Input: Altogether, our data indicate that HPU, besides allowing the bacterial survival in the stomach, could play an important role in the pathogenesis of the gastrointestinal inflammatory disease caused by H. pylori.


Input: Dietary Chlorella protects against heterocyclic amine-induced aberrant gene expression in the rat colon by increasing fecal excretion of unmetabolized PhIP.

heterocyclic amine

PhIP


Input: The food mutagen 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) is one of the most abundant heterocyclic amines formed by cooking meat and fish at high temperature.

2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine

PhIP

heterocyclic amines


Input: PhIP induces colorectal adenoma risk in male rats when administered orally.

PhIP


Input: This study used male Fisher 344 rats to investigate the impact of dietary Chlorella on PhIP metabolism and aberrant colonic gene expression following short-term PhIP treatment.

PhIP

PhIP


Input: High-performance liquid chromatography analysis revealed that fecal excretion of unmetabolized PhIP was significantly increased in rats whose diets were supplemented with Chlorella compared to rats in a PhIP-only group (P < 0. 001).

PhIP

PhIP


Input: Quantitative realtime PCR confirmed that the increase in beta-catenin and cyclin D1 mRNA in the colon induced by PhIP was ameliorated in rats pre-fed with Chlorella (P = 0. 052 for beta-catenin; P = 0. 005 for cyclin D1).

PhIP


Input: The increase in DNA shearing that is a hallmark of caspase-8-mediated apoptosis by PhIP was also significantly diminished in the colons of rats pre-fed Chlorella (P = 0. 012).

PhIP


Input: These results suggested that administering dietary Chlorella with a Western-style diet concomitantly or immediately before mutagen exposure might be beneficial in blocking the absorption of food mutagens such as PhIP.

PhIP


Input: Occurrence of fumonisins in organic and conventional cereal-based products commercialized in France, Germany and Spain.

fumonisins


Input: A fast and effective method for quantitative determination of fumonisins B1 and B2 (FB1 and FB2) in different cereal-based products was developed.

fumonisins B1 and B2


Input: Fumonisins were extracted combining a solid liquid extraction (SLE) pre-treatment and immunoaffinity columns (IACs), which were applied for an effective clean-up.

Fumonisins


Input: Consecutively, high pressure liquid chromatography (HPLC) coupled to hybrid triple quadrupole-linear ion trap mass spectrometer (QTrap (R)) was used for the separation, detection and quantification of targeted mycotoxins.


Input: The analytical method showed acceptable recoveries ranged from 89. 7% to 99. 1%, as well as a relative standard deviation (%, RSD) lower than 12%.


Input: A total of 1250 samples from France, Germany and Spain were analysed.


Input: The incidence of fumonisin B1 and B2 in organic samples were 11. 4% and 11. 3%, respectively.

fumonisin B1 and B2


Input: By contrast, the occurrence of conventional samples was 3. 6% of FB1 and 3. 5% of FB2.


Input: The highest values were obtained in Spanish samples of flour, as an example toasted corn, called gofio that was contaminated with 1201. 7 and 1010. 5 mu gkg (-1) of FB1 and FB2, respectively.


Input: Oral l-glutamine increases active GLP-1 (7-36) amide secretion and improves glycemic control in stretpozotocin-nicotinamide induced diabetic rats.

l-glutamine

amide

stretpozotocin

nicotinamide


Input: l-glutamine is a non-essential amino acid.

l-glutamine

amino acid


Input: It decreased blood sugar, stimulated insulin secretion in type 2 diabetic patients.

sugar


Input: The objective of the present investigation was to evaluate l-glutamine increases glucagon like peptide-1 (GLP-1) (7-36) amide secretion in streptozotocin-nicotinamide (STZ-NTM) induced diabetic Sprague Dawley rats.

l-glutamine

amide

streptozotocin

nicotinamide

STZ

NTM


Input: Molecular docking study was performed to elucidate the molecular basis for GLP-1 receptor agonistic activity.


Input: Type 2 diabetes was induced in overnight fasted Sprague Dawley rats pre-treated with nicotinamide (100mg/kg, i. p.) followed by 20min after administration of streptozotocin (55mg/kg, i. p.).

nicotinamide

streptozotocin


Input: The rats were divided into; I-nondiabetic, II-diabetic control, III-sitagliptin (5mg/kg, p. o.), IV-l-glutamine (250mg/kg, p. o.), V-l-glutamine (500mg/kg, p. o.) and VI-l-glutamine (1000mg/kg, p. o.).

sitagliptin

l-glutamine

l-glutamine

l-glutamine


Input: The l-glutamine and sitagliptin treatment was 8week.

l-glutamine

sitagliptin


Input: Plasma glucose was estimated every week.

glucose


Input: Body weight, food and water intake were recorded daily.


Input: Glycosylated haemoglobin, lipid profile, plasma and colonic active (GLP-1) (7-36) amide, mRNA expression of proglucagon GLP-1, plasma and pancreatic insulin, histology of pancreata and biomarkers of oxidative stress (superoxidase dismutase, reduced glutathione, malondialdehyde, glutathione peroxidase, glutathione S transferase) were measured after 8week.

amide

glutathione

malondialdehyde

glutathione

glutathione


Input: In acute study, the rats were divided into I-glucose (2. 5g/kg, p. o.), II-sitagliptin (5mg/kg, p. o.), III-l-glutamine (250mg/kg, p. o.), IV-l-glutamine (500mg/kg, p. o.) and V-l-glutamine (1000mg/kg, p. o.).

glucose

sitagliptin

l-glutamine

l-glutamine

l-glutamine


Input: Plasma glucose, active GLP-1 (7-36) amide concentration and insulin levels were measured after glucose loading.

glucose

amide

glucose


Input: The docking data indicated that l-glutamine bind to the GLP-1 receptor.

l-glutamine


Input: l-glutamine decreased plasma glucose, increased plasma and pancreatic insulin, increased plasma and colonic active GLP-1 (7-36) amide secretion as well as decreased oxidative stress in streptozotocin-nicotinamide induced diabetic rats.

l-glutamine

glucose

amide

streptozotocin

nicotinamide


Input: Anti-diabetic effects of brown algae derived phlorotannins, marine polyphenols through diverse mechanisms.

phlorotannins

polyphenols


Input: Marine algae are popular and abundant food ingredients mainly in Asian countries, and also well known for their health beneficial effects due to the presence of biologically active components.


Input: The marine algae have been studied for biologically active components and phlorotannins, marine polyphenols are among them.

phlorotannins

polyphenols


Input: Among marine algae, brown algae have extensively studied for their potential anti-diabetic activities.


Input: Majority of the investigations on phlorotannins derived from brown algae have exhibited their various anti-diabetic mechanisms such as alpha-glucosidase and alpha-amylase inhibitory effect, glucose uptake effect in skeletal muscle, protein tyrosine phosphatase 1B (PTP 1B) enzyme inhibition, improvement of insulin sensitivity in type 2 diabetic db/db mice, and protective effect against diabetes complication.

phlorotannins

glucose

tyrosine


Input: In this review, we have made an attempt to discuss the various anti-diabetic mechanisms associated with phlorotannins from brown algae that are confined to in vitro and in vivo.

phlorotannins


Input: Effects of chronic social defeat stress on behavior and choline acetyltransferase, 78-kDa glucose-regulated protein, and CCAAT/enhancer-binding protein (C/EBP) homologous protein in adult mice.

choline

glucose


Input: RATIONALE: Social defeat stress induces physiological and behavioral symptoms, including anxiety, anhedonia, immune deficits, and altered expression of key brain genes.


Input: OBJECTIVES: The present study investigated the effects of social defeat stress on the behaviors and expressions of Chat, Grp78, and chop in the brains of adult mice.


Input: METHODS: Adult mice were divided into susceptible and unsusceptible groups after 10 days of social defeat stress.


Input: In experiment 1, behavioral tests were conducted, and brains were processed for Western blotting at day 27 after stress.


Input: In experiment 2, social avoidance tests were conducted, and brains were processed for Western blotting at day 12 after stress.


Input: RESULTS: The results indicate decreased and increased locomotion and anxiety behavior in all defeated mice.


Input: Decrease in social interaction, increased immobility, and impaired memory performance were only observed in susceptible mice.


Input: A decrease in the Chat level at days 12 and 27 was noted in the prefrontal cortex (PFC), amygdala (Amyg), and dorsal hippocampus (HIP) in defeated mice.


Input: The expression levels of Grp78 and chop measured on days 12 and 27 were significantly greater in the Amyg of susceptible mice.


Input: In the PFC and HIP, defeated mice displayed different patterns in the levels of Grp78 and chop expressions measured on days 12 and 27.


Input: CONCLUSIONS: The present study demonstrated that chronic social defeat stress in mice produces stress-related behaviors.


Input: Different response patterns were noted for Grp78 and chop expression among the groups in terms of brain regions and time-course effects.


Input: Sarothrin from Alkanna orientalis is an antimicrobial agent and efflux pump inhibitor.

Sarothrin


Input: An Alkanna orientalis leaf and flower extract inhibited the growth of Staphylococcus aureus, a pathogen that causes an estimated 478 000 hospitalizations in the US annually.


Input: Bioassay-guided fractionation of A. orientalis resulted in isolation of the flavonoid sarothrin (5, 7, 4'-trihydroxy-3, 6, 8-trimethoxyflavone), which inhibited the growth of Mycobacterium smegmatis (MIC 75 micro M) and S. aureus (MIC > 800 micro M), and possessed efflux pump inhibitory activity.

flavonoid sarothrin

5, 7, 4'-trihydroxy-3, 6, 8-trimethoxyflavone


Input: This is the first report of antimicrobial or efflux pump inhibitory activity of sarothrin, and of its presence in A. orientalis.

sarothrin


Input: Our findings suggest that the effectiveness of A. orientalis extracts is due to a combination of multiple constituents, including sarothrin.

sarothrin


Input: Cell-Laden Hydrogels in Integrated Microfluidic Devices for Long-Term Cell Culture and Tubulogenesis Assays.


Input: A hydrogel biochip combining microfluidic mixing and orthogonal supplementation strategies is developed and validated to allow facile generation of libraries of optically transparent 3D culture microenvironments.


Input: Live, on-chip tracing of embryonic stem cell differentiation and endothelial cell tubulogenesis confirms that the platform can be used to both create communities of discrete 3D microenvironments as well as to locally monitor subsequent divergent responses at both single cell and multi-cell scales.


Input: The interaction of isopenicillin N synthase with homologated substrate analogues delta-(L-alpha-aminoadipoyl)-L-homocysteinyl-D-Xaa characterised by protein crystallography.

isopenicillin N

delta-(L-alpha-aminoadipoyl)-L-homocysteinyl-D-Xaa


Input: Isopenicillin N synthase (IPNS) converts the linear tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV) into bicyclic isopenicillin N (IPN) in the central step in the biosynthesis of penicillin and cephalosporin antibiotics.

