Input: No statistical association was found between the anogenital index (birth weight-adjusted AGD) of male offspring and the concentrations of any parabens in the urine of the mothers suggesting that the parabens were not apparently estrogenically active at the exposure level of the present subjects.

parabens

parabens


Input: The influence of the genetic and non-genetic factors on bone mineral density and osteoporotic fractures in Chinese women.


Input: To investigate the effects of genetic and non-genetic factors on bone mineral densities (BMDs) and osteoporotic fractures.


Input: This was a cross-sectional study to investigate the relationships between 18 SNPs and non-genetic factors with BMDs and osteoporotic fractures in 1012 Chinese Han women.


Input: Five SNPs in genes GPR177, CTNNB1, MEF2C, SOX6, and TNFRSF11B were associated with L1-4 or total hip BMDs.


Input: rs11898505 in SPTBN1 gene was associated with osteoporotic fractures.


Input: Subjects carrying the largest number of risk alleles (highest 10%) not only had lower BMD values as compared to those carrying the least number of risk alleles (lowest 10%), they also had a higher risk of fracture [P = 0. 002, OR = 2. 252, 95% CI (1. 136, 4. 463)].


Input: Results from multivariate stepwise regression analysis revealed that age [P < 0. 001, OR = 1. 038, 95% CI (1. 018, 1. 058)], number of falls in a year [P < 0. 001, OR = 2. 347, 95% CI (1. 459, 3. 774)], the G risk allele in rs11898505 [P = 0. 023, OR = 1. 559, 95% CI (1. 062, 2. 290)], and the L1-4 BMD [P = 0. 017, OR = 0. 286, 95% CI (0. 102, 0. 798)] were associated with the occurrence of osteoporotic fractures.


Input: Genetic (rs11898505) and non-genetic factors (age, number of falls in a year and L1-4 BMD) could work in concert to contribute to the risk of osteoporotic fractures.


Input: Flavonoids and antioxidant activity of flowers of Mexican Crataegus spp.

Flavonoids


Input: Flavonoids and antioxidant activity of extracts of flowers from some Mexican accessions of Crataegus were studied using six accessions with the purpose of contributing to the knowledge of the nutraceutical properties of the accessions of the Germplasm Bank of the Universidad Autonoma Chapingo.

Flavonoids


Input: Flavonoids were identified by HPLC-MS.

Flavonoids


Input: Among the flavonoids, the quercetin 3-O-glucoside (3), quercetin 3-O-rhamnoside (4), quercetin 3-O-rhamnosyl-(1 --> 6)-glucoside (2) and quercetin 3-O-rhamnosyl-(1 --> 2)-[rhamnosyl-(1 --> 6)]-glucoside (1) were assigned.

flavonoids

quercetin 3-O-glucoside

quercetin 3-O-rhamnoside

quercetin 3-O-rhamnosyl-(1 --> 6)-glucoside

quercetin 3-O-rhamnosyl-(1 --> 2)-[rhamnosyl-(1 --> 6)]-glucoside


Input: Flavonoid content and radical scavenging activity explain some of the medicinal properties attributed to flowers of Mexican hawthorns.

Flavonoid


Input: Antioxidant activity of Buglossoides purpureocaerulea (L.) I. M.


Input: Johnst. extracts.


Input: Buglossoides purpureocaerulea is a little-known plant used in the folk tradition for the preparation of a decoction in Sud, Italy, where it is appreciated for its beneficial effects on liver diseases.


Input: These properties may be due to the presence of antioxidant compounds.


Input: This study presents the phenolic characterisation and the antioxidant activity (AA) of B. purpureocaerulea extracts obtained by decoction, ethanol infusion and ethanol and methanol macerations.

ethanol

ethanol

methanol


Input: Total phenols ranged between 69 and 100 mg g (-1) dry weight (DW).


Input: The main compounds were: rosmarinic acid, caffeic acid, lithospermic acid and salvianolic acid C.

rosmarinic acid

caffeic acid

lithospermic acid

salvianolic acid C


Input: The extracts showed a good AA, particularly high for the decoction (142-283 micro mol TE g (-1) DW; TE, Trolox equivalent) and ethanol maceration extract (214-364 micro mol TE g (-1) DW) when determined by DPPH and ferric reducing antioxidant power test, respectively.

Trolox

ethanol

DPPH

ferric


Input: Live-birth rates after HP-hMG stimulation in the long GnRH agonist protocol: association with mid-follicular hCG and progesterone concentrations, but not with LH concentrations.

progesterone


Input: The aim of this retrospective study was to investigate the impact of endogenous and exogenous luteinizing hormone (LH) activity on treatment outcome, when taking into consideration potential confounding variables.


Input: Data were derived from IVF patients (n = 358) stimulated with highly purified menotrophin (HP-hMG) in a long gonadotrophin-releasing hormone (GnRH) agonist protocol.


Input: Simple retrospective logistic regression analysis showed that the mid-follicular exogenous concentrations of human chorionic gonadotrophin (hCG) (p = 0. 027), provided by the HP-hMG preparation, and female age (p = 0. 009) were significantly associated with live-birth rate, while the mid-follicular progesterone concentration (p = 0. 075), the estradiol concentration on last stimulation day (p = 0. 075) and number of embryos transferred (p = 0. 071) were borderline significant.

progesterone

estradiol


Input: Endogenous LH was not associated with live-birth rate; neither at start of stimulation (p = 0. 123), nor in the mid-follicular phase (p = 0. 933) or on the last day of stimulation (p = 0. 589).


Input: In the multiple regression analysis of life birth, mid-follicular hCG (p = 0. 016) was identified as a positive predictor, and age (p = 0. 004) and mid-follicular progesterone (p = 0. 029) as negative predictors.

progesterone


Input: In conclusion, mid-follicular concentrations of exogenous hCG and progesterone, but not endogenous LH, are associated with live-birth rate in IVF patients treated with HP-hMG in a long GnRH agonist cycle.

progesterone


Input: Development and characterization of composite YSZ-PEI electrophoretically deposited membrane for Li-ion battery.

PEI

Li


Input: In this work, the electrophoretic-deposition (EPD) method was used to fabricate pristine and composite ceramic-polymer membranes for application in planar and 3D microbattery configurations.


Input: The major focus was on the effect of polyethyleneimine additive on the morphology, composition, and electrochemical properties of the membrane.

polyethyleneimine


Input: The ionic conductivity, cycleability, and charge/discharge behavior of planar LiFePO (4)/Li cells comprising composite porous YSZ-based membrane with impregnated LiPF (6) EC: DEC electrolyte were found to be similar to the cells with commercial Celgard membrane.

LiFePO (4)

Li

LiPF (6)


Input: Conformal EPD coating of the electrode materials by a thin-film ceramic separator is advantageous for high-power operation and safety of batteries.


Input: Dose response analysis of monophthalates in the murine embryonic stem cell test assessed by cardiomyocyte differentiation and gene expression.

monophthalates


Input: The embryonic stem cell test (EST) is based on compound-induced inhibition of cardiomyocyte differentiation of pluripotent stem cells.


Input: We examined the use of transcriptomics to assess concentration-effect relationships and performed potency ranking within a chemical class.


Input: Three embryotoxic phthalate monoesters, monobutyl phthalate (MBuP), monobenzyl phthalate (MBzP) and mono-(2-ethylhexyl) phthalate (MEHP) and the non-embryotoxic monomethyl phthalate (MMP) were studied for their effects on gene expression.

phthalate monoesters

monobutyl phthalate

MBuP

monobenzyl phthalate

MBzP

mono-(2-ethylhexyl) phthalate

MEHP

monomethyl phthalate

MMP


Input: Effects on gene expression were observed at concentrations that did not inhibit cardiomyocyte differentiation or induce cytotoxicity.


Input: The embryotoxic phthalate monoesters altered the expression of 668 commonly expressed genes in a concentration-dependent fashion.

phthalate monoesters


Input: The same potency ranking was observed for morphology and gene expression (MEHP > MBzP > MBuP > MMP).

MEHP

MBzP

MBuP

MMP


Input: These results indicate that integrating transcriptomics provides a sensitive method to measure the dose-dependent effects of phthalate monoester exposure and enables potency ranking based on a common mode of action within a class of compounds.

phthalate monoester


Input: Transcriptomic approaches may improve the applicability of the EST, in terms of sensitivity and specificity.


Input: The antioxidant and anticancer effects of wild carrot oil extract.


Input: Daucus carota L. ssp.


Input: carota (Apiacea) is used in traditional medicine in Lebanon and in different regions throughout the world.


Input: The present study investigates the in vitro anticancer activities of Daucus carota oil extract (DCOE) on four human cancer cell lines as well as its in vitro antioxidant activity.


Input: DCOE was extracted from the dried umbels with 50: 50 acetone-methanol.

acetone

methanol


Input: The oil extract was analyzed by gas chromatography-mass spectrometry and screened for its antioxidant properties in vitro using 1, 1-diphenyl-2-picryl hydrazyl free radical scavenging assay (DPPH), ferrous ion chelating assay (FIC) and the ferric reducing antioxidant power assay (FRAP).

1, 1-diphenyl-2-picryl hydrazyl

DPPH

ferrous

ferric


Input: The anticancer activity of the oil extract against human colon (HT-29, Caco-2) and breast (MCF-7, MDA-MB-231) cancer cell lines was evaluated using the trypan blue exclusion method and the WST-1 cell proliferation assay.

trypan blue


Input: DCOE exhibited antioxidant activity in all assays used.


Input: The FRAP value was 164 +/- 5. 5 micro mol FeSO4/g, and the IC50 values for DPPH and FIC assays were 2. 1 +/- 0. 03 mg/ml and 0. 43 +/- 0. 02 mg/ml, respectively.

DPPH


Input: Also, DCOE demonstrated a significant increase in cell death and decrease in cell proliferation.


Input: The effect of DCOE on the cell lines exhibited time and dose-dependent responses.


Input: The present study established that DCOE possesses both antioxidant and promising anticancer activities.


Input: Copyright (c) 2012 John Wiley & Sons, Ltd.


Input: Protective Effects of a Purified Saponin Mixture from Astragalus corniculatus Bieb., in vivo Hepatotoxicity Models.

Saponin


Input: In this study, the in vivo effects of a purified saponin mixture (PSM), obtained from Astragalus corniculatus Bieb., were investigated using two in vivo hepatotoxicity models based on liver damage caused by paracetamol (PC) and carbon tetrachloride (CCl4).

saponin

paracetamol

carbon tetrachloride


Input: The effects of PSM were compared with silymarin.

silymarin


Input: Male Wistar rats were challenged orally with 20% CCl4 or PC (2 g/kg) four days after being pre-treated with PSM (100 mg/kg) or silymarin (200 mg/kg).

silymarin


Input: A significant decrease of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase (LDH) activities and glutathione (GSH) levels and an increase of malondialdehyde (MDA) quantity was observed after CCl4 and PC administration alone.

aspartate

alanine

lactate

glutathione

GSH

malondialdehyde

MDA


Input: PSM pre-treatment decreased serum transaminases and LDH activities and MDA levels and increased the levels of cell protector GSH.

MDA

GSH


Input: Biotransformation phase I enzymes were also assessed in both models.


