Input: Alteration of iron metabolism may affect nasopharyngeal colonization as adherence of all mutants to respiratory tract epithelial cells was attenuated.

iron


Input: In conclusion, we elucidated the genetic requirements for M. catarrhalis growth during iron starvation and characterized the roles of the identified genes in bacterial growth and host interaction.

iron


Input: Synaptic plasticity in the hippocampus shows resistance to acute ethanol exposure in transgenic mice with astrocyte-targeted enhanced CCL2 expression.

ethanol


Input: It has been shown that ethanol exposure can activate astrocytes and microglia resulting in the production of neuroimmune factors, including the chemokine CCL2.


Input: The role of these neuroimmune factors in the effects of ethanol on the central nervous system has yet to be elucidated.

ethanol


Input: To address this question, we investigated the effects of ethanol on synaptic transmission and plasticity in the hippocampus from mice that express elevated levels of CCL2 in the brain and their non-transgenic littermate controls.

ethanol


Input: The brains of the transgenic mice simulate one aspect of the alcoholic brain, chronically increased levels of CCL2.


Input: We used extracellular field potential recordings in acutely isolated hippocampal slices to identify neuroadaptive changes produced by elevated levels of CCL2 and how these neuroadaptive changes affect the actions of acute ethanol.

ethanol


Input: Results showed that synaptic transmission and the effects of ethanol on synaptic transmission were similar in the CCL2-transgenic and non-transgenic hippocampus.

ethanol


Input: However, long-term potentiation (LTP), a cellular mechanism thought to underlie learning and memory, in the CCL2-transgenic hippocampus was resistant to the ethanol-induced depression of LTP observed in the non-transgenic hippocampus.

ethanol


Input: Consistent with these results, ethanol pretreatment significantly impaired cued and contextual fear conditioning in non-transgenic mice, but had no effect in CCL2-transgenic mice.

ethanol


Input: These data show that chronically elevated levels of CCL2 in the hippocampus produce neuroadaptive changes that block the depressing effects of ethanol on hippocampal synaptic plasticity and support the hypothesis that CCL2 may provide a neuroprotective effect against the devastating actions of ethanol on hippocampal function.

ethanol

ethanol


Input: Supra-normal stimulation of dopamine D1 receptors in the prelimbic cortex blocks behavioral expression of both aversive and rewarding associative memories through a cyclic-AMP-dependent signaling pathway.

dopamine

cyclic-AMP


Input: Dopamine (DA) receptor transmission through either D (1) or D (2)-like subtypes is involved critically in the processing of emotional information within the medial prefrontal cortex (mPFC).

Dopamine


Input: However the functional role of specific DA D (1)-like receptor transmission in the expression of emotionally salient associative memories (either aversive or rewarding) is not currently understood.


Input: Here we demonstrate that specific activation of DA D (1) receptors in the prelimbic (PLC) division of the mPFC causes a transient block in the behavioral expression of both aversive and rewarding associative memories.


Input: We report that intra-PLC microinfusions of a selective D (1) receptor agonist block the spontaneous expression of an associative olfactory fear memory, without altering the stability of the original memory trace.


Input: Furthermore, using an unbiased place conditioning procedure (CPP), intra-PLC D (1) receptor activation blocks the spontaneous expression of an associative morphine (5 mg/kg; i. p.) reward memory, while leaving morphine-primed memory expression intact.

morphine

morphine


Input: Interestingly, both intra-PLC D (1)-receptor mediated block of either fear-related or reward-related associative memories were dependent upon downstream cyclic-AMP (cAMP) signaling as both effects were rescued by co-administration of a cAMP signaling inhibitor.

cyclic-AMP

cAMP

cAMP


Input: The blockade of both rewarding and aversive associative memories is mediated through a D (1)-specific signaling pathway, as neither forms of spontaneous memory expression were blocked by intra-PLC microinfusions of a D (2)-like receptor agonist.


Input: Our results demonstrate that the spontaneous expression of either rewarding or aversive emotionally salient memories shares a common, D (1)-receptor mediated substrate within the mPFC.


Input: Glucose attenuates impairments in memory and CREB activation produced by an alpha 4 beta 2 but not an alpha 7 nicotinic receptor antagonist.

Glucose


Input: Glucose improves memory for a variety of tasks when administered to rats and mice near the time of training.

Glucose


Input: Prior work indicates glucose may enhance memory by increasing the synthesis and release of the neurotransmitter acetylcholine in the brain.

glucose

acetylcholine


Input: To investigate if specific acetylcholine receptor subtypes may mediate some of the memory-enhancing actions of glucose, we examined the effects of subtype-specific nicotinic acetylcholine receptor antagonists on memory in Fischer-344 rats and also examined the ability of glucose to reverse drug-induced impairments.

acetylcholine

glucose

acetylcholine

glucose


Input: Pre-training peripheral injections of methyllycaconitine (MLA) or dihydro-beta-erythroidine (DH beta E), which are specific alpha 7 and alpha 4 beta 2 nicotinic receptor antagonists, respectively, dose-dependently impaired retention latencies in an inhibitory avoidance task when tested 7-days but not 1 h after training.

methyllycaconitine

MLA

dihydro-beta-erythroidine

DH beta E


Input: Immediate post-training glucose injections attenuated the impairments, but were more effective in attenuating the DH beta E-induced impairments.

glucose

DH beta E


Input: Likewise, peripheral or direct intrahippocampal injections of MLA or DH beta E dose-dependently impaired spatial working memory scores on a spontaneous alternation task.

MLA

DH beta E


Input: Concurrent administration of glucose reversed DH beta E-but not MLA-induced impairments.

glucose

DH beta E

MLA


Input: CREB phosphorylation downstream of cholinergic signaling was assessed 30 min after spontaneous alternation testing and intrahippocampal drug infusions.


Input: Both MLA and DH beta E impaired hippocampal CREB phosphorylation; glucose reversed DH beta E-but not MLA-induced deficits.

MLA

DH beta E

glucose

DH beta E

MLA


Input: The effectiveness of glucose in reversing DH beta E-but not MLA-induced impairments in behavioral performance and CREB phosphorylation suggests that activation of alpha 7 receptors may play an important role in memory enhancement by glucose.

glucose

DH beta E

MLA

glucose


Input: Enantioselective synthesis of derivatives and structure-activity relationship study in the development of NA255 as a novel host-targeting anti-HCV agent.


Input: Hepatitis C virus (HCV) infection represents a serious health-care problem.


Input: Previously we reported the identification of NA255 from our natural products library using a HCV sub-genomic replicon cell culture system.


Input: Herein, we report how the absolute stereochemistry of NA255 was determined and an enantioselective synthetic method for NA255 derivatives was developed.


Input: The structure-activity relationship of the NA255 derivatives and rat pharmacokinetic profiles of the representative compounds are disclosed.


Input: Catalpol inhibits LPS plus IFN-gamma-induced inflammatory response in astrocytes primary cultures.

Catalpol


Input: A large body of evidence suggests that the inflammatory reaction plays an important role in the pathogenesis of neurodegenerative diseases.


Input: Our previous studies described the neuroprotective effects of catalpol in lipopolysaccharide (LPS)-induced inflammatory models, in which catalpol was shown to prevent mesencephalic neuron death and ameliorate cognitive ability animals.

catalpol

catalpol


Input: To further investigate the protective effect and underlying mechanism of catalpol, astrocytes were pretreated with low (0. 1mM) and high dose (0. 5mM) catalpol for 1h prior to LPS plus interferon-gamma stimulation.

catalpol

catalpol


Input: Biochemical analyses showed that NO and ROS production and iNOS activity were significantly reduced by catalpol.

NO

catalpol


Input: Data at transcriptional level also demonstrated that catalpol potently attenuated gene expressions involved in inflammation, such as iNOS, COX-2 and TLR4.

catalpol


Input: In addition, our exploration further revealed that the suppressive action of catalpol on inflammation was mediated via inhibiting nuclear factor-kappa B (NF-kappa B) activation.

catalpol


Input: Collectively, these results suggest that catalpol can exert inhibitory effects on the inflammatory reaction in astrocytes and that inactivation of NF-kappa B could be the major determinant for its anti-inflammatory mechanism.

catalpol


Input: Therefore, catalpol may potentially be a highly effective therapeutic agent in treating neurodegenerative diseases associated with inflammation.

catalpol


Input: Korean red ginseng ameliorates acute 3-nitropropionic acid-induced cochlear damage in mice.

3-nitropropionic acid


Input: 3-Nitropropionic acid (3-NP), a mitochondrial toxin, has been reported to induce an acute cochlear damage.

3-Nitropropionic acid


Input: Korean red ginseng (KRG) is known to have protective effects from some types of hearing loss.


Input: This study aimed to observe the protective effect of KRG in an ototoxic animal model using 3-NP intratympanic injection.


Input: BALB/c mice were classified into 5 groups (n = 15) and dose-dependent toxic effects after intratympanic injection with 3-NP (300-5000 mM) on the left ear were investigated to determine the appropriate toxicity level of 3-NP.


Input: For observation of the protective effects of KRG, 23 mice were grouped into 3-NP (500 mM, n = 12) and KRG + 3-NP groups (300 mg/kg KRG for 7 days before 500 mM 3-NP administration, n = 11).


Input: Auditory brain response (ABR) and cochlear morphological evaluations were performed before and after drug administration.


Input: The ABR thresholds in the 800-5000 mM groups exceeded the maximum recording limit at 16 and 32 kHz 1 day after 3-NP administration.


Input: The ABR threshold in the 500 mM 3-NP + KRG group was significantly lower than that in the 500 mM 3-NP group from post 1 week to 1 month.


Input: The mean type II fibrocyte counts significantly differed between the control and 3-NP groups and between the 3-NP and 3-NP + KRG groups.


Input: Spiral ganglion cell degeneration in the 3-NP group was more severe than that in the 3-NP + KRG group.


Input: This animal model exhibited a dose-dependent hearing loss with histological changes.


Input: KRG administration ameliorated the deterioration of hearing by 3-NP.


Input: Reproductive and developmental toxicity screening test of 3-cyanopyridine in rats.


Input: Crl: CD (SD) rats were given 3-cyanopyridine by gavage at 0, 5, 30 or 180 mg/kg/day.


Input: Males were dosed for 42 days beginning 14 days before mating, and females for 40-53 days beginning 14 days before mating to day 3 of lactation, including throughout the mating and gestation periods.


Input: General toxicity, mainly liver damage, was observed in males at >= 30 mg/kg/day and in females at >= 5 mg/kg/day.


Input: Sertoli cell vacuolation was observed at 180 mg/kg/day, and spermatocyte damages were observed at >= 30 mg/kg/day.


Input: Effects on estrous cycles, corpora lutea and implantations, and unsuccessfully mated females, despite additional mating, were observed at 180 mg/kg/day.


Input: Delayed initiation of delivery, dystocia, and deaths or moribundities of pregnant females were observed at 180 mg/kg/day, and only two pregnant rats delivered live pups at that dose.


Input: The NOAEL for reproductive/developmental toxicity was concluded to be 30 mg/kg/day.


Input: Three-month subchronic intramuscular toxicity study of rotigotine-loaded microspheres in Cynomolgus monkeys.

rotigotine


Input: Continuous dopaminergic stimulation (CDS) is an important drug development strategy in the treatment of Parkinson' s disease (PD).


Input: Rotigotine is a non-ergoline D (3)/D (2)/D (1) dopamine receptor agonist for treating PD.

