Input: Now-a-days, there is a big need to reduce genotoxic effects of mutagenic and carcinogenic agents in environment, which are increased by the technological development.


Input: Lichens produce a wide variety of unique metabolites due to being in various extreme areas and being symbiotic organisms of fungi and algae.


Input: Therefore, this study was planned to search new sources having antimutagenic activity by researching two different lichen species and to determine whether their usage is safe.


Input: With this respect, the mutagenic and antimutagenic properties of methanol extracts of the lichens were determined by the bacterial reverse mutation and sister chromatid exchange assays.

methanol


Input: Furthermore, the malondialdehyde level, superoxide dismutase, glutathione and glutathione peroxidase activities against aflatoxin B1 were determined for understanding the ways in which the lichens showed their genotoxic properties.

malondialdehyde

superoxide

glutathione

glutathione

aflatoxin B1


Input: Rapid cortical bone loss in patients with chronic kidney disease.


Input: Chronic kidney disease (CKD) patients may have high rates of bone loss and fractures, but microarchitectural and biochemical mechanisms of bone loss in CKD patients have not been fully described.


Input: In this longitudinal study of 53 patients with CKD Stages 2-5D, we used dual energy X-ray absorptiometry (DXA), high resolution peripheral quantitative computed tomography (HRpQCT) and biochemical markers of bone metabolism to elucidate effects of CKD on the skeleton.


Input: Median follow-up was 1. 5 years (Range 0. 9 to 4. 3 years); bone changes were annualized and compared to baseline.


Input: By DXA, there were significant declines in areal bone mineral density (BMD) of the total hip and ultradistal radius:-1. 3% (95% CI:-2. 1 to-0. 6) and-2. 4% (95% CI:-4. 0 to-0. 9), respectively.


Input: By HRpQCT at the distal radius, there were significant declines in cortical area, density and thickness, and increases in porosity:-2. 9% (95% CI-3. 7 to-2. 2),-1. 3% (95% CI-1. 6 to-0. 6),-2. 8% (95% CI-3. 6 to-1. 9), and + 4. 2% (95% CI 2. 0 to 6. 4) respectively.


Input: Radius trabecular area increased significantly: + 0. 4% (95% CI 0. 2 to 0. 6), without significant changes in trabecular density or microarchitecture.


Input: Elevated time-averaged levels of parathyroid hormone (PTH) and bone turnover markers predicted cortical deterioration.


Input: Higher levels of serum 25-hydroxyvitamin D predicted decreases in trabecular network heterogeneity.

25-hydroxyvitamin D


Input: These data suggest that significant cortical loss occurs with CKD, which is mediated by hyperparathyroidism and elevated turnover.


Input: Future investigations are required to determine whether these cortical losses can be attenuated by treatments that reduce PTH levels and remodeling rates.


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


Input: New flavonol and diterpenoids from the endophytic fungus Aspergillus sp.

flavonol

diterpenoids


Input: One new flavonol, chlorflavonin A (1), four new diterpenoids, aspergiloids E-H (3, 5-7), together with eight known compounds (2, 4, 8-13) were isolated from solid fermentation of Aspergillus sp.

flavonol

chlorflavonin A

diterpenoids

aspergiloids E-H


Input: (strain no. YXf3), an endophytic fungus from Ginkgo biloba.


Input: Their structures were determined through detailed spectroscopic analysis combined with comparison of NMR spectra data with reported ones.


Input: All of them were screened on cytotoxicity against KB, SGC-7901, SW1116, and A549 cell lines; compounds 4, 9-11 exhibited moderate activities with IC50 values ranging from 6. 74 to 46. 64 micro M.


Input: Unique role of self-assembled monolayers in carbon nanomaterial-based field-effect transistors.

carbon


Input: Molecular self-assembly is a promising technology for creating reliable functional films in optoelectronic devices with full control of thickness and even spatial resolution.


Input: In particular, rationally designed self-assembled monolayers (SAMs) play an important role in modifying the electrode/semiconductor and semiconductor/dielectric interfaces in field-effect transistors.


Input: Carbon nanomaterials, especially single-walled carbon nanotubes and graphene, have attracted intense interest in recent years due to their remarkable physicochemical properties.

Carbon

carbon

graphene


Input: The combination of the advantages of both SAMs and carbon nanomaterials has been opening up a thriving research field.

carbon


Input: In this Review article, the unique role of SAMs acting as either active or auxiliary layers in carbon nanomaterials-based field-effect transistors is highlighted for tuning the substrate effect, controlling the carrier type and density in the conducting channel, and even installing new functionalities.

carbon


Input: The combination of molecular self-assembly and molecular engineering with materials fabrication could incorporate diverse molecular functionalities into electrical nanocircuits, thus speeding the development of nanometer/molecular electronics in the future.


Input: Synthesis of Isoidide through Epimerization of Isosorbide using Ruthenium on Carbon.

Isoidide

Isosorbide

Ruthenium

Carbon


Input: A highly efficient procedure for obtaining resin-grade isoidide through catalytic epimerization of isosorbide using a ruthenium-on-carbon (Ru/C) catalyst is reported.

isoidide

isosorbide

ruthenium

carbon

Ru

C


Input: A comprehensive reaction-parameter variation study involving substrate concentration, catalyst (type of metal, support, and loading), initial pH value, hydrogen pressure, solvent, and reaction temperature demonstrates that superior performance and high selectivity can be achieved.

hydrogen


Input: Epimerization of isosorbide in water (pH 8) at 220 degrees C, under 40 bar of hydrogen, and using a Ru/C catalyst (5% Ru) for 2 h results in a thermodynamic equilibrium mixture containing 55% isoidide, 40% isosorbide, and 5% isomannide.

isosorbide

hydrogen

Ru

C

Ru

isoidide

isosorbide

isomannide


Input: In comparison with previously reported nickel-based catalysts, the Ru/C catalyst is advantageous because it is highly active (as low as 360 ppm Ru) and recyclable.

nickel

Ru

C

Ru


Input: High purity isoidide is obtained by high-vacuum distillation of an equilibrium mixture on a 200 g scale.

isoidide


Input: The high substrate loading (50 wt% in water), high selectivity, and the possibility for substrate reuse makes this procedure highly atom efficient and therefore, highly attractive for industrial use.


Input: Delay and impairment in brain development and function in rat offspring after maternal exposure to methylmercury.

methylmercury


Input: Maternal exposure to the neurotoxin methylmercury (MeHg) has been shown to have adverse effects on neural development of the offspring in man.

methylmercury

MeHg


Input: Little is known about the underlying mechanisms by which MeHg affects the developing brain.

MeHg


Input: To explore the neurodevelopmental defects and the underlying mechanism associated with MeHg exposure, the cerebellum and cerebrum of Wistar rat pups were analyzed by [(18) F] FDG PET functional imaging, field potential analysis, and microarray gene expression profiling.

MeHg

[(18) F] FDG


Input: Female rat pups were exposed to MeHg via maternal diet during intrauterinal and lactational period (from gestational day 6 to postnatal day (PND) 10), and their brain tissues were sampled for the analysis at weaning (PND18-21) and adulthood (PND61-70).

MeHg


Input: The [(18) F] FDG PET imaging and field potential analysis suggested a delay in brain activity and impaired neural function by MeHg.

[(18) F] FDG

MeHg


Input: Genome-wide transcriptome analysis substantiated these findings by showing (1) a delay in the onset of gene expression related to neural development, and (2) alterations in pathways related to both structural and functional aspects of nervous system development.


Input: The latter included changes in gene expression of developmental regulators, developmental phase-associated genes, small GTPase signaling molecules, and representatives of all processes required for synaptic transmission.


Input: These findings were observed at dose levels at which only marginal changes in conventional developmental toxicity endpoints were detected.


Input: Therefore, the approaches applied in this study are promising in terms of yielding increased sensitivity compared with classical developmental toxicity tests.


Input: Thioflavin T and its photoirradiative derivatives: exploring their spectroscopic properties in the absence and presence of amyloid fibrils.

Thioflavin T


Input: In this work, we found that, during storage or after UV irradiation, ThT is demethylated or oxidized, forming three derivatives.

ThT


Input: These three derivatives were purified by high performance liquid chromatography and characterized by mass and nuclear magnetic resonance spectroscopy and the spectroscopic properties of pure ThT and the derivatives carefully compared.

ThT


Input: Our results show that the emission peak at 450 nm results from oxidized ThT and not from the monomeric form of ThT, as previously proposed.

ThT

ThT


Input: The partial conversion of ThT into oxidized and demethylated derivatives has an effect on amyloid detection using ThT assay.

ThT

ThT


Input: Irradiated ThT has the same lag time as pure ThT in the amyloidogenesis of insulin, but the intensity of the emitted fluorescence is significantly decreased.

ThT

ThT


Input: pH-Dependent Aggregation and Disaggregation of Native beta-Lactoglobulin in Low Salt.


Input: The aggregation of beta-lactoglobulin (BLG) near its isoelectric point was studied as a function of ionic strength and pH.


Input: We compared the behavior of native BLG with those of its two isoforms, BLG-A and BLG-B, and with that of a protein with a very similar pI, bovine serum albumin (BSA).


Input: Rates of aggregation were obtained through a highly precise and convenient pH/turbidimetric titration that measures transmittance to +/- 0. 05% T.


Input: A comparison of BLG and BSA suggests that the difference between pHmax (the pH of the maximum aggregation rate) and pI is systematically related to the nature of protein charge asymmetry, as further supported by the effect of localized charge density on the dramatically different aggregation rates of the two BLG isoforms.


Input: Kinetic measurements including very short time periods show well-differentiated first and second steps.


Input: BLG was analyzed by light scattering under conditions corresponding to maxima in the first and second steps.


Input: Dynamic light scattering (DLS) was used to monitor the kinetics, and static light scattering (SLS) was used to evaluate the aggregate structure fractal dimensions at different quench points.


Input: The rate of the first step is relatively symmetrical around pHmax and is attributed to the local charges within the negative domain of the free protein.


Input: In contrast, the remarkably linear pH dependence of the second step is related to the uniform reduction in global protein charge with increasing pH below pI, accompanied by an attractive force due to surface charge fluctuations.


Input: TRAIL-Based Therapeutic Approaches for the Treatment of Pediatric Malignancies.


Input: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a pro-apoptotic ligand that has shown the exquisite ability to trigger extrinsic apoptosis in various types of cancer cells without significant toxicity toward normal cells, when compared to other pro-apoptotic ligands such as tumor necrosis factor (TNF) alpha or Fas ligand.


Input: Consequently, TRAIL-based therapies aim to trigger apoptosis in cancer cells by providing the soluble TRAIL or monoclonal antibodies targeting the death receptors TRAIL-R1 or TRAIL-R2.


Input: In this review, we start by highlighting the relevance of the tumor microenvironment in tumor development and elimination.


Input: We then address conventional and targeted therapeutic approaches for cancer treatment, highlighting the mechanisms involved or targeted.


Input: We describe the extrinsic and intrinsic pro-apoptotic pathways of TRAIL, together with the evidences for its pro-survival signaling, and with the relevance of these pathways in therapy.


Input: Possible mechanisms of resistance to TRAIL-induced apoptosis are highlighted (i. e. c-FLIP, Bcl-2, IAPs, p53, NF-kappa B) and the rationale for the combined administration of TRAIL with drugs targeting these mechanisms is provided.


Input: Preclinical data are reported and show encouraging evidences for TRAIL consideration in pediatric malignancies (i. e., leukemia, lymphomas, neuroblastoma, osteosarcoma, medulloblastoma).