Isopenicillin N

delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine

ACV

isopenicillin N

IPN

penicillin

cephalosporin


Input: Solution-phase incubation experiments have shown that IPNS turns over analogues with a diverse range of side chains in the third (valinyl) position of the substrate, but copes less well with changes in the second (cysteinyl) residue.

valinyl

cysteinyl


Input: IPNS thus converts the homologated tripeptides delta-(L-alpha-aminoadipoyl)-L-homocysteinyl-D-valine (AhCV) and delta-(L-alpha-aminoadipoyl)-L-homocysteinyl-D-allylglycine (AhCaG) into monocyclic hydroxy-lactam products; this suggests that the additional methylene unit in these substrates induces conformational changes that preclude second ring closure after initial lactam formation.

delta-(L-alpha-aminoadipoyl)-L-homocysteinyl-D-valine

AhCV

delta-(L-alpha-aminoadipoyl)-L-homocysteinyl-D-allylglycine

AhCaG

monocyclic hydroxy-lactam

methylene

lactam


Input: To investigate this and solution-phase results with other tripeptides delta-(L-alpha-aminoadipoyl)-L-homocysteinyl-D-Xaa, we have crystallised AhCV and delta-(L-alpha-aminoadipoyl)-L-homocysteinyl-D-S-methylcysteine (AhCmC) with IPNS and solved crystal structures for the resulting complexes.

delta-(L-alpha-aminoadipoyl)-L-homocysteinyl-D-Xaa

AhCV

delta-(L-alpha-aminoadipoyl)-L-homocysteinyl-D-S-methylcysteine

AhCmC


Input: The IPNS: Fe (II): AhCV complex shows diffuse electron density for several regions of the substrate, revealing considerable conformational freedom within the active site.

Fe (II)

AhCV


Input: The substrate is more clearly resolved in the IPNS: Fe (II): AhCmC complex, by virtue of thioether coordination to iron.

Fe (II)

AhCmC

thioether

iron


Input: AhCmC occupies two distinct conformations, both distorted relative to the natural substrate ACV, in order to accommodate the extra methylene group in the second residue.

AhCmC

ACV

methylene


Input: Attempts to turn these substrates over within crystalline IPNS using hyperbaric oxygenation give rise to product mixtures.


Input: 8-(Tosylamino) quinoline inhibits tumour progression through targeting phosphoinositide-3-kinase/Akt pathway.

8-(Tosylamino) quinoline


Input: We examined whether 8-(tosylamino) quinoline (8-TQ), a structural analogue of BAY 11-7082, is able to modulate various tumourigenic responses using various in vitro and in vivo experimental conditions.

8-(tosylamino) quinoline

BAY 11-7082


Input: 8-TQ exhibited the strongest suppressive activity on the proliferation of C6, A431, HeLa and MDA-MB-231 cells with IC550 values ranging from 10 to 30 microM.


Input: According to the analysis of level of active caspase-3, and morphologies of C6, HeLa and MDA-MB-231 cells, it was revealed that 8-TQ is able to induce apoptosis.


Input: Furthermore, this compound strongly diminished the invasion of MDA-MB-231 cells, the migration of HeLa cells, and the new generation of blood vessels under non-toxic conditions.


Input: Reduction of the phospho-form levels of intracellular signalling enzymes by 8-TQ strongly indicated that molecular signalling machineries composed of phosphoinositide 3-kinase (PI3K)/phosphoinositide-dependent kinase-1 (PDK1)/Akt and extracellular-signal-regulated kinase (ERK) could be targeted by 8-TQ treatment.


Input: Indeed, the specific inhibitors (LY294002 and U0126) of PI3K/PDK1/Akt and ERK showed similar anti-cancer properties to 8-TQ.


Input: Finally, 8-TQ intraperitoneally injected suppressed the increase of tumour volume up to 40% compared to vehicle-treated control.


Input: Taken together, our results clearly suggest that 8-TQ might have applications as a novel anti-cancer drug or may be served as a lead compound to be further optimized.


Input: Quinolines as chemotherapeutic agents for leishmaniasis.

Quinolines


Input: The development of leishmanicidal quinolines and their in vitro (promastigote and amastigote) and, where applicable, in vivo activities are reviewed.

quinolines


Input: This survey provides a direct comparison of bioactivity across different species (e. g. L. donovani, L. amazonensis, L. chagasi, L infantum), and in different animal models (e. g. L. donovani Balb/c mice and L. donovani infected hamsters).


Input: The progress of selected quinolines through pre-clinical development and phase I/II trials, and the lead quinoline drugs sitamaquinine and Imiquimod, are discussed in conjunction with delivery systems and combination therapies.

quinolines

quinoline

sitamaquinine

Imiquimod


Input: Identification of a RhoA-and SRF-Dependent Mechanism of Androgen Action that is Associated with Prostate Cancer Progression.

Androgen


Input: Androgen receptor (AR) action is critical for prostate cancer (CaP) progression, but is not inhibited fully by available androgen deprivation therapy (ADT).

Androgen

androgen


Input: One of the limitations to current ADT is that it targets all androgen action in CaP, and other, cells irrespective of clinical relevance.


Input: The resulting off-target effects are responsible for ADT associated side effects that affect negatively a patient' s quality of life.


Input: Isolation of the AR-dependent events that drive CaP progression may lead to novel forms of ADT that are at least as effective but more selective.


Input: Here, an approach is described that starts from insights in the basic mechanism (s) by which AR regulates target gene expression to identify novel drugable targets downstream of AR.


Input: Exploration of the molecular events that underlie androgen regulation of the ARassociated coregulator FHL2 led to the isolation of a novel indirect mechanism of androgen action that is mediated by the secondary transcription factor Serum Response Factor (SRF).

androgen

androgen


Input: Using a combination of oligoarray and in silico analyses, an SRF-dependent fraction of AR action was identified that is enriched in CaP tissues, is able to discriminate between benign and malignant prostate, and correlates with aggressive disease and biochemical failure.


Input: The RhoA signaling axis, a well known upstream stimulator of SRF action that harbors drugable targets, conveyed androgen-responsiveness to SRF, and was activated in CaP where it correlates with increased CaP aggressiveness and poor outcome after surgery.

androgen


Input: A new tetracyclic triterpenoid compound from Mastich.

tetracyclic triterpenoid


Input: A new tetracyclic triterpenoid compound named as mastichinoic acid A (1) was isolated from Mastich.

tetracyclic triterpenoid

mastichinoic acid A


Input: The structure was established as 3, 7-dioxo-11 beta-hydroxy-5 alpha-tirucalla-8, 24 (Z)-dien-26-oic acid by various spectroscopic techniques including MS, 1D, and 2D NMR and HRTOFMS.

3, 7-dioxo-11 beta-hydroxy-5 alpha-tirucalla-8, 24 (Z)-dien-26-oic acid


Input: Cystatin C: an emerging biomarker in cardiovascular disease.


Input: Cystatin C (cys-C) is a small protein molecule (120 amino acid peptide chain, approximately 13kDa) produced by virtually all nucleated cells in the human body.

amino acid


Input: It belongs to the family of papain-like cysteine proteases and its main biological role is the extracellular inhibition of cathepsins.

cysteine


Input: It' s near constant production rate, the fact that it is freely filtered from the glomerular membrane and then completely reabsorbed without being secreted from the proximal tubular cells, made it an almost perfect candidate for estimating renal function.


Input: The strong correlation between chronic kidney disease (CKD) and cardiovascular disease (CVD) along with the growing understanding of the role of cysteinyl cathepsins in the pathophysiology of CVD inspired researchers to explore the potential association of cys-C with CVD.

cysteinyl


Input: Throughout the spectrum of CVD (peripheral arterial disease, stroke, abdominal aortic aneurysm, heart failure, coronary artery disease) adverse outcomes and risk stratification have been associated with high plasma levels of cys-C.


Input: The exact mechanisms behind the observed correlations have not been comprehensively clarified.


Input: Plausible links between high cys-C levels and poor cardiovascular outcome could be impaired renal function, atherogenesis and inflammatory mediators, remodeling of myocardial tissue and others (genetic factors, aging and social habits).


Input: The scope of the present article is to systematically review the current knowledge about cys-C biochemistry, metabolism, methods of detection and quantification and pathophysiological associations with different aspects of CVD.


Input: MicroRNAs and the Heart: Small Things Do Matter.


Input: MicroRNAs are small RNA molecules and constitute a relatively novel class of gene expression regulators, found in the great majority of eukaryotic cells.


Input: Their role in human physiology and pathology is actively being researched with new exciting discoveries continuously coming to the forefront.


Input: MicroRNAs play a crucial role in the biogenesis and function of the cardiovascular system and act as important regulators of various metabolic and signaling pathways in cardiovascular disease.


Input: In this review there will be a summary on current knowledge about the expression, regulation and function of microRNAs in the most common diseases of the cardiovascular system as well as a presentation of and discussion about their promising future role as new biomarkers and therapeutic targets.


Input: Copeptin as a biomarker in cardiac disease.


Input: The introduction of biochemical biomarkers in the evaluation of patients with cardiovascular disease has led to practice-changing advancements in the way these patients are diagnosed and managed.


Input: Measurements of cardiac troponins or brain-type natriuretic peptide (BNP) and its precursor, N-terminal brain-type natriuretic peptide (NT-proBNP), have become indispensable in the evaluation of patients with acute coronary syndromes and heart failure, respectively, constituting an integral part of the diagnostic algorithm and risk stratification of these conditions.


Input: Copeptin, a glycopeptide, part of the prehormone molecule of the antidiuretic hormone-or arginine-vasopressin-has shown considerable promise in this field.

arginine


Input: There is evidence that copeptin might be useful as a diagnostic or prognostic biomarker and risk-stratifier in a range of cardiovascular disease conditions.


Input: The main clinical scenarios where copeptin has been studied as a biomarker are: early rule-out of myocardial infarction in patients with acute chest pain, diagnosis of heart failure in patients with acute dyspnea and determining the prognosis of destabilized or chronic stable heart failure.


Input: The present review is aimed at providing concise information about the molecular structure and biosynthesis of copeptin, the available medical chemistry methods of quantification, and the potential clinical uses of this molecule in patients with heart disease.


Input: High-Resolution Direct-Absorption Spectroscopy of Hydroxymethyl Radical in the CH Symmetric Stretching Region.

Hydroxymethyl

CH


Input: High-resolution, fully rotationally resolved direct absorption spectra of hydroxymethyl radical, CH2OH, are presented in the infrared CH stretching region.

hydroxymethyl

CH


Input: As a result of low rotational temperatures and sub-Doppler linewidths obtained in the slit supersonic expansion, the Ka = 0 <-- 0 band of the symmetric CH stretch for CH2OH has been unambiguously identified and analyzed.

CH


Input: By way of chemical confirmation, hydroxymethyl radical is generated via two different slit jet discharge syntheses: (i) direct dissociation of CH3OH to form CH2OH and (ii) dissociation of Cl2 followed by the radical H atom extraction reaction Cl + CH3OH --> HCl + CH2OH.

hydroxymethyl

H

Cl

HCl


Input: The identified transitions are fit to a Watson A-reduced symmetric top Hamiltonian to yield first precision experimental values for the ground state rotational constants as well as improved values for the symmetric stretch rotational constants and vibrational band origin.


Input: The results both complement and substantially improve upon spectral efforts via previous double resonance ionization detected infrared methods by Feng et al.


Input: [J. Phys. Chem. A, 2004, 108, 7093], as well as offer high-resolution predictions for laboratory and astronomical detection of hydroxymethyl radical in the millimeter-wave region.

hydroxymethyl


Input: Light reflection control in biogenic micro-mirror by diamagnetic orientation.