Rotigotine

ergoline

dopamine


Input: As a new treatment option for CDS, rotigotine-loaded microspheres (RoMS), long-acting sustained-release microspheres with poly (lactide-co-glycolide) as drug carrier, are now being evaluated in clinical trial.

rotigotine

poly (lactide-co-glycolide)


Input: In the present study, the subchronic toxicity in Cynomolgus monkeys has been characterized via intramuscular administration with RoMS at 0, 10, 40 and 160 mg/kg, weekly for 3 months with a 1-month recovery period.


Input: The NOAEL was 10 mg/kg/week.


Input: One male at 160 mg/kg died from an extensive pulmonary embolism.


Input: The major toxicological effects were associated with dopamine agonist-related pharmacodynamic properties of rotigotine (e. g., hyperactivity and stereotype, decreased serum prolactin level) and foreign body removal reaction induced by poly (lactide-co-glycolide) and carboxymethycellulose sodium (e. g., increased mononuclear cells and neutrophils, thymus atrophy and vacuolar degeneration of adrenal cortex, foreign body granuloma with foam cells accumulation at injection sites and foam cells accumulation in spleen and multiple lymph sinuses).

dopamine

rotigotine

poly (lactide-co-glycolide)

sodium


Input: At the end of recovery period, above findings recovered to a normal level or to a certain degree except vacuolar degeneration of adrenal gland.


Input: RoMS has exhibited high safety on monkeys.


Input: In vitro combined cytotoxic effects of pesticide cocktails simultaneously found in the French diet.


Input: Although human populations may be constantly exposed to complex pesticide mixtures through their diet, the human health risk of pesticide exposure is currently assessed on the basis of toxicity data on individual compounds.


Input: To investigate the combined toxic effects of pesticide cocktails previously identified in the French diet, we first studied the cytotoxicity induced by seven cocktails composed of two to six pesticides on human hepatic (HepG2) and colon (Caco-2) cell lines using the MTT and neutral red uptake assays.

MTT

neutral red


Input: Secondly, we challenged to assess the combined effects of the two most cytotoxic cocktails by comparing the measured effects of the mixtures with the predictions based on additive effects on two concepts-independent action (IA) and concentration addition (CA).


Input: For the cocktail composed of dichlorodiphenyltrichloroethane (DDT) and dieldrin, the cytotoxicity of the equimolar cocktail proved greater than the additive effect estimated by the two concepts.

dichlorodiphenyltrichloroethane

DDT

dieldrin


Input: Furthermore, apoptosis induction was higher in equimolar cocktail than predicted by summing the effects of DDT and dieldrin.

DDT

dieldrin


Input: Thus, some supra-additive toxicity was found in the DDT-dieldrin cocktail.

DDT

dieldrin


Input: Nevertheless, if IA and CA models could reveal combined effects of pesticide cocktails, an accurate evaluation remains challenging.


Input: EphrinB2/EphB4 inhibition in the osteoblast lineage modifies the anabolic response to parathyroid hormone.


Input: Previous reports indicate that ephrinB2 expression by osteoblasts is stimulated by parathyroid hormone (PTH) and its related protein (PTHrP) and that ephrinB2/EphB4 signaling between osteoblasts and osteoclasts stimulates osteoblast differentiation while inhibiting osteoclast differentiation.


Input: To determine the role of the ephrinB2/EphB4 interaction in the skeleton, we used a specific inhibitor, soluble EphB4 (sEphB4), in vitro and in vivo.


Input: sEphB4 treatment of cultured osteoblasts specifically inhibited EphB4 and ephrinB2 phosphorylation and reduced mRNA levels of late markers of osteoblast/osteocyte differentiation (osteocalcin, dentin matrix protein-1 [DMP-1], sclerostin, matrix-extracellular phosphoglycoprotein [MEPE]), while substantially increasing RANKL.


Input: sEphB4 treatment in vivo in the presence and absence of PTH increased osteoblast formation and mRNA levels of early osteoblast markers (Runx2, alkaline phosphatase, Collagen 1 alpha 1, and PTH receptor [PTHR1]), but despite a substantial increase in osteoblast numbers, there was no significant change in bone formation rate or in late markers of osteoblast/osteocyte differentiation.


Input: Rather, in the presence of PTH, sEphB4 treatment significantly increased osteoclast formation, an effect that prevented the anabolic effect of PTH, causing instead a decrease in trabecular number.


Input: This enhancement of osteoclastogenesis by sEphB4 was reproduced in vitro but only in the presence of osteoblasts.


Input: These data indicate that ephrinB2/EphB4 signaling within the osteoblast lineage is required for late stages of osteoblast differentiation and, further, restricts the ability of osteoblasts to support osteoclast formation, at least in part by limiting RANKL production.


Input: This indicates a key role for the ephrinB2/EphB4 interaction within the osteoblast lineage in osteoblast differentiation and support of osteoclastogenesis.


Input: Bacteriophages as templates for manufacturing supramolecular structures.


Input: SS phages are genetically enginnered by replacing 2 N-terminal amino acids of the p8 coat protein of the fd phage.

N

amino acids


Input: AGE and zeta potential measurements show that SS phages carry at least 1/4 less net negative surface charge than fd phages.


Input: Morphology and thickness of phages are studied at different counterion concentrations (10 (-3), 10 (-2) and 10 (-1) M) by AFM, SEM and immunofluorescence analyses.


Input: Bundles induced by CoCl2 and CaCl2 are either metallized by chemical reduction or biomineralized for apatite-like material formation.


Input: EDX spectroscopy confirms the presence of Co, P and Ca peaks in mineralized samples.

Co

P

Ca


Input: Such bottom-up manufactured phage scaffolds might be applied in bioengineering studies.


Input: Identification, characterization, and isolation of a common progenitor for osteoclasts, macrophages, and dendritic cells from murine bone marrow and periphery.


Input: Osteoclasts are specialized bone-resorbing cells that derive from monocyte precursors.


Input: We have identified three populations of cells with high osteoclastogenic potential in murine bone marrow, which expressed the phenotype B220 (-) CD3 (-) CD11b (-/low) CD115 (+) and either CD117 (hi), CD117 (intermediate), or CD117 (low).


Input: We have evaluated these populations for their ability to also generate macrophages and dendritic cells.


Input: At a single-cell level, the population expressing higher CD117 levels was able to generate bone-resorbing osteoclasts, phagocytic macrophages, and antigen-presenting dendritic cells in vitro with efficiencies of more than 90%, indicating that there exists a common developmental pathway for these cell types.


Input: Cells with osteoclastogenic potential also exist in blood and peripheral hematopoietic organs.


Input: Their functional meaning and/or their relationship with bone marrow progenitors is not well established.


Input: Hence, we characterized murine peripheral cell populations for their ability to form osteoclasts, macrophages, and dendritic cells in vitro.


Input: The spleen and peripheral blood monocyte progenitors share phenotypic markers with bone marrow progenitors but differ in their expression of CD11b, which was low in bone marrow but high in periphery.


Input: We propose that circulating monocyte progenitors are derived from a common bone marrow osteoclasts/macrophage/dendritic cell progenitor (OcMDC), which we have now characterized at a clonal level.


Input: However, the lineage relationship between the bone marrow and peripheral monocyte progenitors has yet to be defined.


Input: (c) 2013 American Society for Bone and Mineral Research.


Input: Toxicity evaluation of two typical surfactants to Dunaliella bardawil, an environmentally tolerant alga.


Input: Sodium dodecyl benzene sulfonate (SDBS) and cetyl trimethyl ammonium chloride (CTAC) are two kinds of surfactants widely applied in various industries.

Sodium dodecyl benzene sulfonate

SDBS

cetyl trimethyl ammonium chloride

CTAC


Input: The tremendous direct discharge of these surfactants into natural waters has posed a significant threat to ecosystems.


Input: Dunaliella bardawil was employed in the present research to test the toxic effects of SDBS, CTAC, and their mixture on cell growth, cellular morphology, beta-carotene accumulation, and enzymatic activities of superoxide dismutase (SOD) and catalase (CAT).

SDBS

CTAC

beta-carotene

superoxide


Input: The results showed that SDBS at 200, 550, 900, 1, 350, 1, 800, and 2, 400 mg/L and CTAC at 0. 4, 0. 7, 1. 0, 1. 3, 2. 8, and 3. 5 mg/L inhibited algal growth and beta-carotene accumulation, both of which declined and then increased.

SDBS

CTAC

beta-carotene


Input: In particular, CTAC (median inhibitory concentration at 10 days [IC50] (10 d) = 2. 8 +/- 1. 49 mg/L) was more hazardous than SDBS (IC50 (10 d) = 2, 044 +/- 637. 3 mg/L).

CTAC

SDBS


Input: The additive index (AI) calculated from carotene content data was (-4. 10,-1. 67) < 0, indicating an antagonistic effect between SDBS and CTAC.

SDBS

CTAC


Input: Algae cultivated at level 6 of the binary system showed hormesis due to the mitigated toxicity; SDBS at 2, 400 mg/L, CTAC at 3. 5 mg/L, and combined surfactants at level 6 exerted lethal effects on D. bardawil.

SDBS


Input: Both SOD and CAT activities showed similar associations with varied concentrations of surfactants: SOD was significantly promoted by 550 to 1, 800 mg/L SDBS, 0. 7 to 1. 3 mg/L CTAC, and mixtures at levels 2 to 4; CAT was clearly promoted by 900 mg/L SDBS, 0. 4 to 1. 3 mg/L CTAC, and mixtures at levels 2 to 4.

SDBS

CTAC

SDBS

CTAC


Input: Garcinia xanthones as orally active antitumor agents.

xanthones


Input: Using a newly developed strategy whose key step is the regioselective propargylation of hydroxyxanthone substrates, 99 structurally diverse Garcinia natural-product-like xanthones based on gambogic acid were designed and synthesized and their in vitro antitumor activity was evaluated.

hydroxyxanthone

xanthones

gambogic acid


Input: A set of 40 related compounds was chosen for determination of their physicochemical properties including polar surface area, log D 7. 4, aqueous solubility, and permeability at pH 7. 4.


Input: In the light of the in vitro antitumor activity and the physicochemical properties, two compounds were advanced into in vivo efficacy experiments.


Input: The antitumor activity of compound 112, administered po, showed more potent in vivo oral antitumor activity than gambogic acid.

gambogic acid


Input: Absorption, metabolism and excretion of darexaban (YM150), a new direct factor Xa inhibitor in humans.

darexaban


Input: 1. The absorption, metabolism and excretion of darexaban (YM150), a novel oral direct factor Xa inhibitor, were investigated after a single oral administration of [(14) C] darexaban maleate at a dose of 60 mg in healthy male human subjects.

darexaban

[(14) C] darexaban maleate


Input: 2. [(14) C] Darexaban was rapidly absorbed, with both blood and plasma concentrations peaking at approximately 0. 75 h post-dose.

[(14) C] Darexaban


Input: Plasma concentrations of darexaban glucuronide (M1), the pharmacological activity of which is equipotent to darexaban in vitro, also peaked at approximately 0. 75 h.

darexaban glucuronide

darexaban


Input: 3. Similar amounts of dosed radioactivity were excreted via faeces (51. 9%) and urine (46. 4%) by 168 h post-dose, suggesting that at least approximately half of the administered dose is absorbed from the gastrointestinal tract.


Input: 4. M1 was the major drug-related component in plasma and urine, accounting for up to 95. 8% of radioactivity in plasma.


Input: The N-oxides of M1, a mixture of two diastereomers designated as M2 and M3, were also present in plasma and urine, accounting for up to 13. 2% of radioactivity in plasma.