Input: Clinical trials of TRAIL-based therapies on the overall population are in phase I or II, and we put particular focus on the pediatric population, on which only few trials have been conducted or are ongoing.


Input: Finally, we consider emerging cellular therapies based on TRAIL, such as TRAIL-engineered mesenchymal stem cells or' inflammatory' dendritic cells.


Input: Potential Advantages of Using Synchrotron X-ray Based Techniques in Pediatric Research.


Input: Synchrotron radiation (SR), which combines extremely high intensity, high collimation, tunability, and continuous energy spectrum, allows the development of advanced X-ray based techniques that are becoming a uniquely useful tool in life science research, along providing exciting opportunities in biomedical imaging and radiotherapy.


Input: This review summarize emerging techniques and their potential to greatly enhance the exploration of dynamical biological process occurring across various spatial and temporal regimes, from whole body physiology, down to the location of individual chemical species within single cells.


Input: In recent years pediatric research and clinic practice have started to profit from these new opportunities, particularly by extending the diagnostic and therapeutic capabilities of these X-ray based techniques.


Input: In diagnosis, technical advances in DEI and KES imaging modalities have been demonstrated as particularly valuable for children and women since SR allows dose minimization, with significant reductions compared to conventional approaches.


Input: However, the greatest expectations are in the field of SR based radiotherapy, increasingly studies are demonstrating SR radiotherapy provides improved chances of recovery; this is especially the case for pediatric patients.


Input: In addition, we report on the applicability of advanced X-ray microscopy techniques that offer exceptional spatial and quantitative resolution in elemental detection.


Input: These techniques, which are useful for in vitro studies, will be particularly advantageous where investigators seek deeper understanding of diseases where mismetabolism of metals, either physiological important (i. e. Cu, Zn) or outright toxic (i. e. Pb), underlies pathogenesis.

Cu

Zn

Pb


Input: Pharmacogenomic approaches for tailored anti-leukemic therapy in children.


Input: Several lympholytic and cytotoxic agents are used in acute lymphoblastic leukemia (ALL) polychemotherapy.


Input: Genetic variants for cellular components involved in the pharmacokinetics and pharmacodynamics of these drugs can influence the pharmacological response, and molecular characterization of these genetic variants could be helpful for the comprehension of the mechanisms of resistance or increased sensitivity.


Input: The purpose of this review is to carry out an update of recent publications on genes that might influence ALL treatment in terms of outcome and/or toxicity and to underlie the role of genetic variants, particularly single nucleotide polymorphisms (SNP), in predicting clinical response, with particular reference to the current protocol for ALL therapy used in Italy, AIEOP-BFM ALL 2009.


Input: Potential use of polymeric nanoparticles for drug delivery across the blood-brain barrier.


Input: Nanomedicine is certainly one of the scientific and technological challenges of the coming years.


Input: In particular, biodegradable nanoparticles formulated from poly (D, L-lactide-co-glycolide) (PLGA) have been extensively investigated for sustained and targeted delivery of different agents, including recombinant proteins, plasmid DNA, and low molecular weight compounds.

poly (D, L-lactide-co-glycolide)

PLGA


Input: PLGA NPs present some very attractive properties such as biodegradability and biocompatibility, protection of drug from degradation, possibility of sustained release, and the possibility to modify surface properties to target nanoparticles to specific organs or cells.

PLGA


Input: Moreover, PLGA NPs have received the FDA and European Medicine Agency approval in drug delivery systems for parenteral administration, thus reducing the time for human clinical applications.

PLGA


Input: This review in particular deals on surface modification of PLGA NPs and their possibility of clinical applications, including treatment for brain pathologies such as brain tumors and Lysosomal Storage Disorders with neurological involvement.

PLGA


Input: Since a great number of pharmacologically active molecules are not able to cross the Blood-Brain Barrier (BBB) and reach the Central Nervous System (CNS), new brain targeted polymeric PLGA NPs modified with glycopeptides (g7-NPs) have been recently produced.

PLGA


Input: In this review several in vivo biodistribution studies and pharmacological proof-of evidence of brain delivery of model drugs are reported, demonstrating the ability of g7-NPs to create BBB interaction and trigger an efficacious BBB crossing.


Input: Moreover, another relevant development of NPs surface engineering was achieved by conjugating to the surface of g7-NPs, some specific and selective antibodies to drive NPs directly to a specific cell type once inside the CNS parenchyma.


Input: Crotonaldehyde-exposed macrophages induce IL-8 release from airway epithelial cells through NF-kappa B and AP-1 pathways.

Crotonaldehyde


Input: Crotonaldehyde, a highly toxic alpha, beta-unsaturated aldehyde, is a major component of cigarette smoke and a ubiquitous environmental pollutant.

Crotonaldehyde

alpha, beta-unsaturated aldehyde


Input: Crotonaldehyde exposure is known to have adverse effects on respiratory health, but the underlying mechanisms remain obscure.

Crotonaldehyde


Input: To examine the interaction between macrophages and airway epithelial cells after exposure to crotonaldehyde, BEAS-2B and A549 cells were treated with conditioned media from a human monocytic leukemia cell line (THP-1) cells stimulated with crotonaldehyde.

crotonaldehyde

crotonaldehyde


Input: We demonstrate that conditioned media from THP-1 cells stimulated with crotonaldehyde increased interleukin (IL)-8 production, enhanced nuclear factor (NF)-kappa B and AP-1 DNA-binding activity in BEAS-2B and A549 cells.

crotonaldehyde


Input: Analysis of these conditioned media revealed marked increases in tumor necrosis factor (TNF)-alpha, IL-1 beta and IL-8 levels.


Input: Preincubation of conditioned media with either TNF-alpha-or IL-1 beta-neutralizing antibodies reduced IL-8 production.


Input: Furthermore, BEAS-2B and A549 cells directly treated with crotonaldehyde induced increase in IL-8 production.

crotonaldehyde


Input: These data suggest that crotonaldehyde is capable of directly stimulating the production of IL-8 in both macrophages and airway epithelial cells.

crotonaldehyde


Input: Crotonaldehyde-stimulated macrophages also amplify the inflammatory response by enhancing IL-8 release from airway epithelial cells mediated by NF-kappa B and AP-1 pathways through a mechanism involving TNF-alpha and IL-1 beta.

Crotonaldehyde


Input: These findings indicate that crotonaldehyde can cause lung inflammatory response via multiple mechanisms, and may contribute to chronic airway inflammation in smokers.

crotonaldehyde


Input: Sub-acute, moderate-dose, but not short-term, low-dose dietary pre-exposure of mice to perfluorooctanoate aggravates concanavalin A-induced hepatitis.

perfluorooctanoate


Input: Exposure of mice to perfluorooctanoate (PFOA) evokes pronounced hepatomegaly along with significant alterations in both the histological structure and immune status of the liver.

perfluorooctanoate

PFOA


Input: The present study was designed to evaluate the effects of this perfluorochemical on immune-mediated liver damage.


Input: In this connection, the influence of both sub-acute (10 days), moderate-dose (0. 002% w/w = 3 +/- 0. 7mg/kg body weight/day) and short-term (28 days), low-dose (0. 00005% w/w = 70 +/- 2 mu g/kg body weight/day) dietary pretreatment with PFOA on the development of concanavalin A (Con A)-induced liver damage in mice was examined.

PFOA


Input: With sub-acute, moderate, but not short-term, low-dose exposure, PFOA aggravated the acute liver damage caused by Con A, i. e., elevated serum levels of transaminases and led to more pronounced damage of hepatic tissue.

PFOA


Input: This aggravation was associated with significantly enhanced hepatic level of interleukin-6 (IL-6), but unaltered hepatic levels of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin-4 (IL-4).


Input: Moreover, hepatic DNA fragmentation was not changed by sub-acute exposure to the moderate-dose.


Input: Our findings imply that exposure to PFOA may sensitize hepatic parenchymal cells to other toxicants that activate the hepatic immune system and thereby aggravate liver injury during acute inflammation.

PFOA


Input: Antioxidant and Anti-inflammatory Meroterpenoids from the Brown Alga Cystoseira usneoides.

Meroterpenoids


Input: A chemical study of the alga Cystoseira usneoides has led to the isolation of six new meroterpenoids, cystodiones A-F (1-6), together with six known related compounds (7-12).

meroterpenoids

cystodiones A-F


Input: The structures of the new metabolites have been established by spectroscopic techniques.


Input: In antioxidant assays all of the tested meroterpenes, and in particular cystodiones A (1) and B (2), 6-cis-amentadione-1'-methyl ether (7), and amentadione-1'-methyl ether (8), exhibited strong radical-scavenging activity.

meroterpenes

cystodiones A (1) and B

6-cis-amentadione-1'-methyl ether

amentadione-1'-methyl ether


Input: In anti-inflammatory assays, usneoidone Z (11) and its corresponding 6E isomer (12) showed significant activity as inhibitors of the production of the proinflammatory cytokine TNF-alpha in LPS-stimulated THP-1 human macrophages.

usneoidone Z


Input: Zinc oxide nanoparticle induced autophagic cell death and mitochondrial damage via reactive oxygen species generation.

Zinc oxide

oxygen


Input: Zinc oxide nanoparticles (ZnO-np) are used in an increasing number of industrial products such as paint, coating and cosmetics, and in other biological applications.

Zinc oxide

ZnO


Input: There have been many suggestions of a ZnO-np toxicity paradigm but the underlying molecular mechanisms about the toxicity of ZnO-np remain unclear.

ZnO

ZnO


Input: This study was done to determine the potential toxicity of ZnO-np and to assess the toxicity mechanism in normal skin cells.

ZnO


Input: Synthesized ZnO-np generated reactive oxygen species (ROS), as determined by electron spin resonance.

ZnO

oxygen


Input: After uptake into cells, ZnO-np induced ROS in a concentration-and time-dependent manner.

ZnO


Input: To demonstrate ZnO-np toxicity mechanism related to ROS, we detected abnormal autophagic vacuoles accumulation and mitochondria dysfunction after ZnO-np treatment.

ZnO

ZnO


Input: Furthermore mitochondria membrane potential and adenosine-5'-triphosphate (ATP) production are decreased for culture with ZnO-np.

ATP

ZnO


Input: We conclude that ZnO-np leads to cell death through autophagic vacuole accumulation and mitochondria damage in normal skin cells via ROS induction.

ZnO


Input: Accordingly, ZnO-np may cause toxicity and the results highlight and need for careful regulation of ZnO-np production and use.

ZnO

ZnO


Input: In vitro and in vivo evaluation of superparamagnetic iron oxide nanoparticles coated by bisphosphonates: The effects of electrical charge and molecule length.

iron oxide

bisphosphonates


Input: Physicochemical coating properties are often considered to be determining factors for in vivo characteristics of superparamagnetic iron oxide nanoparticles, used as contrast agent in Magnetic Resonance Imaging (MRI).

iron oxide


Input: To investigate the electrical charge (modified by zero, one or two ammonium groups) and the molecule length (3, 5 or 7 methylene chains) effects of bisphosphonate-type coatings, we assessed the complement activation, in vivo plasma and tissue relaxation time alterations of intravenously injected small iron oxide nanoparticles (< 25nm) on male healthy Wistar rats.

ammonium

methylene

bisphosphonate

iron oxide


Input: The presence of ammonium groups induces a weak activation of the complement whatever the size and the concentration of particles, whereas hydroxyethylenebisphosphonate (HEBP)-coated particles are poor complement activators only at the lowest concentration.

ammonium

hydroxyethylenebisphosphonate

HEBP


Input: In vivo, HEBP-coated nanoparticles have the greatest prolonged relaxation time effects, despite their higher negative electrical charge, contrary to two ammonium bearing coatings.