Input: As has become known, most materials, such as proteins and DNA, show orientation under strong magnetic fields.


Input: However, the critical threshold for the magnetic field of the magnetomechanical phenomena is still unknown.


Input: We demonstrate that a thin micro-mirror from a fish scale with high reflectivity exhibits a distinct magnetic response at 100 mT.


Input: A dramatic event under a magnetic field is the decrease of light scattering from guanine crystals as well as rapid rotation against the applied magnetic field.

guanine


Input: Enhancement of light scattering intensity is also observed when the three vectors of light incidence, magnetic field, and observation are orthogonally directed.


Input: The results indicate that biogenic guanine crystals have a large diamagnetic anisotropy along the surface parallel and normal directions.

guanine


Input: The micrometer to submicrometer scale of thin biogenic plates can act as a noninvasively, magnetically controlled micro-mirror for light irradiation control in the micrometer-scale region.


Input: Ideal redox behavior of the high-density self-assembled monolayer of a molecular tripod on a au (111) surface with a terminal ferrocene group.

au (111)

ferrocene


Input: A dyad consisting of a tripod-shaped trithiol with an adamantane core and a terminal ferrocenyl group linked through ap-phenyleneethynylene bridge was synthesized.

trithiol

adamantane

ferrocenyl

phenyleneethynylene


Input: The trithiol formed a stable self-assembled monolayer (SAM) on Au (111), wherein each molecule is bound to the surface by three-point adsorption using all sulfur atoms, with confirmation by PM-IRRAS and XPS analyses.

trithiol

Au (111)

sulfur


Input: Cyclic voltammetry of the SAM showed a line shape typical of an ideal adsorbed system, that is, a monolayer with negligible electrostatic interaction among the terminal ferrocenyl groups.

ferrocenyl


Input: Thus, a rare SAM was achieved, in which the component molecules were isolated from adjacent molecules without the coadsorption of nonelectroactive molecules.


Input: Corticotropin releasing factor and catecholamines enhance glutamatergic neurotransmission in the lateral subdivision of the central amygdala.

catecholamines


Input: Glutamatergic neurotransmission in the central nucleus of the amygdala (CeA) plays an important role in many behaviors including anxiety, memory consolidation and cardiovascular responses.


Input: While these behaviors can be modulated by corticotropin releasing factor (CRF) and catecholamine signaling, the mechanism (s) by which these signals modify CeA glutamatergic neurotransmission remains unclear.

catecholamine


Input: Utilizing whole-cell patch-clamp electrophysiology recordings from neurons in the lateral subdivision of the CeA (CeAL), we show that CRF, dopamine (DA) and the beta-adrenergic receptor agonist isoproterenol (ISO) all enhance the frequency of spontaneous excitatory postsynaptic currents (sEPSC) without altering sEPSC kinetics, suggesting they increase presynaptic glutamate release.

dopamine

isoproterenol

ISO

glutamate


Input: The effect of CRF on sEPSCs was mediated by a combination of CRFR1 and CRFR2 receptors.


Input: While previous work from our lab suggests that CRFRs mediate the effect of catecholamines on excitatory transmission in other subregions of the extended amygdala, blockade of CRFRs in the CeAL failed to significantly alter effects of DA and ISO on glutamatergic transmission.

catecholamines

ISO


Input: These findings suggest that catecholamine and CRF enhancement of glutamatergic transmission onto CeAL neurons occurs via distinct mechanisms.

catecholamine


Input: While CRF increased spontaneous glutamate release in the CeAL, CRF caused no significant changes to optogenetically evoked glutamate release in this region.

glutamate

glutamate


Input: The dissociable effects of CRF on different types of glutamatergic neurotransmission suggest that CRF may specifically regulate spontaneous excitatory transmission.


Input: Testing for departures from additivity in mixtures of perfluoroalkyl acids (PFAAs).

perfluoroalkyl acids

PFAAs


Input: This study is a follow-up to a paper by Carr et al. that determined a design structure to optimally test for departures from additivity in a fixed ratio mixture of four perfluoroalkyl acids (PFAAs) using an in vitro transiently-transfected COS-1 PPAR alpha reporter model with a mixing ratio that is based on average serum levels in NHANES subjects.

perfluoroalkyl acids

PFAAs


Input: Availability of information regarding potential for additivity of PFAAs in mixtures is critically important for risk assessors who are concerned with the ability of the compounds to affect human health and impact ecological systems.

PFAAs


Input: It is clear that exposures are not to single compounds, but to mixtures of the PFAAs.

PFAAs


Input: This paper presents the results from the data collected using the design from Carr et al. along with subsequent analyses that were performed to classify the relationships among mixtures of PFAAs.

PFAAs


Input: A non-linear logistic additivity model was employed to predict relative luciferase units (RLU), an indicator of PPAR alpha activation.


Input: The results indicated a less than additive relationship among the four PFAAs.

PFAAs


Input: To determine if the possible " antagonism " is from the competition among or between carboxylates and sulfonates, four different binary mixtures were also studied.

carboxylates

sulfonates


Input: There was a less than additive relationship in all four binary mixtures.


Input: These findings are generally similar to two other reports of interfering interactions between PFAAs in mixtures.

PFAAs


Input: The most conservative interpretation for our data would be an assumption of additivity (and lack of a greater than additive interaction), with a potential for antagonistic interactions.


Input: Bioactivation of bisphenol A and its analogs (BPF, BPAF, BPZ and DMBPA) in human liver microsomes.

bisphenol A

BPF

BPAF

BPZ

DMBPA


Input: Bisphenol A analogs are a class of chemicals known as diphenylmethanes, which contain two benzene rings separated by one central carbon atom, usually with a para-hydroxy group on both benzene rings.

Bisphenol A

diphenylmethanes

benzene

para-hydroxy

benzene


Input: Bisphenol A (BPA) can induce an uterotrophic response in immature CD-1 mice and elicits estrogenic responses in many other experimental systems.

Bisphenol A

BPA


Input: Besides highlighting endocrine effects, a number of metabolic studies provide strong support for the idea that reactive species of BPA are formed in vitro and in vivo that can form covalent adducts with nucleophilic macromolecules and/or produce oxidative stress.

BPA


Input: We used a liquid chromatography with a triple quadrupole tandem mass spectrometry (LC-MS/MS) for the detection of metabolites and glutathione conjugates of BPA and its analogs (BPF, BPAF, BPZ and DMBPA) in human liver microsomes (HLM) or with recombinant CYP isozymes in the presence of NADPH and GSH as a trapping agent.

glutathione

BPA

BPF

BPAF

BPZ

DMBPA

NADPH

GSH


Input: We have confirmed that BPA and its structural analogs form hydroxylated metabolites and electrophilic species during bioactivation in HLM and CYP isozymes.

BPA


Input: These results provided important mechanistic insight into the metabolic fate of BPA structural analogs in vitro.

BPA


Input: Human induced pluripotent stem cells and their use in drug discovery for toxicity testing.


Input: Predicting human safety risks of novel xenobiotics remains a major challenge, partly due to the limited availability of human cells to evaluate tissue-specific toxicity.


Input: Recent progress in the production of human induced pluripotent stem cells (hiPSCs) may fill this gap.


Input: hiPSCs can be continuously expanded in culture in an undifferentiated state and then differentiated to form most cell types.


Input: Thus, it is becoming technically feasible to generate large quantities of human cell types and, in combination with relatively new detection methods, to develop higher-throughput in vitro assays that quantify tissue-specific biological properties.


Input: Indeed, the first wave of large scale hiSC-differentiated cell types including patient-derived hiPSCS are now commercially available.


Input: However, significant improvements in hiPSC production and differentiation processes are required before cell-based toxicity assays that accurately reflect mature tissue phenotypes can be delivered and implemented in a cost-effective manner.


Input: In this review, we discuss the promising alignment of hiPSCs and recently emerging technologies to quantify tissue-specific functions.


Input: We emphasize liver, cardiovascular, and CNS safety risks and highlight limitations that must be overcome before routine screening for toxicity pathways in hiSC-derived cells can be established.


Input: Water deficit and heat affect the tolerance to high illumination in hibiscus plants.


Input: This work studies the effects of water deficit and heat, as well as the involvement of chlororespiration and the ferredoxin-mediated cyclic pathway, on the tolerance of photosynthesis to high light intensity in Hibiscus rosa-sinensis plants.


Input: Drought and heat resulted in the down-regulation of photosynthetic linear electron transport in the leaves, although only a slight decrease in variable fluorescence (Fv)/maximal fluorescence (Fm) was observed, indicating that the chloroplast was protected by mechanisms that dissipate excess excitation energy to prevent damage to the photosynthetic apparatus.


Input: The incubation of leaves from unstressed plants under high light intensity resulted in an increase of the activity of electron donation by nicotinamide adenine dinucleotide phosphate (NADPH) and ferredoxin to plastoquinone, but no increase was observed in plants exposed to water deficit, suggesting that cyclic electron transport was stimulated by high light only in control plants.

nicotinamide adenine dinucleotide phosphate

NADPH

plastoquinone


Input: In contrast, the activities of the chlororespiration enzymes (NADH dehydrogenase (NDH) complex and plastid terminal oxidase (PTOX)) increased after incubation under high light intensity in leaves of the water deficit plants, but not in control plants, suggesting that chlororespiration was stimulated in stressed plants.

NADH


Input: The results indicate that the relative importance of chlororespiration and the cyclic electron pathway in the tolerance of photosynthesis to high illumination differs under stress conditions.


Input: When plants were not subjected to stress, the contribution of chlororespiration to photosynthetic electron flow regulation was not relevant, and another pathway, such as the ferredoxin-mediated cyclic pathway, was more important.


Input: However, when plants were subjected to water deficit and heat, chlororespiration was probably essential.


Input: Controlled formation of mono-and dihydroxy-resolvins from EPA and DHA using soybean 15-lipoxygenase.

mono-and dihydroxy-resolvins

EPA

DHA


Input: Resolvins and protectins are important anti-inflammatory and pro-resolution compounds derived from the enzymatic oxidation of omega-3 fatty acids all-cis-5, 8, 11, 14, 17-eicosapentaenoic acid (EPA) and all-cis-4, 7, 10, 13, 16, 19-docosahexaenoic acid (DHA).

Resolvins

omega-3 fatty acids all-cis-5, 8, 11, 14, 17-eicosapentaenoic acid

EPA

all-cis-4, 7, 10, 13, 16, 19-docosahexaenoic acid

DHA


Input: We have developed a simple, controlled method to synthesize an array of resolvin and protectin analogs from fatty acid starting materials using soybean 15-lipoxygenase.

resolvin

fatty acid


Input: The conditions were optimized for the production of both mono-and dihydroxy derivatives, with enzyme concentration and pH found to have a significant effect on the reaction products.

mono-and dihydroxy


Input: The methods were applied to five biologically important omega-3 and omega-6 fatty acid substrates.

omega-3 and omega-6 fatty acid


Input: Mono-and dihydroxy compounds were successfully synthesized from all substrates and the products were characterized by normal phase (NP) HPLC, GC-MS, TOF-MS, UV-visible (UV-vis) spectroscopy, and NMR spectroscopy.