Input: In the CCl4 hepatotoxicity model, pre-treatment with PSM or silymarin resulted in significantly increased activities of ethylmorphine-N-demethylase and aniline 4-hydroxylase activity and cytochrome P450, compared to the CCl4 only group.

silymarin

ethylmorphine

N

aniline


Input: Neither silymarin nor PSM influenced PC biotransformation.

silymarin


Input: Our results suggest that PSM, obtained from A. corniculatus, Bieb. showed in vivo hepatoprotective and antioxidant activities against CCl4 and PC-induced liver damage comparable to that of silymarin.

silymarin


Input: Copyright (c) 2012 John Wiley & Sons, Ltd.


Input: Influence of low ultrasound intensity on the degradation of dextran catalyzed by dextranase.


Input: In our current research work, the effect of ultrasound irradiation on the enzymatic activity and enzymatic hydrolysis kinetic parameters of dextran catalysis by dextranase were investigated.


Input: Furthermore, the effects of ultrasound irradiation on the structure of dextranase were investigated with the aid of fluorescence spectroscopy and circular dichroism (CD) spectroscopy.


Input: The maximum activity of dextranase was observed when the sample was treated with ultrasound at 25 kHz, 40 W for 15 min, under which the enzyme activity increased by 13. 43% compared the routine thermal incubation at 50 degrees C.


Input: Experimental Kinetics results, demonstrated that, both the V (max) and K (M) values of dextranase increased with ultrasound-treated compared with the incubation at 50 degrees C.


Input: Likewise, both the catalytic and specificity constants were higher under the effects of an ultrasonic field, indicating that, the substrate is converted into the product at an increased rate when compared with the incubation at 50 degrees C.


Input: On the other hand, fluorescence and CD spectra reflected that the ultrasound irradiation had increased the number of tryptophan on dextranase surface with increased alpha-helix by 15. 74% and reduced random coil by 5. 41% upon ultrasound-treated dextranase protein compared to the control, which were helpful for the improvement of its activity.

tryptophan


Input: Atomoxetine modulates spontaneous and sensory-evoked discharge of locus coeruleus noradrenergic neurons.

Atomoxetine


Input: Atomoxetine (ATM) is a potent norepinephrine (NE) uptake inhibitor and increases both NE and dopamine synaptic levels in prefrontal cortex, where it is thought to exert its beneficial effects on attention and impulsivity.

Atomoxetine

ATM

norepinephrine


Input: At the behavioral level, ATM has been shown to cause improvements on the measures of executive functions, such as response inhibition, working memory and attentional set shifting across different species.

ATM


Input: However, the exact mechanism of action for ATM' s effects on cognition is still not clear.

ATM


Input: One possible target for the cognitive enhancing effects of ATM is the noradrenergic locus coeruleus (LC), the only source of NE to key forebrain areas such as cerebral cortex and hippocampus.

ATM


Input: Although it is known that ATM increases NE availability overall by blocking reuptake of NE, the effects of this agent on impulse activity of LC neurons have not been reported.

ATM


Input: Here, the effect of ATM (0. 1-1 mg/kg, ip) on NE-LC neurons was investigated by recording extracellular activity of LC neurons in isoflurane-anesthetized rats.

ATM

isoflurane


Input: ATM caused a significant decrease of the tonic activity of LC single-units, although leaving intact the sensory-evoked excitatory component of LC phasic response.

ATM


Input: Moreover, the magnitude of the inhibitory component of LC response to paw stimulation was increased after 1 mg/kg of ATM and its duration was prolonged at 0. 3 mg/kg.

ATM


Input: Together, these effects of ATM produced an increase in the phasic-to-tonic ratio of LC phasic response to sensory stimulation.

ATM


Input: ATM also modulated the average sensory-evoked local field potential (LFP) and spike-field coherence in LC depending on the dose tested.

ATM


Input: The lower dose (0. 1 mg/kg) significantly decreased early positive and negative components of the sensory-evoked LFP response.


Input: Higher doses (0. 3-1 mg/kg) initially increased and then decreased the amplitude of components of the evoked fields, whereas the spike-field coherence was enhanced by 1 mg/kg ATM across frequency bands.

ATM


Input: Finally, coherence between LC fields and EEG signals was generally increased by 1 mg/kg ATM, whereas 0. 1 and 0. 3 mg/kg respectively decreased and increased coherence values in specific frequency bands.

ATM


Input: Taken together these results suggest that ATM effects on LC neuronal activity are dose-dependent, with different doses affecting different aspects of LC firing.

ATM


Input: This modulation of activity of LC-NE neurons may play a role in the cognitive effects of ATM.

ATM


Input: This article is part of a Special Issue entitled' Cognitive Enhancers'.


Input: Could maternal exposure to the antidepressants fluoxetine and St.

fluoxetine


Input: John' s Wort induce long-term reproductive effects on male rats?


Input: Based on the limited number of studies that have investigated the adverse effects of maternal treatment with antidepressants on the development of male descendents, this study was carried out in rat in order to evaluate if maternal exposure to fluoxetine (FLX) or St.

fluoxetine

FLX


Input: John' s Wort (SJW) could disrupt the development of male offspring.


Input: The dams were treated daily, by gavage, with 7. 5 mg/kg of FLX or 100 mg/kg SJW during pregnancy and lactation.

FLX


Input: The reproductive and behavior parameters were analyzed in male pups.


Input: Results showed decreases in the weight of the full seminal vesicle and in the number of spermatozoa.


Input: Moreover, FLX-exposed pups presented reduced seminiferous epithelium height and diameter of seminiferous tubules.

FLX


Input: The present study shows that maternal exposure to FLX, but not SJW could interfere on reproductive parameters in adult male rats.

FLX


Input: Telomere shortening and DNA damage of embryonic stem cells induced by cigarette smoke.


Input: Embryonic stem cells (ESCs) provide a valuable in vitro model for testing toxicity of chemicals and environmental contaminants including cigarette smoke.


Input: Mouse ESCs were acutely or chronically exposed to smoke components, cigarette smoke condensate (CSC), or cadmium, an abundant component of CSC, and then evaluated for their self-renewal, apoptosis, DNA damage and telomere function.

cadmium


Input: Acute exposure of ESCs to high dose of CSC or cadmium increased DNA damage and apoptosis.

cadmium


Input: Yet, ESCs exhibited a remarkable capacity to recover following absence of exposure.


Input: Chronic exposure of ESCs to low dose of CSC or cadmium resulted in shorter telomeres and DNA damage.

cadmium


Input: Together, acute exposure of ESCs to CSC or cadmium causes immediate cell death and reduces pluripotency, while chronic exposure of ESCs to CSC or cadmium leads to DNA damage and telomere shortening.

cadmium

cadmium


Input: Notably, a sub-proportion of ESCs during passages is selected to resist to smoke-induced oxidative damage to telomeres.


Input: Electrophoretic deposition of the thiophene-based copolymer and its composites with C60.

thiophene


Input: Electrophoretic deposition is a useful and efficient technique to deposit conjugated polymers, if suitable suspension of the target polymer is obtained.


Input: Unfortunately, neither general theory nor universal procedure for the preparation of a suspension suitable for electrophoretic deposition has seemed to be established yet.


Input: Thus, accumulation of individual knowledge is still important in this area.


Input: Here, the preparation of suspensions of a thiophene-based polymer poly (3-octylthiophene-2, 5-diyl-co-3-decyloxythiophene-2, 5-diyl) (POT-co-DOT) and their application to the electrophoretic deposition have been reported.

thiophene

poly (3-octylthiophene-2, 5-diyl-co-3-decyloxythiophene-2, 5-diyl)

POT-co-DOT


Input: The suspensions of POT-co-DOT with various good/poor solvents ratios were easily obtained by mixing a toluene solution of the polymer and acetonitrile.

POT-co-DOT

toluene

acetonitrile


Input: The composition of the dispersion medium significantly affects the surface morphology of the film prepared by the electrophoretic deposition in the suspension.


Input: Composite films consisting of POT-co-DOT and C (60) have also been successfully prepared by electrophoretic deposition.

POT-co-DOT

C (60)


Input: Because the optical absorption peak at 333 nm in C (60) showed neither significant broadening nor a red shift, C (60) molecules were expected to be well-dispersed in the composite films.

C (60)

C (60)


Input: A photovoltaic device with a composite film prepared from a POT-co-DOT/C (60) = 2: 1 suspension showed 10 times larger short-circuit current density and 5 times larger power conversion efficiency than a device with pure POT-co-DOT, although further work is required to improve the device performance.

POT-co-DOT

C (60)

POT-co-DOT


Input: Structural requirements for effective oximes-Evaluation of kinetic in vitro data with phosphylated human AChE and structurally different oximes.

oximes

oximes


Input: Treatment of poisoning by various organophosphorus (OP) nerve agents with established acetylcholinesterase (AChE) reactivators (oximes) is insufficient.

organophosphorus

oximes


Input: In consequence, extensive research programs have been undertaken in various countries in the past decades to identify more effective oximes.

oximes


Input: The efficacy of new compounds has been investigated with different in vitro and in vivo models which hamper the comparison of results from different laboratories.


Input: The crucial mechanism of action of oximes is the reactivation of phosphylated AChE.

oximes


Input: The kinetic properties of these compounds can be quantified in vitro with isolated AChE from different origin.


Input: It was tempting to evaluate the reactivation kinetics of a series of oximes with various OP inhibitors performed under identical experimental conditions in order to get insight into structural requirements for adequate affinity and reactivity towards inhibited AChE.

oximes


Input: The determination of reactivation rate constants with bispyridinium oximes having different linkers, bearing oxime group (s) at different positions and having in part additional substituents revealed that (a) the reactivating potency was dependent on the position of the oxime groups and of additional substituents, (b) small modifications of the oxime structure had an in part marked effect on the kinetic properties and (c) no single oxime had an adequate reactivating potency with AChE inhibited by structurally different OP.

bispyridinium oximes

oxime

oxime

oxime

oxime


Input: These and previous studies underline the necessity to investigate in detail the kinetic properties of novel oximes and that the identification of a single oxime being effective against a broad range of structurally different OP will remain a major challenge.

oximes

oxime


Input: Evaluation of seven drug metabolisms and clearances by cryopreserved human primary hepatocytes cultivated in microfluidic biochips.


Input: We present characterization of the metabolic performance of human cryopreserved hepatocytes cultivated in a platform of parallelized microfluidic biochips.


Input: The RTqPCR analysis revealed that the mRNA levels of the cytochromes P450 (CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4) were reduced after the adhesion period (when compared to the post-thawing step).


Input: The microfluidic perfusion played a part in stabilizing and partially recovering the levels of the HNF4 alpha, PXR, OAPT2, CYP 1A2, 2B6, 2C19 and 3A4 mRNA on contrary to non-perfused cultures.


Input: Fluorescein diacetate staining and P-gp mRNA level illustrated the hepatocytes' polarity in the biochips.

Fluorescein diacetate


Input: Drug metabolism was assessed using midazolam, tolbutamide, caffeine, omeprazole, dextromethorphan, acetaminophen and repaglinide as probes.

midazolam

tolbutamide

caffeine

omeprazole

dextromethorphan

acetaminophen

repaglinide


Input: Metabolite detection and quantification revealed that CYP1A2 (via the detection of paraxanthine), CYP3A4 (via 1-OH-midazolam, and omeprazole sulfone detection), CYP2C8 (via hydroxyl-repaglinide detection), CYP2C19 (via hydroxy-omeprazole detection) and CYP2D6 (via dextrorphan detection) were functional in our microfluidic configurations.

paraxanthine

omeprazole sulfone

hydroxyl-repaglinide

hydroxy-omeprazole

dextrorphan


Input: Furthermore, the RTqPCR analysis showed that the drugs acted as inductors leading to overexpression of mRNA levels when compared to post-thawing values (such as for HNF4 alpha, PXR and CYP3A4 by dextromethorpahn and omeprazole).

dextromethorpahn

omeprazole


Input: Finally, intrinsic in vitro biochip clearances were extracted using a PBPK model for predictions.