HEBP

ammonium


Input: No significant differences were observed between mono-ammonium molecular coatings.

mono-ammonium


Input: Electrospinning covalently cross-linking biocompatible hydrogelators.


Input: Many hydrogel materials of interest are homogeneous on the micrometer scale.


Input: Electrospinning, the formation of sub-micrometer to micrometer diameter fibers by a jet of fluid formed under an electric field, is one process being explored to create rich microstructures.


Input: However, electrospinning a hydrogel system as it reacts requires an understanding of the gelation kinetics and corresponding rheology near the liquid-solid transition.


Input: In this study, we correlate the structure of electrospun fibers of a covalently cross-linked hydrogelator with the corresponding gelation transition and kinetics.


Input: Polyethylene oxide (PEO) is used as a carrier polymer in a chemically cross-linking poly (ethylene glycol)-high molecular weight heparin (PEG-HMWH) hydrogel.

Polyethylene oxide

PEO

poly (ethylene glycol)

PEG


Input: Using measurements of gelation kinetics from multiple particle tracking microrheology (MPT), we correlate the material rheology with the the formation of stable fibers.


Input: An equilibrated, cross-linked hydrogel is then spun and the PEO is dissolved.

PEO


Input: In both cases, microstructural features of the electrospun fibers are retained, confirming the covalent nature of the network.


Input: The ability to spin fibers of a cross-linking hydrogel system ultimately enables the engineering of materials and microstructural length scales suitable for biological applications.


Input: Exploring the genetic basis of chronic periodontitis: a genome-wide association study.


Input: Chronic periodontitis (CP) is a common oral disease that confers substantial systemic inflammatory and microbial burden and is a major cause of tooth loss.


Input: Here, we present the results of a genome-wide association study of CP that was carried out in a cohort of 4504 European Americans (EA) participating in the Atherosclerosis Risk in Communities (ARIC) Study (mean age-62 years, moderate CP-43% and severe CP-17%).


Input: We detected no genome-wide significant association signals for CP; however, we found suggestive evidence of association (P < 5 x 10 (-6)) for six loci, including NIN, NPY, WNT5A for severe CP and NCR2, EMR1, 10p15 for moderate CP.


Input: Three of these loci had concordant effect size and direction in an independent sample of 656 adult EA participants of the Health, Aging, and Body Composition (Health ABC) Study.


Input: Meta-analysis pooled estimates were severe CP (n = 958 versus health: n = 1909)-NPY, rs2521634 [G]: odds ratio [OR = 1. 49 (95% confidence interval (CI = 1. 28-1. 73, P = 3. 5 x 10 (-7)))]; moderate CP (n = 2293)-NCR2, rs7762544 [G]: OR = 1. 40 (95% CI = 1. 24-1. 59, P = 7. 5 x 10 (-8)), EMR1, rs3826782 [A]: OR = 2. 01 (95% CI = 1. 52-2. 65, P = 8. 2 x 10 (-7)).


Input: Canonical pathway analysis indicated significant enrichment of nervous system signaling, cellular immune response and cytokine signaling pathways.


Input: A significant interaction of NUAK1 (rs11112872, interaction P = 2. 9 x 10 (-9)) with smoking in ARIC was not replicated in Health ABC, although estimates of heritable variance in severe CP explained by all single nucleotide polymorphisms increased from 18 to 52% with the inclusion of a genome-wide interaction term with smoking.


Input: These genome-wide association results provide information on multiple candidate regions and pathways for interrogation in future genetic studies of CP.


Input: In vivo binding of the dopamine-1 receptor PET tracers [(11) C] NNC112 and [(11) C] SCH23390: a comparison study in individuals with schizophrenia.

dopamine

[(11) C] NNC112

[(11) C] SCH23390


Input: RATIONALE: A deficit in dopamine-1 (D1) receptor function in the prefrontal cortex is suggested to play a role in the cognitive dysfunction observed in patients with schizophrenia.

dopamine


Input: However, the results from positron emission tomography imaging studies of D1 receptor levels in individuals with schizophrenia are mixed.


Input: OBJECTIVES: The aim of this investigation was to determine whether the in vivo characteristics of the different D1 receptor tracers used in previous reports, [(11) C] SCH23390 and [(11) C] NNC112, may have contributed to these discrepancies reported in the literature.

[(11) C] SCH23390

[(11) C] NNC112


Input: METHODS: Eight patients with schizophrenia and 12 healthy control subjects were scanned with both [(11) C] SCH23390 and [(11) C] NNC112.

[(11) C] SCH23390

[(11) C] NNC112


Input: RESULTS: [(11) C] SCH23390 and [(11) C] NNC112 binding potentials in both patients and control subjects were compared and no tracer by diagnosis interactions were observed.

[(11) C] SCH23390

[(11) C] NNC112


Input: CONCLUSIONS: The results of this study suggest that differences in the binding of [(11) C] SCH23390 and [(11) C] NNC112 observed in previous studies are not due to differences in the in vivo behavior of these tracers.

[(11) C] SCH23390

[(11) C] NNC112


Input: Replication of genetic effects of MC4R polymorphisms on body mass index in a Korean population.


Input: Obesity is associated with a variety of adverse health risks.


Input: Several genome-wide association studies of obesity have identified candidate genes, including the fat mass and obesity-associated gene (FTO) and the melanocortin-4 receptor (MC4R) gene.


Input: We carried out a replication study of MC4R and FTO variants in a Korean cohort.


Input: A total of 2, 281 subjects in the Bundang-gu region were analyzed using selected markers.


Input: Another 8, 826 subjects in the Ansung/Ansan city were used for a meta-analysis.


Input: Two single nucleotide polymorphisms (SNPs) in FTO and one SNP in the MC4R gene were genotyped.


Input: Multivariate linear regression models were employed to test for genotypic effects on obesity traits while adjusting for age and sex using an additive model.


Input: The SNP rs17782313 near the MC4R gene was associated with mean body mass index in the Bundang-gu cohort (effect per allele 0. 288 kg/m (2), p = 0. 0023).


Input: The p value for meta-analysis of rs17782313 in all 11, 107 individuals in the Bundang-gu and Ansung/Ansan cohorts was 2. 82 x 10 (-6) (effect per allele 0. 22 kg/m (2)).


Input: Two SNPs in FTO were significantly associated with weight (effect per allele 0. 969 kg, p = 0. 011 for rs9939609; 0. 943, p = 0. 014 for rs8050136) but not with body mass index.


Input: This study demonstrates that genetic variants in MC4R influence obesity traits in Korean adults.


Input: Decorin Potentiates Interferon-gamma Activity in a Model of Allergic Inflammation.


Input: The proteoglycan decorin modulates leukocyte recruitment during delayed-type hypersensitivity responses.


Input: Decorin-deficient (Dcn (-/-)) mice show reduced edema formation during the first 24 h with a concurrent attenuated recruitment of CD8 (+) leukocytes in the inflamed Dcn (-/-) ears.


Input: The aim of this study was to elucidate the molecular pathways affected by the loss of decorin.


Input: In vivo, reduced numbers of CD8 (+) cells in Dcn (-/-) ears correlated with a reduced interferon-gamma (Ifn-gamma) and CXCL-10 expression.


Input: In vitro, Dcn (-/-) lymphocytes displayed an increased adhesion to brain microvascular (bEnd. 3) endothelial cells.


Input: Decorin treatment of bEnd. 3 increased Icam1 and down-regulated Vcam1 expression after TNF-alpha stimulation.


Input: However, Dcn (-/-) and wild-type lymphocytes produced IFN-gamma after activation with CD3 epsilon.


Input: Upon incubation with decorin, endothelial cells and fibroblasts responded differently to IFN-gamma and TNF-alpha; CCL2 in bEnd. 3 cells was more prominently up-regulated by TNF-alpha compared with IFN-gamma.


Input: Notably, both factors were more potent in the presence of decorin.


Input: Compared with TNF-alpha, IFN-gamma treatment induced significantly more CXCL-10, and both factors increased synthesis of CXCL-10 in the presence of decorin.


Input: The response to IFN-gamma was similar in Dcn (-/-) and wild-type fibroblasts, an additional source of CXCL-10.


Input: However, addition of decorin yielded significantly more CXCL-10.


Input: Notably, decorin increased the stability of IFN-gamma in vitro and potentiated IFN-gamma-induced activation of STAT-1.


Input: Furthermore, only dermatan sulfate influenced IFN-gamma signaling by significantly increasing CXCL-10 expression in contrast to decorin protein core alone.

sulfate


Input: Our data demonstrate that decorin modulates delayed-type hypersensitivity responses by augmenting the induction of downstream effector cytokines of IFN-gamma and TNF-alpha, thereby influencing the recruitment of CD8 (+) lymphocytes into the inflamed tissue.


Input: (+)-Laburnamine, a Natural Selective Ligand and Partial Agonist for the alpha 4 beta 2 Nicotinic Receptor Subtype.

(+)-Laburnamine


Input: (+)-Laburnamine (1), a rare alkaloid extracted from Laburnum anagyroides seeds (~ 4 mg from 1 kg), was shown to bind with high affinity (Ki, 293 nM) to the alpha 4 beta 2 nicotinic receptor subtype, which is, respectively, 126 and 136 times higher than to the alpha 3 beta 4 (Ki 37 mu M) and alpha 7 subtypes (Ki 40 mu M).

(+)-Laburnamine


Input: When its ability to release [(3) H]-dopamine from striatal slices was tested in a functional assay, compound 1 behaved as a partial agonist with an EC50 of 5. 8 mu M and an Emax that was 43% that of nicotine.

[(3) H]-dopamine

nicotine


Input: When incubated with nicotine in the same assay, 1 prevented a maximal effect from being reached.

nicotine


Input: Grazing-incidence neutron-induced fluorescence probes density profiles of labeled molecules at solid/liquid interfaces.


Input: We report on the use of characteristic prompt gamma-fluorescence after neutron capture induced by an evanescent neutron wave to probe densities and depth profiles of labeled molecules at solid/liquid interfaces.


Input: In contrast to classical scattering techniques and X-ray fluorescence, this method of " grazing-incidence neutron-induced fluorescence " combines direct chemical specificity, provided by the label, with sensitivity to the interface, inherent to the evanescent wave.


Input: We demonstrate that the formation of a supported lipid membrane can be quantitatively monitored from the characteristic fluorescence of (157) Gd (3 +) ions bound to the headgroup of chelator lipids.

(157) Gd (3 +)


Input: Moreover, we were able to localize the (157) Gd (3 +) ions along the surface normal with nanometer precision.

(157) Gd (3 +)


Input: This first proof of principle with a well-defined model system suggests that the method has a great potential for biology and soft matter studies where spatial resolution and chemical sensitivity are required.


Input: Power spectral density of free-standing viscoelastic films by adiabatic approximation.


Input: In a previous study, we calculated the surface dynamics of noisy viscoelastic supported films by using an adiabatic approximation.


Input: An expression was derived for the time-dependent power spectral density (PSD), which was found to produce good agreement with experiment.


Input: In this study, we extend the treatment to viscoelastic free-standing films.


Input: Two sets of surface capillary normal modes, namely, the squeezing and bending modes, were found.