Mono-and dihydroxy


Input: The methods could be further applied to any polyunsaturated fatty acids containing the cis-1, 4, 7, 10-undecatetraene moiety to produce a range of novel compounds with potential biological activity.

polyunsaturated fatty acids

cis-1, 4, 7, 10-undecatetraene


Input: Biomimetic metal oxides for the extraction of nanoparticles from water.

metal oxides


Input: Contamination of nanomaterials in the environment will pose significant health risks in the future.


Input: A viable purification method is necessary to address this problem.


Input: Here we report the synthesis and application of a series of metal oxides prepared using a biological template for the removal of nanoparticles from the aqueous environment.

metal oxides


Input: A simple synthesis of metal oxides such as ZnO, NiO, CuO, Co3O4 and CeO2 employing eggshell membrane (ESM) as a biotemplate is reported.

metal oxides

ZnO

NiO

CuO


Input: The morphology of the metal oxide powders was characterized using electron microscopes and the lattice structure was established using X-ray diffraction methods.

metal oxide


Input: Extraction of nanoparticles from water was carried out to compare the efficiency of metal oxides.

metal oxides


Input: NiO showed good extraction efficiency in removing gold and silver nanoparticles from spiked water samples within an hour.

NiO

silver


Input: Easy access and enhanced stability of metal oxides makes them interesting candidates for applications in industrial effluent treatments and water purifications.

metal oxides


Input: Exendin-4 protects hypoxic islets from oxidative stress and improves islet transplantation outcome.


Input: Oxidative stress produced during pancreatic islet isolation leads to significant beta-cell damage.


Input: Homeostatic cytokines secreted subsequently to islet transplantation damage beta-cells by generating oxygen free radicals.

oxygen


Input: In this study, exendin-4, a glucagon-like peptide-1 analog improved islet transplantation outcome by increasing the survival of diabetic recipient mice from 58% to 100%.


Input: We hypothesized that this beneficial effect was due to the ability of exendin-4 to reduce oxidative stress.


Input: Further experiments showed that it significantly reduced the apoptotic rate of cultured beta-cells subjected to hypoxia or to IL-1 beta.


Input: Reduction of apoptotic events was confirmed in pancreatic islet grafts of exendin-4-treated mice.


Input: Exendin-4 enhanced Akt phosphorylation of beta-cells and insulin released from them.


Input: It even augmented insulin secretion from islets cultivated at hypoxic conditions.


Input: Exposure to hypoxia led to a decrease in the activation of Akt, which was reversed when beta-cells were pretreated with exendin-4.


Input: Moreover, exendin-4 increased the activity of redox enzymes in a hypoxia-treated beta-cell line and reduced reactive oxygen species production in isolated pancreatic islets.

oxygen


Input: Recovery from diabetes in mice transplanted with hypoxic islets was more efficient when they received exendin-4.


Input: In conclusion, exendin-4 rescued islets from oxidative stress caused by hypoxia or due to cytokine exposure.


Input: It improved the outcome of syngenic and xenogenic islet transplantation.


Input: Exposure to phototoxic NSAIDs and quinolones is associated with an increased risk of melanoma.

quinolones


Input: PURPOSE: Ultraviolet radiation exposure is the most important exogenous risk factor for cutaneous malignancies.


Input: It is possible that phototoxic drugs promote the development of cutaneous melanoma (CM) by intensifying the effect of ultraviolet light on the skin.


Input: We investigated the association between the use of common systemic phototoxic drugs and development of CM.


Input: METHODS: This study was a case-control study in a Dutch population-based cohort.


Input: The drug dispensing data was obtained from PHARMO, a Dutch drug dispensing and hospital admissions registry, and linked to PALGA, the nationwide pathology network of the Netherlands.


Input: The cases were patients diagnosed with pathologically confirmed primary CM between 1991 and 2004.


Input: Controls were sampled from the PHARMO population.


Input: Exposure to systemic phototoxic drugs was measured and included antimicrobial agents, diuretics, antipsychotic drugs, antidiabetic drugs, cardiac drugs, antimalarials and nonsteroidal anti-inflammatory drugs (NSAIDs).


Input: A multivariate conditional logistic regression analysis was performed to study the association between exposure to phototoxic drugs and CM.


Input: RESULTS: The study population included 1, 318 cases and 6, 786 controls.


Input: Any phototoxic drug during the study period was dispensed for 46% of the cases and 43% of the controls (p = 0. 012).


Input: The use of quinolones [odds ratio (OR) 1. 33, 95% confidence interval (CI) 1. 01-1. 76] and propionic acid derivative NSAIDs (OR 1. 33, 95% CI 1. 14-1. 54) had a positive association with CM.

quinolones

propionic acid


Input: CONCLUSIONS: Our study shows that the use of phototoxic drugs is associated with an increased risk of developing CM.


Input: Even a short-term use of phototoxic quinolones and propionic acid derivative NSAIDs may increase the risk for CM.

quinolones

propionic acid


Input: Patient education to promote sun-protective behaviour is essential to avoid immediate adverse effects and possible long-term effects of phototoxic drugs.


Input: A randomised trial of enteric-coated nutrient pellets to stimulate gastrointestinal peptide release and lower glycaemia in type 2 diabetes.


Input: AIMS/HYPOTHESES: Glucagon-like peptide-1 (GLP-1), an important mediator of postprandial glycaemia, could potentially be stimulated by delivering small quantities of nutrient to a long length of distal gut.


Input: We aimed to determine whether enteric-coated pellets, releasing small amounts of lauric acid throughout the ileum and colon, could reduce glycaemic responses to meals in type 2 diabetes, associated with stimulation of GLP-1.

lauric acid


Input: METHODS: Eligible patients, who had type 2 diabetes controlled by diet or metformin, were each studied on two occasions in a hospital setting.

metformin


Input: After an overnight fast, patients consumed 5 g active pellets (47% lauric acid by weight) or placebo with breakfast (T = 0 min) and lunch (T = 240 min), in a crossover design with order randomised by the hospital pharmacy and allocation concealed by numbered containers.


Input: Patients and investigators making measurements were blinded to the intervention.


Input: Blood was sampled frequently for blood glucose (the primary outcome) and hormone assays.

glucose


Input: RESULTS: Eight patients were randomised (four to receive either intervention first), and all completed the study without adverse effects.


Input: Blood glucose was lower after breakfast (T = 0-240 min, area under the curve (AUC) 2, 075 +/- 368 vs 2, 216 +/- 163 mmol/l x min) and lunch (T = 240-480 min, AUC 1, 916 +/- 115 vs 2, 088 +/- 151 mmol/l x min) (p = 0. 02 for each) after active pellets than after placebo.

glucose


Input: Plasma GLP-1 concentrations were higher after breakfast (p = 0. 08) and lunch (p = 0. 04) for active pellets.


Input: While there were no differences in insulin or glucose-dependent insulinotropic polypeptide concentrations, glucagon concentrations were higher after breakfast and lunch (p = 0. 002 for each) for active pellets.

glucose


Input: CONCLUSIONS/INTERPRETATION: Delivering small amounts of nutrient to the ileum and colon can stimulate substantial endogenous GLP-1 release and attenuate postprandial glycaemia.


Input: This novel approach has therapeutic potential in type 2 diabetes.


Input: TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000600842.


Input: FUNDING: The study was funded by Meyer Nutriceuticals.


Input: Interindividual variability of carboxymethylenebutenolidase homolog, a novel olmesartan medoxomil hydrolase, in the human liver and intestine.

olmesartan medoxomil


Input: Olmesartan medoxomil (OM) is a prodrug-type angiotensin II type 1 receptor antagonist.

Olmesartan medoxomil


Input: OM is rapidly converted into its active metabolite olmesartan by multiple hydrolases in humans, and we recently identified carboxymethylenebutenolidase homolog (CMBL) as one of the OM bioactivating hydrolases.

olmesartan


Input: In the present study, we further investigated the interindividual variability of mRNA and protein expression of CMBL and OM-hydrolase activity using 40 individual human liver and 30 intestinal specimens.


Input: In the intestinal samples, OM-hydrolase activity strongly correlated with the CMBL protein expression, clearly indicating that CMBL is a major contributor to the prodrug bioactivation in human intestine.


Input: The protein and activity were highly distributed in the proximal region (duodenum and jejunum) and decreased to the distal region of the intestine.


Input: Although there was high interindividual variability (16-fold) in both the protein and activity in the intestinal segments from the duodenum to colon, the interindividual variability in the duodenum and jejunum was relatively small (3. 0-and 2. 4-fold, respectively).


Input: In the liver samples, the interindividual variability in the protein and activity was 4. 1-and 6. 8-fold, respectively.


Input: No sex differences in the protein and activity were shown in the human liver or intestine.


Input: A genetically engineered Y155C mutant of CMBL, which was caused by a single nucleotide polymorphism rs35489000, showed significantly lower OM-hydrolase activity than the wild-type protein although no minor allele was genotyped in the 40 individual liver specimens.


Input: Minireview: ubiquitination-regulated G protein-coupled receptor signaling and trafficking.


Input: G protein-coupled receptors (GPCRs) are the largest and most diverse superfamily of membrane proteins and mediate most cellular responses to hormones and neurotransmitters.


Input: Posttranslational modifications are considered the main regulators of all GPCRs.


Input: In addition to phosphorylation, glycosylation, and palmitoylation, increasing evidence as reviewed here reveals that ubiquitination also regulates the magnitude and temporospatial aspects of GPCR signaling.


Input: Posttranslational protein modification by ubiquitin is a key molecular mechanism governing proteins degradation.


Input: Ubiquitination mediates the covalent conjugation of ubiquitin, a highly conserved polypeptide of 76 amino acids, to protein substrates.

amino acids


Input: This process is catalyzed by 3 enzymes acting in tandem: an E1, ubiquitin-activating enzyme; an E2, ubiquitin-carrying enzyme; and an E3, ubiquitin ligase.


Input: Ubiquitination is counteracted by deubiquitinating enzymes that deconjugate ubiquitin-modified proteins and rescue the substrate from proteasomal degradation.


Input: Although ubiquitination is known to target many GPCRs for lysosomal or proteasomal degradation, emerging findings define novel roles for the basal status of ubiquitination and for rapid deubiquitination and transubiquitination controlling cell surface expression and cellular responsiveness of some GPCRs.


Input: In this review, we highlight the classical and novel roles of ubiquitin in the regulation of GPCR function, signaling, and trafficking.


Input: Synthesis of novel bis-anthraquinone derivatives and their biological evaluation as antitumor agents.

bis-anthraquinone


Input: Cancer has become a major worldwide problem and drug resistance now is one of the most important problems in treatment of cancer.


Input: Anthraquinone derivatives represent one of the most important drugs that can be used in treatment of many types of cancer.

Anthraquinone


Input: In this study two series of novel bis-anthraquinone derivatives have been synthesized.

bis-anthraquinone


Input: Five of these compounds were chosen to be evaluated for their antitumor activity against human cancer cell lines by the National Cancer Institute (NCI, USA).


Input: Marked activity was shown for the tested compounds (2-6).


Input: The most active one was compound 6 with mean value-67. 00 against all cell lines.


Input: Compounds 7 and 8 were found inactive.


Input: Severe hypoglycemia from helicobacter pylori triple-drug therapy and insulin detemir drug interaction.