N-oxides


Input: In faeces, darexaban was the major drug-related component, and N-demethyl darexaban (M5) was detected as a minor metabolite.

darexaban

N-demethyl darexaban


Input: 5. These findings suggested that, following oral administration of darexaban in humans, M1 is quickly formed during first-pass metabolism via UDP-glucuronosyltransferases, exerting its pharmacological activity in blood before being excreted into urine and faeces.

darexaban

UDP


Input: Fabrication of 3-dimensional cellular constructs via microstereolithography using a simple, three-component, poly (ethylene glycol) acrylate-based system.

poly (ethylene glycol) acrylate


Input: A novel method for the production of inhibitor-and solvent-free resins suitable for three-dimensional (3D) microstereolithography is reported.


Input: Using an exemplar poly (ethylene glycol)-based resin, the control of features in the X, Y, and Z planes is demonstrated such that complex structures can be manufactured.

poly (ethylene glycol)


Input: Human mesenchymal stem cells cultured on the manufactured scaffolds remained viable during the 7 day assessment period, with proliferation rates comparable to those observed on tissue culture polystyrene.

polystyrene


Input: These data suggest that this novel, yet simple, method is suitable for the production of 3D scaffolds for tissue engineering and regenerative medicine applications.


Input: 8, 8-dialkyldihydroberberines with potent antiprotozoal activity.

8, 8-dialkyldihydroberberines


Input: Semisynthetic 8, 8-dialkyldihydroberberines (8, 8-DDBs) were found to possess mid-to low-nanomolar potency against Plasmodium falciparum blood-stage parasites, Leishmania donovani intracellular amastigotes, and Trypanosoma brucei brucei bloodstream forms.

8, 8-dialkyldihydroberberines

8, 8-DDBs


Input: For example, 8, 8-diethyldihydroberberine chloride (5b) exhibited in vitro IC50 values of 77, 100, and 5. 3 nM against these three parasites, respectively.

8, 8-diethyldihydroberberine chloride


Input: In turn, two 8, 8-dialkylcanadines, obtained by reduction of the corresponding 8, 8-DDBs, were much less potent against these parasites in vitro.

8, 8-dialkylcanadines

8, 8-DDBs


Input: While the natural product berberine is a weak DNA binder, the 8, 8-DDBs displayed no affinity for DNA, as assessed by changes in the melting temperature of poly (dA. dT) DNA.

8, 8-DDBs

poly (dA. dT)


Input: Selected 8, 8-DDBs showed efficacy in mouse models of visceral leishmaniasis and African trypanosomiasis, with 8, 8-dimethyldihydroberberine chloride (5a) reducing liver parasitemia by 46% in L. donovani-infected BALB/c mice when given at an intraperitoneal dose of 10 mg/kg/day for five days.

8, 8-DDBs

8, 8-dimethyldihydroberberine chloride


Input: The 8, 8-DDBs may thus serve as leads for discovering new antimalarial, antileishmanial, and antitrypanosomal drug candidates.


Input: Stiripentol is anticonvulsant by potentiating GABAergic transmission in a model of benzodiazepine-refractory status epilepticus.

Stiripentol

benzodiazepine


Input: Benzodiazepines (BZDs) are first-line therapy for treatment of status epilepticus (SE).

Benzodiazepines

BZDs


Input: However, BZD treatment is negatively affected by seizure duration due to decreases in BZD-sensitive GABA (A) receptors during prolonged SE.

BZD

BZD


Input: Stiripentol (STP) is an anticonvulsant that is used as add-on treatment for Dravet Syndrome.

Stiripentol

STP


Input: Recent studies have shown that STP is a positive allosteric modulator of the GABA (A) receptor.

STP


Input: The subunit selectivity of STP at this receptor suggests that it would be anticonvulsant in both brief as well as prolonged SE.

STP


Input: We tested this possibility by comparing the ability of STP and diazepam (DZP), a commonly used BZD, to terminate behavioral convulsions in a rodent model of pharmacoresistant SE.

STP

diazepam

DZP

BZD


Input: We found that STP was anticonvulsant in this model and remained effective during prolonged SE, unlike DZP which exhibited a 14 fold increase in its ED (50).

STP

DZP


Input: Whole cell recording from hippocampal slices from these animals revealed that STP potentiated GABAergic IPSCs, as well as tonic GABAergic current by acting at a site on the GABA (A) receptor separate from the BDZ binding site.

STP

BDZ


Input: Potentiation of GABAergic currents by STP remained intact during prolonged SE, while potentiation by DZP was lost.

STP

DZP


Input: Both IPSC potentiation and anticonvulsant activity of STP were greater in younger animals than in adults.

STP


Input: These findings suggest that at doses that yield therapeutically relevant concentrations, STP is anticonvulsant by potentiating GABAergic inhibition and that the subunit selectivity profile of STP enables it to remain effective despite GABA (A) receptor subunit changes during prolonged SE.

STP

STP


Input: Regulation of serotonin (5-HT) function by a VGLUT1 dependent glutamate pathway.

serotonin

glutamate


Input: Unraveling the mechanisms of 5-HT neuron control might provide new insights into depression pathophysiology.


Input: In addition to the inhibitory 5-HT1A autoreceptors, cortico-raphe glutamatergic descending pathways are suggested to modulate 5-HT activity in the DRN.


Input: Here we studied how decreased VGLUT1 levels in the brain stem affect glutamate regulation of 5-HT function.

glutamate


Input: VGLUT1 +/-mice (C57BL/6) and wild type (WT) littermates were used.


Input: VGLUT1 expression in the DRN, 5-HT turnover and immuno histochemical analysis of neuronal activity in different areas was studied.


Input: Moreover, the functionality of the inhibitory 5-HT1A autoreceptor was assessed using electrophysiological, biochemical and pharmacological approaches.


Input: VGLUT1 immunoreactivity was markedly lower in the DRN of the VGLUT1 +/-mice and specifically, in the surroundings of GABA and 5-HT cell bodies.

GABA


Input: These mice showed decreased induced neuronal activity in 5-HT cells bodies and in different forebrain areas, as well as decreased hippocampal cell proliferation and 5-HT turnover.


Input: Further, 5-HT1A autoreceptor desensitization was evidenced by electrophysiological studies, GTP-gamma-S coupling to 5-HT1A autoreceptor and a lower hypothermic response to 5-HT1A activation.

GTP-gamma-S


Input: This study shows first time that VGLUT1 dependent glutamate innervation of the DRN could modulate 5-HT function.

glutamate


Input: Solid-state NMR studies of micelle-templated mesoporous solids.


Input: In this tutorial review we intend to give an overview of the potential of NMR spectroscopy, and in particular solid-state NMR, in characterising micelle-templated mesoporous materials.


Input: Different topics are covered including the study of formation mechanisms, the characterisation of structures, textures, surfaces and interfaces, functionalisation, dynamic properties and structure-reactivity correlations.


Input: Some selected examples illustrate the variety of information provided by this spectroscopy.


Input: Particular attention is paid to recent technological and/or methodological developments.


Input: Metabolism and pharmacokinetics of 3-n-butylphthalide (NBP) in humans: the role of cytochrome P450s and alcohol dehydrogenase in biotransformation.

NBP

alcohol


Input: 3-n-Butylphthalide (NBP) is a cardiovascular drug currently used for the treatment of cerebral ischemia.

NBP


Input: The present study aims to investigate the metabolism, pharmacokinetics, and excretion of NBP in humans and identify the enzymes responsible for the formation of major metabolites.

NBP


Input: NBP underwent extensive metabolism after an oral administration of 200 mg NBP and 23 metabolites were identified in human plasma and urine.

NBP

NBP


Input: Principal metabolic pathways included hydroxylation on alkyl side chain, particularly at 3-, omega-1-, and omega-carbons, and further oxidation and conjugation.

alkyl

3-, omega-1-, and omega-carbons


Input: Approximately 81. 6% of the dose was recovered in urine, mainly as NBP-11-oic acid (M5-2) and glucuronide conjugates of M5-2 and mono-hydroxylated products.

NBP-11-oic acid


Input: 10-Keto-NBP (M2), 3-hydroxy-NBP (M3-1), 10-hydroxy-NBP (M3-2), and M5-2 were the major circulating metabolites, wherein the areas under the curve values were 1. 6-, 2. 9-, 10. 3-, and 4. 1-fold higher than that of NBP.

NBP


Input: Reference standards of these four metabolites were obtained through microbial biotransformation by Cunninghamella blakesleana.


Input: In vitro phenotyping studies demonstrated that multiple cytochrome P450 (P450) isoforms, especially CYP3A4, 2E1, and 1A2, were involved in the formation of M3-1, M3-2, and 11-hydroxy-NBP.


Input: Using M3-2 and 11-hydroxy-NBP as substrates, human subcellular fractions experiments revealed that P450, alcohol dehydrogenase, and aldehyde dehydrogenase catalyzed the generation of M2 and M5-2.

alcohol

aldehyde


Input: Formation of M5-2 was much faster than that of M2, and M5-2 can undergo beta-oxidation to yield phthalide-3-acetic acid in rat liver homogenate.

phthalide-3-acetic acid


Input: Overall, our study demonstrated that NBP was well absorbed and extensively metabolized by multiple enzymes to various metabolites prior to urinary excretion.

NBP


Input: Pharmacokinetics, metabolism, and excretion of the antidiabetic agent ertugliflozin (PF-04971729) in healthy male subjects.

ertugliflozin


Input: The disposition of ertugliflozin (PF-04971729), an orally active selective inhibitor of the sodium-dependent glucose cotransporter 2, was studied after a single 25-mg oral dose of [(14) C]-ertugliflozin to healthy human subjects.

ertugliflozin

sodium

glucose

[(14) C]-ertugliflozin


Input: Mass balance was achieved with approximately 91% of the administered dose recovered in urine and feces.


Input: The total administered radioactivity excreted in feces and urine was 40. 9% and 50. 2%, respectively.


Input: The absorption of ertugliflozin in humans was rapid with a T (max) at ~ 1. 0 hour.

ertugliflozin


Input: Of the total radioactivity excreted in feces and urine, unchanged ertugliflozin collectively accounted for ~ 35. 3% of the dose, suggestive of moderate metabolic elimination in humans.

ertugliflozin


Input: The principal biotransformation pathway involved glucuronidation of the glycoside hydroxyl groups to yield three regioisomeric metabolites, M4a, M4b, and M4c (~ 39. 3% of the dose in urine), of which M4c was the major regioisomer (~ 31. 7% of the dose).

hydroxyl


Input: The structure of M4a and M4c were confirmed to be ertugliflozin-4-O-beta-and-3-O-beta-glucuronide, respectively, via comparison of the HPLC retention time and mass spectra with authentic standards.

ertugliflozin-4-O-beta-and-3-O-beta-glucuronide


Input: A minor metabolic fate involved oxidation by cytochrome P450 to yield monohydroxylated metabolites M1 and M3 and des-ethyl ertugliflozin (M2), which accounted for ~ 5. 2% of the dose in excreta.

des-ethyl ertugliflozin


Input: In plasma, unchanged ertugliflozin and the corresponding 4-O-beta-(M4a) and 3-O-beta-(M4c) glucuronides were the principal components, which accounted for 49. 9, 12. 2, and 24. 1% of the circulating radioactivity.

ertugliflozin


Input: Overall, these data suggest that ertugliflozin is well absorbed in humans, and eliminated largely via glucuronidation.