Input: The frequency dispersion relation of the former resembles that of supported films.


Input: The latter is distinctively different and diverges at long wavelengths.


Input: By incorporating the experimental conditions, we obtained satisfactory agreement between theory and experiment.


Input: Microneedle/nanoencapsulation-mediated transdermal delivery: Mechanistic insights.


Input: A systematic study was undertaken to gain more insight into the mechanism of transdermal delivery of nanoencapsulated model dyes across microneedle (MN)-treated skin, a complex process not yet explored.


Input: Rhodamine B (Rh B) and fluorescein isothiocyanate (FITC) as model hydrophilic and hydrophobic small/medium-size molecules, respectively, were encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) and delivered through full thickness porcine skin pretreated with MN array.

Rhodamine B

Rh B

fluorescein isothiocyanate

FITC

poly lactic-co-glycolic acid

PLGA


Input: Permeation through MN-treated skin was affected by physicochemical characteristics of NPs and the encapsulated dyes.


Input: Dye flux was enhanced by smaller particle size, hydrophilicity, and negative zeta potential of NPs.


Input: Regarding encapsulated dyes, solubility at physiological pH and potential interaction with skin proteins proved to outweigh molecular weight as determinants of skin permeation.


Input: Data were verified using confocal laser scanning microscopy imaging.


Input: Findings coupled with the literature data are supportive of a mechanism involving influx of NPs, particularly of smaller size, deep into MN-created channels, generating depot dye-rich reservoirs.


Input: Molecular diffusion of the released dye across viable skin layers proceeds at a rate determined by its molecular characteristics.


Input: Data obtained provide mechanistic information of importance to the development of formulation strategies for more effective intradermal and transdermal MN-mediated delivery of nanoencapsulated therapeutic agents.


Input: Correlation between aflatoxin M1 content of breast milk, dietary exposure to aflatoxin B1 and socioeconomic status of lactating mothers in Ogun State, Nigeria.

aflatoxin M1

aflatoxin B1


Input: Aflatoxin M1 (AF M1), a hydroxylated metabolite of AF B1, is an important toxin that can contaminate the milk of lactating mothers.

Aflatoxin M1

AF M1

AF B1


Input: A correlation study was conducted to determine the relationship between AF M1 content of breast milk, dietary exposure to AF B1 and socioeconomic status of lactating mothers in the three Senatorial districts of Ogun State, Nigeria.

AF M1

AF B1


Input: Equal amounts of breast milk (20ml) and food rations (40kg) obtained from 50 volunteer lactating mothers and eighty-two frequently consumed food commodities in the preceding month were used for the study.


Input: The level of contamination of the foods by AF B1 was low (0. 16-0. 33 mu g/kg) and differed significantly (p < 0. 05) across the state but did not exceed the EU limit of 2 mu g/kg.

AF B1


Input: The occurrence level of AF B1 was however high (93. 75-94. 45%) and was more pronounced in Ogun East Senatorial district (94. 45%).

AF B1


Input: Eighty-two percent of the breast milk was contaminated with AF M1 (3. 49-35ng/l) and 16% exceeded the EU limit of 25ng/l while a 100% occurrence risk was recorded in Ogun Central Senatorial district.

AF M1


Input: The socioeconomic status of the mothers also significantly influenced their dietary exposure and exposure risk of the sucklings to AF M1.

AF M1


Input: Preclinical Assessment of Ketamine.

Ketamine


Input: BACKGROUND: Ketamine is used as a general anesthetic, and recent data suggest that anesthetics can cause neurodegeneration and/or neuroprotection.

Ketamine


Input: The precise mechanisms are not completely understood.


Input: AIMS: This review is to examine the work on ketamine and to address how developmental biology may be utilized when combined with biochemical, pathological, and pharmacokinetic assessments to produce a bridging model that may decrease the uncertainty in extrapolating preclinical data to human conditions.

ketamine


Input: RESULTS: Advantages of using preclinical models to study critical issues related to ketamine anesthesia have been described.

ketamine


Input: These include the relationships between ketamine-induced neurotoxicity/protection and the preclinical models/approaches in elucidating mechanisms associated with ketamine exposure.

ketamine

ketamine


Input: CONCLUSIONS: The discussions focus on the following: (1) the doses and time-course over which ketamine is associated with damage to, or protection of, neural cells, (2) how ketamine directs or signals neural cells to undergo apoptosis or necrosis, (3) how such exposures can trigger mitochondrial dysfunction, (4) how antioxidants and knockdowns of specific transcription modulators or receptors affect neurotoxicity induced by ketamine, and (5) whether the potential neural damage can be monitored after ketamine exposure in living animals using positron emission tomography.

ketamine

ketamine

ketamine

ketamine


Input: Cell cycle arrest, extracellular matrix changes and intrinsic apoptosis in human melanoma cells are induced by Boron Neutron Capture Therapy.

Boron


Input: Boron Neutron Capture Therapy (BNCT) involves the selective accumulation of boron carriers in tumor tissue followed by irradiation with a thermal or epithermal neutron beam.

Boron


Input: This therapy is therefore a cellular irradiation suited to treat tumors that have infiltrated into healthy tissues.


Input: BNCT has been used clinically to treat patients with cutaneous melanomas which have a high mortality.


Input: Human normal melanocytes and melanoma cells were treated with BNCT at different boronophenylalanine concentrations for signaling pathways analysis.

boronophenylalanine


Input: BNCT induced few morphological alterations in normal melanocytes, with a negligible increase in free radical production.


Input: Melanoma cells treated with BNCT showed significant extracellular matrix (ECM) changes and a significant cyclin D1 decrease, suggesting cell death by necrosis and apoptosis and cell cycle arrest, respectively.


Input: BNCT also induced a significant increase in cleaved caspase-3 and a decrease in the mitochondrial electrical potential with selectivity for melanoma cells.


Input: Normal melanocytes had no significant differences due to BNCT treatment, confirming the data from the literature regarding the selectivity of BNCT.


Input: The results from this study suggest that some signaling pathways are involved in human melanoma treatment by BNCT, such as cell cycle arrest, ECM changes and intrinsic apoptosis.


Input: Placental transfer of (125) Iodinated humanized immunoglobulin G2 Delta a in the Sprague Dawley rat.


Input: Antibody-like biopharmaceuticals cross the placenta by utilizing transport pathways available for transfer of maternal antibodies to the conceptus.


Input: To characterize the timing and magnitude of this transfer in the rat, embryo/fetal biodistribution of maternally administered radiolabeled humanized IgG2 was quantified over the course of gestation using gamma counting and whole body autoradiography.


Input: The result was humanized IgG2 found in rat embryo/fetal tissues as early as gestation day 11 with a > 1000-fold increase in the amount of total IgG2 by day 21.


Input: The concentration of IgG2 in rat embryo/fetal tissues generally remained unchanged from gestation day 11 to 17 with a slight increase from day 17 to 21.


Input: In addition, fetal-maternal tissue concentration ratios remained stable during organogenesis with a slight increase from gestation day 17 to 21.


Input: Based on the empirical amount of antibody present in the embryo/fetus during specific developmental windows, direct antibody binding to biological targets could potentially result in adverse developmental outcomes.


Input: Carrier free rapamycin loaded drug eluting stent: In vitro and in vivo evaluation.

rapamycin


Input: In the search for improving the performance of drug eluting stent (DES) various developments are in progress worldwide including use of carrier free DES, use of biodegradable polymers, biodegradable stents etc.


Input: In this work, carrier free-rapamycin (RM) coated DES has been prepared, and evaluated by in vitro and in vivo procedures necessary for clinical development.

rapamycin


Input: In vitro drug release from the developed stents was carried in different release media, normal saline-isopropanol (NS-IP), phosphate buffer (PB), phosphate buffer saline (PBS) and in human plasma.

isopropanol

phosphate

phosphate


Input: Simultaneously, drug released at site of implantation and biocompatibility of developed stents was determined after subcutaneous implantation in the SD rats.


Input: Developed stent coating method enables fabrication of controllable and homogeneous crystalline RM coatings on stent scaffolds.


Input: Continuous release of RM was observed in different release conditions with different release rate, maximum in NS-IP and least in PB.


Input: Similarly, after subcutaneous implantation of these stents, RM was found in surrounding tissues and in implanted stent up to 28days.


Input: Biocompatibility studies showed no evidence for presence of necrosis, foreign body giant cell reaction or any type of increased severity of inflammatory reaction, proving potential of developed stents for further clinical development.


Input: Polyalkylcyanoacrylates as in situ formed diffusion barriers in multimaterial drug carriers.

Polyalkylcyanoacrylates


Input: Polymeric hydrogels typically release their drug payload rapidly due to their high water content and the diffusivity for drug molecules.


Input: This study proposes a multimaterial system to sustain the release by covering the hydrogel with a poly (alkyl-2-cyanoacrylate) [PACA]-based film, which should be formed by an in situ polymerization on the hydrogel surface initiated upon contact with water.

poly (alkyl-2-cyanoacrylate)

PACA


Input: A series of PACA-hydrogel hybrid systems with increasing PACA side chain hydrophobicity was prepared using physically crosslinked alginate films and hydrophilic diclofenac sodium as model hydrogel/drug system.

PACA

PACA

diclofenac sodium


Input: Successful synthesis of PACA at the hydrogel surface was confirmed and the PACA layer was identified to be most homogeneous for poly (n-butyl-2-cyanoacrylate) on both the micro-and nanolevel.

PACA

PACA

poly (n-butyl-2-cyanoacrylate)


Input: At the same time, the diclofenac release from the hybrid systems was substantially sustained from ~ 1day for unmodified hydrogels up to > 14days depending on the type of PACA employed as diffusion barrier.

diclofenac

PACA


Input: Overall, in situ polymerized PACA films on hydrogels may be widely applicable to various hydrogel matrices, different matrix sizes as well as more complex shaped hydrogel carriers.

PACA


Input: Comparison of the metabolic effects of sustained CCK1 receptor activation alone and in combination with upregulated leptin signalling in high-fat-fed mice.


Input: AIMS/HYPOTHESIS: Cholecystokinin (CCK) and leptin are important hormones with effects on energy balance.


Input: The present study assessed the biological effects of (pGlu-Gln)-CCK-8 and [D-Leu-4]-OB3, smaller isoforms of CCK and leptin, respectively.


Input: METHODS: The actions and overall therapeutic use of (pGlu-Gln)-CCK-8 and [D-Leu-4]-OB3, alone and in combination, were evaluated in normal and high-fat-fed mice.


Input: RESULTS: (pGlu-Gln)-CCK-8 had prominent (p < 0. 01 to p < 0. 001), acute feeding-suppressive effects, which were significantly augmented (p < 0. 05 to p < 0. 01) by [D-Leu-4]-OB3.


Input: In agreement, the acute dose-dependent glucose-lowering and insulinotropic actions of (pGlu-Gln)-CCK-8 were significantly enhanced by concurrent administration of [D-Leu-4]-OB3.

glucose


Input: Twice daily injection of (pGlu-Gln)-CCK-8 alone and in combination with [D-Leu-4]-OB3 in high-fat-fed mice for 18 days decreased body weight (p < 0. 05 to p < 0. 001), energy intake (p < 0. 01), circulating triacylglycerol (p < 0. 01), non-fasting glucose (p < 0. 05 to p < 0. 001) and triacylglycerol deposition in liver and adipose tissue (p < 0. 001).

triacylglycerol

triacylglycerol


Input: All treatment regimens improved glucose tolerance (p < 0. 05 to p < 0. 001) and insulin sensitivity (p < 0. 001).

glucose


Input: Combined treatment with (pGlu-Gln)-CCK-8 and [D-Leu-4]-OB3 resulted in significantly lowered plasma insulin levels, normalisation of circulating LDL-cholesterol and decreased triacylglycerol deposition in muscle.

cholesterol

triacylglycerol


Input: These effects were superior to either treatment regimen alone.