Input: The biochip predictions were compared to literature in vitro data and in vivo situations.


Input: Vitamin A deficiency disturbs collagen IV and laminin composition and decreases matrix metalloproteinase concentrations in rat lung.

Vitamin A


Input: Partial reversibility by retinoic acid.

retinoic acid


Input: Vitamin A is essential for lung development and pulmonary cell differentiation.

Vitamin A


Input: Its deficiency leads to altered lung structure and function and to basement membrane architecture and composition disturbances.


Input: Previously, we showed that lack of retinoids thickens the alveolar basement membrane and increases collagen IV, which are reversed by retinoic acid, the main biologically active vitamin A form.

retinoids

retinoic acid

vitamin A


Input: This study analyzed how vitamin A deficiency affects the subunit composition of collagen IV and laminin of lung basement membranes and pulmonary matrix metalloproteinase content, plus the recovering effect of all-trans-retinoic acid.

vitamin A

all-trans-retinoic acid


Input: Male weanling pups were fed a retinol-adequate/-deficient diet until 60 days old.

retinol


Input: A subgroup of vitamin-A-deficient pups received daily intraperitoneal all-trans-retinoic acid injections for 10 days.

vitamin-A

all-trans-retinoic acid


Input: Collagen IV and laminin chain composition were modified in vitamin-A-deficient rats.

vitamin-A


Input: The protein and mRNA contents of chains alpha 1 (IV), alpha 3 (IV) and alpha 4 (IV) increased; those of chains alpha 2 (IV) and alpha 5 (IV) remained unchanged; and the protein and mRNA contents of laminin chains alpha 5, beta 1 and gamma 1 decreased.


Input: The mRNA of laminin chains alpha 2 and alpha 4 also decreased.


Input: Matrix metalloproteinases 2 and 9 decreased, but the tissue inhibitors of metalloproteinases 1 and 2 did not change.


Input: Treating vitamin-A-deficient rats with retinoic acid reversed all alterations, but laminin chains alpha 2, alpha 4 and alpha 5 and matrix metalloproteinase 2 remained low.

vitamin-A

retinoic acid


Input: In conclusion, vitamin A deficiency alters the subunit composition of collagen IV and laminin and the lung' s proteolytic potential, which are partly reverted by retinoic acid.

vitamin A

retinoic acid


Input: These alterations could contribute to impaired lung function and predispose to pulmonary disease.


Input: The alignment of barium ferrite nanoparticles from their suspensions in electric and magnetic fields.

barium ferrite


Input: The alignment of plate-like barium ferrite nanoparticles, with diameters of 10-350 nm and thicknesses of 3-10 nm, in electric and/or magnetic fields was studied.

barium ferrite


Input: Stable suspensions were prepared in 1-butanol with dodecylbenzenesulphonic acid as a surfactant.

dodecylbenzenesulphonic acid


Input: The deposits were produced from the suspensions with classic electrophoretic deposition, electrophoretic deposition in a magnetic field, and with drying in a magnetic field.


Input: The experiments, supported by theoretical calculations, show that the alignment of the nanoplates in the deposits was determined by the interplay between the hydrodynamic, electric, and magnetic forces.


Input: The preferential alignment of the nanoplates in plane with the substrate coincided with their magnetic orientation, and it increased with the shape anisotropy of the particles.


Input: The deposits were sintered at 1150 degrees C for 5 h to obtain ceramic films, which showed a magnetic orientation up to 90%.


Input: Sclerostin antibody improves skeletal parameters in a Brtl/+ mouse model of osteogenesis imperfecta.


Input: Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by osteopenia and easy susceptibility to fracture.


Input: Symptoms are most prominent during childhood.


Input: Although antiresorptive bisphosphonates have been widely used to treat pediatric OI, controlled trials show improved vertebral parameters but equivocal effects on long-bone fracture rates.


Input: New treatments for OI are needed to increase bone mass throughout the skeleton.


Input: Sclerostin antibody (Scl-Ab) therapy is potently anabolic in the skeleton by stimulating osteoblasts via the canonical wnt signaling pathway, and may be beneficial for treating OI.


Input: In this study, Scl-Ab therapy was investigated in mice heterozygous for a typical OI-causing Gly --> Cys substitution in col1a1.

Gly

Cys


Input: Two weeks of Scl-Ab successfully stimulated osteoblast bone formation in a knock-in model for moderately severe OI (Brtl/+) and in WT mice, leading to improved bone mass and reduced long-bone fragility.


Input: Image-guided nanoindentation revealed no alteration in local tissue mineralization dynamics with Scl-Ab.


Input: These results contrast with previous findings of antiresorptive efficacy in OI both in mechanism and potency of effects on fragility.


Input: In conclusion, short-term Scl-Ab was successfully anabolic in osteoblasts harboring a typical OI-causing collagen mutation and represents a potential new therapy to improve bone mass and reduce fractures in pediatric OI.


Input: Hospitalized osteoporotic vertebral fracture increases the risk of stroke: a population-based cohort study.


Input: The association between osteoporosis and cardiovascular diseases has been demonstrated.


Input: Higher cardiovascular risk has also been correlated with vertebral fractures.


Input: However, the association between osteoporotic vertebral fracture and the possibly higher risk of stroke remains uncertain.


Input: This study aimed to evaluate the incidence, risk, and type of stroke in patients with osteoporotic vertebral fracture.


Input: Patients with osteoporotic vertebral fracture were identified (n = 380) and 10 age-and sex-matched controls per case (comparison group, n = 3795) were chosen from a nationwide representative cohort of 999, 997 people from 1998 to 2005.


Input: Both groups were followed-up for stroke events for 3 years, matched by propensity scores with adjustments for covariates such as comorbidities (ie, hypertension, diabetes, arrhythmia, or coronary heart diseases) and exposure to medications (ie, aspirin, lipid lowering drug, or nitrates), and assessed by Kaplan-Meier and Cox regression analyses.

aspirin

nitrates


Input: The incidence rate of stroke in the osteoporotic vertebral fracture group (37. 5 per 1000 person-years; 95% confidence interval [CI], 27. 5-51. 2) was significantly higher than in the comparison group (14. 0 per 1000 person-years; 95% CI, 12. 0-16. 4, p < 0. 001).


Input: Stroke was more likely to occur in the osteoporotic vertebral fracture patients than in the normal controls (crude hazard ratio [HR] 2. 68, 95% CI 1. 89-3. 79, p < 0. 001; adjusted HR 2. 71, 95% CI 1. 90-3. 86, p < 0. 001).


Input: In conclusion, patients with osteoporotic vertebral fracture have a higher risk of stroke (ie, both ischemic and hemorrhagic) and require stroke prevention strategies.


Input: Three new diarylbutane lignans from the resin of Bursera fagaroides.

diarylbutane lignans


Input: Three new diarylbutane lignans, named 9-acetyl-9'-pentadecanoil-dihydroclusin (1), 2, 3-demethoxy-secoisolintetralin monoacetate (4) and dihydroclusin monoacetate (5), have been isolated from the resin of Bursera fagaroides, together with two known ones, 2, 3-demethoxy-secoisolintetralin diacetate (2) and dihydroclusin diacetate (3).

diarylbutane lignans

2, 3-demethoxy-secoisolintetralin monoacetate

dihydroclusin monoacetate

2, 3-demethoxy-secoisolintetralin diacetate

dihydroclusin diacetate


Input: The complete structure assignments were obtained by means of (1) H and (13) C NMR spectra.

(1) H

(13) C


Input: Pelargonium graveolens L' Her. and Artemisia arborescens L. essential oils: Chemical composition, antifungal activity against Rhizoctonia solani and insecticidal activity against Rhysopertha dominica.


Input: The chemical composition of the Pelargonium graveolens essential oil allowed the identification of 15 compounds (93. 86% of the total essential oil).


Input: The major fractions were citronellol (35%) and geraniol (28. 8%).

citronellol

geraniol


Input: The chemical composition of the Artemisia arborescens essential oil revealed twenty-one compounds representing 93. 57% of the total essential oil.


Input: The main compounds were chamazulene (31. 9%) and camphor (25. 8%).

chamazulene

camphor


Input: The insecticidal effects were tested towards the insect Rhysopertha dominica.


Input: Results revealed that these two essential oils were highly effective against R. dominica at the dose of 50 micro L on Petri dish of 8. 5 cm of diameter.


Input: The antifungal activity was evaluated against Rhizoctonia solani and results showed that both of the essential oils were highly active at a dose of 12. 5 micro L/20 mL of PDA.


Input: Moreover, the inhibitory effect of P. graveolens essential oil was evidenced as stronger than that of the A. arborescens oil for all the tested doses.


Input: A new cyclonerol derivative from a marine-derived fungus Ascotricha sp.

cyclonerol


Input: A new sesquiterpene, ascotrichic acid (1), was isolated from a marine-derived fungus Ascotricha sp., together with the other two known analogues, cyclonerodiol (2) and 10 (Z)-cyclonerotriol (3).

sesquiterpene

cyclonerodiol

10 (Z)-cyclonerotriol


Input: Its structure was established by spectroscopic methods (1D and 2D NMR, HR-ESI-MS).


Input: Methylselenol, a selenium metabolite, modulates p53 pathway and inhibits the growth of colon cancer xenografts in Balb/c mice.

Methylselenol

selenium


Input: It is has been hypothesized that methylselenol is a critical selenium metabolite for anticancer activity in vivo.

methylselenol

selenium


Input: In this study, we used a protein array which contained 112 different antibodies known to be involved in the p53 pathway to investigate the molecular targets of methylselenol in human HCT116 colon cancer cells.

methylselenol


Input: The array analysis indicated that methylselenol exposure changed the expression of 11 protein targets related to the regulation of cell cycle and apoptosis.

methylselenol


Input: Subsequently, we confirmed these proteins with the Western blotting approach, and found that methylselenol increased the expression of GADD 153 and p21 but reduced the level of c-Myc, E2F1 and Phos p38 MAP kinase.

methylselenol


Input: Similar to our previous report on human HCT116 colon cancer cells, methylselenol also inhibited cell growth and led to an increase in G1 and G2 fractions with a concomitant drop in S-phase in mouse colon cancer MC26 cells.

methylselenol


Input: When the MC26 cells were transplanted to their immune-competent Balb/c mice, methylselenol-treated MC26 cells had significantly less tumor growth potential than that of untreated MC26 cells.

methylselenol


Input: Taken together, our data suggest that methylselenol modulates the expression of key genes related to cell cycle and apoptosis and inhibits colon cancer cell proliferation and tumor growth.

methylselenol


Input: Effects of biotin supplementation in the diet on insulin secretion, islet gene expression, glucose homeostasis and beta-cell proportion.

biotin

glucose


Input: Besides its role as a carboxylase cofactor, biotin has a wide repertoire of effects on gene expression, development and metabolism.

biotin


Input: Pharmacological concentrations of biotin enhance insulin secretion and the expression of genes and signaling pathways that favor islet function in vitro.

biotin


Input: However, the in vivo effects of biotin supplementation on pancreatic islet function are largely unknown.

biotin


Input: In the present study, we investigated whether in vivo biotin supplementation in the diet has positive effects in rodent pancreatic islets.

biotin


Input: Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet over 8 weeks postweaning and tested for glucose homeostasis, insulin secretion, islet gene expression and pancreatic morphometry.

biotin

glucose


Input: Insulin secretion increased from the islets of biotin-supplemented mice, together with the messenger RNA (mRNA) expression of several transcription factors regulating insulin expression and secretion, including forkhead box A2, pancreatic and duodenal homeobox 1 and hepatocyte nuclear factor 4 alpha.

biotin


Input: The mRNA abundance of glucokinase, Cacna1d, acetyl-CoA carboxylase, and insulin also increased.

acetyl-CoA


Input: Consistent with these effects, glucose tolerance improved, and glucose-stimulated serum insulin levels increased in biotin-supplemented mice, without changes in fasting glucose levels or insulin tolerance.

glucose

glucose

biotin

glucose


Input: Biotin supplementation augmented the proportion of beta cells by enlarging islet size and, unexpectedly, also increased the percentage of islets with alpha cells at the islet core.