Input: Two drugs commonly used in triple-drug therapy for treatment of a Helicobacter pylori infection, clarithromycin and omeprazole, have rarely been associated with hypoglycemia when given alone.

clarithromycin

omeprazole


Input: No documented interactions between H. pylori treatment with clarithromycin, amoxicillin, and omeprazole and insulin detemir have been previously reported.

clarithromycin

amoxicillin

omeprazole


Input: This case report describes an 82-year-old man with drug-controlled type 2 diabetes who experienced severe hypoglycemia during treatment for a H. pylori infection in an outpatient setting.


Input: His diabetes treatment included 32 units of insulin detemir once/day at bedtime and insulin aspart, determined by carbohydrate intake, 3 times/day with meals.

carbohydrate


Input: After 5 days of clarithromycin 500 mg twice/day, amoxicillin 500 mg twice/day, and omeprazole 20 mg twice/day for treatment of the H. pylori infection, the patient experienced hypoglycemia and self-discontinued clarithromycin.

clarithromycin

amoxicillin

omeprazole

clarithromycin


Input: Insulin detemir was decreased to 15 units and hypoglycemia reoccurred.


Input: Insulin detemir was further decreased to 10 units without further symptoms of hypoglycemia for the remainder of the H. pylori treatment.


Input: Once treatment was completed, the patient was instructed to resume taking 32 units of insulin detemir once/day.


Input: His blood glucose concentration returned to a baseline value, and he denied experiencing further hypoglycemic episodes.

glucose


Input: Health care practitioners should be aware of this possible drug interaction and anticipate that insulin detemir dosage adjustments may be required during treatment of H. pylori infection to avoid significant adverse events.


Input: An Intracellular Domain Fragment of the p75 Neurotrophin Receptor (p75NTR) Enhances Tropomyosin Receptor Kinase A (TrkA) Receptor Function.


Input: Facilitation of nerve growth factor (NGF) signaling by the p75 neurotrophin receptor (p75 (NTR)) is critical for neuronal survival and differentiation.


Input: However, the interaction between p75 (NTR) and TrkA receptors required for this activity is not understood.


Input: Here, we report that a specific 29-amino acid peptide derived from the intracellular domain fragment of p75 (NTR) interacts with and potentiates binding of NGF to TrkA-expressing cells, leading to increased neurite outgrowth in sympathetic neurons as a result of enhanced Erk1/2 and Akt signaling.

amino acid


Input: An endogenous intracellular domain fragment of p75 (NTR) (p75 (ICD)) containing these 29 amino acids is produced by regulated proteolysis of the full-length receptor.

amino acids


Input: We demonstrate that generation of this fragment is a requirement for p75 (NTR) to facilitate TrkA signaling in neurons and propose that the juxtamembrane region of p75 (ICD) acts to cause a conformational change within the extracellular domain of TrkA.


Input: This finding provides new insight into the mechanism by which p75 (NTR) and TrkA interact to enhance neurotrophic signaling.


Input: H-H and Si-H Bond Addition to Fe = NNR2 Intermediates Derived from N2.

H-H

Si-H

Fe = NNR2


Input: The synthesis and characterization of Fe-diphosphineborane complexes are described in the context of N2 functionalization chemistry.

Fe-diphosphineborane


Input: Iron aminoimides can be generated at room temperature under 1 atm N2 and are shown to react with E-H bonds from PhSiH3 and H2.

Iron aminoimides

E-H


Input: The resulting products derive from delivery of the E fragment to N alpha and the H atom to B.

H

B


Input: The flexibility and lability of the Fe-BPh interactions in these complexes engender this reactivity.

Fe-BPh


Input: Anion-Exchange Reactions on a Robust Phosphonium Photopolymer for the Controlled Deposition of Ionic Gold Nanoclusters.


Input: UV curing (photopolymerization) is ubiquitous in many facets of industry ranging from the application of paints, pigments, and barrier coatings all the way to fiber optic cable production.


Input: To date no reports have focused on polymerizable phosphonium salts under UV irradiation, and despite this dearth of examples, they potentially offer numerous substantial advantages to traditional UV formulation components.


Input: We have generated a highly novel coating based on UV-curable trialkylacryloylphosphonium salts that allow for the fast (seconds) and straightforward preparation of ion-exchange surfaces amenable to a roll-to-roll process.

trialkylacryloylphosphonium salts


Input: We have quantified the surface charges and exploited their accessibility by employing these surfaces in an anion exchange experiment by which [Au25L18] (-) (L = SCH2CH2Ph) nanocrystals can be assembled into the solid state.

[Au25L18] (-)


Input: This unprecedented application of such surfaces offers a paradigm shift in the emerging chemistry of Au25 research where the nanocrystals remain single and intact and where the integrity of the cluster and its solution photophysical properties are resilient in the solid state.


Input: The specific loading of [Au25L18] (-) on the substrates has been determined and the completely reversible loading and unloading of intact nanocrystals to and from the surface has been established.

[Au25L18] (-)


Input: In the solid state, the assembly has an incredible mechanical resiliency, where the surface remains undamaged even when subjected to repeated Scotch tests.


Input: Bioactivity of tomato hybrid powder: antioxidant compounds and their biological activities.


Input: Abstract The antioxidant and cytotoxic activities and the polyphenolic and anthocyanin contents of tomato hybrid powders were studied.

polyphenolic

anthocyanin


Input: Tomato powders were obtained, starting from the fresh fruits that had undergone an industrial process of drying and pulverization at two different temperatures.


Input: Antioxidant activities were evaluated in different extracts by using spectrophotometric assays: 2, 2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid and N, N-dimethyl-p-phenylenediamine dihydrochloride cation radical inhibition for lipophilic and hydrophilic extracts, respectively, and 2, 2-diphenyl-1-picrylhydrazyl radical scavenging assay for polyphenolic extracts.

2, 2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid

N, N-dimethyl-p-phenylenediamine dihydrochloride

2, 2-diphenyl-1-picrylhydrazyl

polyphenolic


Input: Moreover, polyphenolic and anthocyanin contents were also carried out to detect the presence of these bioactive compounds.

polyphenolic

anthocyanin


Input: The effect of cytotoxic activity in vitro of tomato hybrid powder extracts on T47D (human breast carcinoma) cells was also evaluated.


Input: Results showed good antioxidant activities in lipophilic, polyphenolic, and hydrophilic extracts of samples that were obtained at a lower temperature.

polyphenolic


Input: Extracts of the sample obtained at a higher temperature presented moderate antioxidant activity, lower than the extracts of other samples, which was probably due to the loss of labile antioxidant compounds during the industrial process.


Input: Very interesting was the presence of anthocyanins in both samples, even if in traces, and also a moderate cytotoxicity of a lipophilic extract on T47D cells.

anthocyanins


Input: Therefore, tomato hybrid powders, on the basis of their multifunctional properties, could have a biotechnological application in agri-food or cosmetic industries as an additive for improving nutritional and/or bioactive qualities of commercial products used in daily nutrition and cosmetics.


Input: Directing cluster formation of au nanoparticles from colloidal solution.

au


Input: Discrete clusters of closely spaced Au nanoparticles can be utilized in devices from photovoltaics to molecular sensors because of the formation of strong local electromagnetic field enhancements when illuminated near their plasmon resonance.

Au


Input: In this study, scalable, chemical self-organization methods are shown to produce Au nanoparticle clusters with uniform nanometer interparticle spacing.

Au


Input: The performance of two different methods, namely electrophoresis and diffusion, for driving the attachment of Au nanoparticles using a chemical cross-linker on chemically patterned domains of polystyrene-block-poly (methyl methacrylate) (PS-b-PMMA) thin films are evaluated.

Au

polystyrene

poly (methyl methacrylate)

PMMA


Input: Significantly, electrophoresis is found to produce similar surface coverage as diffusion in 1/6th of the processing time with an ~ 2-fold increase in the number of Au nanoparticles forming clusters.

Au


Input: Furthermore, average interparticle spacing within Au nanoparticle clusters was found to decrease from 2-7 nm for diffusion deposition to approximately 1-2 nm for electrophoresis deposition, and the latter method exhibited better uniformity with most clusters appearing to have about 1 nm spacing between nanoparticles.

Au


Input: The advantage of such fabrication capability is supported by calculations of local electric field enhancements using electromagnetic full-wave simulations from which we can estimate surface-enhanced Raman scattering (SERS) enhancements.


Input: In particular, full-wave results show that the maximum SERS enhancement, as estimated here as the fourth power of the local electric field, increases by a factor of 100 when the gap goes from 2 to 1 nm, reaching values as large as 10 (10), strengthening the usage of electrophoresis versus diffusion for the development of molecular sensors.


Input: Encapsulation of Hydrophobic Drugs in Pluronic F127 Micelles: Effects of Drug Hydrophobicity, Solution Temperature, and pH.

Pluronic F127


Input: Three drugs, ibuprofen, aspirin, and erythromycin, are encapsulated in spherical Pluronic F127 micelles.

ibuprofen

aspirin

erythromycin

Pluronic F127


Input: The shapes and the size distributions of the micelles in dilute, aqueous solutions, with and without drugs, are ascertained using cryo-scanning electron microscopy and dynamic light scattering (DLS) experiments, respectively.


Input: Uptake of drugs above a threshold concentration is seen to reduce the critical micellization temperature of the solution.


Input: The mean hydrodynamic radii and polydispersities of the micelles are found to increase with decrease in temperature and in the presence of drug molecules.


Input: The hydration of the micellar core at lower temperatures is verified using fluorescence measurements.


Input: Increasing solution pH leads to the ionization of the drugs incorporated in the micellar cores.


Input: This causes rupture of the micelles and release of the drugs into the solution at the highest solution pH value of 11. 36 investigated here and is studied using DLS and fluorescence spectrocopy.


Input: Design, synthesis, and biological evaluation of indenoisoquinoline rexinoids with chemopreventive potential.

indenoisoquinoline rexinoids


Input: Nuclear receptors, such as the retinoid X receptor (RXR), are proteins that regulate a myriad of cellular processes.


Input: Molecules that function as RXR agonists are of special interest for the prevention and control of carcinogenesis.


Input: The majority of these ligands possess an acidic moiety that is believed to be key for RXR activation.


Input: This communication presents the design, synthesis, and biological evaluation of both acidic and nonacidic indenoisoquinolines as new RXR ligands.

indenoisoquinolines


Input: In addition, a comprehensive structure-activity relationship study is presented that identifies the important features of the indenoisoquinoline rexinoids.

indenoisoquinoline rexinoids


Input: The ease of modification of the indenoisoquinoline core and the lack of the necessity of a carboxyl group for activity make them an attractive and unusual family of RXR agonists.

indenoisoquinoline

carboxyl


Input: This work establishes a structural foundation for the design of new and novel rexinoid cancer chemopreventive agents.


Input: Nanoparticle film assemblies as platforms for electrochemical biosensing-factors affecting the amperometric signal enhancement of hydrogen peroxide.

hydrogen peroxide


Input: Factors affecting the enhanced amperometric signal observed at electrodes modified with polyelectrolyte-gold nanoparticle (Au-NP) composite films, which are potential interfaces for first-generation biosensors, were systematically investigated and optimized for hydrogen peroxide (H2O2) detection.