Input: There were no changes in overall locomotor activity or respiratory exchange ratio, but treatment with (pGlu-Gln)-CCK-8 significantly reduced (p < 0. 001) energy expenditure.


Input: CONCLUSIONS/INTERPRETATION: These studies highlight the potential of (pGlu-Gln)-CCK-8 alone and in combination with [D-Leu-4]-OB3 in the treatment of obesity and diabetes.


Input: Effect of surface morphology on friction of graphene on various substrates.

graphene


Input: The friction of graphene on various substrates, such as SiO2, h-BN, bulk-like graphene, and mica, was investigated to characterize the adhesion level between graphene and the underlying surface.

graphene

graphene

mica

graphene


Input: The friction of graphene on SiO2 decreased with increasing thickness and converged around the penta-layers due to incomplete contact between the two surfaces.

graphene


Input: However, the friction of graphene on an atomically flat substrate, such as h-BN or bulk-like graphene, was low and comparable to that of bulk-like graphene.

graphene

graphene

graphene


Input: In contrast, the friction of graphene folded onto bulk-like graphene was indistinguishable from that of mono-layer graphene on SiO2 despite the ultra-smoothness of bulk-like graphene.

graphene

graphene

graphene

graphene


Input: The characterization of the graphene' s roughness before and after folding showed that the corrugation of graphene induced by SiO2 morphology was preserved even after it was folded onto an atomically flat substrate.

graphene

graphene


Input: In addition, graphene deposited on mica, when folded, preserved the same corrugation level as before the folding event.

graphene

mica


Input: Our friction measurements revealed that graphene, once exfoliated from the bulk crystal, tends to maintain its corrugation level even after it is folded onto an atomically flat substrate and that ultra-flatness in both graphene and the substrate is required to achieve the intimate contact necessary for strong adhesion.

graphene

graphene


Input: Protein fibrillation and nanoparticle interactions: opportunities and challenges.


Input: Due to their ultra-small size, nanoparticles (NPs) have distinct properties compared with the bulk form of the same materials.


Input: These properties are rapidly revolutionizing many areas of medicine and technology.


Input: NPs are recognized as promising and powerful tools to fight against the human brain diseases such as multiple sclerosis or Alzheimer' s disease.


Input: In this review, after an introductory part on the nature of protein fibrillation and the existing approaches for its investigations, the effects of NPs on the fibrillation process have been considered.


Input: More specifically, the role of biophysicochemical properties of NPs, which define their affinity for protein monomers, unfolded monomers, oligomers, critical nuclei, and other prefibrillar states, together with their influence on protein fibrillation kinetics has been described in detail.


Input: In addition, current and possible-future strategies for controlling the desired effect of NPs and their corresponding effects on the conformational changes of the proteins, which have significant roles in the fibrillation process, have been presented.


Input: Developmental Changes in the Expression and Function of Cytochrome P450 3A Isoforms: Evidence from In Vitro and In Vivo Investigations.


Input: The aim of this review is to discuss our current understanding of the developmental changes of the drug-metabolizing enzyme cytochrome P450 (CYP) 3A and its impact on drug therapy.


Input: In the last 10 years, several methods have been used to study the ontogeny of specific CYP3A isoforms in vitro and in vivo.


Input: Although most studies confirm previous findings that CYP3A4/5 activity is low at birth and reaches adult values in the first years of life, there are still important gaps in our knowledge of the exact developmental patterns of individual CYP3A isoforms, especially in this age range.


Input: Moreover, most in vivo clinical studies have also failed to cover the whole pediatric age range.


Input: To date, this information gap still hampers the design of age-specific dosing guidelines of CYP3A substrate drugs, especially in neonates and infants.


Input: Innovative study methods, including opportunistic sampling and sensitive analytical assays used in combination with physiologically based pharmacokinetics, and population pharmacokinetic model concepts may help to improve our understanding of the ontogeny of CYP3A and aid the application of this knowledge in clinical practice.


Input: Nanoparticle Accumulation in Angiogenic Tissues: Towards Predictable Pharmacokinetics.


Input: Nanoparticles are increasingly used in medical applications such as drug delivery, imaging, and biodiagnostics, particularly for cancer.


Input: The design of nanoparticles for tumor delivery has been largely empirical, owing to a lack of quantitative data on angiogenic tissue sequestration.


Input: Using fluorescence correlation spectroscopy, the deposition rate constants of nanoparticles into angiogenic blood vessel tissue are determined.


Input: It is shown that deposition is dependent on surface charge.


Input: Moreover, the size dependency strongly suggests that nanoparticles are taken up by a passive mechanism that depends largely on geometry.


Input: These findings imply that it is possible to tune nanoparticle pharmacokinetics simply by adjusting nanoparticle size.


Input: Tubulin: an example of targeted chemotherapy.


Input: Anticancer drugs directed against the microtubule, including taxanes and vinca alkaloids, have been the backbone of many chemotherapy regimes for decades.

taxanes

vinca alkaloids


Input: These drugs have, however, significant limitations, which have prompted the development of novel microtubule targeting agents (MTAs).


Input: This article will discuss MTAs for anticancer therapies and recent debates regarding their mechanisms of action.


Input: Furthermore, the limitations of taxanes, including hypersensitivity reactions, neurotoxicity, drug resistance and lack of validated biomarkers to guide therapy will be discussed, all of which have driven the development of novel agents.

taxanes


Input: The mechanisms of action and drug development of new generations of MTAs will also be outlined.


Input: Agents demonstrating utility in Phase III clinical trials, including eribulin, ixabepilone, cabazitaxel and trastuzumab-DM1 will be highlighted, as well as novel agents currently in development and future directions for MTAs.

eribulin

ixabepilone

cabazitaxel


Input: Hierarchical or not?


Input: Effect of the length scale and hierarchy of the surface roughness on omniphobicity of lubricant-infused substrates.


Input: Lubricant-infused textured solid substrates are gaining remarkable interest as a new class of omni-repellent nonfouling materials and surface coatings.


Input: We investigated the effect of the length scale and hierarchy of the surface topography of the underlying substrates on their ability to retain the lubricant under high shear conditions, which is important for maintaining nonwetting properties under application-relevant conditions.


Input: By comparing the lubricant loss, contact angle hysteresis, and sliding angles for water and ethanol droplets on flat, microscale, nanoscale, and hierarchically textured surfaces subjected to various spinning rates (from 100 to 10 000 rpm), we show that lubricant-infused textured surfaces with uniform nanofeatures provide the most shear-tolerant liquid-repellent behavior, unlike lotus leaf-inspired superhydrophobic surfaces, which generally favor hierarchical structures for improved pressure stability and low contact angle hysteresis.

ethanol


Input: On the basis of these findings, we present generalized, low-cost, and scalable methods to manufacture uniform or regionally patterned nanotextured coatings on arbitrary materials and complex shapes.


Input: After functionalization and lubrication, these coatings show robust, shear-tolerant omniphobic behavior, transparency, and nonfouling properties against highly contaminating media.


Input: Effect of stachydrine on endoplasmic reticulum stress-induced apoptosis in rat kidney after unilateral ureteral obstruction.

stachydrine


Input: Our study aimed at determining the effect of stachydrine on the PERK, CHOP, and caspase-3 in rat kidney with RIF.

stachydrine


Input: Rats were randomly divided into control group, model group, enalapril group, high stachydrine group, medium stachydrine group, and low stachydrine group.

enalapril

stachydrine

stachydrine

stachydrine


Input: RIF models of five groups were developed by unilateral ureteral obstruction except the control group.


Input: The rats were sacrificed 12 days after surgery and blood samples were collected.


Input: Serum creatinine (Scr) and blood urea nitrogen (BUN) levels were detected.

creatinine

nitrogen


Input: Renal tubular damage index was determined by HE staining.


Input: The area percentage of RIF was determined by the Masson method.


Input: Expressions of PERK, CHOP, and caspase-3 in kidney were determined by immunohistochemistry.


Input: Tubulointerstitial injury index, RIF, serum Scr, BUN level, and expressions of PERK, CHOP, and caspase-3 were different between the model and treatment groups (P < 0. 05; P < 0. 01).


Input: The expressions of PERK, CHOP, and caspase-3 in nephridial tissue were reduced (P < 0. 05), tubulointerstitial injury and RIF were reduced (P < 0. 05), and Scr and BUN were lower (P < 0. 05) in the high stachydrine group than those in the enalapril group.

stachydrine

enalapril


Input: The expressions of PERK, CHOP, and caspase-3 were reduced in the endoplasmic reticulum stress-related apoptosis pathway after stachydrine treatment.

stachydrine


Input: Consequently, apoptosis was prevented, and RIF was inhibited.


Input: Uncinataflavone, a new flavonoid with a methyl benzoate substituent from Selaginella uncinata.

Uncinataflavone

flavonoid

methyl benzoate


Input: Uncinataflavone (1), a new flavonoid, together with four known compounds (2-5), was isolated from Selaginella uncinata (Desv.) Spring.

Uncinataflavone

flavonoid


Input: Compounds 2 and 3 were isolated from the genus selaginella for the first time.


Input: The structure of the new compound was determined as methyl 3-(5, 7-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-6-yl)-4-methoxybenzoate by means of spectroscopic evidence, including UV, IR, 1D and 2D NMR analyses as well as HR-ESI-MS.

methyl 3-(5, 7-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-6-yl)-4-methoxybenzoate


Input: These compounds (1-5) were evaluated for the antioxidant activity in 1, 1-diphenyl-2-picrylhydrazyl assay system.

1, 1-diphenyl-2-picrylhydrazyl


Input: The antiviral effect of 7-hydroxyisoflavone against Enterovirus 71 in vitro.


Input: Enterovirus 71 (EV71) is the major causative agent of hand foot and mouth disease.


Input: And EV71 causes epidemics worldwide, particularly in the Asia-Pacific region.


Input: Unfortunately, currently there is no approved vaccine or antiviral drug for EV71-induced disease prevention and therapy.


Input: In screening for anti-EV71 candidates, we found that 7-hydroxyisoflavone was active against EV71.


Input: 7-Hydroxyisoflavone exhibited strong antiviral activity against three different EV71 strains.


Input: The 50% inhibitory concentration range was between 3. 25 and 4. 92 mu M by cytopathic effect assay.


Input: 7-Hydroxyisoflavone could reduce EV71 viral RNA and protein synthesis in a dose-dependent manner.


Input: Time course study showed that treatment of Vero cells with 7-hydroxyisoflavone at indicated times after EV71 inoculation (0-6 h) resulted in significant antiviral activity.


Input: Results showed that 7-hydroxyisoflavone acted at an early step of EV71 replication.


Input: 7-Hydroxyisoflavone also exhibited strong antiviral activity against coxsackievirus B2, B3, and B6.


Input: In short, 7-hydroxyisoflavone may be used as a lead compound for anti-EV71 drug development.