Input: The role of cytochrome P450-dependent metabolism in the regulation of mouse hepatic growth hormone signaling components and target genes by 3-methylcholanthrene.


Input: 3-Methylcholanthrene (MC) is a readily metabolized aryl hydrocarbon receptor (AHR) agonist.

aryl hydrocarbon


Input: MC disrupts expression of mouse hepatic growth hormone (GH) signaling components and suppresses cytochrome P450 2D9 (Cyp2d9), a male-specific gene controlled by pulsatile GH via signal transducer and activator of transcription 5b (STAT5b).


Input: To determine if these effects of MC depend on hepatic microsomal P450-mediated activity, we examined biologic responses to MC treatment in liver Cpr-null (LCN) mice with hepatocyte-specific conditional deletion of NADPH-cytochrome P450 oxidoreductase (POR).

NADPH


Input: MC caused mild induction of Por and a hepatic inflammatory marker in wild-type mice, whereas MC caused strong induction of AHR target genes, Cyp1a1, Cyp1a2, and Cyp1b1 in wild-type and LCN mice.


Input: Two mouse hepatic STAT5b target genes, Cyp2d9 and major urinary protein 2 (Mup2), were suppressed by MC in wild-type mice, and the CYP2D9 mRNA response was maintained in LCN mice.


Input: In wild-type mice only, MC decreased hepatic GH receptor (GHR) mRNA but increased GHR protein levels.


Input: There was an apparent impairment of STAT5 phosphorylation by MC in wild-type and LCN mice, but large interanimal variation prevented achievement of statistical significance.


Input: In vehicle-treated mice, basal levels of MUP2 mRNA, GHR mRNA, GHR protein, and the activation status of extracellular signal-regulated kinase 2 and Akt were influenced by hepatic Por genetic status.


Input: These results indicate that the effects of MC on hepatic GH signaling components and target genes are complex, involving aspects that are both dependent and independent of hepatic microsomal P450-mediated activity.


Input: Stroke prevention: from available antiplatelet drugs to novel molecular targets.


Input: Stroke is the third most common cause of death in the industrialized countries and adequate primary and secondary prevention strategies are mandatory.


Input: In addition to lifestyle-changes and correction of cardiovascular risk factors, the mainstay of the atherothrombotic stroke prevention is represented by antiplatelet treatment.


Input: Although aspirin and thienopyridines have proved their efficacy in the prevention of arterial thrombotic events, limited efficacy, increased risk of bleeding, significant inter-individual variability in the response and extended duration of action that cannot be reversed if the need for haemostasis or emergency surgery arises represent major limitations of these drugs.

aspirin

thienopyridines


Input: Moreover, despite recommendations and guidelines about stroke prevention, registries data clearly suggest an underuse of antiplatelet drugs, mainly because of bleeding episodes fear.


Input: At variance with newer anticoagulant drugs, which showed a series of advantages as compared with the traditional warfarin treatment, newer antiplatelet drugs have only partially overcome these limitations.

warfarin


Input: Although ad hoc studies on their efficacy in the stroke prevention are currently lacking, newer antiplatelet agents (mainly ticagrelor and prasugrel) do not provide a significant better protection over and above aspirin and/or clopidogrel in the prevention of atherothrombotic stroke.

ticagrelor

prasugrel

aspirin

clopidogrel


Input: In addition, a significantly increased bleeding risk has been reported in subjects receiving these new thienopyridines.

thienopyridines


Input: According to these data, the identification of further molecular targets is needed, in order to design future antiplatelet drugs.


Input: In this review, after summarizing major literature data about traditional and newer antiplatelet drugs, we will specifically focus on novel potential target candidates for antiplatelet therapy.


Input: Spo0A links de novo fatty acid synthesis to sporulation and biofilm development in Bacillus subtilis.

fatty acid


Input: During sporulation in Bacillus subtilis, the committed-cell undergoes substantial membrane rearrangements to generate two cells of different sizes and fates: the mother cell and the forespore.


Input: Here, we demonstrate that the master transcription factor Spo0A reactivates lipid synthesis during development.


Input: Maximal Spo0A-dependent lipid synthesis occurs during the key stages of asymmetric division and forespore engulfment.


Input: Spo0A reactivates the accDA operon that encodes the carboxylase component of the acetyl-CoA carboxylase enzyme, which catalyses the first and rate-limiting step in de novo lipid biosynthesis, malonyl-CoA formation.

acetyl-CoA

malonyl-CoA


Input: The disruption of the Spo0A-binding box in the promoter region of accDA impairs its transcriptional reactivation and blocks lipid synthesis.


Input: The Spo0A-insensitive accDA (0A) cells were proficient in planktonic growth but defective in sporulation (sigma (E) activation) and biofilm development (cell cluster formation and water repellency).


Input: Exogenous fatty acid supplementation to accDA (0A) cells overcomes their inability to synthesize lipids during development and restores sporulation and biofilm proficiencies.

fatty acid


Input: The transient exclusion of the lipid synthesis regulon from the forespore and the known compartmentalization of Spo0A and ACP in the mother cell suggest that de novo lipid synthesis is confined to the mother cell.


Input: The significance of the Spo0A-controlled de novo lipid synthesis during B. subtilis development is discussed.


Input: The mycobacterial binuclear iron monooxygenases require a specific chaperonin-like protein for functional expression in a heterologous host.

iron


Input: The mimABCD gene clusters in Mycobacterium smegmatis strain mc (2) 155 and Mycobacterium goodii strain 12523 encode binuclear iron monooxygenases that oxidize propane and phenol.

iron

propane

phenol


Input: In this study, we attempted to express each mimABCD gene cluster in a heterologous host.


Input: The actinomycetous strain Rhodococcus opacus B-4, which is phylogenetically close to Mycobacterium, was selected as the host.


Input: Each mimABCD gene cluster was cloned into the Rhodococcus-Escherichia coli shuttle vector, pTip-QC2, and then introduced into R. opacus cells.


Input: Although whole-cell assays were performed with phenol as a substrate, the transformed R. opacus cells did not oxidize this substrate.

phenol


Input: SDS/PAGE analysis revealed that the oxygenase large subunit MimA was expressed in the insoluble fraction of R. opacus cells.

SDS


Input: We found that a gene designated mimG, which lies downstream of mimABCD, exhibits similarity in the amino acid sequence of its product with the products of genes encoding the chaperonin GroEL.

amino acid


Input: When the mimG gene was cloned and coexpressed with each mimABCD gene cluster in R. opacus strain B-4, this host successfully acquired oxidation activity towards phenol.

phenol


Input: SDS/PAGE and western blotting analyses demonstrated that MimA was clearly soluble when in the presence of MimG.

SDS


Input: These results indicated that MimG played essential roles in the productive folding of MimA, and that the resulting soluble MimA protein led to the active expression of MimABCD.


Input: Assessment of pre-and postoperative endocrine function in 94 patients with Rathke' s cleft cyst.


Input: We reviewed 94 patients with Rathke' s cleft cyst (RCC) who were surgically treated at Nippon Medical School Hospital between December 1995 and July 2009 to clarify the effect of surgery on their endocrine function.


Input: In our statistical analysis we considered their age and sex, the cyst volume, and preoperative MRI findings.


Input: Using simple linear-and multiple regression analysis we evaluated the association between these factors and their preoperative hormone baseline levels.


Input: To assess pre-and postoperative anterior pituitary function we subjected the results of various hormone loading tests to the Wilcoxon rank sum test.


Input: Surgery improved headache and visual impairment in most patients and elevated PRL levels were significantly normalized after surgery (p = 0. 004).


Input: However, pre-and postoperative anterior pituitary hormone loading tests revealed that the levels of GH, TSH, LH, and FSH were not improved significantly by surgery.


Input: Although the ACTH loading test showed postoperative improvement, the change was not statistically significant.


Input: We suggest that RCC patients with headache or visual impairment are good candidates for surgery.


Input: We also recommend that patients with hyperprolactinemia and those with ACTH deficiency whose MRI findings reveal low-intensity on T1WI and high-intensity on T2WI are likely to benefit from surgery.


Input: In contrast, RCC patients with other hormone dysfunctions do not appear to benefit from surgical intervention.


Input: High electrochemical performance based on ultrathin porous CuO nanobelts grown on Cu substrate as integrated electrode.

CuO

Cu


Input: A facile and low-cost approach has been developed to fabricate porous CuO nanobelts directly grown on a Cu substrate.

CuO

Cu


Input: The as-prepared CuO samples can be directly used as integrated electrodes for lithium-ion batteries and pseudo-supercapacitors without the addition of other ancillary materials such as carbon black or a binder to enhance electrode conductivity and cycling stability.

CuO

lithium

carbon black


Input: The unique nanostructural features endow them with excellent electrochemical performance as demonstrated by high capacities of 640 mA h g (-1) after 100 cycles at 0. 2 C rate and an excellent specific capacitance of 340 F g (-1), which corresponds to the energy density of 45 W h kg (-1).


Input: The cyclability of the electrode demonstrates only a 10-15% loss in capacitance over 5000 cycles.


Input: On the origin of the halo stabilization.


Input: Monte Carlo simulations show that charge-regulation alone can cause highly charged zirconium nanoparticles to adsorb to a similarly charged or neutral silica particle and thereby stabilizing the latter.

zirconium

silica


Input: This mechanism, referred to as halo stabilization, is quite general and applicable in a range of systems provided that pH, van der Waals forces, and dissociation constants of the charge-regulating particles are properly chosen.


Input: In our modeling we see an overall attraction at low volume fractions of nanoparticles, while at higher a repulsive barrier is created, stabilizing the microparticles and protecting them from aggregation.


Input: The charge-regulation mechanism also turns the silica surface from positively charged, without nanoparticles, to negatively charged in the presence of nanoparticles.

silica


Input: Comparison of splicing factor 3b inhibitors in human cells.


Input: Name your splice: FR901464 analogues and herboxidiene inhibit constitutive splicing, most likely by inhibiting spliceosomal subunit SF3b.

herboxidiene


Input: A parallel comparison of these compounds in a cell-based assay system showed meayamycin B as the most potent splicing inhibitor among these small molecules.

meayamycin B


Input: Contaminant-mobilizing capability of fullerene nanoparticles (nC60): Effect of solvent-exchange process in nC60 formation.

fullerene


Input: Fullerene nanoparticles (nC (60)) in aqueous environments can significantly enhance the transport of hydrophobic organic contaminants by serving as a contaminant carrier.

Fullerene

nC (60)


Input: In the present study, the authors examine the effect of the solvent-exchange process on nC (60) aggregate formation and, subsequently, on nC (60)' s contaminant-mobilizing capability.

nC (60)

nC (60)


Input: A series of nC (60) samples were prepared using a modified toluene-water solvent-exchange method through the inclusion of a secondary organic solvent in the phase transfer of molecular C (60) in toluene to nC (60) in water.

nC (60)

toluene

C (60)

toluene

nC (60)


Input: Two groups of solvents--a water-miscible group and a non-water-miscible group-of varied polarity were selected as secondary solvents.