Au

hydrogen peroxide


Input: Polyelectrolyte multilayer films embedded with citrate-stabilized gold nanoparticles exhibited high sensitivity toward the oxidation of H2O2.

citrate


Input: From this Au-NP film assembly, the importance of Au-NP ligand protection, film permeability, the density of Au-NPs within the film, and electronic coupling between Au-NPs (interparticle) and between the film and the electrode (interfacial) were evaluated.

Au

Au

Au

Au


Input: Using alternative Au-NPs, including those stabilized with thiols, polymers, and bulky ligands, suggests that the amperometric enhancement of H2O2 is optimized at poly-l-lysine-linked film assemblies embedded with Au-NPs possessing small, charged, and conductive (conjugated) peripheral ligands.

Au

thiols

poly-l-lysine

Au


Input: As a potential application of these Au-NP film assemblies, an enhanced amperometric signal for H2O2 oxidation was shown for modified " needle " electrodes.

Au


Input: The overall aim of this research is to gain a greater understanding of designing electrochemical sensing strategies that incorporate Au-NPs and target specific analytes.

Au


Input: A new " immunological " role for adipocytes in obesity.


Input: Obesity-induced insulin resistance is associated with low-grade adipose tissue inflammation, but the mechanism driving this process remains unclear.


Input: In this issue of Cell Metabolism, a study by Deng et al.


Input: (2013) demonstrates a direct immunological role of adipocytes in instigating adipose inflammation via a MHCII-dependent process.


Input: Iron and diabetes risk.

Iron


Input: Iron overload is a risk factor for diabetes.

Iron


Input: The link between iron and diabetes was first recognized in pathologic conditions-hereditary hemochromatosis and thalassemia-but high levels of dietary iron also impart diabetes risk.

iron

iron


Input: Iron plays a direct and causal role in diabetes pathogenesis mediated both by beta cell failure and insulin resistance.

Iron


Input: Iron also regulates metabolism in most tissues involved in fuel homeostasis, with the adipocyte in particular serving an iron-sensing role.

Iron

iron


Input: The underlying molecular mechanisms mediating these effects are numerous and incompletely understood but include oxidant stress and modulation of adipokines and intracellular signal transduction pathways.


Input: Identification of a SIRT1 mutation in a family with type 1 diabetes.


Input: Type 1 diabetes is caused by autoimmune-mediated beta cell destruction leading to insulin deficiency.


Input: The histone deacetylase SIRT1 plays an essential role in modulating several age-related diseases.


Input: Here we describe a family carrying a mutation in the SIRT1 gene, in which all five affected members developed an autoimmune disorder: four developed type 1 diabetes, and one developed ulcerative colitis.


Input: Initially, a 26-year-old man was diagnosed with the typical features of type 1 diabetes, including lean body mass, autoantibodies, T cell reactivity to beta cell antigens, and a rapid dependence on insulin.


Input: Direct and exome sequencing identified the presence of a T-to-C exchange in exon 1 of SIRT1, corresponding to a leucine-to-proline mutation at residue 107.

leucine

proline


Input: Expression of SIRT1-L107P in insulin-producing cells resulted in overproduction of nitric oxide, cytokines, and chemokines.

nitric oxide


Input: These observations identify a role for SIRT1 in human autoimmunity and unveil a monogenic form of type 1 diabetes.


Input: Going where traditional markers have not gone before: utility of and promise for RAD sequencing in marine invertebrate phylogeography and population genomics.


Input: Characterization of large numbers of single-nucleotide polymorphisms (SNPs) throughout a genome has the power to refine the understanding of population demographic history and to identify genomic regions under selection in natural populations.


Input: To this end, population genomic approaches that harness the power of next-generation sequencing to understand the ecology and evolution of marine invertebrates represent a boon to test long-standing questions in marine biology and conservation.


Input: We employed restriction-site-associated DNA sequencing (RAD-seq) to identify SNPs in natural populations of the sea anemone Nematostella vectensis, an emerging cnidarian model with a broad geographic range in estuarine habitats in North and South America, and portions of England.


Input: We identified hundreds of SNP-containing tags in thousands of RAD loci from 30 barcoded individuals inhabiting four locations from Nova Scotia to South Carolina.


Input: Population genomic analyses using high-confidence SNPs resulted in a highly-resolved phylogeography, a result not achieved in previous studies using traditional markers.


Input: Plots of locus-specific FST against heterozygosity suggest that a majority of polymorphic sites are neutral, with a smaller proportion suggesting evidence for balancing selection.


Input: Loci inferred to be under balancing selection were mapped to the genome, where 90% were located in gene bodies, indicating potential targets of selection.


Input: The results from analyses with and without a reference genome supported similar conclusions, further highlighting RAD-seq as a method that can be efficiently applied to species lacking existing genomic resources.


Input: We discuss the utility of RAD-seq approaches in burgeoning Nematostella research as well as in other cnidarian species, particularly corals and jellyfishes, to determine phylogeographic relationships of populations and identify regions of the genome undergoing selection.


Input: Engineered iron-oxide-based nanoparticles as enhanced t1 contrast agents for efficient tumor imaging.

iron-oxide


Input: We report the design and synthesis of small-sized zwitterion-coated gadolinium-embedded iron oxide (GdIO) nanoparticles, which exhibit a strong T1 contrast effect for tumor imaging through enhanced permeation and retention effect and the ability to clear out of the body in living subjects.

gadolinium

iron oxide

GdIO


Input: The combination of spin-canting effects and the collection of gadolinium species within small-sized GdIO nanoparticles led to a significantly enhanced T1 contrast effect.

gadolinium

GdIO


Input: For example, GdIO nanoparticles with a diameter of ~ 4. 8 nm exhibited a high r1 relaxivity of 7. 85 mM (-1). S (-1) and a low r2/r1 ratio of 5. 24.

GdIO


Input: After being coated with zwitterionic dopamine sulfonate molecules, the 4. 8 nm GdIO nanoparticles showed a steady hydrodynamic diameter (~ 5. 2 nm) in both PBS buffer and fetal bovine serum solution, indicating a low nonspecific protein absorption.

dopamine sulfonate

GdIO


Input: This study provides a valuable strategy for the design of highly sensitive iron-oxide-based T1 contrast agents with relatively long circulation half-lives (~ 50 min), efficient tumor passive targeting (SKOV3, human ovarian cancer xenograft tumor as a model), and the possibility of rapid renal clearance after tumor imaging.

iron-oxide


Input: Variations on glutamate binding in channel-gated receptors.

glutamate


Input: In this issue of Structure, Lomash and colleagues report on the crystal structure and ligand binding properties of a primitive eukaryote glutamate-gated ion channel: AvGluR1.

glutamate


Input: Degradation of MAC13243 and studies of the interaction of resulting thiourea compounds with the lipoprotein targeting chaperone LolA.

thiourea


Input: The discovery of novel small molecules that function as antibacterial agents or cellular probes of biology is hindered by our limited understanding of bacterial physiology and our ability to assign mechanism of action.


Input: We previously employed a chemical genomic strategy to identify a novel small molecule, MAC13243, as a likely inhibitor of the bacterial lipoprotein targeting chaperone, LolA.


Input: Here, we report on the degradation of MAC13243 into the active species, S-(4-chlorobenzyl) isothiourea.

S-(4-chlorobenzyl) isothiourea


Input: Analogs of this compound (e. g., A22) have previously been characterized as inhibitors of the bacterial actin-like protein, MreB.


Input: Herein, we demonstrate that the antibacterial activity of MAC13243 and the thiourea compounds are similar; these activities are suppressed or sensitized in response to increases or decreases of LolA copy number, respectively.

thiourea


Input: We provide STD NMR data which confirms a physical interaction between LolA and the thiourea degradation product of MAC13243, with a Kd of ~ 150 mu M.

thiourea


Input: Taken together, we conclude that the thiourea series of compounds share a similar cellular mechanism that includes interaction with LolA in addition to the well-characterized target MreB.

thiourea


Input: Hinokitiol inhibits platelet activation ex vivo and thrombus formation in vivo.

Hinokitiol


Input: Hinokitiol is a tropolone-related bioactive compound that has been used in hair tonics, cosmetics, and food as an antimicrobial agent.

Hinokitiol


Input: Recently, hinokitiol has attracted considerable interest because of its anticancer activities.

hinokitiol


Input: Platelet activation plays a crucial role in atherothrombotic processes.


Input: We examined the effects of hinokitiol treatment on platelet activation using human platelets.

hinokitiol


Input: In the present study, hinokitiol (1 and 2 mu M) inhibited the collagen-induced aggregation of human platelets, but did not inhibit the activation of platelets by other agonists, including thrombin, arachidonic acid, and ADP.

hinokitiol

arachidonic acid

ADP


Input: Hinokitiol inhibited the phosphorylation of phospholipase C (PLC) gamma 2, protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), and Akt in collagen-activated human platelets, and significantly reduced intracellular calcium mobilization and hydroxyl radical (OH) formation.

Hinokitiol

calcium

hydroxyl

OH


Input: Hinokitiol also reduced the PKC activation and platelet aggregation stimulated by PDBu.

Hinokitiol


Input: In addition, hinokitiol significantly prolonged thrombogenesis in mice.

hinokitiol


Input: Hinokitiol did not influence the binding of a fluorescent triflavin probe to the alpha IIb beta 3 integrin on platelet membrane, and neither ODQ nor SQ22536 significantly reversed the hinokitiol-mediated inhibition of platelet aggregation.

Hinokitiol

ODQ

hinokitiol


Input: In conclusion, hinokitiol may inhibit platelet activation by inhibiting the PLC gamma 2-PKC cascade and hydroxyl radical formation, followed by suppressing the activation of MAPKs and Akt.

hinokitiol

hydroxyl


Input: Our study suggests that hinokitiol may represent a potential therapeutic agent for the prevention or treatment of thromboembolic disorders.

hinokitiol


Input: The insecticidal neurotoxin Aps III is an atypical knottin peptide that potently blocks insect voltage-gated sodium channels.


Input: One of the most potent insecticidal venom peptides described to date is Aps III from the venom of the trapdoor spider Apomastus schlingeri.


Input: Aps III is highly neurotoxic to lepidopteran crop pests, making it a promising candidate for bioinsecticide development.


Input: However, its disulfide-connectivity, three-dimensional structure, and mode of action have not been determined.

disulfide


Input: Here we show that recombinant Aps III (rAps III) is an atypical knottin peptide; three of the disulfide bridges form a classical inhibitor cystine knot motif while the fourth disulfide acts as a molecular staple that restricts the flexibility of an unusually large beta hairpin loop that often houses the pharmacophore in this class of toxins.

disulfide

cystine

disulfide


Input: We demonstrate that the irreversible paralysis induced in insects by rAps III results from a potent block of insect voltage-gated sodium channels.

sodium


Input: Channel block by rAps III is voltage-independent insofar as it occurs without significant alteration in the voltage-dependence of channel activation or steady-state inactivation.