Input: Two new tri-nor-eudesmanolides from Inula racemosa.

tri-nor-eudesmanolides


Input: Two new tri-nor-eudesmane-type sesquiterpenoids were isolated from the roots of Inula racemosa, and their structures were elucidated as 8-oxo-tri-nor-eudesm-6-en-5 alpha-ol (1) and tri-nor-eudesm-5-en-7 beta, 8 beta-diol (2).

tri-nor-eudesmane

sesquiterpenoids

8-oxo-tri-nor-eudesm-6-en-5 alpha-ol

tri-nor-eudesm-5-en-7 beta, 8 beta-diol


Input: The cytotoxic activity of compound 1 against five human cancer cell lines had been tested, but exhibited no cytotoxic activity.


Input: Spectral Phonon Scattering from Sub-10 nm Surface Roughness Wavelengths in Metal-Assisted Chemically Etched Si Nanowires.

Si


Input: Frequency dependence in phonon surface scattering is a debated topic in fundamental phonon physics.


Input: Recent experiments and theory suggest such a phenomenon, but an independent agreement between the two remains elusive.


Input: We report low-temperature dependence of thermal conductivity in silicon nanowires fabricated using a two-step, metal-assisted chemical etch.

silicon


Input: By reducing etch rates down to 0. 5 nm/s from the typical > 100 nm/s, we report controllable roughening of nanowire surfaces and selectively focus on moderate roughness scales rather than the extreme scales investigated previously.


Input: This critically enables direct comparison with perturbation-based spectral scattering theory.


Input: Using experimentally characterized surface roughness, we show that a multiple scattering theory provides excellent agreement and explanation of the observed low-temperature dependence of rough surface nanowires.


Input: The theory does not employ any fitting parameters.


Input: A 5-10 nm roughness correlation length is typical in metal-assisted chemical etching and resonantly scatters dominant phonons in silicon, leading to the observed ~ T (1. 6-2. 4) behavior.

silicon


Input: Our work provides fundamental and quantitative insight into spectral phonon scattering from rough surfaces.


Input: This advances applications of nanowires in thermoelectric energy conversion.


Input: A new flavanol from Cynomorium songaricum.

flavanol


Input: A new flavanol, named songarin A (1), was isolated from Cynomorium songaricum Rupr.

flavanol

songarin A


Input: The structure was established on the basis of spectroscopic methods including 2D NMR techniques.


Input: Compound 1 displayed the protective effect against d-galactosamine-induced HepG2 damage and reduced the damage from 58. 64% to 22. 26%.

d-galactosamine


Input: Progress, challenges, and opportunities in two-dimensional materials beyond graphene.

graphene


Input: Graphene' s success has shown that it is possible to create stable, single and few-atom-thick layers of van der Waals materials, and also that these materials can exhibit fascinating and technologically useful properties.

Graphene


Input: Here we review the state-of-the-art of 2D materials beyond graphene.

graphene


Input: Initially, we will outline the different chemical classes of 2D materials and discuss the various strategies to prepare single-layer, few-layer, and multilayer assembly materials in solution, on substrates, and on the wafer scale.


Input: Additionally, we present an experimental guide for identifying and characterizing single-layer-thick materials, as well as outlining emerging techniques that yield both local and global information.


Input: We describe the differences that occur in the electronic structure between the bulk and the single layer and discuss various methods of tuning their electronic properties by manipulating the surface.


Input: Finally, we highlight the properties and advantages of single-, few-, and many-layer 2D materials in field-effect transistors, spin-and valley-tronics, thermoelectrics, and topological insulators, among many other applications.


Input: Protein Targets of Thioacetamide Metabolites in Rat Hepatocytes.

Thioacetamide


Input: Thioacetamide (TA) has long been known as a hepatotoxicant whose bioactivation requires S-oxidation to thioacetamide S-oxide (TASO) and then to the very reactive S, S-dioxide (TASO2).

Thioacetamide

S

thioacetamide S-oxide

TASO

S, S-dioxide


Input: The latter can tautomerize to form acylating species capable of covalently modifying cellular nucleophiles including phosphatidylethanolamine (PE) lipids and protein lysine side chains.

phosphatidylethanolamine

lysine


Input: Isolated hepatocytes efficiently oxidize TA to TASO but experience little covalent binding or cytotoxicity because TA is a very potent inhibitor of the oxidation of TASO to TASO2.

TASO

TASO


Input: However, hepatocytes treated with TASO show extensive covalent binding to both lipids and proteins accompanied by extensive cytotoxicity.

TASO


Input: In this work, we treated rat hepatocytes with [(14) C]-TASO and submitted the mitochondrial, microsomal, and cytosolic fractions to 2DGE, which revealed a total of 321 radioactive protein spots.

[(14) C]-TASO


Input: To facilitate the identification of target proteins and adducted peptides, we also treated cells with a mixture of TASO/[(13) C2D3]-TASO.

TASO

[(13) C2D3]-TASO


Input: Using a combination of 1DGE-and 2DGE-based proteomic approaches, we identified 187 modified peptides (174 acetylated, 50 acetimidoylated, and 37 in both forms) from a total of 88 nonredundant target proteins.


Input: Among the latter, 57 are also known targets of at least one other hepatotoxin.


Input: The formation of both amide-and amidine-type adducts to protein lysine side chains is in contrast to the exclusive formation of amidine-type adducts with PE phospholipids.

amide

amidine

lysine

amidine


Input: Thiobenzamide (TB) undergoes the same two-step oxidative bioactivation as TA, and it also gives rise to both amide and amidine adducts on protein lysine side chains but only amidine adducts to PE lipids.

Thiobenzamide

amide

amidine

lysine

amidine


Input: Despite their similarity in functional group chemical reactivity, only 38 of 62 known TB target proteins are found among the 88 known targets of TASO.

TASO


Input: The potential roles of protein modification by TASO in triggering cytotoxicity are discussed in terms of enzyme inhibition, protein folding, and chaperone function, and the emerging role of protein acetylation in intracellular signaling and the regulation of biochemical pathways.

TASO


Input: PF-04859989 as a template for structure-based drug design: identification of new pyrazole series of irreversible KAT II inhibitors with improved lipophilic efficiency.

pyrazole


Input: The structure-based design, synthesis, and biological evaluation of a new pyrazole series of irreversible KAT II inhibitors are described herein.

pyrazole


Input: The modification of the inhibitor scaffold of 1 and 2 from a dihydroquinolinone core to a tetrahydropyrazolopyridinone core led to discovery of a new series of potent KAT II inhibitors with excellent physicochemical properties.

dihydroquinolinone

tetrahydropyrazolopyridinone


Input: Compound 20 is the most potent and lipophilically efficient of these new pyrazole analogs, with a k (inact)/K (i) value of 112, 000 M (-1) s (-1) and lipophilic efficiency (LipE) of 8. 53.

pyrazole


Input: The X-ray crystal structure of 20 with KAT II demonstrates key features that contribute to this remarkable potency and binding efficiency.


Input: Design, synthesis and antithrombotic evaluation of novel dabigatran prodrugs containing methyl ferulate.

dabigatran

methyl ferulate


Input: A novel series of prodrugs containing dabigatran and methyl (E)-3-(4-hydroxy-2-methoxyphenyl) propenoate (methyl ferulate) were synthesized.

dabigatran

methyl (E)-3-(4-hydroxy-2-methoxyphenyl) propenoate

methyl ferulate


Input: All of them reveal the effect of thrombin-induced anti-platelet aggregation in vitro.


Input: In addition, in vivo experiment shows that one of the target compounds, X-2 (ED50 = 3. 7 +/- 1. 0 mu mol/kg) possesses a more potent activity for inhibiting venous thrombosis than that of dabigatran etexilate (ED50 = 7. 8 +/- 1. 5 mu mol/kg).

dabigatran etexilate


Input: A new series of N2-substituted-5-(p-toluenesulfonylamino) phthalimide analogues as alpha-glucosidase inhibitors.

N2-substituted-5-(p-toluenesulfonylamino) phthalimide


Input: Several members of a new family of non-sugar-type alpha-glycosidase inhibitors, bearing a 5-(p-toluenesulfonylamino) phthalimide moiety and various substituent at the N2 position, were synthesized and their activities were investigated.

sugar

5-(p-toluenesulfonylamino) phthalimide


Input: The newly synthesized compounds displayed different inhibition profile towards yeast alpha-glycosidase and rat intestinal alpha-glycosidase.


Input: Almost all the compounds had strong inhibitory activities against yeast alpha-glycosidase.


Input: Regarding rat intestinal alpha-glycosidase, only analogs with N2-aromatic substituents displayed varying degrees of inhibitory activities on rat intestinal maltase and lactase and nearly all compounds showed no inhibition against rat intestinal alpha-amylase.


Input: Structure-activity relationship studies indicated that 5-(p-toluenesulfonylamino) phthalimide moiety is a favorable scaffold to exert the alpha-glucosidase inhibitory activity and substituents at the N2 position have considerable influence on the efficacy of the inhibition activities.

5-(p-toluenesulfonylamino) phthalimide


Input: Efficient synthesis and antimicrobial activity of some novel S-beta-d-glucosides of 5-aryl-1, 2, 4-triazole-3-thiones derivatives.

S-beta-d-glucosides

5-aryl-1, 2, 4-triazole-3-thiones


Input: A series of 3-S-beta-d-glucosides-4-arylideneamino-5-aryl-1, 2, 4-triazoles were rationally designed and synthesized according to the principle of superposition of bioactive substructures by the combination of 1, 2, 4-triazole, Schiff base and glucosides.

3-S-beta-d-glucosides-4-arylideneamino-5-aryl-1, 2, 4-triazoles

1, 2, 4-triazole

Schiff base

glucosides


Input: The structures of the target compounds have been characterized by (1) H NMR, (13) C NMR, IR, MS and HRMS.

(1) H

(13) C


Input: All the newly synthesized compounds have been evaluated for their antimicrobial activities in vitro against Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 8099) as well as Monilia albican (ATCC 10231).


Input: The bioactive assay showed that most of the tested compounds displayed variable inhibitory effects on the growth of the Gram-positive bacterial strain (Staphylococcus aureus), Gram-negative bacterial strains (Escherichia coli) and fungal strains (Monilia albican).


Input: All the target compounds exhibited better antifungal activity than antibacterial activity.


Input: Especially, compounds 6b, 6c, 6f, 6j, 6k and 6l showed excellent activity against fungus Monilia albican with MIC values of 16 mu g/mL.


Input: Noradrenergic control of the bed nucleus of the stria terminalis in stress and reward.


Input: The bed nucleus of the stria terminalis (BNST) is a group of inter-connected subnuclei that play critical roles in stress-reward interactions.


Input: An interesting feature of this brain region is the massive noradrenergic input that it receives.


Input: Important roles for norepinephrine in this region have been documented in a number of stress and reward related behaviors.

norepinephrine


Input: This work has been paralleled over the last several years by efforts to understand the actions of norepinephrine on neuronal function in the region.

norepinephrine


Input: In this review, we will summarize the current state of these research areas.


Input: The two faces of the pharmacological interaction of mGlu2 and 5-HT2A-Relevance of receptor heterocomplexes and interaction through functional brain pathways.


Input: Important functional interactions between the metabotropic glutamate 2 (mGlu2) and 5-hydroxytryptamine2A (5-HT2A) neurotransmitter receptors have been established based on electrophysiological, biochemical and behavioral evidence.

glutamate


Input: Over the last several years, dimerization between 5-HT2A and mGlu2 receptors has been proposed to account for the functional cross-talk between these two receptors in the prefrontal cortex.


Input: The pros and cons for the existence of a heteromeric complex between 5-HT2A and mGlu2 receptors will be reviewed here.


