, glycoaldehyde, glyceraldehyde and hydroxypyruvate have also been shown to be autoxidizable.

Fructose

glycoaldehyde

glyceraldehyde

hydroxypyruvate


Input: In this study, however, fructose did not cause protein carbonylation itself and instead protected against apparent carbonylation by Fenton' s reagent; fructose did not form significant levels of dicarbonyl compounds over a period of 6 days under standard conditions (37 degrees C, pH 7. 4).

fructose

fructose

dicarbonyl


Input: In contrast, dihydroxyacetone, a fructose metabolite, caused protein carbonylation and autoxidized to form dicarbonyls, which effects were further potentiated under oxidative stress conditions (Fenton' s reaction).

dihydroxyacetone

fructose

dicarbonyls


Input: Natural polyphenols were tested for their ability to protect against glyoxal-and methylglyoxal-induced cytotoxicity, reactive oxygen species formation and improved mitochondrial membrane potential maintenance.

polyphenols

glyoxal

methylglyoxal

oxygen


Input: The polyphenols investigated were gallic acid, methyl gallate, ethyl gallate, propyl gallate, rutin and curcumin.

polyphenols

gallic acid

methyl gallate

ethyl gallate

propyl gallate

rutin

curcumin


Input: The polyphenols were assayed using primary and GSH-depleted hepatocytes.

polyphenols

GSH


Input: The polyphenols were also investigated for their rescuing ability and were found to provide greater hepatoprotection when toxins were pre-incubated for 30 min before adding the polyphenols.

polyphenols

polyphenols


Input: However, rutin was less protective when rescuing hepatocytes, perhaps, because rutin metabolites may scavenge reactive oxygen species more effectively than rutin itself.

rutin

rutin

oxygen

rutin


Input: The longer the alkyl group attached to the gallate compound, the more cytoprotective the polyphenol was.

alkyl

gallate

polyphenol


Input: However, the gallates with longer alkyl groups were less able to scavenge reactive oxygen species, and to maintain the mitochondrial membrane potential.

gallates

alkyl

oxygen


Input: Aldo-keto reductases in retinoid metabolism: search for substrate specificity and inhibitor selectivity.

retinoid


Input: Biological activity of natural retinoids requires the oxidation of retinol to retinoic acid (RA) and its binding to specific nuclear receptors in target tissues.

retinoids

retinol

retinoic acid


Input: The first step of this pathway, the reversible oxidoreduction of retinol to retinaldehyde, is essential to control RA levels.

retinol

retinaldehyde


Input: The enzymes of retinol oxidation are NAD-dependent dehydrogenases of the cytosolic medium-chain (MDR) and the membrane-bound short-chain (SDR) dehydrogenases/reductases.

retinol

NAD


Input: Retinaldehyde reduction can be performed by SDR and aldo-keto reductases (AKR), while its oxidation to RA is carried out by aldehyde dehydrogenases (ALDH).

Retinaldehyde

aldehyde


Input: In contrast to SDR, AKR and ALDH are cytosolic.


Input: A common property of these enzymes is that they only use free retinoid, but not retinoid bound to cellular retinol binding protein (CRBP).

retinoid

retinoid

retinol


Input: The relative contribution of each enzyme type in retinoid metabolism is discussed in terms of the different subcellular localization, topology of membrane-bound enzymes, kinetic constants, binding affinity of CRBP for retinol and retinaldehyde, and partition of retinoid pools between membranes and cytoplasm.

retinoid

retinol

retinaldehyde

retinoid


Input: The development of selective inhibitors for AKR enzymes 1B1 and 1B10, of clinical relevance in diabetes and cancer, granted the investigation of some structure-activity relationships.


Input: Kinetics with the 4-methyl derivatives of retinaldehyde isomers was performed to identify structural features for substrate specificity.

retinaldehyde


Input: Hydrophilic derivatives were better substrates than the more hydrophobic compounds.


Input: We also explored the inhibitory properties of some synthetic retinoids, known for binding to retinoic acid receptors (RAR) and retinoid X receptors (RXR).

retinoids

retinoic acid

retinoid


Input: Consistent with its substrate specificity towards retinaldehyde, AKR1B10 was more effectively inhibited by synthetic retinoids than AKR1B1.

retinaldehyde

retinoids


Input: A RAR beta/gamma agonist (UVI2008) inhibited AKR1B10 with the highest potency and selectivity, and docking simulations predicted that its carboxyl group binds to the anion-binding pocket.

carboxyl


Input: Toxicological analysis of limonene reaction products using an in vitro exposure system.

limonene