Input: Thus, rAps III appears to be a pore blocker that plugs the outer vestibule of insect voltage-gated sodium channels.

sodium


Input: This mechanism of action contrasts strikingly with virtually all other sodium channel modulators isolated from spider venoms that act as gating modifiers by interacting with one or more of the four voltage-sensing domains of the channel.

sodium


Input: Absence of correlation between oxysterol accumulation in lipid raft microdomains, calcium increase, and apoptosis induction on 158N murine oligodendrocytes.

oxysterol

calcium


Input: There is some evidence that oxidized derivatives of cholesterol, 7-ketocholesterol (7KC) and 7 beta-hydroxycholesterol (7 beta OHC), are increased in the plasma of patients with neurodegenerative diseases associated with demyelinization of the central nervous system (CNS).

cholesterol

7 beta-hydroxycholesterol

7 beta OHC


Input: It was therefore of interest to investigate the effects of these oxysterols on oligodendrocytes, the myelin-forming cells in the CNS.

oxysterols


Input: To this end, 158N murine oligodendrocytes were treated with 7KC or 7 beta OHC inducing an apoptotic mode of cell death characterized by condensation/fragmentation of the nuclei, dephosphorylation of Akt and GSK3, mitochondrial depolarization involving Mcl-1, and caspase-3 activation.

7 beta OHC


Input: In contrast, under treatment with 27-hydroxycholesterol (27OHC), no cell death was observed.


Input: When the cells were stained with Fura-2, no significant Ca (2 +) rise was found with the different oxysterols, whereas strong signals were detected with ionomycin used as positive control.

Ca (2 +)

oxysterols

ionomycin


Input: At concentrations which induced apoptosis, 7KC but not 7 beta OHC accumulated in lipid rafts.

7 beta OHC


Input: Although not cytotoxic, 27OHC was mainly detected in lipid rafts.


Input: It is noteworthy that alpha-tocopherol (but not ellagic acid and resveratrol) was able to counteract 7KC-and 7 beta OHC-induced apoptosis and to decrease the accumulation of 7KC and 27OHC in lipid rafts.

alpha-tocopherol

ellagic acid

resveratrol

7 beta OHC


Input: Thus, in 158N cells, the ability of oxysterols to trigger a mode of cell death by apoptosis involving GSK-3 and caspase-3 activation is independent of the increase in the Ca (2 +) level and of their accumulation in lipid raft microdomains.

oxysterols

Ca (2 +)


Input: Intact inhibitory control processes in abstinent drug abusers (I): A functional neuroimaging study in former cocaine addicts.

cocaine


Input: Neuroimaging studies in current cocaine dependent (CD) individuals consistently reveal cortical hypoactivity across regions of the response inhibition circuit (RIC).

cocaine


Input: Dysregulation of this critical executive network is hypothesized to account for the lack of inhibitory control that is a hallmark of the addictive phenotype, and chronic abuse is believed to compound the issue.


Input: A crucial question is whether deficits in this circuit persist after drug cessation, and whether recovery of this system will be seen after extended periods of abstinence, a question with implications for treatment course and outcome.


Input: Utilizing functional magnetic resonance imaging (fMRI), we examined activation in nodes of the RIC in abstinent CD individuals (n = 27) and non-using controls (n = 45) while they performed a motor response inhibition task.


Input: In contrast to current users, these abstinent individuals, despite extended histories of chronic cocaine-abuse (average duration of use = 8. 2 years), performed the task just as efficiently as non-users.

cocaine


Input: In line with these behavioral findings, no evidence for between-group differences in activation of the RIC was found and instead, robust activations were apparent in both groups within the well-characterized nodes of the RIC.


Input: Similarly, our complementary Electroencephalography (EEG) investigation also showed an absence of behavioral and electrophysiological deficits in abstinent drug abusers.


Input: These results are consistent with an amelioration of neurobiological deficits in inhibitory circuitry following drug cessation, and could help explain how long-term abstinence is maintained.


Input: Finally, regression analyses revealed a significant association between level of activation in the right insula with inhibition success and increased abstinence duration in the CD cohort suggesting that this region may be integral to successful recovery from cocaine addiction.

cocaine


Input: New plant sources of the anti-cancer alkaloid, camptothecine from the Icacinaceae taxa, India.

camptothecine


Input: In this study, the production of camptothecine and its derivatives, in thirteen species of the family Icacinaceae, namely, Apodytes dimidiata, Codiocarpus andamanicus, Gomphandra comosa, Gomphandra coriacea, Gomphandra polymorpha, Gomphandra tetrandra, Iodes cirrhosa, Iodes hookeriana, Miquelia dentata, Miquelia kleinii, Natsiatum herpeticum, Pyrenacantha volubilis and Sarcostigma kleinii is reported.

camptothecine


Input: Seeds of M. dentata were found to produce the highest content of camptothecine (1. 0-1. 4% by dry weight of seeds).

camptothecine


Input: Full scan LC-MS and ESI-MS/MS analysis of M. dentata revealed, besides camptothecine, a number of other derivatives, namely, 10-hydroxycamptothecine, 9-methoxycamptothecine, 20-deoxycamptothecine.

camptothecine


Input: Crude extract preparations of the seeds of M. dentata were effective against a breast cancer cell line (IC50 = 3. 82 mu g/ml for MDA MB273 cell lines) and two ovarian cancer cell lines (IC50 = 2. 8 mu g/ml for NCI/ADR-RES and 4. 5 mu g/ml for SKOV).


Input: These results are the first reports of camptothecine and its derivatives in these species and offer rich alternative plant sources for the anticancer compound, camptothecine.

camptothecine

camptothecine


Input: Continuous IV Crotalidae Polyvalent Immune Fab (Ovine) (FabAV) for selected North American Rattlesnake bite patients.


Input: BACKGROUND: In patients bitten by North American rattlesnakes and treated with Crotalidae Polyvalent Immune Fab (Ovine) (FabAV), late hematologic abnormalities-persistent, recurrent, or late, new onset of hypofibrinogenemia, prolonged PT/INR, prolonged PTT, and/or thrombocytopenia beyond 48 h post-envenomation-are common, difficult to manage, and may result in morbidity and mortality are common, difficult to manage, and may result in morbidity and mortality.


Input: The optimal management of late hematologic abnormalities, particularly the use of further treatment with antivenom, has not been well defined.


Input: The current FabAV treatment regimen is to give antivenom as a bolus dose over a one-hour period.


Input: We describe our experience using a continuous intravenous infusion of FabAV for late hematologic effects and/or associated bleeding complications in rattlesnake envenomation.


Input: METHODS: This is a retrospective, observational case series of patients envenomated by North American rattlesnakes at three medical centers managed with a continuous intravenous infusion of FabAV for late hematologic abnormalities and/or associated bleeding complications.


Input: Indications, dilution and infusion protocols, and duration of therapy were individualized.


Input: RESULTS: Five cases were identified between July 2010 and September 2011.


Input: All patients had profound late hematologic abnormalities and/or were associated with bleeding complications.


Input: Several patients had received repeat bolus infusions of FabAV, with or without human blood products, with either inadequate or only transient beneficial response.


Input: All patients were then managed with a continuous intravenous infusion of FabAV and all appeared to respond to the continuous intravenous infusion of FabAV, titrated to effect, with cessation of progression and, in most cases, improvement in hematologic abnormalities.


Input: Rates of infusion varied from 2 to 4 vials per 24 h (mean = 3. 1 +/- 0. 4 vials/day).


Input: The termination of FabAV infusion was between day 6 and day 14 from the time of envenomation (mean = 10 +/- 3 days), after which hematologic values were normalized or were normalizing in all patients and continued to do so.


Input: DISCUSSION: The use of FabAV as a continuous intravenous infusion, particularly after the acute phase of envenomation has passed, provides a continuous source of circulating antibodies to neutralize venom components reaching circulation from tissue stores and allows natural replenishment of hematologic factors such as platelets and/or fibrinogen.


Input: This method is an efficient use of FabAV, avoiding the wasteful excess of a bolus dose, may be more effective, eliminating the potential for destruction of hematologic factors when protective antivenom levels are lost between bolus FabAV doses, and appears to be safe.


Input: Further assessments of the stability and sterility of the product during infusion are needed.


Input: The need to continue hospitalization is the major drawback, but continued observation and inpatient care may be needed for other indications (e. g. bleeding) in this subset of patients.


Input: CONCLUSIONS: A continuous intravenous infusion of FabAV between 2 and 4 vials per day, titrated to effect, and continued for 6-14 days post-envenomation appeared to be associated with reversal of late hematologic effects of rattlesnake envenomation and, when combined with indicated human blood products, control of significant bleeding.


Input: Continuous intravenous infusion of FabAV may be safer, more efficacious, and more cost-effective than observation without FabAV treatment or as-needed bolus dosing in selected patients with late hematologic abnormalities.


Input: In vitro interceptive and reparative effects of myo-inositol against copper-induced oxidative damage and antioxidant system disturbance in primary cultured fish enterocytes.

myo-inositol

copper


Input: Copper (Cu) is essential for normal cellular processes in most eukaryotic organisms but is toxic in excess.

Copper

Cu


Input: Our previous study reported that a nutrient antioxidant, myo-inositol (MI), can protect fish from Cu-induced oxidative injury; however, the mechanisms involved are not fully understood.

myo-inositol

Cu


Input: Therefore, the present study aimed to analyze potential pathways.


Input: First, to investigate the hypothesis that MI protects enterocytes against Cu toxicity via the intercept pathway, enterocytes were treated with different concentrations of MI (0-75mg/L medium) in the presence of 6mg/L of Cu for 24h (Experiment 1).

Cu

Cu


Input: Next, we investigated the potential reparative role of MI after a Cu challenge (Experiment 2).

Cu


Input: The results of Experiment 1 indicated that cells exposed to Cu alone for 24h exhibited increases in lactate dehydrogenase release (LDH), malondialdehyde (MDA) formation and protein oxidation (P < 0. 05).

Cu

lactate

malondialdehyde

MDA


Input: Notably, a dose-dependent inhibitory effect on LDH release was observed with all doses of MI.


Input: Moreover, co-treatment with MI completely inhibited Cu-induced protein carbonyl (PC) formation.

Cu

carbonyl


Input: However, Cu-induced lipid peroxidation was not altered by MI co-treatment.

Cu


Input: Additionally, Cu exposure suppressed total-superoxide dismutase (T-SOD), CuZnSOD and catalase (CAT) activities, and these changes were completely blocked by co-treatment with sufficient MI concentrations.

Cu

superoxide


Input: In contrast, cells exposed to Cu exhibited adaptive increases in reduced glutathione (GSH) content and the activities of anti-hydroxyl radical (AHR), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR).

Cu

reduced glutathione

GSH

glutathione

glutathione

S

glutathione


Input: Interestingly, the Cu-stimulated increases in these antioxidants were blocked by co-treatment with sufficient MI concentrations.

Cu


Input: The results of Experiment 2 indicated that cell injury (LDH release), lipid peroxidation (MDA formation) and protein oxidation induced by Cu were reversed by subsequent MI treatment.

MDA

Cu


Input: Meanwhile, Cu-induced decreases in alkaline phosphatase (AKP), anti-superoxide anion (ASA), T-SOD and CuZnSOD activities were completely restored by subsequent MI treatment, while the reduced CAT activity was partially restored.

Cu

superoxide


Input: However, MI rescues partially restored the adaptive increase in GPx activity induced by Cu, whereas the adaptive increase in reduced GSH content was completely reversed by 75mg/L of MI.

Cu

reduced GSH


Input: However, subsequent MI treatments did not alter the induction of GST activity by Cu.

Cu


Input: In conclusion, we demonstrated for the first time that MI not only protected enterocytes from Cu-induced oxidative damage but also increased the repair activity in primary enterocytes after challenge with Cu.