Input: The involvement of a secondary solvent in the phase transfer process had only small effects on the particle size and distribution, zeta potential, and mobility of the nC (60) products but significantly influenced the capability of nC (60) to enhance the transport of 2, 2', 5, 5'-polychlorinated biphenyl (PCB) in a saturated sandy soil column, regardless of whether the secondary solvent was water-miscible or non-water-miscible.

nC (60)

nC (60)

2, 2', 5, 5'-polychlorinated biphenyl

PCB


Input: The two groups of secondary solvents appear to affect the aggregation properties of nC (60) in water via different mechanisms.

nC (60)


Input: In general, nC (60) products made with a secondary water-miscible solvent have stronger capabilities to enhance PCB transport.

nC (60)

PCB


Input: Taken together, the results indicate that according to formation conditions and solvent constituents, nC (60) will vary significantly in its interactions with organic contaminants, specifically as related to adsorption or desorption as well as transport in porous media.

nC (60)


Input: Evaluation of whole effluent toxicity data characteristics and use of Welch' s T-test in the test of significant toxicity analysis.


Input: The U. S.


Input: Environmental Protection Agency (U. S. EPA) and state agencies evaluate the toxicity of effluent and surface water samples based on statistical endpoints derived from multiconcentration tests (e. g., no observed effect concentration, EC25).


Input: The test of significant toxicity (TST) analysis is a two-sample comparison test that uses Welch' s t test to compare organism responses in a sample (effluent or surface water) with responses in a control or site sample.


Input: In general, any form of t test (Welch' s t included) is appropriate only if the data meet assumptions of normality and homogeneous variances.


Input: Otherwise, nonparametric tests are recommended.


Input: TST was designed to use Welch' s t as the statistical test for all whole effluent toxicity (WET) test data.


Input: The authors evaluated the suitability of using Welch' s t test for analyzing two-sample toxicity (WET) data, and within the TST approach, by examining the distribution and variances of data from over 2, 000 WET tests and by conducting multiple simulations of WET test data.


Input: Simulated data were generated having variances and nonnormal distributions similar to observed WET test data for control and the effluent treatment groups.


Input: The authors demonstrate that (1) moderately unequal variances (similar to WET data) have little effect on coverage of the t test or Welch t test (for normally distributed data), and (2) for nonnormally distributed data (similar in distribution to WET data) TST, using Welch' s t test, has close to nominal coverage on the basis of simulations with up to a ninefold difference in variance between the effluent and control groups (~ 95th percentile based on observed WET test data).


Input: Xenobiotic receptor humanized mice and their utility.


Input: The nuclear receptors pregnane X receptor, constitutive androstane receptor, and peroxisome proliferator-activated receptor alpha have important endogenous functions and are also involved in the induction of drug-metabolizing enzymes and transporters in response to exogenous xenobiotics.

androstane


Input: Though not belonging to the same protein family, the Per-Sim-ARNT domain receptor aryl hydrocarbon receptor functionally overlaps with the three nuclear receptors in many aspects and is therefore included in this review.

aryl hydrocarbon


Input: Significant species differences in ligand affinity and biological responses as a result of activation of these receptors have been described.


Input: Several xenobiotic receptor humanized mice have been created to overcome these species differences and to provide in vivo models that are more predictive for human responses.


Input: This review provides an overview of the different xenobiotic receptor humanized mouse models described to date and will summarize how these models can be applied in basic research and improve drug discovery and development.


Input: Some of the key applications in the evaluation of drug induction, drug-drug interactions, nongenotoxic carcinogenicity, other toxicity, or efficacy studies are described.


Input: We also discuss relevant considerations in the interpretation of such data and potential future directions for the use of xenobiotic receptor humanized mice.


Input: The relationship between carotid intima-media thickness and endogenous androgens in young women with polycystic ovary syndrome in Taiwan.

androgens


Input: Polycystic ovary syndrome (PCOS) is a common and complex female endocrinopathy that is associated with multiple vascular risk factors.


Input: Our objective was to investigate the relationship between carotid intima-media thickness (CIMT) and endogenous androgens in young Taiwanese-Chinese women with PCOS.

androgens


Input: We measured CIMT with B-mode ultrasound in 42 young PCOS patients and 43 controls.


Input: Atherosclerosis-associated profiles and endocrinological parameters were also measured.


Input: The results showed that although Taiwanese-Chinese PCOS patients tend to possess more risk factors for atherosclerosis than controls, there was no evidence to support that they have a greater CIMT at this age.


Input: Furthermore, androstenedione appears to be inversely associated with CIMT.

androstenedione


Input: Histopathological effects of waterborne copper nanoparticles and copper sulphate on the organs of rainbow trout (Oncorhynchus mykiss).

copper

copper sulphate


Input: It is unclear whether copper nanoparticles are more toxic than traditional forms of dissolved copper.

copper

copper


Input: This study aimed to describe the pathologies in gill, gut, liver, kidney, brain and muscle of juvenile rainbow trout, Oncorhynchus mykiss, exposed in triplicate to either a control (no added Cu), 20 or 100 mu g l (-1) of either dissolved Cu (as CuSO (4)) or Cu-NPs (mean primary particle size of 87 +/- 27 nm) in a semi-static waterborne exposure regime.

Cu

Cu

CuSO (4)

Cu


Input: Fish were sampled at days 0, 4, and 10 for histology.


Input: All treatments caused organ injuries, and the kinds of pathologies observed with Cu-NPs were broadly of the same type as CuSO (4) including: hyperplasia, aneurisms, and necrosis in the secondary lamellae of the gills; swelling of goblet cells, necrosis in the mucosa layer and vacuole formation in the gut; hepatitis-like injury and cells with pyknotic nuclei in the liver; damage to the epithelium of some renal tubules and increased Bowman' s space in the kidney.

Cu

CuSO (4)


Input: In the brain, some mild changes were observed in the nerve cell bodies in the telencephalon, alteration in the thickness of the mesencephalon layers, and enlargement of blood vessel on the ventral surface of the cerebellum.


Input: Changes in the proportional area of muscle fibres were observed in skeletal muscle.


Input: Overall the data showed that pathology from CuSO (4) and Cu-NPs were of similar types, but there were some material-type effects in the severity or incidence of injuries with Cu-NPs causing more injury in the intestine, liver and brain than the equivalent concentration of CuSO (4) by the end of the experiment, but in the gill and muscle CuSO (4) caused more pathology.

CuSO (4)

Cu

Cu

CuSO (4)

CuSO (4)


Input: Pharmacological and behavioral characterization of the novel CRF (1) antagonist BMS-763534.


Input: BMS-763534 is a potent (CRF (1) IC (50) = 0. 4 nM) and selective (> 1000-fold selectivity vs. all other sites tested) CRF (1) receptor antagonist (pA2 = 9. 47 vs. CRF (1)-mediated cAMP production in Y79 cells).

cAMP


Input: BMS-763534 accelerated the dissociation of (125) I-o-CRF from rat frontal cortex membrane CRF (1) receptors consistent with a negative allosteric modulation of CRF binding.

(125) I


Input: BMS-763534 produced dose-dependent increases in CRF (1) receptor occupancy and anxiolytic efficacy; lowest effective anxiolytic dose = 0. 56 mg/kg, PO, which was associated with 71 +/- 5% CRF (1) receptor occupancy of frontoparietal CRF (1) receptors.


Input: Sedative/ataxic effects of BMS-763534 were only observed at high dose multiples (54-179 x) relative to the lowest dose required for anxiolytic efficacy.


Input: At doses of 5-to 18-fold higher than the lowest efficacious dose in the anxiety assay, BMS-763534 shared subjective effects with the benzodiazepine chlordiazepoxide.

chlordiazepoxide


Input: Interestingly BMS-790318, the O-demethylated metabolite of BMS-763534, showed weak affinity for the TBOB site of the GABA (A) receptor (67% inhibition at 10 mu M) and augmented GABA evoked currents (EC (50) = 1. 6 mu M).

O

TBOB

GABA

GABA


Input: Thus, the unanticipated signal in the drug discrimination assay may have resulted from an interaction of the metabolite BMS-790318 with the TBOB site on the GABA (A) channel where it appears to behave as an allosteric potentiator of GABA evoked currents.

TBOB

GABA

GABA


Input: Chemical characterization, antioxidant and cytotoxic activities of Brazilian red propolis.


Input: Propolis is known for a long time for its health benefits and biological activities.


Input: Here, the red variety from the northeast of Brazil was chemically analyzed and extracts were investigated regarding their antioxidant and antitumor activity.


Input: Hydroalcoholic extracts, obtained from the red propolis, revealed polyphenol content, 2, 2-diphenyl-1-picrylhydrazyl scavenging potential and enzymatic activities for catalase-like and superoxide dismutase-like.

polyphenol

2, 2-diphenyl-1-picrylhydrazyl

superoxide


Input: Cytotoxic activity was evaluated for human laryngeal epidermoid carcinoma cell (Hep-2), human cervical adenocarcinoma (HeLa) and human normal epithelial embryonic kidney (Hek-293).


Input: Survival analysis for non-tumor cell line showed greater IC50 compared to tumor cell lines, suggesting an increased sensitivity that may correlate with the higher proliferative index of the tumor vs. normal cells.


Input: Our results indicate that the Brazilian red propolis is capable of inhibiting cancer cell growth and constitutes an excellent source of antioxidant and antitumor natural agent.


Input: Anti-inflammatory properties of anthraquinones and their relationship with the regulation of P-glycoprotein function and expression.

anthraquinones


Input: There is a growing interest in natural products that potentially have anti-inflammatory properties and inhibit P-glycoprotein (P-gp) function.


Input: In this report, we assessed the effects of anthraquinone derivatives from rhubarb on LPS-induced RAW 264. 7 macrophages to determine their anti-inflammatory potential.

anthraquinone


Input: The derivatives were also tested in Caco-2 cell lines to evaluate the inhibition of the drug efflux function of P-gp.


Input: The transport abilities were examined and the cellular accumulation of rhodamine-123 (R-123) was also measured.


Input: Electorphoretic mobility shift assay (EMSA) was performed to check the activator protein-1 (AP-1) DNA binding affinity.


Input: Five anthraquinones were tested to determine their inhibitory activities on NO production and the protein and mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2).

anthraquinones

NO

nitric oxide


Input: Furthermore, the level of prostaglandin E (2) (PGE (2)) was determined in LPS-induced RAW264. 7 macrophages.

prostaglandin E (2)

PGE (2)


Input: Emodin was found to be the most potent inhibitor, and it also reduced paw swelling in the mouse model of carrageenan-induced paw edema.

Emodin


Input: In Caco-2 cells, emodin elevated the accumulation of R-123 and decreased the efflux ratio of R-123, which indicates the inhibition of P-gp function.


Input: The inhibition of COX-2 protein by emodin paralleled the decrease in P-gp expression.


Input: In addition, mitogen-activated protein kinase (MAPK) expression was decreased through the prevention of AP-1 DNA binding, which leads to downregulation in the expression of P-gp.


Input: Our data indicate that the decrease of P-gp expression is caused by the decreased expression of COX-2 through the MAPK/AP-1 pathway.


Input: Based on our results, we suggest that anti-inflammatory drugs with COX-2 inhibitory activity might be used to modulate P-gp function and expression.


Input: Structure sensitivity of CO oxidation on Co3O4: a DFT study.

CO


Input: The reaction mechanism of CO oxidation on the Co (3) O (4) (110) and Co (3) O (4) (111) surfaces is investigated by means of spin-polarized density functional theory (DFT) within the GGA + U framework.

CO

Co (3) O (4)

Co (3) O (4)


Input: Adsorption situation and complete reaction cycles for CO oxidation are clarified.