Biotin


Input: mRNA expression of neural cell adhesion molecule 1, an adhesion protein participating in the maintenance of islet architecture, decreased in biotin-supplemented islets.

biotin


Input: These findings provide, for the first time, insight into how biotin supplementation exerts its effects on function and proportion of beta cells, suggesting a role for biotin in the prevention and treatment of diabetes.

biotin

biotin


Input: Chronic caffeine prevents changes in inhibitory avoidance memory and hippocampal BDNF immunocontent in middle-aged rats.

caffeine


Input: Beneficial effects of caffeine on memory processes have been observed in animal models relevant to neurodegenerative diseases and aging, although the underlying mechanisms remain unknown.

caffeine


Input: Because brain-derived neurotrophic factor (BDNF) is associated with memory formation and BDNF' s actions are modulated by adenosine receptors, the molecular targets for the psychostimulant actions of caffeine, we here compare the effects of chronic caffeine (1 mg/mL drinking solution for 30 days) on short-and long term memory and on levels of hippocampal proBDNF, mature BDNF, TrkB and CREB in young (3 month old) and middle-aged (12 month old) rats.

adenosine

caffeine

caffeine


Input: Caffeine treatment substantially reduced i) age-related impairments in the two types of memory in an inhibitory avoidance paradigm, and ii) parallel increases in hippocampal BDNF levels.

Caffeine


Input: In addition, chronic caffeine increased proBDNF and CREB concentrations, and decreased TrkB levels, in hippocampus regardless of age.

caffeine


Input: These data provide new evidence in favor of the hypothesis that modifications in BDNF and related proteins in the hippocampus contribute to the pro-cognitive effects of caffeine on age-associated losses in memory encoding.

caffeine


Input: This article is part of a Special Issue entitled' Cognitive Enhancers'.


Input: Cognitive enhancement by omega-3 fatty acids from child-hood to old age: findings from animal and clinical studies.

omega-3 fatty acids


Input: Omega-(n)-3 polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are major components of neuronal membranes and have a wide range of functions, from modulating synaptic plasticity and neurochemistry, to neuroimmune-modulation and neuroprotection.

Omega-(n)-3 polyunsaturated fatty acids

PUFAs

docosahexaenoic acid

DHA

eicosapentaenoic acid

EPA


Input: Thus, it is not surprising that n-3 PUFA are widely acknowledged to have cognitive-enhancing effects.

PUFA


Input: Although clinical evidence is somewhat conflicting, probably in large part due to methodological issues, animal studies have consistently demonstrated that n-3 PUFA are indispensable for proper brain development, may enhance cognitive function in healthy, adult individuals and attenuate cognitive impairment in aging and age-related disorders, such as dementia.

PUFA


Input: This review discusses and integrates up to date evidence from clinical and animal studies investigating the cognitive-enhancing effects of n-3 PUFA during development, child-and adult-hood, as well as old-age with associated neurodegenerative diseases, such as Alzheimer' s disease.

PUFA


Input: Furthermore, we cover the major underlying biochemical and neurophysiological mechanisms by which n-3 PUFA mediate these effects on cognition.

PUFA


Input: This article is part of a Special Issue entitled' Cognitive Enhancers'.


Input: Interaction of tumor cells with the immune system: implications for dendritic cell therapy and cancer progression.


Input: There is a continuous demand for preclinical modeling of the interaction of dendritic cells with the immune system and cancer cells.


Input: Recent progress in gene expression profiling with nucleic acid microarrays, in silico modeling and in vivo cell and animal approaches for non-clinical proof of safety and efficacy of these immunotherapies is summarized.


Input: Immunoinformatic approaches look promising to unfold this potential, although still unstable and difficult to interpret.


Input: Animal models have progressed a great deal in recent years, finally narrowing the gap from bench to bedside.


Input: However, translation to the clinic should be done with precaution.


Input: The most significant results concerning clinical benefit might come from detailed immunologic investigations made during well designed clinical trials of dendritic-cell-based therapies, which in general prove safe.


Input: Matching biochemical and functional efficacies confirm ZIP as a potent competitive inhibitor of PKM zeta in neurons.

ZIP


Input: PKM zeta is an autonomously active, atypical protein kinase C (aPKC) isoform that is both necessary and sufficient for maintaining long-term potentiation (LTP) and long-term memory.


Input: The myristoylated zeta-pseudosubstrate peptide, ZIP, potently inhibits PKM zeta biochemically in vitro, within cultured cells, and within neurons in hippocampal slices, and reverses LTP maintenance and erases long-term memory storage.

myristoylated zeta-pseudosubstrate peptide

ZIP


Input: A recent study (Wu-Zhang et al., 2012), however, suggested ZIP was not effective on a PKM zeta fusion protein overexpressed in cultured cells.

ZIP


Input: Chelerythrine, a redox-sensitive PKC inhibitor that inhibits PKM zeta and disrupts LTP maintenance and memory storage, was also reported by Wu-Zhang et al.

Chelerythrine


Input: (2012) not to inhibit the expressed PKM zeta fusion protein.


Input: However, the efficacy of inhibitors on endogenous enzymes in cells may not be adequately assessed in expression systems in which levels of expression of exogenous enzymes greatly exceed those of endogenous enzymes.


Input: Thus, we show, biochemically, that when PKM zeta reaches a level beyond that necessary for substrate phosphorylation such that much of the enzyme is excess or' spare' kinase, ZIP and chelerythrine do not effectively block substrate phosphorylation.

ZIP

chelerythrine


Input: We also show that the cellular overexpression techniques used by Wu-Zhang et al.


Input: (2012) increase kinase levels ~ 30-40 fold above normal levels in transfected cells.


Input: Using a mathematical model we show that at such level of overexpression, standard concentrations of inhibitor should have no noticeable effect.


Input: Furthermore, we demonstrate the standard concentrations of ZIP, but not scrambled ZIP, inhibit the ability of PKM zeta to potentiate AMPAR responses at postsynaptic sites, the physiological function of the kinase.

ZIP

ZIP


Input: Wu-Zhang et al.


Input: (2012) had also claimed that staurosporine, a general kinase inhibitor that does not effectively inhibit PKM zeta biochemically in vitro, nonetheless indirectly blocked the PKM zeta fusion protein overexpressed in cultured cells by inhibiting phosphoinositide-dependent protein kinase-1 (PDK1).

staurosporine


Input: However, here we show that staurosporine does not affect PDK1 phosphorylation of the endogenous PKM zeta in hippocampal slices.

staurosporine


Input: Thus, the biochemical in vitro effects of PKM zeta inhibitors correspond with their intracellular effects, and ZIP and chelerythrine, together with scrambled ZIP and staurosporine as controls, are effective tools to examine the function of PKM zeta in neurons.

ZIP

chelerythrine

ZIP

staurosporine


Input: This article is part of a Special Issue entitled' Cognitive Enhancers'.


Input: NT, NPY and PGP 9. 5 presence in myomeytrium and in fibroid pseudocapsule and their possible impact on muscular physiology.


Input: The uterine myoma pseudocapsule is a neurovascular bundle surrounding fibroid, containing neuropeptides, probably involved in uterine scar healing.


Input: We studied neurotensin (NT), neuropeptide tyrosine (NPY), and protein gene product 9. 5 (PGP 9. 5) nerve fibres in the pseudocapsule neurovascular bundle of intramural uterine fibroids on 67 no pregnant women by intracapsular myomectomy sparing the neurovascular bundle, sampling full thickness specimens of the pseudocapsule of uterine fibroids (PUF) and normal myometrium (NM) obtained from the fundus uteri (FU) and the uterine body (UB).

neurotensin

tyrosine


Input: The samples were sent for histological and immunofluorescent analyses and compared by morphometrical quantification.


Input: The Conventional Unit (C. U.) difference of NT, NPY, and PGP 9. 5 nerve fibres was statistically analyzed.


Input: Our results showed that NT, NPY, and PGP 9. 5 neurofibers are almost equally present in PUF as in NM of a no pregnant uterus.


Input: As all of these neuropeptides are present in the uterine muscle and can affect muscle contractility, uterine peristalsis and muscular healing.


Input: A myomectomy respecting the pseudocapsule neurofibers should facilitate smooth muscle scarring and promote restoration of normal uterine peristalsis with a possible positive influence on fertility.


Input: Increased expression of transthyretin in leptin-deficient ob/ob mice is not causative for their major phenotypic abnormalities.


Input: The hormone leptin is a critical regulator of adipogenesis and energy metabolism.


Input: Similarly, leptin-deficient ob/ob mice display various metabolic abnormalities, including not only obesity and insulin resistance, but also hypogonadism and high bone mass.


Input: By genome-wide expression analysis using hypothalamus RNA from wild-type and ob/ob mice, we observed the increased expression of the gene for transthyretin (Ttr) in the latter, as confirmed by quantitative real-time-polymerase chain reaction.


Input: Because Ttr encodes a carrier protein for retinol transport, and because we further found increased retinol levels in the serum of ob/ob mice, we investigated whether the additional absence of Ttr would influence the ob/ob phenotype.


Input: It was found that Ttr-deficient ob/ob mice were indistinguishable from ob/ob littermates in terms of body weight, as well as serum glucose, insulin and cholesterol levels.

glucose

cholesterol


Input: Although all of these parameters were identical to wild-type controls in Ttr-deficient mice, we found that the sole deletion of Ttr caused a significant increase of trabecular bone mass, bone marrow adiposity and mean adipocyte area in white adipose tissue.


Input: Interestingly, all these latter parameters were highest in Ttr-deficient ob/ob mice, and only in these mice did we observe a full penetrance of liver steatosis at 24 weeks of age.


Input: Taken together, our data demonstrate that the increased expression of Ttr in ob/ob mice does not cause (but rather attenuates) their phenotypic abnormalities.


Input: Effects of fenofibrate, a PPAR-alpha ligand, on the haemodynamics of glycerol-induced renal failure in rats.

fenofibrate

glycerol


Input: The modulating effect of peroxisome proliferator-activated receptor alpha ligand on haemodynamic effects of phenylepherine (PE), angiotensin II (AII), endothelin 1 (ET1), acetylcholine (Ach), sodium nitroprusside (SNP) and isoproterenol (ISO) were evaluated in glycerol-induced acute kidney injury in rats.

phenylepherine

acetylcholine

Ach

sodium nitroprusside

SNP

isoproterenol

ISO

glycerol


Input: The effect of PE on fenofibrate-treated animals was a dose-dependent increase in mean arterial blood pressure (MAP).

fenofibrate


Input: For AII and ET1, MAP was also increased for the fenofibrate group but not in a dose-dependent fashion.

fenofibrate


Input: On the medullary blood flow (MBF), while the lower doses of PE and AII increased the perfusion unit on the fenofibrate-treated group, the higher doses decreased the perfusion unit.

fenofibrate


Input: The ET1 increased the perfusion unit on this group but not in dose-dependent fashion.