Cu

Cu


Input: Moreover, MI-mediated increases in antioxidant enzyme activities contributed to lipid and protein oxidant repair.


Input: Effects of metal burden and food avoidance on the transfer of metals from naturally contaminated prey to a marine predator Nassarius siquijorensis.


Input: Nassarid snails are important opportunistic scavengers widely found in marine intertidal shores and trophic transfer is a predominant source of metal accumulation in these species, thus there is a significant need to understand the controls of metal trophic transfer.


Input: In the present study, we took advantage of a severely contaminated estuary and collected two prey organisms (oysters Crassostrea angulata and barnacles Fistulobalanus albicostatus) with different contamination histories.


Input: These naturally contaminated prey were fed to a marine neogastropod Nassarius siquijorensis for a period of up to 7 weeks.


Input: We then investigated the influences of prey type, metal burden, and subcellular distribution in the prey on the metal accumulation, trophic transfer, and potential toxicity on N. siquijorensis.


Input: We demonstrated an obvious negative relationship between the trophic transfer and the metal concentration in prey or the metal dosage.


Input: N. siquijorensis exhibited food avoidance behavior to the Cu contaminated food, which effectively reduced the metal ingestion and resulted in a decrease of trophic transfer, as well as a potential toxic effect from dietary exposure.

Cu


Input: On the other hand, our results also implied the metal-specific impact of subcellular metal distribution in prey on the trophic transfer to N. siquijorensis.


Input: Our study suggested that metal burden and feeding avoidance should be considered in studying the trophic transfer of metals in marine benthic food chain.


Input: Effects of salinity stress on Bufo balearicus and Bufo bufo tadpoles: Tolerance, morphological gill alterations and Na (+)/K (+)-ATPase localization.

Na (+)

K (+)


Input: Freshwater habitats are globally threatened by human-induced secondary salinization.


Input: Amphibians are generally poorly adapted to survive in saline environments.


Input: We experimentally investigated the effects of chronic exposure to various salinities (5%, 10%, 15%, 20%, 25%, 30% and 35% seawater, SW) on survival, larval growth and metamorphosis of tadpoles from two amphibian populations belonging to two species: the green toad Bufo balearicus and the common toad Bufo bufo.


Input: In addition, gill morphology of tadpoles of both species after acute exposure to hypertonic conditions (20%, 25%, and 30% SW) was examined by light and electron microscopy.


Input: Tadpoles experienced 100% mortality above 20% SW in B. balearicus while above 15% SW in B. bufo.


Input: We detected also sublethal effects of salinity stress on growth and metamorphosis.


Input: B. bufo cannot withstand chronic exposure to salinity above 5% SW, tadpoles grew slower and were significantly smaller than those in control at metamorphosis.


Input: B. balearicus tolerated salinity up to 20% SW without apparent effects during larval development, but starting from 15% SW tadpoles metamorphosed later and at a smaller size compared with control.


Input: We also revealed a negative relation between increasing salt concentration and gill integrity.


Input: The main modifications were increased mucous secretion, detachment of external layer, alteration of epithelial surface, degeneration phenomena, appearance of residual bodies, and macrophage immigration.


Input: These morphological alterations of gill epithelium can interfere with respiratory function and both osmotic and acid-base regulation.


Input: Significant variations in branchial Na (+)/K (+)-ATPase activity were also observed between two species; moreover an increase in enzyme activity was evident in response to SW exposure.

Na (+)

K (+)


Input: Epithelial responses to increasing salt concentration were different in the populations belonging to two species: the intensity of histological and ultrastructural pathology in B. bufo was greater and we noticed the appearance in exposed samples of the tubular vesicle cells (TVCs).


Input: Taken together, our results demonstrated that increased salinity of freshwater may give cause for concern and must be considered a stressor for amphibians as well as other pollutants.


Input: Evaluation of some selected blood parameters and histopathology of liver and kidney of rats fed protein-substituted mucuna flour and derived protein rich product.


Input: This comparative study reports the nutritional and toxicological characteristics of Mucuna pruriens flour and a protein-rich product developed from it.


Input: The protein-rich mucuna product (PRMP) was obtained by the three steps procedure: protein solubilization, heat-coagulation and sieving.


Input: Three weeks rats (n = 6 per group) were fed for 28days on standard protein-substituted rat feed with mucuna flour or PRMP.


Input: The experimental design was a factorial design with three mucuna accessions (Velvet, Black and White) and two treatments (flour and PRMP).


Input: The protein content ranged 27. 2-31. 5g/100g for flour and 58. 8-61. 1% for PRMP.


Input: Processing flour into PRMP led to a significant (p < 0. 05) reduction of tannins (50%), total polyphenols (50%) and trypsin inhibitors (94%).

tannins

polyphenols


Input: The rats fed PMRP diets witnessed weight gain similar to casein, while those fed mucuna flour lost weight.


Input: The levels of total cholesterol, HDL-cholesterol and LDL-cholesterol observed in animals groups fed mucuna flour and PRMP were significantly lower (p < 0. 05) than the control group.

cholesterol

cholesterol

cholesterol


Input: In addition lymphocytes, granulocytes, red blood cells, hemoglobin and hematocrit of rats fed mucuna flour were significantly (p < 0. 05) lower than values in other rats groups.


Input: Kidneys glomerular sclerosis and high creatinine levels were observed in group fed mucuna flour.

creatinine


Input: PRMP then represents a good alternative of using mucuna proteins for human nutrition.


Input: Structure-property relationship for cellular accumulation of macrolones in human polymorphonuclear leukocytes (PMNs).

macrolones


Input: Macrolones are a new class of antimicrobial compounds consisting of a macrolide scaffold linked to a 4-quinolone-3-carboxylic acid moiety via C (4'') position of a macrolide.

Macrolones

macrolide

4-quinolone-3-carboxylic acid

C

macrolide


Input: As macrolides are known to possess favorable pharmacokinetic properties by accumulating in inflammatory cells, in this study we determined the intensity of accumulation in human polymorphonuclear leukocytes (PMNs) of 57 compounds of the macrolone class and analyzed the relationship between the molecular structure and this cellular pharmacokinetic property.

macrolides

macrolone


Input: Accumulation of macrolones ranged from 0 to 5. 5-fold higher than the standard macrolide azithromycin.

macrolones

macrolide azithromycin


Input: Distinct structural features in all three considered molecule parts: the macrolide scaffold, quinolone moiety and the linker, affect cellular accumulation.

macrolide

quinolone


Input: Interestingly, while the parent macrolide, azithromycin, accumulates approximately 3-fold more than clarithromycin, among macrolones all clarithromycin derivatives accumulated in PMNs significantly more than their azithromycin counterparts.

macrolide

azithromycin

clarithromycin

macrolones

clarithromycin

azithromycin


Input: Modeling cellular accumulation of macrolones with simple molecular descriptors, as well as with the measured octanol-water distribution coefficient, revealed that the number of hydrogen bond donors and secondary amide groups negatively contribute to macrolone accumulation, while lipophilicity makes a positive contribution.

macrolones

octanol

hydrogen

secondary amide

macrolone


Input: Assessing vehicle effects on skin absorption using artificial membrane assays.


Input: A vast number of variations in drug/vehicle combinations may come into contact with skin.


Input: Evaluating the effect of potential drug, vehicle and skin interactions for all possible combinations is a daunting task.


Input: A practical solution is a rapid screening technique amenable to high throughput approaches (e. g. 96-well plates).


Input: In this study, three artificial membranes (isopropyl myristate (IPM), certramides and Strat-M (TM)) were evaluated for their ability to predict the skin permeability of caffeine, cortisone, diclofenac sodium, mannitol, salicylic acid and testosterone applied in propylene glycol, water and ethanol as unsaturated and saturated concentrations.

isopropyl myristate

IPM

certramides

caffeine

cortisone

diclofenac sodium

mannitol

salicylic acid

testosterone

propylene glycol

ethanol


Input: Resultant absorption data was compared to porcine skin diffusion cell data.


Input: The correlations (r (2)) between membrane and diffusion cell data from saturated and unsaturated concentrations were 0. 38, 0. 47 and 0. 56 for the Strat-M (TM), certramide and IPM membranes, respectively.

certramide

IPM


Input: This relationship improved when only saturated concentrations were evaluated (r (2) = 0. 60, 0. 63 and 0. 66 for the Strat-M (TM), certramide and IPM membranes, respectively).

certramide

IPM


Input: A correlation between membrane retention and the amount remaining in skin had r (2) values of 0. 73 (Strat-M (TM)), 0. 67 (certramides), and 0. 67 (IPM).

certramides

IPM


Input: Quantitative structure-permeability relationship models for each membrane identified different physicochemical factors influencing the absorption process.


Input: Although further investigations exploring complex topical formulations are required, these results suggest potential use as an initial screening approach to assist in narrowing the selection of formulations to be evaluated with a more biologically intact model, thereby assisting in the development of new topical formulations.


Input: Multiple dosing of simvastatin inhibits airway mucus production of epithelial cells: Implications in the treatment of chronic obstructive airway pathologies.

simvastatin


Input: BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by mucus hyper-production.


Input: This pathology, together with other inflammatory contributions, leads to airway obstruction and breathing complications.


Input: Newer therapeutic approaches are of increased interest, including the use of HMG-CoA reductase inhibitors.

HMG-CoA


Input: Retrospective studies have shown that statins are effective in reducing patient mortality and blood cytokines levels.

statins


Input: These findings suggest statins may also provide a new therapeutic approach in COPD treatment.

statins


Input: PURPOSE: The aim of the present work was to study the transport of SV across Calu-3 epithelial cells and to investigate its pharmacological action with respect to reduction in mucus production.


Input: METHODS: Calu-3 cells were grown under liquid covered culture (LCC) conditions for transport studies in order to demonstrate the ability of SV to transport across the monolayer.


Input: For mucus detection, cells were grown under air interface culture (AIC) conditions.


Input: Samples collected for microscope analysis were stained with alcian blue; images of the stained cell surface were acquired and the mucus was quantified as the RGBB ratio.

alcian blue


Input: RESULTS: SV was transported through the cell monolayer and' retained' inside the Calu-3 cells.


Input: Colour analysis of stained Calu-3 monolayers microscope-images showed that chronic administration of SV for 14days caused a significant inhibition in mucus production.


Input: CONCLUSION: These findings suggest that local delivery of SV directly to the lungs may provide a promising treatment and potential disease management approach of COPD, with significant effects on mucus reduction.


Input: Novel 5-(benzyloxy) pyridin-2 (1H)-one derivatives as potent c-Met inhibitors.

5-(benzyloxy) pyridin-2 (1H)-one


Input: A series of novel 5-(benzyloxy) pyridin-2 (1H)-ones were designed, synthesized and biologically evaluated for c-Met inhibition.

5-(benzyloxy) pyridin-2 (1H)-ones


Input: Various amides and benzoimidazoles at C-3 position were investigated.

amides

benzoimidazoles


Input: A potent compound 12b with a c-Met IC50 of 12nM was identified.


Input: This compound exhibited potent inhibition of EBC-1 cell associated with c-Met constitutive activation and showed high selectivity for c-Met than other tested 11 kinases.


Input: The binding model 12b with c-Met was disclosed by docking analysis.