Input: First, the fundamental criteria needing to establish evidence for heteromeric complexes will be reviewed.


Input: Then, the in vitro evidence for and against heteromeric complexes between 5-HT2A and mGlu2 receptors will be discussed in regard to physical and functional interactions.


Input: Finally, the data with native in situ mGlu2 and 5-HT2A receptors will be discussed with respect to whether heteromeric complexes or a simple functional interaction between two distinct GPCRs based on brain network activity is the more simple explanation for a range of in vivo data.


Input: Reversal of P-glycoprotein-mediated multidrug resistance is induced by mollugin in MCF-7/adriamycin cells.

mollugin


Input: P-glycoprotein (P-gp), an important efflux transporter, is encoded by the MDR1 class of genes and is a central element of the multidrug resistance (MDR) phenomenon in cancer cells.


Input: In the present study, we investigated whether mollugin, purified from roots of Rubica cordifolia L., down-regulated MDR1 expression in MCF-7/adriamycin (MCF-7/adr) cells, a human breast multidrug-resistant cancer cell line.

mollugin

adriamycin


Input: Mollugin treatment significantly inhibited MDR1 expression by blocking MDR1 transcription.

Mollugin


Input: Mollugin treatment also significantly increased intracellular accumulation of the fluorescently-tagged P-gp substrate, rhodamine-123.

Mollugin


Input: The suppression of MDR1 promoter activity and protein expression was mediated through mollugin-induced activation of AMP-activated protein kinase (AMPK).

mollugin

AMP


Input: Furthermore, mollugin inhibited MDR1 expression through the suppression of NF-kappa B and CREB activation.

mollugin


Input: Interestingly, mollugin also inhibited COX-2 expression.

mollugin


Input: These results suggest that mollugin treatment enhanced suppression of P-gp expression by inhibiting the NF-kappa B signaling pathway and COX-2 expression, as well as attenuating CRE transcriptional activity through AMPK activation.

mollugin


Input: Membranar effects exerted in vitro by polyphenols-quercetin, epigallocatechin gallate and curcumin-on HUVEC and Jurkat cells, relevant for diabetes mellitus.

polyphenols

quercetin

epigallocatechin gallate

curcumin


Input: Polyphenols are largely studied for their beneficial action in various pathologies, but the correlation with their effects on cell membranes is still elusive.

Polyphenols


Input: In the present study we assessed the effects exerted in vitro by quercetin, epigallocatechin gallate and curcumin on membrane fluidity and transmembrane potential of human umbilical vein endothelial cells and Jurkat T lymphoblasts, in experimental conditions mimicking diabetes mellitus, i. e. high glucose conditions or increased concentration of advanced glycation end products.

quercetin

epigallocatechin gallate

curcumin

glucose


Input: Results showed that the investigated polyphenols had beneficial effects on cell membranes altered in diabetic conditions, by restoring transmembrane potential and by membrane " stiffening ".

polyphenols


Input: Moreover, they limited the release of pro-inflammatory factors, like monocyte chemotactic protein-1.


Input: These effects were more obvious for cells exposed to advanced glycation end products specific for the late stages of diabetes.


Input: Apparently, the inhibitory action of polyphenols on lipid peroxidation was associated with a decrease of membrane fluidity.

polyphenols


Input: Concluding, our in vitro study highlighted the potential beneficial action of polyphenols mainly in the late stages of diabetes, exerted at the level of membrane fluidity and transmembrane potential, accompanied by an anti-inflammatory effect on endothelial and immune cells.

polyphenols


Input: miR-21 confers cisplatin resistance in gastric cancer cells by regulating PTEN.

cisplatin


Input: Resistance to chemotherapy is a major obstacle for the effective treatment of cancers.


Input: The mechanism of chemo-resistance is still poorly understood, however, mounting evidence supports a role for microRNAs (miRNAs) in modulating key cellular pathways mediating response to chemotherapy.


Input: microRNA-21 (miR-21) has been implicated in many cancers and contributed to chemo-resistance, but its role in gastric cancer drug resistance still remains unexplored.


Input: The aim of this study was to investigate whether miR-21 mediated resistance of the gastric cancer cell line SGC7901 to the chemotherapeutic agent cisplatin (DDP).

cisplatin

DDP


Input: Our study found that the expression of miR-21 upregulated in the cisplatin resistant cell line SGC7901/DDP compared to its parental line SGC7901.

cisplatin

DDP


Input: Moreover, over-expression of miR-21 significantly decreased antiproliferative effects and apoptosis induced by cisplatin, while knockdown of miR-21 dramatically increased antiproliferative effects and apoptosis induction by cisplatin.

cisplatin

cisplatin


Input: In addition, miR-21 induced cell survival and cisplatin resistance through downregulating the expression of phosphatase and tension homolog deleted on chromosome 10 (PTEN) and activation of Akt pathway.

cisplatin


Input: Inhibition of Akt using PI3K inhibitor LY 294002 could abrogate miR-21 induced cell survival.

LY 294002


Input: These results suggest that miR-21 may provide a novel mechanism for understanding cisplatin resistance in gastric cancer by modulating PTEN/PI3K/Akt pathway.

cisplatin


Input: p-Cresol induces disruption of cardiomyocyte adherens junctions.

p-Cresol


Input: Higher serum levels of p-cresol in chronic kidney disease populations have been associated with increased cardiovascular mortality.

p-cresol


Input: However, studies on how p-cresol affects intercellular junctions between cardiomyocytes were limited.

p-cresol


Input: This study investigated the effect of p-cresol on adherens junction (AJ) of neonatal cultured cardiomyocytes and its underlying mechanism.

p-cresol


Input: A loss of N-cadherin and p120-catenin (p120ctn) immunostaining from cell-cell contact sites was noted by p-cresol treatment.

p-cresol


Input: In addition, p-cresol disrupted AJs by inducing formation of intercellular gaps.

p-cresol


Input: Our previous study has revealed that p-cresol increased intracellular calcium levels and activated protein kinase C alpha (PKC alpha) by phosphorylation.

p-cresol

calcium


Input: The PKC alpha activation was involved in the p-cresol-mediated AJ disassembly, since pharmacological inhibition of PKC alpha abolished the above-mentioned p-cresol effect.

p-cresol

p-cresol


Input: This PKC alpha activation also led to the serine dephosphorylation of p120ctn and caused the dissociation of p120ctn from N-cadherin.

serine


Input: This hypothesis was further confirmed in H9c2 cells by siRNA approach.


Input: SiRNA knockdown of PKC alpha prevented p-cresol-induced serine dephosphorylation of p120ctn and splitting of AJ.

p-cresol


Input: In conclusion, p-cresol caused PKC alpha-dependent AJ disassembly of cardiomyocytes, which might be related to asychronized contraction.

p-cresol


Input: ZEB2 zinc-finger missense mutations lead to hypomorphic alleles and a mild Mowat-Wilson syndrome.

zinc


Input: Mowat-Wilson syndrome (MWS) is a severe intellectual disability (ID)-distinctive facial gestalt-multiple congenital anomaly syndrome, commonly associating microcephaly, epilepsy, corpus callosum agenesis, conotruncal heart defects, urogenital malformations and Hirschsprung disease (HSCR).


Input: MWS is caused by de novo heterozygous mutations in the ZEB2 gene.


Input: The majority of mutations lead to haplo-insufficiency through premature stop codons or large gene deletions.


Input: Only three missense mutations have been reported so far; none of which resides in a known functional domain of ZEB2.


Input: In this study, we report and analyze the functional consequences of three novel missense mutations, p. Tyr1055Cys, p. Ser1071Pro and p. His1045Arg, identified in the highly conserved C-zinc-finger (C-ZF) domain of ZEB2.

zinc


Input: Patients' phenotype included the facial gestalt of MWS and moderate ID, but no microcephaly, heart defects or HSCR.


Input: In vitro studies showed that all the three mutations prevented binding and repression of the E-cadherin promoter, a characterized ZEB2 target gene.


Input: Taking advantage of the zebrafish morphant technology, we performed rescue experiments using wild-type (WT) and mutant human ZEB2 mRNAs.


Input: Variable, mutation-dependent, embryo rescue, correlating with the severity of patients' phenotype, was observed.


Input: Our data provide evidence that these missense mutations cause a partial loss of function of ZEB2, suggesting that its role is not restricted to repression of E-cadherin.


Input: Functional domains other than C-ZF may play a role in early embryonic development.


Input: Finally, these findings broaden the clinical spectrum of ZEB2 mutations, indicating that MWS ought to be considered in patients with lesser degrees of ID and a suggestive facial gestalt, even in the absence of congenital malformation.


Input: Potent vasorelaxant analogs from chemical modification and biotransformation of isosteviol.

isosteviol


Input: Isosteviol (1) has been reported to exhibit moderate vasorelaxant activity.

Isosteviol


Input: In order to enhance the bioactivity of this compound, chemical modification of 1 to the dihydro analog, ent-16 beta-hydroxybeyeran-19-oic acid (2), was undertaken.

ent-16 beta-hydroxybeyeran-19-oic acid


Input: Compound 2 was then converted to the corresponding acetate derivative, ent-16 beta-acetoxybeyeran-19-oic acid (3).

acetate

ent-16 beta-acetoxybeyeran-19-oic acid


Input: Biotransformation of compounds 1-3 by the fungus Cunninghamella echinulata NRRL 1386 was investigated and the metabolites 4-9 were obtained.


Input: The substrates and their metabolites were subjected to in vitro rat aorta relaxant activity evaluation.


Input: The metabolite 4, ent-7 alpha-hydroxy-16-ketobeyeran-19-oic acid, exhibited the most highly potent activity, with EC50 of 3. 46 nM, whereas the parent compound 1 showed relatively low activity (EC50 57. 41 nM).

ent-7 alpha-hydroxy-16-ketobeyeran-19-oic acid


Input: A 17-fold increase in vasorelaxant activity of the analog 4 relative to compound 1 is of particular significant.


Input: Compound 4 exerted vasorelaxant activity at particularly low concentration and the vasorelaxant profile reached maximum at relatively low concentration, especially when compared with acetylcholine, the positive control.

acetylcholine


Input: A novel insulin mimetic vanadium-flavonol complex: Synthesis, characterization and in vivo evaluation in STZ-induced rats.

vanadium-flavonol

STZ


Input: Since 1985, when Heyliger et al., first demonstrated a serendipitous discovery that oral administration of 0. 8 mg/ml of sodium orthovanadate in drinking water to streptozotocin-induced diabetic rats resulted in normoglycemia, numerous extensive studies have been pursued on the anti-diabetic and insulinomimetic actions of vanadium.

sodium orthovanadate

streptozotocin

vanadium


Input: The acceptance of vanadium compounds as promising therapeutic antidiabetic agents has been slowed due to the concern for chronic toxicity associated with vanadium accumulation.

vanadium

vanadium


Input: In order to circumvent the toxic effects of vanadium, we have taken up a combinational approach wherein a novel vanadium-flavonol complex was synthesized, characterized and its toxic as well as insulin mimetic potential was evaluated in STZ-induced experimental diabetes in rats.

vanadium

vanadium-flavonol

STZ


Input: The results indicate that the complex is non-toxic and possess anti-diabetic activity.