Input: The effects of PE and AII on the cortical blood flow (CBF) of fenofibrate-treated group is similar to that of MBF for the same group but not for ET1.

fenofibrate


Input: The effect of Ach, SNP and ISO in all the groups was the decrease in MAP.

Ach

SNP

ISO


Input: ISO caused dose-dependent increase in MBF of fenofibrate-treated group.

ISO

fenofibrate


Input: The effect of Ach, SNP and ISO on the CBF perfusion unit was that of the increase for the fenofibrate-treated group.

Ach

SNP

ISO

fenofibrate


Input: The study showed that fenofibrate did not attenuate increased blood pressure induced by PE, AII and ET1 but caused enhanced vasodilation by Ach, SNP and ISO.

fenofibrate

Ach

SNP

ISO


Input: Incretin and pancreatic hormone secretion in Caucasian non-diabetic carriers of the TCF7L2 rs7903146 risk T allele.


Input: We characterised 62 non-diabetic, middle-aged, Caucasians with and without the T risk allele of rs7903146 in transcription factor 7-like 2 (TCF7L2) with regard to secretion of insulin, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) as well as insulin sensitivity and endogenous glucose production.

glucose

glucose


Input: All participants had a 3-h oral glucose tolerance test (OGTT), an intravenous glucose tolerance test and a euglycaemic, hyperinsulinaemic clamp.

glucose

glucose


Input: After adjustment for age and sex, risk T allele carriers had higher haemoglobin A1c levels (p = 0. 030), reduced first-phase insulin response (p = 0. 048), higher peripheral insulin sensitivity (p = 0. 050) and lower fasting GIP concentrations (p = 0. 003) than CC allele carriers.


Input: The latter was also reflected by lower total GIP secretion during the OGTT (p = 0. 018).


Input: We found no significant differences in endogenous glucose production, hepatic insulin sensitivity or fasting concentrations of glucose, insulin, glucagon and GLP-1 between the groups.

glucose

glucose


Input: The findings suggest that the effect of TCF7L2 on diabetes risk may include reduced secretion of GIP.


Input: Aurora A kinase (AURKA) in normal and pathological cell division.


Input: Temporally and spatially controlled activation of the Aurora A kinase (AURKA) regulates centrosome maturation, entry into mitosis, formation and function of the bipolar spindle, and cytokinesis.


Input: Genetic amplification and mRNA and protein overexpression of Aurora A are common in many types of solid tumor, and associated with aneuploidy, supernumerary centrosomes, defective mitotic spindles, and resistance to apoptosis.


Input: These properties have led Aurora A to be considered a high-value target for development of cancer therapeutics, with multiple agents currently in early-phase clinical trials.


Input: More recently, identification of additional, non-mitotic functions and means of activation of Aurora A during interphase neurite elongation and ciliary resorption have significantly expanded our understanding of its function, and may offer insights into the clinical performance of Aurora A inhibitors.


Input: Here we review the mitotic and non-mitotic functions of Aurora A, discuss Aurora A regulation in the context of protein structural information, and evaluate progress in understanding and inhibiting Aurora A in cancer.


Input: The R740S mutation in the V-ATPase a3 subunit increases lysosomal pH, impairs NFATc1 translocation, and decreases in vitro osteoclastogenesis.


Input: Vacuolar H (+)-ATPase (V-ATPase), a multisubunit enzyme located at the ruffled border and in lysosomes of osteoclasts, is necessary for bone resorption.

H (+)


Input: We previously showed that heterozygous mice with an R740S mutation in the a3 subunit of V-ATPase (+/R740S) have mild osteopetrosis resulting from an ~ 90% reduction in proton translocation across osteoclast membranes.


Input: Here we show that lysosomal pH is also higher in +/R740S compared with wild-type (+/+) osteoclasts.


Input: Both osteoclast number and size were decreased in cultures of +/R740S compared with +/+ bone marrow cells, with concomitant decreased expression of key osteoclast markers (TRAP, cathepsin K, OSCAR, DC-STAMP, and NFATc1), suggesting that low lysosomal pH plays an important role in osteoclastogenesis.


Input: To elucidate the molecular mechanism of this inhibition, NFATc1 activation was assessed.


Input: NFATc1 nuclear translocation was significantly reduced in +/R740S compared with +/+ cells; however, this was not because of impaired enzymatic activity of calcineurin, the phosphatase responsible for NFATc1 dephosphorylation.


Input: Protein and RNA expression levels of regulator of calcineurin 1 (RCAN1), an endogenous inhibitor of NFATc1 activation and a protein degraded in lysosomes, were not significantly different between +/R740S and +/+ osteoclasts, but the RCAN1/NFATc1 ratio was significantly higher in +/R740S versus +/+ cells.


Input: The lysosomal inhibitor chloroquine significantly increased RCAN1 accumulation in +/+ cells, consistent with the hypothesis that higher lysosomal pH impairs RCAN1 degradation, leading to a higher RCAN1/NFATc1 ratio and consequently NFATc1 inhibition.

chloroquine


Input: Our data indicate that increased lysosomal pH in osteoclasts leads to decreased NFATc1 signaling and nuclear translocation, resulting in a cell autonomous impairment of osteoclastogenesis in vitro.


Input: Metabolic profiling of TRPV1 antagonists of the benzothiazole amide series: implications for in vitro genotoxicity assessment.

benzothiazole amide


Input: In vitro metabolic profiling and in vitro genotoxicity assessment are important aspects of the drug discovery program as they eliminate harmful compounds from further development.


Input: In standard in vitro genotoxicity testing, induced rat liver S9 is used as an exogenous bio-activation system for detecting promutagens.


Input: In this study we show that rat liver S9 is an insufficient system regarding the conversion of TRPV1 antagonists of the benzothiazole amide series into relevant in vivo metabolites.

benzothiazole amide


Input: Human and rat hepatocyte experiments demonstrated generation of an aryl amine metabolite that was subsequently N-acetylated.

aryl amine

N


Input: The hydrolyzed metabolites as well as the parent compound were also metabolized into glutathione (GSH) conjugates.

glutathione

GSH


Input: Rat liver S9 exhibited a very low amide hydrolysis capacity and no formation of GSH conjugates when supplemented with NADPH and GSH.

amide

GSH

NADPH

GSH


Input: The discrepancy in metabolic capability between hepatocytes and rat liver S9 led to confounding results in in vitro genotoxicity assessment for this chemical class as judged by the results of Ames test, mouse lymphoma assay, SOS/umu test and Comet assay in rat hepatocytes.


Input: This study highlights the pivotal role that understanding the mechanism of metabolite formation has in interpreting as well as designing reliable and relevant in vitro genotoxicity experiments.


Input: The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy.


Input: The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres.


Input: This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT).


Input: Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n = 86) and females with MECP2 mutations (n = 920) was sourced from the InterRett database.


Input: Available photographs of CDKL5 patients were examined for dysmorphic features.


Input: The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined.


Input: Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations.


Input: Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features.


Input: Less than one-quarter met the criteria for early-onset seizure variant RTT.


Input: Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common.


Input: The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies.


Input: Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria.


Input: Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant.


Input: The impact of FANCD2 deficiency on formaldehyde-induced toxicity in human lymphoblastoid cell lines.

formaldehyde


Input: Formaldehyde (FA), a major industrial chemical and ubiquitous environmental pollutant, has recently been classified by the International Agency for Research on Cancer as a human leukemogen.

Formaldehyde


Input: The major mode of action of FA is thought to be the formation of DNA-protein cross-links (DPCs).


Input: Repair of DPCs may be mediated by the Fanconi anemia pathway; however, data supporting the involvement of this pathway are limited, particularly in human hematopoietic cells.


Input: Therefore, we assessed the role of FANCD2, a critical component of the Fanconi anemia pathway, in FA-induced toxicity in human lymphoblast cell models of FANCD2 deficiency (PD20 cells) and FANCD2 sufficiency (PD20-D2 cells).


Input: After treatment of the cells with 0-150 mu M FA for 24 h, DPCs were increased in a dose-dependent manner in both cell lines, with greater increases in FANCD2-deficient PD20 cells.


Input: FA also induced cytotoxicity, micronuclei, chromosome aberrations, and apoptosis in a dose-dependent manner in both cell lines, with greater increases in cytotoxicity and apoptosis in PD20 cells.


Input: Increased levels of gamma-ATR and gamma-H2AX in both cell lines suggested the recognition of FA-induced DNA damage; however, the induction of BRCA2 was compromised in FANCD2-deficient PD20 cells, potentially reducing the capacity to repair DPCs.


Input: Together, these findings suggest that FANCD2 protein and the Fanconi anemia pathway are essential to protect human lymphoblastoid cells against FA toxicity.


Input: Future studies are needed to delineate the role of this pathway in mitigating FA-induced toxicity, particularly in hematopoietic stem cells, the target cells in leukemia.


Input: AKRs expression in peripheral blood lymphocytes from smokers: The role of body mass index.


Input: Aldo-keto reductases (AKRs) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons (PAHs), generating metabolites (o-quinones) and reactive oxygen species (ROS), which are capable of initiating and promoting carcinogenesis.

Aldo-keto

polycyclic aromatic hydrocarbons

PAHs

o-quinones

oxygen


Input: Exposure to PAHs, their metabolites, and ROS further increase AKRs isoform expression that may amplify oxidative damage.

PAHs


Input: Human AKR enzymes are highly polymorphic, and allelic variants may contribute to different AKRs expression in individuals.


Input: Despite the importance of AKRs in PAHs metabolism, there are no studies that evaluate, in general human populations, the effect of PAHs on AKRs expression in peripheral blood lymphocytes (PBLs).

PAHs

PAHs


Input: The aim of this study was to determine the effect of tobacco smoke exposure, and AKR1A1 * 2 and AKR1C3 * 2 polymorphisms, on AKR1A1 and AKR1C1-AKR1C3 messenger RNA (mRNA) levels in PBLs from smokers.


Input: In the smoker group, there is a statistically significant positive association between AKR1A1, AKR1C1, and AKR1C3 mRNA induction and urine cotinine levels in individuals with a body mass index (BMI) less than 25.

cotinine


Input: However, AKR1A1 * 2 and AKR1C3 * 2 alleles did not influence AKR1A1 and AKR1C1-AKR1C3 mRNA levels.


Input: These results suggest that AKRs induction by PAHs in smokers' PBLs is associated with BMI; therefore, the role of adipose tissue accumulation in PAHs' effects needs further investigation.

PAHs

PAHs


Input: Novel non-canonical TGF-beta signaling networks: emerging roles in airway smooth muscle phenotype and function.


Input: The airway smooth muscle (ASM) plays an important role in the pathophysiology of asthma and chronic obstructive pulmonary disease (COPD).


Input: ASM cells express a wide range of receptors involved in contraction, growth, matrix protein production and the secretion of cytokines and chemokines.


Input: Transforming growth factor beta (TGF-beta) is one of the major players in determining the structural and functional abnormalities of the ASM in asthma and COPD.