CO


Input: The results indicate that 1) the U value can affect the calculated energetic result significantly, not only the absolute adsorption energy but also the trend in adsorption energy; 2) CO can directly react with surface lattice oxygen atoms (O (2f)/O (3f)) to form CO (2) via the Mars-van Krevelen reaction mechanism on both (110)-B and (111)-B; 3) pre-adsorbed molecular O (2) can enhance CO oxidation through the channel in which it directly reacts with molecular CO to form CO (2) [O (2) (a) + CO (g) --> CO (2) (g) + O (a)] on (110)-A/(111)-A; 4) CO oxidation is a structure-sensitive reaction, and the activation energy of CO oxidation follows the order of Co (3) O (4) (111)-A (0. 78 eV) > Co (3) O (4) (111)-B (0. 68 eV) > Co (3) O (4) (110)-A (0. 51 eV) > Co (3) O (4) (110)-B (0. 41 eV), that is, the (110) surface shows higher reactivity for CO oxidation than the (111) surface; 5) in addition to the O (2f), it was also found that Co (3 +) is more active than Co (2 +), so both O (2f) and Co (3 +) control the catalytic activity of CO oxidation on Co (3) O (4), as opposed to a previous DFT study which concluded that either Co (3 +) or O (2f) is the active site.

CO

oxygen

O

O

CO (2)

O (2)

CO

CO

CO (2)

O (2)

CO

CO (2)

O

CO

CO

Co (3) O (4)

Co (3) O (4)

Co (3) O (4)

Co (3) O (4)

CO

O

Co (3 +)

Co (2 +)

O

Co (3 +)

CO

Co (3) O (4)

Co (3 +)

O


Input: Conformational dynamics of Kir3. 1/Kir3. 2 channel activation via delta-opioid receptors.


Input: This study assessed how conformational information encoded by ligand binding to delta-opioid receptors (DORs) is transmitted to Kir3. 1/Kir3. 2 channels.


Input: Human embryonic kidney 293 cells were transfected with bioluminescence resonance energy transfer (BRET) donor/acceptor pairs that allowed us to evaluate independently reciprocal interactions among signaling partners.


Input: These and coimmunoprecipitation studies indicated that DORs, G beta gamma, and Kir3 subunits constitutively interacted with one another.


Input: G alpha oA associated with DORs and G beta gamma, but despite being part of the complex, no evidence of its direct association with the channel was obtained.


Input: DOR activation by different ligands left DOR-Kir3 interactions unmodified but modulated BRET between DOR-G alpha oA, DOR-G beta gamma, G alpha oA-G beta gamma, and G beta gamma-Kir3 interfaces.


Input: Ligand-induced BRET changes assessing G beta gamma-Kir3. 1 subunit interaction 1) followed similar kinetics to those monitoring the G alpha oA-G beta gamma interface, 2) displayed the same order of efficacy as those observed at the DOR-G beta gamma interface, 3) were sensitive to pertussis toxin, and 4) were predictive of whether a ligand could evoke channel currents.


Input: Conformational changes at the G beta gamma/Kir3 interface were lost when Kir3. 1 subunits were replaced by a mutant lacking essential sites for G beta gamma-mediated activation.


Input: Thus, conformational information encoded by agonist binding to the receptor is relayed to the channel via structural rearrangements that involve repositioning of G beta gamma with respect to DORs, G alpha oA, and channel subunits.


Input: Further, the fact that BRET changes at the G beta gamma-Kir3 interface are predictive of a ligand' s ability to induce channel currents points to these conformational biosensors as screening tools for identifying GPCR ligands that induce Kir3 channel activation.


Input: Ginkgo biloba extract attenuates hippocampal neuronal loss and cognitive dysfunction resulting from trimethyltin in mice.

trimethyltin


Input: The present study was an attempt to investigate the neuromodulatory potential of Ginkgo biloba extract (GBE) against hippocamapal structural and functional damages induced by trimethyltin (TMT) a potent neurotoxicant.

trimethyltin

TMT


Input: Male Balb/C mice were administered with Ginkgo biloba extract for 14 days at a dose of 70 mg/kg body weight interperitoneally and on 11-day of treatment animals were exposed to Trimethyltin (2. 5 mg/kg b. w) single intraperitoneal injection.

Trimethyltin


Input: The co-administered of TMT with GBE showed marked improvement in memory and aggressive behavior.

TMT


Input: Which were in turn reflected in the levels of serotonin and acetylcholine esterase.

serotonin

acetylcholine


Input: The conjunctive treatment also showed significant decrease in oxidative stress as assessed by MDA levels and the antioxidant enzymes (GSH, GSSH, GPX, total glutathione, Catalase and Superoxide dismutase) which were depressed by TMT treatment was significantly improved by GBE.

MDA

GSH

GSSH

glutathione

Superoxide

TMT


Input: Correspondingly, induction of Bcl-2 mitochondrial apoptotic pathway by trimethyltin was down regulated by Ginkgo biloba treatment.

trimethyltin


Input: The structural analysis of dentate gyrus revealed improvement in degenerating neurons by treatment with GBE.


Input: Therefore, it is suggested that prophylactic treatment of Ginkgo biloba extract protects against the trimethyltin induced neurodegenration by multiple mechanism involved in its antioxidant effects and may be useful in developing therapies against neurodegenration.

trimethyltin


Input: Seizure control by ketogenic diet-associated medium chain fatty acids.

fatty acids


Input: The medium chain triglyceride (MCT) ketogenic diet is used extensively for treating refractory childhood epilepsy.

triglyceride


Input: This diet increases the plasma levels of medium straight chain fatty acids.

fatty acids


Input: A role for these and related fatty acids in seizure control has not been established.

fatty acids


Input: We compared the potency of an established epilepsy treatment, Valproate (VPA), with a range of MCT diet-associated fatty acids (and related branched compounds), using in vitro seizure and in vivo epilepsy models, and assessed side effect potential in vitro for one aspect of teratogenicity, for liver toxicology and in vivo for sedation, and for a neuroprotective effect.

Valproate

VPA

fatty acids


Input: We identify specific medium chain fatty acids (both prescribed in the MCT diet, and related compounds branched on the fourth carbon) that provide significantly enhanced in vitro seizure control compared to VPA.

fatty acids

VPA


Input: The activity of these compounds on seizure control is independent of histone deacetylase inhibitory activity (associated with the teratogenicity of VPA), and does not correlate with liver cell toxicity.

VPA


Input: In vivo, these compounds were more potent in epilepsy control (perforant pathway stimulation induced status epilepticus), showed less sedation and enhanced neuroprotection compared to VPA.

VPA


Input: Our data therefore implicates medium chain fatty acids in the mechanism of the MCT ketogenic diet, and highlights a related new family of compounds that are more potent than VPA in seizure control with a reduced potential for side effects.

fatty acids

VPA


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


Input: Etazolate, an alpha-secretase activator, reduces neuroinflammation and offers persistent neuroprotection following traumatic brain injury in mice.

Etazolate


Input: Traumatic brain injury (TBI) evokes an intense neuroinflammatory reaction that is essentially mediated by activated microglia and that has been reported to act as a secondary injury mechanism that further promotes neuronal death.


Input: It involves the excessive production of inflammatory cytokines and the diminution of neuroprotective and neurotrophic factors, such as the soluble form alpha of the amyloid precursor protein (sAPP alpha), generated by the activity of alpha-secretases.


Input: Hence, the aim of this study was to examine the effects of etazolate, an alpha-secretase activator, on acute and belated post-TBI consequences.

etazolate


Input: The mouse model of TBI by mechanical percussion was used and injured mice received either the vehicle or etazolate at the dose of 1, 3 or 10 mg/kg at 2 h post-TBI.

etazolate


Input: Neurological score, cerebral oe dema, IL-1 beta and sAPP alpha levels, microglial activation and lesion size were evaluated from 6 to 24 h post-TBI.


Input: Spontaneous locomotor activity was evaluated from 48 h to 12 weeks post-TBI, memory function at 5 weeks and olfactory bulb lesions at 13 weeks post-TBI.


Input: A single administration of etazolate exerted a dose-dependent anti-inflammatory and anti-oe dematous effect accompanied by lasting memory improvement, reduction of locomotor hyperactivity and olfactory bulb tissue protection, with a therapeutic window of at least 2 h.

etazolate


Input: These effects were associated with the restoration of the levels of the sAPP alpha protein post-TBI.


Input: Taken together, these results highlight for the first time the therapeutic interest of an alpha-secretase activator in TBI.


Input: Vitamin D receptor signaling mechanisms: integrated actions of a well-defined transcription factor.

Vitamin D


Input: The main physiological actions of the biologically most active metabolite of vitamin D, 1 alpha, 25-dihydroxyvitamin D (3) (1 alpha, 25 (OH) (2) D (3)), are calcium and phosphorus uptake and transport and thereby controlling bone formation.

vitamin D

1 alpha, 25-dihydroxyvitamin D (3)

1 alpha, 25 (OH) (2) D (3)

calcium

phosphorus


Input: Other emergent areas of 1 alpha, 25 (OH) (2) D (3) action are in the control of immune functions, cellular growth and differentiation.

1 alpha, 25 (OH) (2) D (3)


Input: All genomic actions of 1 alpha, 25 (OH) (2) D (3) are mediated by the transcription factor vitamin D receptor (VDR) that has been the subject of intense study since the 1980' s.

1 alpha, 25 (OH) (2) D (3)

vitamin D


Input: Thus, vitamin D signaling primarily implies the molecular actions of the VDR.

vitamin D


Input: In this review, we present different perspectives on the VDR that incorporate its role as transcription factor and member of the nuclear receptor superfamily, its dynamic changes in genome-wide locations and DNA binding modes, its interaction with chromatin components and its primary protein-coding and non-protein coding target genes and finally how these aspects are united in regulatory networks.


Input: By comparing the actions of the VDR, a relatively well-understood and characterized protein, with those of other transcription factors, we aim to build a realistic positioning of vitamin D signaling in the context of other intracellular signaling systems.

vitamin D


Input: Biochemical and biological characterization of two serine proteinases from Colombian Crotalus durissus cumanensis snake venom.

serine


Input: Two clotting serine proteinases, named Cdc SI and Cdc SII, were isolated and characterized for the first time from Colombian Crotalus durissus cumanensis snake venom.

serine


Input: The enzymes were purified using two chromatographic steps: molecular exclusion on Sephacryl S-200 and RP-HPLC on C8 Column.


Input: The molecular masses of the proteins, determined by MALDI-TOF mass spectrometry, were 28, 561. 4 and 28, 799. 2 Da for Cdc SI and Cdc SII, respectively.


Input: The aim of the present study was to evaluate enzymatic, coagulant and toxic properties of the two enzymes.


Input: The serine proteinases hydrolyzed specific chromogenic substrate (BaPNA) and exhibited a Michaelis-Menten behavior.

serine


Input: Cdc SI had V (max) of 0. 038 +/- 0. 003 nmol/min and K (M) of 0. 034 +/- 0. 017 mM, while Cdc SII displayed values of V (max) of 0. 267 +/- 0. 011 nmol/min and K (M) of 0. 145 +/- 0. 023 mM.


Input: N-terminal sequences were VIGGDEXNIN and VIGGDICNINEHNFLVALYE for Cdc SI and Cdc SII, respectively.

N


Input: Molecular masses, N-terminal sequences, inhibition assays, and enzymatic profile suggest that Cdc SI and Cdc SII belong to the family of snake venom thrombin-like enzymes.

N


Input: These serine proteinases differed in their clotting activity on human plasma, showing a minimum coagulant dose of 25 mu g and 0. 571 mu g for Cdc SI and Cdc SII, respectively.

serine


Input: Enzymes also showed coagulant activity on bovine fibrinogen and degraded chain alpha of this protein.