Input: GPER: A novel target for non-genomic estrogen action in the cardiovascular system.

estrogen


Input: A key to harnessing the enormous therapeutic potential of estrogens is understanding the diversity of estrogen receptors and their signaling mechanisms.

estrogens

estrogen


Input: In addition to the classic nuclear estrogen receptors (i. e., ER alpha and ER beta), over the past decade a novel G-protein-coupled estrogen receptor (GPER) has been discovered in cancer and other cell types.

estrogen

estrogen


Input: More recently, this non-genomic signaling mechanism has been found in blood vessels, and mediates vasodilatory responses to estrogen and estrogen-like agents; however, downstream signaling events involved acute estrogen action remain unclear.

estrogen

estrogen

estrogen


Input: The purpose of this review is to discuss the latest knowledge concerning GPER modulation of cardiovascular function, with a particular emphasis upon how activation of this receptor could mediate acute estrogen effects in the heart and blood vessels (i. e., vascular tone, cell growth and differentiation, apoptosis, endothelial function, myocardial protection).

estrogen


Input: Understanding the role of GPER in estrogen signaling may help resolve some of the controversies associated with estrogen and cardiovascular function.

estrogen

estrogen


Input: Moreover, a more thorough understanding of GPER function could also open significant opportunities for the development of new pharmacological strategies that would provide the cardiovascular benefits of estrogen while limiting the potentially dangerous side effects.

estrogen


Input: Monitoring abacavir bioactivation in humans: Screening for an aldehyde metabolite.

abacavir

aldehyde


Input: The anti-HIV drug abacavir is associated with idiosyncratic hypersensitivity reactions and cardiotoxicity.

abacavir


Input: Although the mechanism underlying abacavir-toxicity is not fully understood, drug bioactivation to reactive metabolites may be involved.

abacavir


Input: This work was aimed at identifying abacavir-protein adducts in the hemoglobin of HIV patients as biomarkers of abacavir bioactivation and protein modification.

abacavir

abacavir


Input: The protocol received prior approval from the Hospital Ethics Committee, patients gave their written informed consent and adherence was controlled through a questionnaire.


Input: Abacavir-derived Edman adducts with the N-terminal valine of hemoglobin were analyzed by an established liquid chromatography-electrospray ionization-tandem mass spectrometry method.

Abacavir

N

valine


Input: Abacavir-valine adducts were detected in three out of ten patients.

Abacavir

valine


Input: This work represents the first evidence of abacavir-protein adduct formation in humans.

abacavir


Input: The data confirm the ability of abacavir to modify self-proteins and suggest that the molecular mechanism (s) of some abacavir-induced adverse reactions may require bioactivation.

abacavir

abacavir


Input: Refinement of the ECETOC approach to identify endocrine disrupting properties of chemicals in ecotoxicology.


Input: To use and implement an assessment scheme for the evaluation of endocrine disrupting properties of chemicals in ecotoxicology, the types of effect need to be agreed.


Input: Effects that merit further consideration in this context should fulfil the following three criteria: caused by an endocrine mode of action, be adverse, and be relevant at the population level to reflect the protection goal of ecotoxicological assessments.


Input: Thereafter, a comparison of effect values, regardless of the causative mechanisms, should be made, firstly to determine if endocrine toxicity generates the lowest endpoint within a taxon, and secondly if it is the lowest endpoint compared to that of other taxa living in the same compartment.


Input: These comparisons inform on two levels of specificity and determine if endocrine-mediated side-effects determine the ecotoxicological profile of a chemical.


Input: Various quantitative measures for the assessment of potency are also presented, which could assist in determining how to handle substances in the risk assessment when a regulatory concern is identified.


Input: Finally, derogation criteria should be defined for compounds that were designed as endocrine disruptors for non-vertebrates and those for which there is' negligible exposure'.


Input: This paper discusses and provides proposals on how to apply these concepts for assessment of substances.


Input: Family history of alcoholism interacts with alcohol to affect brain regions involved in behavioral inhibition.

alcoholism


Input: RATIONALE: Impulsive behavior is associated with both alcohol use disorders and a family history of alcoholism (FHA).

alcohol


Input: One operational definition of impulsive behavior is the stop-signal task (SST) which measures the time needed to stop a ballistic hand movement.


Input: OBJECTIVE: Employ functional magnetic resonance imaging (fMRI) to study right frontal responses to stop signals in heavy drinking subjects with and without FHA, and as a function of alcohol exposure.

alcohol


Input: METHODS: Twenty-two family history-positive (FHP; age = 22. 7 years, SD = 1. 9) and 18 family history-negative (FHN; age = 23. 7, SD = 1. 8) subjects performed the SST in fMRI in two randomized visits: once during intravenous infusion of alcohol, clamped at a steady-state breath alcohol (BrAC) concentration of 60 mg/dL, and once during infusion of placebo saline.

alcohol

alcohol


Input: An independent reference group (n = 13, age = 23. 7, SD = 1. 8) was used to identify a priori right prefrontal regions activated by successful inhibition (Inh) trials, relative to " Go " trials that carried no need for inhibition [Inh > Go].


Input: RESULTS: FHA interacted with alcohol exposure in right prefrontal cortex, where alcohol reduced [Inh > Go] activation in FHN subjects but not in FHP subjects.

alcohol

alcohol


Input: Within this right frontal cortical region, stop-signal reaction time also correlated negatively with [Inh > Go] activation, suggesting that the [Inh > Go] activity was related to inhibitory behavior.


Input: CONCLUSIONS: The results are consistent with the low level of response theory (Schuckit, J Stud Alcohol 55: 149-158, 1980; Quinn and Fromme, Alcohol Clin Exp Res 35: 1759-1770, 2011), with FHP being less sensitive to alcohol' s effects.

Alcohol

Alcohol

alcohol


Input: 3-Hydroxyazetidine carboxylic acids: non-proteinogenic amino acids for medicinal chemists.

3-Hydroxyazetidine carboxylic acids

amino acids


Input: The formation from D-glucose of both enantiomers of 2, 4-dideoxy-2, 4-iminoribonic acid is the first chemical synthesis of unprotected 3-hydroxyazetidine carboxylic acids.

D-glucose

2, 4-dideoxy-2, 4-iminoribonic acid

3-hydroxyazetidine carboxylic acids


Input: The long-term stability of 3-hydroxyazetidine amides is established at acidic and neutral pH and implies their value as non-proteinogenic amino acid components of peptides, providing medicinal chemists with a new class of peptide isosteres.

3-hydroxyazetidine amides

amino acid


Input: The structure of N, 3-O-dibenzyl-2, 4-dideoxy-2, 4-imino-D-ribonic acid was established by X-ray crystallographic analysis.

N, 3-O-dibenzyl-2, 4-dideoxy-2, 4-imino-D-ribonic acid


Input: An N-methylazetidine amide derivative is a specific inhibitor of beta-hexosaminidases at the micromolar level, and is only the second example of potent inhibition of any glycosidase by an amide of a sugar amino acid related to an iminosugar.

N-methylazetidine amide

amide

sugar amino acid

iminosugar


Input: The Role of Surface Chemistry on the Toxicity of Ag Nanoparticles.

Ag


Input: The role of surface chemistry on the toxicity of Ag nanoparticles is investigated using Saccharomyces cerevisiae yeast as a platform for evaluation.

Ag


Input: Combining the shape-controlled synthesis of Ag nanoparticles with a comprehensive characterization of their physicochemical properties, an understanding is formed of the correlation between the physicochemical parameters of nanoparticles and the inhibition growth of yeast cells upon the introduction of nanoparticles into the cell culture system.

Ag


Input: Capping agents, surface facets, and sample stability-the three experimental parameters that are inherent from the wet-chemical synthesis of Ag nanoparticles-have a strong impact on toxicity evaluation.

Ag


Input: Hence, it is important to characterize surface properties of Ag nanoparticles in the nature of biological media and to understand the role that surface chemistry may interplay to correlate the physicochemical properties of nanoparticles with their biological response upon exposure.

Ag


Input: This work demonstrates the great importance of surface chemistry in designing experiments for reliable toxicity evaluation and in mitigating the toxicity of Ag nanoparticles for their safe use in future commercialization.

Ag


Input: Hybridization of Phenylthiolate-and Methylthiolate-Adatom Species at Low Coverage on the Au (111) Surface.

Phenylthiolate

Methylthiolate

Au (111)


Input: Using scanning tunneling microscopy we observed reaction products of two chemisorbed thiolate species, methylthiolate and phenylthiolate, on the Au (111) surface.

thiolate

methylthiolate

phenylthiolate

Au (111)


Input: Despite the apparent stability, organometallic complexes of methylthiolate and phenylthiolate with the gold-adatom (RS-Au-SR, with R-the hydrocarbon group) undergo a stoichiometric exchange reaction, forming hybridized CH3S-Au-SPh complexes.

organometallic

methylthiolate

phenylthiolate

RS-Au-SR

hydrocarbon


Input: Complementary density functional theory calculations suggest that the reaction is most likely mediated by a monothiolate RS-Au complex bonded to the gold surface, which forms a trithiolate RS-Au-(SR)-Au-SR complex as a key intermediate.

RS-Au

trithiolate RS-Au-(SR)-Au-SR


Input: This work therefore reveals the novel chemical reactivity of the low-coverage " striped " phase of alkanethiols on gold and strongly points to the involvement of monoadatom thiolate intermediates in this reaction.

alkanethiols

thiolate


Input: By extension, such intermediates may be involved in the self-assembly process itself, shedding new light on this long-standing problem.


Input: Targeted d4 dopamine receptors: implications for drug discovery and therapeutic development.

dopamine


Input: A wealth of preclinical and clinical literature has established functional associations of CNS dopamine (DA) and its multiple G protein-coupled receptor (GPCR) types in the integration of key neurological processes linked to complex behavioral activities.

dopamine


Input: Conversely, an equivalent vast literature supports the role of aberrant CNS DA expression and DA receptor signaling in the etiology and persistence of major psychiatric illnesses and has established selective targeting of DA-ergic systems as a cornerstone of pharmacotherapeutic intervention and current neuroleptic drug development.


Input: The present short review focuses on potential functional/behavioral alterations linked to polymorphisms in the primary DNA sequence of the DA receptor type 4 (DRD4) gene in reference to major psychiatric illnesses.


Input: The potential clinical relevance of major polymorphisms of the DRD4 gene are discussed within the context of practical aspects of typical and atypical neuroleptic drug usage within afflicted populations of psychiatric patients.


Input: It is anticipated that additional complementary molecular, biochemical, and behavioral studies of DRD4 gene polymorphisms will provide essential information for selective targeting of heterogeneous populations of CNS D4 receptors and advance drug discovery and therapeutic development efforts for highly efficacious treatment of psychiatric illnesses.


Input: Polyclonal Antibody to Soman-Tyrosine.

Soman

Tyrosine


Input: Soman forms a stable, covalent bond with tyrosine 411 of human albumin, with tyrosines 257 and 593 in human transferrin, and with tyrosine in many other proteins.

Soman

tyrosine

tyrosines

tyrosine


Input: The pinacolyl group of soman is retained, suggesting that pinacolyl methylphosphonate bound to tyrosine could generate specific antibodies.

pinacolyl

soman

pinacolyl methylphosphonate

tyrosine


Input: Tyrosine in the pentapeptide RYGRK was covalently modified with soman simply by adding soman to the peptide.

Tyrosine

pentapeptide

soman

soman


Input: The phosphonylated-peptide was linked to keyhole limpet hemocyanin, and the conjugate was injected into rabbits.


Input: The polyclonal antiserum recognized soman-labeled human albumin, soman-mouse albumin, and soman human transferrin but not nonphosphonylated control proteins.

soman

soman

soman