Input: It is increasingly evident that TGF-beta functions as a master switch, controlling a network of intracellular and autocrine signaling loops that effect ASM phenotype and function.


Input: In this review, the various elements that participate in non-canonical TGF-beta signaling, including MAPK, PI3K, WNT/beta-catenin, and Ca (2 +), are discussed, focusing on their effect on ASM phenotype and function.

Ca (2 +)


Input: In addition, new aspects of ASM biology and their possible association with non-canonical TGF-beta signaling will be discussed.


Input: Nitrogen, oxygen or sulfur containing heterocyclic compounds as analgesic drugs used as modulators of the nitroxidative stress.

Nitrogen

oxygen

sulfur


Input: Numerous lines of evidence suggest that heterocyclic compounds used as analgesic, anti-inflammatory and anti-migraine agents can be potent regulators of the nitroxidative stress and targeting free nitrogen and oxygen radicals is a very promising strategy for future pain management.

nitrogen

oxygen


Input: Both classical analgesics (nonsteroidal anti-inflammatory drugs, opioid drugs) and many analgesic adjuvants, including desipramine, duloxetine, fluoxetine, paroxetine, escitalopram, phenytoin or carbamazepine and alpha-lipoic acid can modulate the balance between pro-oxidant and antioxidant processes in the mammalian tissues and these properties of drugs such as indomethacin, meloxicam, tenoxicam, valdecoxib or some metabolites of analgesic drugs formed by the activity of tissue peroxidases may contribute to their clinical efficacy and drug-related toxic effects, including gastrointestinal ulcers, hepatic failure, agranulocytosis, aplastic anemia, neutropenia, opiate-induced hyperalgesia and tolerance.

desipramine

duloxetine

fluoxetine

paroxetine

escitalopram

phenytoin

carbamazepine

alpha-lipoic acid

indomethacin

meloxicam

tenoxicam

valdecoxib


Input: The antioxidant capacities of novel heterocyclic compounds, including the compounds acting either by prevention of formation or catalyzed decomposition of peroxynitrite anion (ONOO-), namely the peroxynitrite decomposition catalysts or as superoxide (O2 *-)-scavengers which are the functional mimetics of superoxide dismutase (SOD) enzymes (SODm), as well as the derivatives of 6-nitro-3, 4-methylenedioxyphenyl-Nacylhydrazone (LASSBio-881) or gamma-butyrolactone (LPP1, BM113, BM113A, BM138 and BM138A) are also discussed as potent and promising future heterocyclic analgesics.

peroxynitrite

ONOO-

peroxynitrite

superoxide

O2 *-

superoxide

6-nitro-3, 4-methylenedioxyphenyl-Nacylhydrazone

gamma-butyrolactone


Input: Heat shock proteins and heat shock factor 1 in carcinogenesis and tumor development: an update.


Input: Heat shock proteins (HSP) are a subset of the molecular chaperones, best known for their rapid and abundant induction by stress.


Input: HSP genes are activated at the transcriptional level by heat shock transcription factor 1 (HSF1).


Input: During the progression of many types of cancer, this heat shock transcriptional regulon becomes co-opted by mechanisms that are currently unclear, although evidently triggered in the emerging tumor cell.


Input: Concerted activation of HSF1 and the accumulation of HSPs then participate in many of the traits that permit the malignant phenotype.


Input: Thus, cancers of many histologies exhibit activated HSF1 and increased HSP levels that may help to deter tumor suppression and evade therapy in the clinic.


Input: We review here the extensive work that has been carried out and is still in progress aimed at (1) understanding the oncogenic mechanisms by which HSP genes are switched on, (2) determining the roles of HSF1/HSP in malignant transformation and (3) discovering approaches to therapy based on disrupting the influence of the HSF1-controlled transcriptome in cancer.


Input: Microfabricated nanotopological surfaces for study of adhesion-dependent cell mechanosensitivity.


Input: Cells exhibit high sensitivity and diverse responses to the intrinsic nanotopography of the extracellular matrix through their nanoscale cellular sensing machinery.


Input: A simple microfabrication method for precise control and spatial patterning of the local nanoroughness on glass surfaces by using photolithography and reactive ion etching is reported.


Input: It is demonstrated that local nanoroughness as a biophysical cue could regulate a diverse array of NIH/3T3 fibroblast behaviors, including cell morphology, adhesion, proliferation, migration, and cytoskeleton contractility.


Input: The capability to control and further predict cellular responses to nanoroughness might suggest novel methods for developing biomaterials mimicking nanotopographic structures in vivo for functional tissue engineering.


Input: The human Aurora kinase inhibitor danusertib is a lead compound for anti-trypanosomal drug discovery via target repurposing.

danusertib


Input: New drugs for neglected tropical diseases such as human African trypanosomiasis (HAT) are needed, yet drug discovery efforts are not often focused on this area due to cost.


Input: Target repurposing, achieved by the matching of essential parasite enzymes to those human enzymes that have been successfully inhibited by small molecule drugs, provides an attractive means by which new drug optimization programs can be pragmatically initiated.


Input: In this report we describe our results in repurposing an established class of human Aurora kinase inhibitors, typified by danusertib (1), which we have observed to be an inhibitor of trypanosomal Aurora kinase 1 (TbAUK1) and effective in parasite killing in vitro.

danusertib


Input: Informed by homology modeling and docking, a series of analogs of 1 were prepared that explored the scope of the chemotype and provided a nearly 25-fold improvement in cellular selectivity for parasite cells over human cells.


Input: Chemoprevention of benzo (a) pyrene-induced colon polyps in ApcMin mice by resveratrol.

benzo (a) pyrene

resveratrol


Input: Human dietary exposure to benzo (a) pyrene (BaP) has generated interest with regard to the association of BaP with gastrointestinal carcinogenesis.

benzo (a) pyrene

BaP

BaP


Input: Since colon cancer ranks third among cancer-related mortalities, it is necessary to evaluate the effect of phytochemicals on colon cancer initiation and progression.


Input: In this study, we investigated the preventive effects of resveratrol (RVT) on BaP-induced colon carcinogenesis in Apc (Min) mouse model.

resveratrol

RVT

BaP


Input: For the first group of mice, 100 mu g BaP/kg body weight was administered to mice in peanut oil via oral gavage over a 60-day period.

BaP


Input: For the second group, RVT was coadministered with BaP at a dose of 45 mu g/kg.

RVT

BaP


Input: For the third group, RVT was administered for 1 week prior to BaP exposure for 60 days.

RVT

BaP


Input: Jejunum, colon and liver were collected at 60 days post BaP and RVT exposure; adenomas in jejunum and colon were counted and subjected to histopathology.

BaP

RVT


Input: RVT reduced the number of colon adenomas in BaP + RVT-treated mice significantly compared to that in mice that received BaP alone.

RVT

BaP

RVT

BaP


Input: While dysplasia of varying degrees was noted in colon of BaP-treated mice, the dysplasias were of limited occurrence in RVT-treated mice.

BaP

RVT


Input: To ascertain whether the tumor inhibition is a result of altered BaP-induced toxicity of tumor cells, growth, apoptosis and proliferation of adenocarcinoma cells were assessed posttreatment with RVT and BaP.

BaP

RVT

BaP


Input: Cotreatment with RVT increased apoptosis and decreased cell proliferation to a greater extent than with BaP alone.

RVT

BaP


Input: Overall, our observations reveal that RVT inhibits colon tumorigenesis when given together with BaP and holds promise as a therapeutic agent.

RVT

BaP


Input: Microcrack density and nanomechanical properties in the subchondral region of the immature piglet femoral head following ischemic osteonecrosis.


Input: Development of a subchondral fracture is one of the earliest signs of structural failure of the immature femoral head following ischemic osteonecrosis, and this eventually leads to a flattening deformity of the femoral head.


Input: The mechanical and mineralization changes in the femoral head preceding subchondral fracture have not been elucidated.


Input: We hypothesized that ischemic osteonecrosis leads to early material and mechanical alterations in the bone of the subchondral region.


Input: The purpose of this investigation was to assess the bone of the subchondral region for changes in the histology of bone cells, microcrack density, mineral content, and nanoindentation properties at an early stage of ischemic osteonecrosis in a piglet model.


Input: This large animal model has been shown to develop a subchondral fracture and femoral head deformity resembling juvenile femoral head osteonecrosis.


Input: The unoperated, left femoral head of each piglet (n = 8) was used as a normal control, while the right side had a surgical ischemia induced by disrupting the femoral neck vessels with a ligature.


Input: Hematoxylin and eosin (H & E) staining and TUNEL assay were performed on femoral heads from 3 piglets.

Hematoxylin

eosin


Input: Quantitative backscattered electron imaging, nanoindentation, and microcrack assessments were performed on the subchondral region of both control and ischemic femoral heads from 5 piglets.


Input: H & E staining and TUNEL assay showed extensive cell death and an absence of osteoblasts in the ischemic side compared to the normal control.


Input: Microcrack density in the ischemic side (3. 2 +/- 0. 79 cracks/mm (2)) was significantly higher compared to the normal side (0. 27 +/- 0. 27 cracks/mm (2)) in the subchondral region (p < 0. 05).


Input: The weighted mean of the weight percent distribution of calcium (CaMean) also was significantly higher in the ischemic subchondral region (p < 0. 05).

calcium


Input: Furthermore, the nanoindentation modulus within localized areas of subchondral bone was significantly increased in the ischemic side (16. 8 +/- 2. 7GPa) compared to the normal control (13. 3 +/- 3. 2GPa) (p < 0. 05).


Input: Taken together, these results support the hypothesis that the nanoindentation modulus of the subchondral trabecular bone is increased in the early stage of ischemic osteonecrosis of the immature femoral head and makes it more susceptible to microcrack formation.


Input: We postulate that continued loading of the hip joint when there is a lack of bone cells to repair the microcracks due to ischemic osteonecrosis leads to microcrack accumulation and subsequent subchondral fracture.


Input: The major indole alkaloid N, beta-D-glucopyranosyl vincosamide from leaves of Psychotria leiocarpa Cham.

indole alkaloid N, beta-D-glucopyranosyl vincosamide


Input: & Schltdl.


Input: is not an antifeedant but shows broad antioxidant activity.


Input: N, beta-D-glucopyranosyl vincosamide (GPV), a major alkaloid of Psychotria leiocarpa, constitutes up to 2. 5% of the dry weight in leaves.

N, beta-D-glucopyranosyl vincosamide

GPV


Input: Alkaloid content was not elicited by mechanical wounding or jasmonate.


Input: At concentrations found in natural conditions or 2. 5 fold higher, GPV did not inhibit herbivory in two unrelated generalist models (Helix aspersa and Spodoptera frugiperda) or in a specific interaction model (Heliconius erato fed with Passiflora suberosa).

GPV


Input: In situ staining assay showed quenching activity of hydrogen peroxide by GPV.

hydrogen peroxide

GPV


Input: Exposure of P. leiocarpa to acute UV-B stress did not change GPV or chlorophyll content, indicating high tolerance to this stress by the species.

GPV

chlorophyll


Input: In vitro antioxidant tests against singlet oxygen, superoxide anions and hydroxyl radicals showed efficient quenching activity of the alkaloid.

oxygen

superoxide

hydroxyl


Input: GPV was not effective as antifeedant, but it may act indirectly in P. leiocarpa protection against oxidative stress generated upon wounding, UV exposure and perhaps other environmental stresses.