Input: Toxins lack hemorrhagic and myotoxic activities, but are capable to induce defibrin (ogen) ation, moderate edema, and an increase in vascular permeability.


Input: These serine proteinases may contribute indirectly to the local hemorrhage induced by metalloproteinases, by causing blood clotting disturbances, and might also contribute to cardiovascular alterations characteristic of patients envenomed by C.

serine


Input: d. cumanensis in Colombia.


Input: Solubility-pH profiles of some acidic, basic and amphoteric drugs.


Input: The solubility vs. pH profiles of five ionizable drugs of different nature (a monoprotic acid, a monoprotic base, a diprotic base and two amphoteric compounds showing a zwitterionic species each one) have been determined through two different methodologies: the classical shake-flask (S-F) and the potentiometric Cheqsol methods using in both instances the appropriate Henderson-Hasselbalch (H-H) or derived relationships.


Input: The results obtained independently from both approaches are consistent.


Input: A critical revision about the influence of the electrolyte used as buffering agent in the S-F method on the obtained solubility values is also performed.


Input: Thus, some deviations of the experimental points with respect the H-H profiles can be attributed to specific interactions between the buffering electrolyte and the drug due to the hydrotrophic character of citric and lactic acids.

citric and lactic acids


Input: In other cases, the observed deviations are independent of the buffers used since they are caused by the formation of new species such as drug aggregates (cefadroxil) or the precipitation of a salt from a cationic species of the analyzed compound (quetiapine).

cefadroxil

quetiapine


Input: APLF promotes the assembly and activity of non-homologous end joining protein complexes.


Input: Non-homologous end joining (NHEJ) is critical for the maintenance of genetic integrity and DNA double-strand break (DSB) repair.


Input: NHEJ is regulated by a series of interactions between core components of the pathway, including Ku heterodimer, XLF/Cernunnos, and XRCC4/DNA Ligase 4 (Lig4).


Input: However, the mechanisms by which these proteins assemble into functional protein-DNA complexes are not fully understood.


Input: Here, we show that the von Willebrand (vWA) domain of Ku80 fulfills a critical role in this process by recruiting Aprataxin-and-PNK-Like Factor (APLF) into Ku-DNA complexes.


Input: APLF, in turn, functions as a scaffold protein and promotes the recruitment and/or retention of XRCC4-Lig4 and XLF, thereby assembling multi-protein Ku complexes capable of efficient DNA ligation in vitro and in cells.


Input: Disruption of the interactions between APLF and either Ku80 or XRCC4-Lig4 disrupts the assembly and activity of Ku complexes, and confers cellular hypersensitivity and reduced rates of chromosomal DSB repair in avian and human cells, respectively.


Input: Collectively, these data identify a role for the vWA domain of Ku80 and a molecular mechanism by which DNA ligase proficient complexes are assembled during NHEJ in mammalian cells, and reveal APLF to be a structural component of this critical DSB repair pathway.


Input: Herb-drug interaction of Fucus vesiculosus extract and amiodarone in rats: a potential risk for reduced bioavailability of amiodarone in clinical practice.

amiodarone

amiodarone


Input: Fucus vesiculosus is a seaweed claimed to be useful for obesity management.


Input: Therefore, considering the relationship between obesity and cardiovascular diseases, this work aimed to assess the potential for an herb-drug interaction among a standardized F. vesiculosus extract (GMP certificate) and amiodarone (a narrow therapeutic index drug) in rats.

amiodarone


Input: In a first pharmacokinetic study, rats were simultaneously co-administered with a single-dose of F. vesiculosus (575 mg/kg, p. o.) and amiodarone (50 mg/kg, p. o.); in a second study, rats were pre-treated during 14 days with F. vesiculosus (575 mg/kg/day, p. o.) and received amiodarone (50 mg/kg, p. o.) on the 15th day.

amiodarone

amiodarone


Input: Rats of the control groups received the corresponding volume of vehicle.


Input: After analysis of the pharmacokinetic data it deserves to be highlighted the significant decrease in the peak plasma concentration of amiodarone (55. 4%) as well as the reduction of systemic exposure to the parent drug (~ 30%) following the simultaneous co-administration of F. vesiculosus extract and amiodarone.

amiodarone

amiodarone


Input: This paper reports, for the first time, the herb-drug interaction between F. vesiculosus and amiodarone, which determined a considerable decrease on amiodarone bioavailability in rats.

amiodarone

amiodarone


Input: Therefore, the therapeutic efficacy of amiodarone may be compromised by the concurrent administration of herbal slimming medicines/dietary supplements containing F. vesiculosus.

amiodarone


Input: Garlic-derived diallyl disulfide modulates peroxisome proliferator activated receptor gamma co-activator 1 alpha in neuroblastoma cells.

diallyl disulfide


Input: The peroxisome proliferator activated receptor gamma co-activator 1 alpha (PGC1 alpha) is an inducible transcriptional co-activator with direct function in the induction of mitochondrial biogenesis.


Input: In the present report we show that, in SH-SY5Y neuroblastoma cells, garlic-derived diallyl disulfide (DADS) is able to increase PGC1 alpha expression in a ROS-dependent manner and to induce mitochondrial biogenesis at early stage of treatment that precede cell cycle arrest and apoptosis outcome.

diallyl disulfide


Input: In particular, we demonstrate that DADS elicits: i) the increase of PGC1 alpha within nuclear compartment; ii) the decrease of PGC1 alpha non-active acetylated form; iii) the induction of nuclear-encoded mitochondrial genes such as TFAM and TFBM1.


Input: We also show an accumulation of PGC1 alpha within mitochondria along with an increased association with the regulatory D-Loop region of mtDNA and a concomitant augmented expression of mitochondrial RNA.


Input: Such events are related to a prompt elevation of mitochondrial mass, as assessed by evaluating the content of mtDNA.


Input: We show that the induction of mitochondrial biogenesis is directed to dampen the cytotoxic effect of DADS.


Input: Indeed, PGC1 alpha overexpression or down-regulation prevents or exacerbates mtDNA loss and apoptosis.


Input: Overall the data highlight an anti-apoptotic role of PGC1 alpha-mediated mitochondrial biogenesis in neuroblatoma cells and suggest PGC1 alpha as a potential target for enhancing the effectiveness of therapy in aggressive neuroblastoma with high drug-resistance.


Input: Hyaluronic acid-dependent protection in H9C2 cardiomyocytes: a cell model of heart ischemia-reperfusion injury and treatment.


Input: Hyaluronic acid (HA), a glycosaminoglycan with high molecular weight, has been reported to promote cell proliferation and serves as an important extracellular matrix component.


Input: The aim of this study was to in vitro investigate whether HA is able to reduce reactive oxygen species (ROS)-induced heart ischemia-reperfusion injury and activate the cardiomyocyte' s damage surveillance systems.

oxygen


Input: Accordingly, rattus cardiomyocyte line, H9C2, was treated with H (2) O (2) as a heart ischemia-reperfusion model followed by incubation with low molecular weight hyaluronan (LMW-HA, 100 kDa) or high molecular weight hyaluronan (HMW-HA, 1000 kDa) and proteomic analysis was performed to investigate the physiologic protection of HA in H (2) O (2)-induced ischemia-reperfusion in cardiomyocyte.

H (2) O (2)

H (2) O (2)


Input: Our data demonstrated that HA treatment does protect cardiomyocyte in the ROS-induced ischemia-reperfusion model and the molecular weight of HA is a crucial factor.


Input: HMW-HA has been shown to significantly facilitate cell migration and wound healing via cytoskeletal rearrangement.


Input: Additionally, 2D-DIGE combined MALDI-TOF/TOF analysis showed that HMW-HA might modulate biosynthetic pathways, cell migration, cell outgrowth and protein folding to stimulate wound healing as well as prevent these ischemia-reperfusion-damaged cardiomyocytes from cell death.


Input: To our knowledge, we report for the first time the cell repair mechanism of HMW-HA against ischemia-reperfusion-damage in cardiomyocytes based on cell biology and proteomic analysis.


Input: Characterization of epitopes recognized by monoclonal antibodies: experimental approaches supported by freely accessible bioinformatic tools.


Input: Monoclonal antibodies (mAbs) have been used successfully both in research and for clinical purposes.


Input: The possible use of protective mAbs directed against different microbial pathogens is currently being considered.


Input: The fine definition of the epitope recognized by a protective mAb is an important aspect to be considered for possible development in epitope-based vaccinology.


Input: The most accurate approach to this is the X-ray resolution of mAb/antigen crystal complex.


Input: Unfortunately, this approach is not always feasible.


Input: Under this perspective, several surrogate epitope mapping strategies based on the use of bioinformatics have been developed.


Input: In this article, we review the most common, freely accessible, bioinformatic tools used for epitope characterization and provide some basic examples of molecular visualization, editing and computational analysis.


Input: Rat fertility and embryo fetal development: influence of exposure to the Wi-Fi signal.


Input: In recent decades, concern has been growing about decreasing fecundity and fertility in the human population.


Input: Exposure to non-ionizing electromagnetic fields (EMF), especially radiofrequency (RF) fields used in wireless communications has been suggested as a potential risk factor.


Input: For the first time, we evaluated the effects of exposure to the 2450MHz Wi-Fi signal (1h/day, 6days/week) on the reproductive system of male and female Wistar rats, pre-exposed to Wi-Fi during sexual maturation.


Input: Exposure lasted 3 weeks (males) or 2 weeks (females), then animals were mated and couples exposed for 3 more weeks.


Input: On the day before delivery, the fetuses were observed for lethality, abnormalities, and clinical signs.


Input: In our experiment, no deleterious effects of Wi-Fi exposure on rat male and female reproductive organs and fertility were observed for 1h per days.


Input: No macroscopic abnormalities in fetuses were noted, even at the critical level of 4W/kg.


Input: Combination chemotherapy using core-shell nanoparticles through the self-assembly of HPMA-based copolymers and degradable polyester.

HPMA

polyester


Input: The preparation of core-shell polymeric nanoparticles simultaneously loaded with docetaxel (DTXL) and doxorubicin (DOX) is reported herein.

docetaxel

DTXL

doxorubicin

DOX


Input: The self-assembly of the aliphatic biodegradable copolyester PBS/PBDL (poly (butylene succinate-co-butylene dilinoleate)) and HPMA-based copolymers (N-(2-hydroxypropyl) methacrylamide-based copolymers) hydrophobically modified by the incorporation of cholesterol led to the formation of narrow-size-distributed (PDI < 0. 10) sub-200-nm polymeric nanoparticles suitable for passive tumor-targeting drug delivery based on the size-dependent EPR (enhanced permeability and retention) effect.

PBS

PBDL

poly (butylene succinate-co-butylene dilinoleate)

HPMA

N-(2-hydroxypropyl) methacrylamide

cholesterol


Input: The PHPMA provided to the self-assembled nanoparticle stability against aggregation as evaluated in vitro.

PHPMA


Input: The highly hydrophobic drug docetaxel (DTXL) was physically entrapped within the PBS/PBDL copolyester core and the hydrophilic drug doxorubicin hydrochloride (DOX. HCl) was chemically conjugated to the reactive PHPMA copolymer shell via hydrazone bonding that allowed its pH-sensitive release.

docetaxel

DTXL

PBS

PBDL

doxorubicin hydrochloride

DOX. HCl

PHPMA

hydrazone


Input: This strategy enabled the combination chemotherapy by the simultaneous DOX and DTXL drug delivery.

DOX

DTXL


Input: The structure of the nanoparticles was characterized in detail using static (SLS), dynamic (DLS) and electrophoretic (ELS) light scattering besides transmission electron microscopy (TEM).