GPV


Input: Assessment of developmental delay in the zebrafish embryo teratogenicity assay.


Input: In this study we analyzed some aspects of the assessment of developmental delay in the zebrafish embryotoxicity/teratogenicity test and explored the suitability of acetylcholinesterase (AChE) activity as a biochemical marker and as a higher throughput alternative to morphological endpoints such as head-trunk angle, tail length and morphological score.


Input: Embryos were exposed from 4 to 52 h post-fertilization (hpf) to a selection of known embryotoxic/teratogen compounds (valproic acid, retinoic acid, caffeine, sodium salicylate, glucose, hydroxyurea, methoxyacetic acid, boric acid and paraoxon-methyl) over a concentration range.

valproic acid

retinoic acid

caffeine

sodium salicylate

glucose

hydroxyurea

methoxyacetic acid

boric acid

paraoxon-methyl


Input: They were evaluated for AChE activity, head-trunk angle, tail length and several qualitative parameters integrated in a morphological score.


Input: In general, the different patterns of the concentration-response curves allowed distinguishing between chemicals that produced growth retardation (valproic and methoxyacetic acid) and chemicals that produced non-growth-delay related malformations.

valproic and methoxyacetic acid


Input: An acceptable correlation between the morphological score, AChE activity and head-trunk angle as markers of developmental delay was observed, being AChE activity particularly sensitive to detect delay in the absence of malformations.


Input: Human and cattle ergotism since 1900: Symptoms, outbreaks, and regulations.


Input: Ergotism in humans and cattle are caused by several species of Claviceps that infect rye and other cereal grains.


Input: Symptoms in humans vary greatly and are generally classified as convulsive, gangrenous, or gastrointestinal (enteric).


Input: Cattle are particularly susceptible to both gangrenous and hyperthermic ergotism (also called summer syndrome).


Input: The prevalence of ergotism has decreased as knowledge of the fungus has increased, mainly through implementation of regulations and advances in milling procedures.


Input: However, outbreaks in humans have recently occurred in lower socioeconomic populations of Ethiopia (1977 and 2001) and India (1975) with devastating results.


Input: Prominent outbreaks in cattle have occurred in Australia (1987), the United States (1996), South Africa (1996-1997), and Brazil (1999) and, as opposed to human cases, they do not appear to be bound by economic development.


Input: This review provides a detailed summary of all major ergot epidemics since 1900 in both humans and cattle.


Input: Special attention is devoted to the ergotism symptoms and to the regulations surrounding the control of ergot in the food supply.


Input: RETRACTED: Effects of nanometer-sized silver materials on survival response of Caspian roach (Rutilus rutilus caspicus).

silver


Input: RETRACTED.


Input: Extracellular and intracellular anti-mutagenic effects of bile pigments in the Salmonella typhimurium reverse mutation assay.


Input: In vitro anti-genotoxic properties of bile pigments have been explored and confirmed recently.


Input: Despite these reports mechanisms to explain DNA protection by endogenous bile pigments remain unclear.


Input: Surprisingly, the quantification of cellular pigment absorption which could represent a fundamental prerequisite for intracellular (e. g., anti-mutagenic) effects, has not been explored.


Input: Therefore, we aimed to measure the amounts of un-/conjugated bilirubin as well as biliverdin absorbed into colonies of Salmonella typhimurium, utilising HPLC analyses, and to observe whether intracellular compound concentrations could predict anti-genotoxic effects.

bilirubin

biliverdin


Input: HPLC analyses confirmed that bacterial bile pigment absorption was concentration-dependent.


Input: Plate bile pigment concentrations were inversely associated with genotoxicity of all tested mutagens, irrespective of strain and test conditions.


Input: However, protection against frame-shift mutation in strain TA98 most strongly depended on the bacterial absorption of bilirubin and biliverdin, which indicates that bile pigments can protect by intercepting mutations extracellularly and specifically inhibit frame-shift mutations intracellularly.

bilirubin

biliverdin


Input: Chemicals inducing acute irritant contact dermatitis mobilize intracellular calcium in human keratinocytes.

calcium


Input: Intracellular Ca (2 +) increase is a common feature of multiple cellular pathways associated with receptor and channel activation, mediator secretion and gene regulation.

Ca (2 +)


Input: We investigated the possibility of using this Ca (2 +) signal as a biomarker for a reaction to chemical irritants of normal human keratinocytes (NHK) in submerged primary cell culture.

Ca (2 +)


Input: We tested 14 referenced chemical compounds classified as strong (seven), weak (four) or non-(three) irritants in acute irritant contact dermatitis.


Input: We found that the strong irritant compounds tested at 20-40 mM induced an intracellular Ca (2 +) increase measurable by spectrofluorimetry in an automated test.

Ca (2 +)


Input: Weak and non-irritant compounds however did not increase intracellular Ca (2 +) concentration.

Ca (2 +)


Input: We further investigated the mechanisms by which the amine heptylamine, classified as a R34 corrosive compound, increases intracellular Ca (2 +).

amine heptylamine

Ca (2 +)


Input: Heptylamine (20mM) induced an ATP release that persisted in the absence of intra-and extra-cellular Ca (2 +).

Heptylamine

ATP

Ca (2 +)


Input: In addition, we found that this ATP activates NHK purinergic receptors that subsequently cause the increase in intracellular Ca (2 +) from sarcoplasmic reticular stores.

ATP

Ca (2 +)


Input: We conclude that measuring the intracellular Ca (2 +) concentration in NHK is a suitable and easy way of determining any potential reaction to soluble chemical compounds.

Ca (2 +)


Input: Comparison of two in vitro systems to assess cellular effects of nanoparticles-containing aerosols.


Input: Inhalation treatment with nanoparticle containing aerosols appears a promising new therapeutic option but new formulations have to be assessed for efficacy and toxicity.


Input: We evaluated the utility of a VITROCELL (R) 6 PT-CF + PARI LC SPRINT (R) Baby Nebulizer (PARI BOY) system compared with a conventional MicroSprayer.


Input: A549 cells were cultured in the air-liquid interface, exposed to nanoparticle aerosols and characterized by measurement of transepithelial electrical resistance and staining for tight junction proteins.


Input: Deposition and distribution rates of polystyrene particles and of carbon nanotubes on the cells were assessed.

polystyrene

carbon


Input: In addition, cytotoxicity of aerosols containing polystyrene particles was compared with cytotoxicity of polystyrene particles in suspension tested in submersed cultures.

polystyrene

polystyrene


Input: Exposure by itself in both exposure systems did not damage the cells.


Input: Deposition rates of aerosolized polystyrene particles were about 700 times and that of carbon nanotubes about 4 times higher in the MicroSprayer than in the VITROCELL (R) 6 PT-CF system.

polystyrene

carbon


Input: Cytotoxicity of amine-functionalized polystyrene nanoparticles was significantly higher when applied as an aerosol on cell cultured in air-liquid interface culture compared with nanoparticle suspensions tested in submersed culture.

amine

polystyrene


Input: The higher cytotoxicity of aerosolized nanoparticles underscores the importance of relevant exposure systems.


Input: The AChE membrane-binding tail PRiMA is down-regulated in muscle and nerve of mice with muscular dystrophy by merosin deficiency.


Input: Since Duchenne muscular dystrophy was attributed to mutations in the dystrophin gene, more than 30 genes have been found to be causally related with muscular dystrophies, about half of them encoding proteins of the dystrophin-glycoprotein complex (DGC).


Input: Through laminin-2, the DGC bridges the muscle cytoskeleton and the extracellular matrix.


Input: Decreased levels of PRiMA-linked acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) have been observed in dystrophic muscle and nerve of dystrophin-deficient (mdx) and laminin-2 deficient (Lama2dy) mice.


Input: To help explain these observations, the relative content of AChE, BuChE and PRiMA mRNAs were compared in normal and Lama2dy mouse muscle and sciatic nerve.


Input: The 17-fold lower level of PRiMA mRNA in Lama2dy muscle explained the deficit in PRiMA-linked ChEs.


Input: This would increase acetylcholine availability and, eventually, the desensitization of nicotinic receptors.


Input: Abnormal development of the Schwann cells led to peripheral neuropathy in the Lama2dy mouse.


Input: Compared with normal nerve, dystrophic nerve displayed 4-fold less AChE-T mRNA, 3-fold more BuChE mRNA and 2. 5-fold less PRiMA mRNA, which agreed with the lower AChE activity in dystrophic nerve, its increased BuChE activity and the specific drop in PRiMA-linked BuChE.


Input: The widely accepted role of glial cells as the source of BuChE, the observed dysmyelination of Lama2dy nerve and its increased BuChE activity support the idea that BuChE up-regulation is related with the aberrant differentiation of the Schwann cells.


Input: Superhydrophobic graphene foams.

graphene


Input: The static and dynamic wetting properties of a 3D graphene foam network are reported.

graphene


Input: The foam is synthesized using template-directed chemical vapor deposition and contains pores several hundred micrometers in dimension while the walls of the foam comprise few-layer graphene sheets that are coated with Teflon.

graphene

Teflon


Input: Water contact angle measurements reveal that the foam is superhydrophobic with an advancing contact angle of ~ 163 degrees while the receding contact angle is ~ 143 degrees.


Input: The extremely water repellent nature of the foam is also confirmed when impacting water droplets are able to completely rebound from the surface.


Input: Such superhydrophobic graphene foams show potential in a variety of applications ranging from anti-sticking and self-cleaning to anti-corrosion and low-friction coatings.

graphene


Input: Effects of mycophenolic acid alone and in combination with its metabolite mycophenolic acid glucuronide on rat embryos in vitro.

mycophenolic acid

mycophenolic acid glucuronide


Input: Mycophenolic acid (MPA) is an immunosuppressive agent that acts as a selective, non-reversible inhibitor of the enzyme inosine-5'-monophosphate dehydrogenase (IMPDH).

Mycophenolic acid

MPA


Input: Malformations have been described in children after maternal exposure to mycophenolate.

mycophenolate


Input: However, the causal link is unclear in most cases because women had been treated with a combination of drugs and birth defects may have other causes.


Input: Therefore, it is important to study the action of this drug and its main metabolite on embryonic tissue.


Input: We studied the teratogenic potential of MPA and its major metabolite, the mycophenolic acid glucuronide (MPAG) in the rat whole-embryo culture.

MPA

mycophenolic acid glucuronide

MPAG


Input: A total of 147 day 9. 5 embryos were cultivated for 48 h in the standard medium containing 85% serum.


Input: We tested MPA at concentrations of 0. 1; 0. 25; 0. 5; 0. 75 mg/l (0. 31; 0. 78; 1. 56; 2. 34 mu M) and MPA glucuronide at concentrations of 3; 10; 30; 100 mg/l (6. 04; 20. 14; 60. 43; 201. 43 mu M).

MPA

MPA glucuronide


Input: Both substances are highly protein bound, and MPA glucuronide might displace MPA from protein binding.

MPA glucuronide

MPA


Input: Therefore, we examined whether the effects of MPA can be enhanced when studied in combination with the glucuronide.

MPA


Input: Furthermore, the focus was on additional endpoints to the standard evaluation of cultivated embryos, such as development of cranial nerves [trigeminal nerve (V), facial nerve (VII), glossopharyngeal nerve (IX), vagus nerve (X)] after staining with an antibody against 2H3 neurofilament.


Input: Ultrastructural changes were evaluated by electron microscopy.


Input: At a concentration of 0. 75 mg MPA/l medium, all embryos showed dysmorphic changes.

MPA


Input: Embryos exposed to 0. 25 mg MPA/l medium showed impaired development of nerves, and at 0. 1 mg/l, no effects were detectable.

MPA


Input: Concentration-dependent ultrastructural changes, such as signs of apoptosis, were found by electron microscopy.


Input: The examination of the metabolite in this assay showed that at a concentration of 100 mg MPAG/l, the embryos exhibited distinct malformations.

MPAG


Input: This is probably caused by MPA, which was detectable at 0. 6% in the material used for our experiments.

MPA


Input: The combination of the parent compound (0. 03; 0. 1; 0. 25 mg/l) with its metabolite MPAG (3 mg/l) did not cause enhanced toxicity under our experimental conditions.

MPAG


Input: IMPDH, the target enzyme of MPA, could be detected in rat embryos on day 9. 5 of embryonic development as well as at the end of the culture period 48 h later.

MPA


Input: In summary, MPA impairs embryonic development at low, therapeutically relevant concentrations, but the glucuronide does not exhibit such a potential.

MPA


Input: Activity of MPA is not enhanced by MPAG.

MPA

MPAG


Input: Catalytic activities of a cocaine hydrolase engineered from human butyrylcholinesterase against (+)-and (-)-cocaine.

cocaine

(+)-and (-)-cocaine


Input: It can be argued that an ideal anti-cocaine medication would be one that accelerates cocaine metabolism producing biologically inactive metabolites via a route similar to the primary cocaine-metabolizing pathway, i. e., hydrolysis catalyzed by butyrylcholinesterase (BChE) in plasma.

cocaine

cocaine

cocaine


Input: However, wild-type BChE has a low catalytic efficiency against naturally occurring (-)-cocaine.

(-)-cocaine


Input: Interestingly, wild-type BChE has a much higher catalytic activity against unnatural (+)-cocaine.

(+)-cocaine


Input: According to available positron emission tomography (PET) imaging analysis using [(11) C] (-)-cocaine and [(11) C] (+)-cocaine tracers in human subjects, only [(11) C] (-)-cocaine was observed in the brain, whereas no significant [(11) C] (+)-cocaine signal was observed in the brain.

[(11) C] (-)-cocaine

[(11) C] (+)-cocaine

[(11) C] (-)-cocaine

[(11) C] (+)-cocaine


Input: The available PET data imply that an effective therapeutic enzyme for treatment of cocaine abuse could be an exogenous cocaine-metabolizing enzyme with a catalytic activity against (-)-cocaine comparable to that of wild-type BChE against (+)-cocaine.

cocaine

cocaine

(-)-cocaine

(+)-cocaine


Input: Our recently designed A199S/F227A/S287G/A328 W/Y332G mutant of human BChE has a considerably improved catalytic efficiency against (-)-cocaine and has been proven active in vivo.

(-)-cocaine


Input: In the present study, we have characterized the catalytic activities of wild-type BChE and the A199S/F227A/S287G/A328 W/Y332G mutant against both (+)-and (-)-cocaine at the same time under the same experimental conditions.

(+)-and (-)-cocaine


Input: Based on the obtained kinetic data, the A199S/F227A/S287G/A328 W/Y332G mutant has a similarly high catalytic efficiency (kcat/KM) against (+)-and (-)-cocaine, and indeed has a catalytic efficiency (kcat/KM = 1. 84 x 10 (9) M (-1) min (-1)) against (-)-cocaine comparable to that (kcat/KM = 1. 37 x 10 (9) M (-1) min (-1)) of wild-type BChE against (+)-cocaine.

(+)-and (-)-cocaine

(-)-cocaine

(+)-cocaine


Input: Thus, the mutant may be used to effectively prevent (-)-cocaine from entering brain and producing physiological effects in the enzyme-based treatment of cocaine abuse.

(-)-cocaine


Input: An unusual cause of factitious arthritis.


Input: Septic arthritis and toxic synovitis are clinical conditions that can develop in association with various causes and involve symptoms such as pain, swelling, redness, sensitivity and restricted movement in the joint.


Input: A 42-year-old male presented to the emergency department with severe joint pain and nausea after injecting a 1-cc mixture of turpentine oil, eucalyptus oil, mint oil and thyme oil, which he purchased from an alternative medicine store, into his right knee with a syringe because of chronic knee pain.


Input: Ballottement and sensitivity were present at physical examination.


Input: Knee puncture yielded 60 cc of cloudy fluid.


Input: There was no growth in the material obtained.


Input: Improvement was observed following subsequent arthroscopic washing of the joint space and IV antibiotherapy, and the patient was discharged on day 21 of hospitalization with oral antibiotic and analgesic therapy.


Input: Intra-articular injection of foreign bodies into the knee joint space for therapeutic purposes, as in this case report, is a very rare occurrence, but may lead to potentially complicated arthritis.


Input: Repair efficiency and PUVA therapeutic response variation in patients with vitiligo.


Input: Vitiligo is an acquired depigmentation disorder affecting 0. 1% to > 8. 8% in Indian population.


Input: Psoralen and ultraviolet A radiation (PUVA) is a gold standard treatment for vitiligo, however, response is still empirical.

Psoralen


Input: In order to investigate whether drug response variation is influenced by the repair ability of PUVA treated vitiligo subjects, single cell gel electrophoresis (SCGE) for genotoxicity and serum malonaldehyde (MDA) for cytotoxicity were performed on 107 subjects (77 cases and 30 healthy controls) in South Indian population.

malonaldehyde

MDA


Input: In vitro repair ability was assessed by considering the residual damage.


Input: A significant difference was observed between the patients and controls with regard to their mean values of DNA damage and MDA levels (p < 0. 05).

MDA


Input: On categorization to fast and slow responders based on the time of response, patients exhibited a significant deviation in residual DNA damage, suggestive of variation with respect to DNA repair efficiency (p < 0. 05).


Input: This is the first study to our knowledge with respect to PUVA drug response variation in vitiligo in relation to DNA repair.


Input: Large systematic studies on DNA repair may help in a better understanding of the mechanisms involved in the PUVA drug response variation.


Input: Liver glycogen loading dampens glycogen synthesis seen in response to either hyperinsulinemia or intraportal glucose infusion.

glucose


Input: The purpose of this study was to determine the effect of liver glycogen loading on net hepatic glycogen synthesis during hyperinsulinemia or hepatic portal vein glucose infusion in vivo.

glucose


Input: Liver glycogen levels were supercompensated (SCGly) in two groups (using intraportal fructose infusion) but not in two others (Gly) during hyperglycemic-normoinsulinemia.

fructose


Input: Following a 2-h control period during which fructose infusion was stopped, there was a 2-h experimental period in which the response to hyperglycemia plus either 4 x basal insulin (INS) or portal vein glucose infusion (PoG) was measured.

fructose

glucose


Input: Increased hepatic glycogen reduced the percent of glucose taken up by the liver that was deposited in glycogen (74 +/- 3 vs. 53 +/- 5% in Gly + INS and SCGly + INS, respectively, and 72 +/- 3 vs. 50 +/- 6% in Gly + PoG and SCGly + PoG, respectively).

glucose


Input: The reduction in liver glycogen synthesis in SCGly + INS was accompanied by a decrease in both insulin signaling and an increase in AMPK activation, whereas only the latter was observed in SCGly + PoG.


Input: These data indicate that liver glycogen loading impairs glycogen synthesis regardless of the signal used to stimulate it.


Input: A bioactive probe of the oxidative pentose phosphate cycle: novel strategy to reverse radioresistance in glucose deprived human colon cancer cells.

pentose phosphate

glucose


Input: The specific effects of glucose deprivation on oxidative pentose phosphate cycle (OPPC) function, thiol homeostasis, protein function and cell survival remain unclear due to lack of a glucose-sensitive chemical probe.

glucose

pentose phosphate

thiol

glucose


Input: Using p53 wild type and mutant human colon cells, we determined the effects of hydroxyethyl disulfide (HEDS) on NADPH, GSH, GSSG, total glutathione, total non-protein and protein thiol levels, the function of the DNA repair protein Ku, and the susceptibility to radiation-induced free radicals under normal glucose or glucose-deprived conditions.

hydroxyethyl disulfide

HEDS

NADPH

GSH

GSSG

glutathione

glucose

glucose


Input: HEDS is rapidly detoxified in normal glucose but triggered a p53-independent metabolic stress in glucose depleted state that caused loss of NADPH, protein and non-protein thiol homeostasis and Ku function, and enhanced sensitivity of both p53 wild type and mutant cells to radiation induced oxidative stress.

HEDS

glucose

glucose

NADPH

thiol


Input: Additionally, high concentration of HEDS alone induced cell death in p53 wild type cells without significant effect on p53 mutant cells.

HEDS


Input: HEDS offers a useful tool to gain insights into how glucose metabolism affects OPPC dependent stress-induced cellular functions and injury, including in tumor cells, where our findings imply a novel therapeutic approach to target glucose deprived tumor.

HEDS

glucose

glucose


Input: Our work introduces a novel probe to address cancer metabolism and ischemic pathology.


Input: Genetic perspectives on the origin of clicks in Bantu languages from southwestern Zambia.


Input: Some Bantu languages spoken in southwestern Zambia and neighboring regions of Botswana, Namibia, and Angola are characterized by the presence of click consonants, whereas their closest linguistic relatives lack such clicks.


Input: As clicks are a typical feature not of the Bantu language family, but of Khoisan languages, it is highly probable that the Bantu languages in question borrowed the clicks from Khoisan languages.


Input: In this paper, we combine complete mitochondrial genome sequences from a representative sample of populations from the Western Province of Zambia speaking Bantu languages with and without clicks, with fine-scaled analyses of Y-chromosomal single nucleotide polymorphisms and short tandem repeats to investigate the prehistoric contact that led to this borrowing of click consonants.


Input: Our results reveal complex population-specific histories, with female-biased admixture from Khoisan-speaking groups associated with the incorporation of click sounds in one Bantu-speaking population, while concomitant levels of potential Khoisan admixture did not result in sound change in another.


Input: Furthermore, the lack of sequence sharing between the Bantu-speaking groups from southwestern Zambia investigated here and extant Khoisan populations provides an indication that there must have been genetic substructure in the Khoisan-speaking indigenous groups of southern Africa that did not survive until the present or has been substantially reduced.


Input: Clinical pharmacology of etoposide in children undergoing autologous stem cell transplantation for various solid tumours.

etoposide


Input: 1. The population pharmacokinetics of high-dose etoposide was studied in a group of young children and adolescents.


Input: 2. Twenty-six children and adolescent were administered high-dose etoposide as a continuous infusion over 24 h.

etoposide


Input: Etoposide plasma concentration-time data was modelled using NONMEM (R) 7.

Etoposide


Input: The effect of age, weight, serum creatinine (SCr), and gender on pharmacokinetic parameters (CL and V (d)) were determined by a nonlinear mixed effect model.

creatinine


Input: 3. The pharmacokinetics of etoposide based on BSA dosing was best described with a 1-compartment structural model which was parameterised in terms of clearance (CL) and volume of distribution (V (d)).

etoposide


Input: An exponential error model was used to explain intersubject variability and a proportional error model was used to describe residual or intrapatient variability.


Input: The final model parameter estimates for the typical (normalised to 70 kg) values of CL and V (d) were 2. 31 L/hr and 17. 5 L, respectively.


Input: The CL and V (d) allometrically increased with weight with the power of 3/4 and 1, respectively.