Input: The use of nanoparticles simultaneously loaded with DTXL and DOX provided a more efficient suppression of tumor-cell growth in mice bearing EL-4 T cell lymphoma when compared to the effect of nanoparticles loaded with either DTXL or DOX separately.

DTXL

DOX

DTXL

DOX


Input: Additionally, the obtained self-assembled nanoparticles enable further development of targeting strategies based on the use of multiple ligands attached to an HPMA copolymer on the particle surface for simultaneous passive and active targeting and different combination therapies.

HPMA


Input: Iron excess disturbs metabolic status and relative gonad mass in rats on high fat, fructose, and salt diets.

Iron

fructose


Input: The aim of this study was to assess the metabolic and physiological changes in rats fed a diet high in fat, fructose, and salt, and with excess iron level.

fructose

iron


Input: Mineral status was also estimated.


Input: Wistar rats were assigned to groups fed either a standard control diet (C) or a diet high in fat, fructose, and salt.

fructose


Input: The noncontrol diets contained either normal (M) or high level (MFe) of iron.

iron


Input: After 6 weeks, the length and weight of the rats were measured, and the animals were euthanized.


Input: The kidneys and gonads were collected, and blood samples were taken.


Input: Serum levels of insulin, nitric oxide, and iron were measured.

nitric oxide

iron


Input: The iron, zinc, copper, and calcium concentrations of tissues were determined.

iron

zinc

copper

calcium


Input: It was found that the M diet led to a significant increase in the relative kidney mass of the rats compared with the control group.


Input: Among the rats fed the M diet, markedly higher serum level of iron and lower levels of zinc and copper were observed in tissues, while significantly higher calcium levels were found in the gonads.

iron

zinc

copper

calcium


Input: The MFe diet resulted in decreased obesity index, insulin level, and nitric oxide serum concentration in the rats, when compared with both the M and C diets.

nitric oxide


Input: The high iron level in the modified diet increased the relative mass of the gonads.

iron


Input: The excess iron level in the diet disturbed the zinc, copper, and calcium status of tissues.

iron

zinc

copper

calcium


Input: The decrease in insulin and nitric oxide in rats fed the diet high in iron, fat, fructose, and salt was associated with disorders of zinc, copper, and calcium status, as well as with an increase in the relative mass of the gonads.

nitric oxide

iron

fructose

zinc

copper

calcium


Input: Retraction note to: The effect of lead acetate toxicity on experimental male albino rat.

lead acetate


Input: Retraction to: Biol Trace Elem Res 144 (1-3): 1120-1132, DOI 10. 1007/s12011-011-9149-z.


Input: Article has been retracted due to duplicate publication.


Input: Periphyton responses to nutrient and atrazine mixtures introduced through agricultural runoff.

atrazine


Input: Agricultural runoff often contains pollutants with antagonistic impacts.


Input: The individual influence of nutrients and atrazine on periphyton has been extensively studied, but their impact when introduced together and with multiple agricultural pollutants is less clear.

atrazine


Input: We simulated a field-scale runoff pulse into a riverine wetland that mimicked pollutant composition typical of field runoff of the Mississippi River Alluvial Plain.


Input: Periphyton biomass and functional responses were measured for 2 weeks along a 500 m section.


Input: Additionally, laboratory chamber assays were used to identify potential periphyton changes due to nutrients, atrazine, and their interactions.

atrazine


Input: Generally, nutrients stimulated, and atrazine reduced chlorophyll a (Chl a) in chambers.

atrazine

chlorophyll a

Chl a


Input: In the wetland, nutrient and atrazine relationships with periphyton were weaker, and when found, were often opposite of trends in chambers.

atrazine


Input: Total nitrogen (TN) was inversely related to Chl a, and total phosphorus was inversely related to respiration (R) rates.

nitrogen

Chl a

phosphorus


Input: Atrazine (10-20 mu g L (-1) in the wetland) had a positive relationship with ash-free dry mass (AFDM), and weakened the relationship between TN and AFDM.

Atrazine


Input: Wetland periphyton biomass was better correlated to total suspended solids than nutrients or atrazine.

atrazine


Input: Periphyton function was resilient as periphyton gross primary production (GPP)/R ratios were not strongly impacted by runoff.


Input: However, whole-system GPP and R decreased over the 2-week period, suggesting that although periphyton metabolism recovered quickly, whole-system metabolism took longer to recover.


Input: The individual and combined impacts of nutrients and atrazine in complex pollutant mixtures can vary substantially from their influence when introduced separately, and non-linear impacts can occur with distance downstream of the pollutant introduction point.

atrazine


Input: Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach.


Input: Developmental neurotoxicity (DNT) and many forms of reproductive toxicity (RT) often manifest themselves in functional deficits that are not necessarily based on cell death, but rather on minor changes relating to cell differentiation or communication.


Input: The fields of DNT/RT would greatly benefit from in vitro tests that allow the identification of toxicant-induced changes of the cellular proteostasis, or of its underlying transcriptome network.


Input: Therefore, the' human embryonic stem cell (hESC)-derived novel alternative test systems (ESNATS)' European commission research project established RT tests based on defined differentiation protocols of hESC and their progeny.


Input: Valproic acid (VPA) and methylmercury (MeHg) were used as positive control compounds to address the following fundamental questions: (1) Does transcriptome analysis allow discrimination of the two compounds?

Valproic acid

VPA

methylmercury

MeHg


Input: (2) How does analysis of enriched transcription factor binding sites (TFBS) and of individual probe sets (PS) distinguish between test systems?


Input: (3) Can batch effects be controlled?


Input: (4) How many DNA microarrays are needed?


Input: (5) Is the highest non-cytotoxic concentration optimal and relevant for the study of transcriptome changes?


Input: VPA triggered vast transcriptional changes, whereas MeHg altered fewer transcripts.

MeHg


Input: To attenuate batch effects, analysis has been focused on the 500 PS with highest variability.


Input: The test systems differed significantly in their responses (< 20% overlap).


Input: Moreover, within one test system, little overlap between the PS changed by the two compounds has been observed.


Input: However, using TFBS enrichment, a relatively large' common response' to VPA and MeHg could be distinguished from' compound-specific' responses.

VPA

MeHg


Input: In conclusion, the ESNATS assay battery allows classification of human DNT/RT toxicants on the basis of their transcriptome profiles.


Input: Therapy of adrenal insufficiency: an update.


Input: Adrenal insufficiency may be caused by the destruction or altered function of the adrenal gland with a primary deficit in cortisol secretion (primary adrenal insufficiency) or by hypothalamic-pituitary pathologies determining a deficit of ACTH (secondary adrenal insufficiency).

cortisol


Input: The clinical picture is determined by the glucocorticoid deficit, which may in some conditions be accompanied by a deficit of mineralcorticoids and adrenal androgens.

androgens


Input: The substitutive treatment is aimed at reducing the signs and symptoms of the disease as well as at preventing the development of an addisonian crisis, a clinical emergency characterized by hypovolemic shock.


Input: The oral substitutive treatment should attempt at mimicking the normal circadian profile of cortisol secretion, by using the lower possible doses able to guarantee an adequate quality of life to patients.

cortisol


Input: The currently available hydrocortisone or cortisone acetate preparations do not allow an accurate reproduction of the physiological secretion pattern of cortisol.

hydrocortisone

cortisone acetate

cortisol


Input: A novel dual-release formulation of hydrocortisone, recently approved by EMEA, represents an advancement in the optimization of the clinical management of patients with adrenal insufficiency.

hydrocortisone


Input: Future clinical trials of immunomodulation or immunoprevention will test the possibility to delay (or prevent) the autoimmune destruction of the adrenal gland in autoimmune Addison' s disease.


Input: Chemical constituents from the fungus Amauroderma amoiensis and their in vitro acetylcholinesterase inhibitory activities.


Input: One new compound named amauroamoienin (1), together with thirteen known compounds (2-14), was isolated from the EtOAc extract of Amauroderma amoiensis.

amauroamoienin

EtOAc


Input: The structures of these compounds were elucidated by the analysis of 1D and 2D spectroscopic data and the MS technique.


Input: The bioassays of inhibitory activities of these isolates against acetylcholinesterase were evaluated, and compounds 1, 3, and 5 exhibited acetylcholinesterase inhibitory activities.


Input: Three-dimensional hierarchical GeSe2 nanostructures for high performance flexible all-solid-state supercapacitors.


Input: Highly flexible stacked and in-plane all-solid-state supercapacitors are fabricated on 3D hierarchical GeSe2 nanostructures with high performance, and, when configured as a self-powered photodetector nanosystem, can be used to power CdSe nanowire photodetectors.

CdSe


Input: Bottom-up nutrient and top-down fish impacts on insect-mediated mercury flux from aquatic ecosystems.

mercury


Input: Methyl mercury (MeHg) is one of the most hazardous contaminants in the environment, adversely affecting the health of wildlife and humans.

Methyl mercury

MeHg


Input: Recent studies have demonstrated that aquatic insects biotransport MeHg and other contaminants to terrestrial consumers, but the factors that regulate the flux of MeHg out of aquatic ecosystems via emergent insects have not been studied.

MeHg

MeHg


Input: The authors used experimental mesocosms to test the hypothesis that insect emergence and the associated flux of MeHg from aquatic to terrestrial ecosystems is affected by both bottom-up nutrient effects and top-down fish consumer effects.

MeHg


Input: In the present study, nutrient addition led to an increase in MeHg flux primarily by enhancing the biomass of emerging insects whose tissues were contaminated with MeHg, whereas fish decreased MeHg flux primarily by reducing the biomass of emerging insects.

MeHg

MeHg

MeHg


Input: Furthermore, the authors found that these factors are interdependent such that the effects of nutrients are more pronounced when fish are absent, and the effects of fish are more pronounced when nutrient concentrations are high.


Input: The present study is the first to demonstrate that the flux of MeHg from aquatic to terrestrial ecosystems is strongly enhanced by bottom-up nutrient effects and diminished by top-down consumer effects.

MeHg


Input: Characterizing the lateral friction of nanoparticles on on-chip integrated black lipid membranes.


Input: The use of nanoparticles (NPs) in biomedical applications creates a need for appropriate model systems to systematically investigate NP-membrane interactions under well-defined conditions.


Input: Black lipid membranes (BLMs) are free-floating membranes with defined composition that are ideally suited for characterizing NP-membrane interactions free of any potential perturbation through a supporting substrate.


Input: Herein, arrays of microfabricated BLMs are integrated into a chip-based platform that is compatible with high-speed optical NP tracking.


Input: This system is used to investigate the lateral diffusion of 40 nm gold spheres tethered to biotinylated lipids through antibody-functionalized ligands (single-stranded DNA or polyethylene glycol).

polyethylene glycol


Input: Although the NPs show an almost free and ergodic diffusion, their lateral motion is subject to substantial drag at the membrane surface, which leads to systematically smaller diffusion coefficients than those obtained for lipids in the membrane through fluorescence recovery after photobleaching.


Input: The lateral mobility of the NPs is influenced by the chemical composition and salt concentration at the NP-membrane interface, but is independent of the ligand density in the membrane.


Input: Together with the observation that nanoprisms, which have a larger relative contact area with the membrane than spherical NPs, show an even slower diffusion, these findings indicate that the lateral mobility of NPs tethered in close vicinity to a membrane is significantly reduced by the friction at the NP-membrane interface.


Input: A new class of room-temperature multiferroic thin films with bismuth-based supercell structure.

bismuth