Input: The influx of AC was temperature-, pH-and Na (+)-dependent.

Na (+)


Input: Glucose markedly decreased the absorption of AC.

Glucose


Input: However, the efflux of AC was temperature-and pH-dependent, but Na (+)-independent.

Na (+)


Input: Cyclosporin A and verapamil, both inhibitors of P-glycoprotein (P-gp), significantly decreased the efflux of AC.

Cyclosporin A

verapamil


Input: In addition, MK-571, an inhibitor of multidrug resistance-associated protein 2 (MRP2), exhibited the same trend but to a lesser extent.


Input: These results indicate that both the influx and efflux of AC across Caco-2 monolayers were through an active process.


Input: A pH-dependent carrier-mediated transport system was the major absorption mechanism and a sodium-dependent glucose transporter may be involved.

sodium

glucose


Input: The active efflux of AC across Caco-2 cells was mediated mainly by ABC-transporter P-gp.


Input: It is involved in reducing the toxicity of AC to organisms and is the major reasons for the poor absorption of AC in vivo.


Input: Retrospective exposure data for baby and children care products: An analysis of 48 clinical studies.


Input: To conduct a reliable safety assessment, accurate exposure information for cosmetic products and ingredients is needed.


Input: The aim of the present retrospective study was to determine the amount per application and the daily exposure for some of the most commonly used baby cosmetic products.


Input: Consumption data from 48 clinical studies performed on 1481 babies and children (from 0 to 10years old) were reviewed and used to conduct a probabilistic evaluation of dermal exposure.


Input: Six categories of products were reviewed: rinseoff products for hair and body; rinse-off products for the whole body; leave-on products for face and body; cleansers for face and body; diaper dermatitis treatment products; shampoos.


Input: Subjects were provided with products and recorded detailed daily usage information over a 1-4-week period, depending on the study.


Input: Products were weighed at the start and upon completion of each study in order to determine the total amount of product used.


Input: The mean, median, standard deviation and 95th percentile were calculated for daily consumption and exposure, for several age groups from 0 to 10years old.


Input: This study provides current baby cosmetic exposure information for commonly used products which will be useful for risk assessment purposes.


Input: A protocol for the classification of wet mass in extrusion-spheronization.


Input: In this study, a structured protocol for the classification of wet mass in extrusion-spheronization was developed to predict formation and pellet quality.


Input: The wet masses of 120 formulae were prepared taking microcrystalline celluloses as pelletization aid and lactose, hydroxypropyl methylcellulose grades, herbal medicines as model drugs.

lactose

hydroxypropyl


Input: Physical properties of the wet masses such as hardness, adhesiveness, springiness, cohesiveness, chewiness, and resilience were tested, respectively, using a texture analyzer.


Input: Particles were produced by spheronization process, and the quality of spherical pellets was also evaluated.


Input: Data were analyzed by principal component analysis, factor analysis, and classification analysis.


Input: The wet masses could be classified into five groups taking the ratio of hardness to springiness (Ha/Sp) as the first classification index and chewiness, resilience as the second and the third classification index.


Input: The wet masses of different classification could correspondingly form the different shapes.


Input: So, a new protocol could be devised, for example, if the range of Ha/Sp of the wet masses was 30, 992-47, 689g, at the same time, the value of chewiness was less than 4842, and the value of resilience was no more than 0. 139; it would form spherical pellets under the experimental condition.


Input: These results demonstrate that the proposed protocol could be a valuable asset in a formulation development project to assess the physical properties of wet masses and to predict formation and pellet quality.


Input: So, the tedious and expensive pre-production (pre-formulation and optimization) work could be considerably reduced.


Input: Frequency of the GPR7 Tyr135Phe allelic variant in lean and obese subjects.


Input: Background: GPR7, the endogenous coupled receptor for neuropeptide B and neuropeptide W, is expressed in several regions of the Central Nervous System (CNS), which are involved in the regulation of feeding behaviour.


Input: GPR7 affects the regulation of energy balance through a mechanism independent of leptin and melanocortin pathways.


Input: Aim: Aim of this study was to investigate whether GPR7 gene mutations can be detected in human subjects and, in that event, if they are differently distributed among lean and obese subjects.


Input: Subjects and Methods: The coding region of GPR7 were sequenced in 150 obese patients and 100 normal-weight unrelated controls.


Input: Functional studies of the allelic variants were performed.


Input: Results: One genetic GPR7 variant was found (Tyr135Phe-rs33977775) in obese subjects (13, 3%) and lean control (25%).


Input: Functional studies did not reveal significant differences between the wild type and the Tyr135Phe allelic variants in their NPW mediated capacity to inhibit forskolin-induced cAMP production.

forskolin

cAMP


Input: Conclusions: Screening of GPR7 gene mutations among lean and obese subjects revealed a Tyr135Phe allelic variant that was fairly common in the study population.


Input: As indicated by in vitro and in silico studies, this variant is unlikely to cause a functional derangement of the receptor.


Input: Resolving the phylogenetic history of the short-necked turtles, genera Elseya and Myuchelys (Testudines: Chelidae) from Australia and New Guinea.


Input: Phylogenetic relationships and taxonomy of the short-necked turtles of the genera Elseya, Myuchelys, and Emydura in Australia and New Guinea have long been debated as a result of conflicting hypotheses supported by different data sets and phylogenetic analyses.


Input: To resolve this contentious issue, we analyzed sequences from two mitochondrial genes (cytochrome b and ND4) and one nuclear intron gene (R35) from all species of the genera Elseya, Myuchelys, Emydura, and their relatives.


Input: Phylogenetic analyses using three methods (maximum parsimony, maximum likelihood, and Bayesian inference) produce a single, well resolved, and strongly corroborated hypothesis, which provides support for the three genera, with the exception that the genus Myuchelys is paraphyletic-Myuchelys purvisi is the sister taxon to the remaining Elseya, Myuchelys and Emydura.


Input: A new genus is proposed for the species Myuchelys purvisi to address this paraphyletic relationship.


Input: Time-calibration analysis suggests that diversification of the group in Australia coincides with periods of aridification in the late Eocene and between the mid-Miocene and early Pliocene.


Input: Other speciation events occurred during the faunal exchange between Australia and the island of New Guinea during the late Miocene and early Pliocene.


Input: Lineages distributed in New Guinea are likely influenced by the complex geologic history of the island, and include cryptic species diversity.


Input: Determination of pediatric reference levels of FT3, FT4 and TSH measured with ECLusys kits.


Input: Reference ranges for serum thyroid hormones free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) in children were set using the assay kits currently used in clinical settings.

triiodothyronine

thyroxine


Input: A total of 342 children (111 males and 231 females) who were negative for antithyroid antibodies (TgAb, TPOAb) and were found to have no abnormalities on ultrasonographic examination of the thyroid gland were divided into 6 age groups: 4-6 years (45 children), 7-8 years (40), 9-10 years (53), 11-12 years (65), 13-14 years (83), and 15 years (56) for the study.


Input: FT3, FT4 and TSH levels were determined by electrochemiluminescence immunoassay (ECLIA) (ECLusys FT3, FT4 and TSH). The reference range for FT3 (pg/mL) was 2. 91-4. 70 for the age group of 4-6 years, 3. 10-5. 10 for the age group of 7-8 years, 3. 10-4. 87 for the age group of 9-10 years, 2. 78-4. 90 for the age group of 11-12 years, 2. 77-4. 59 for the age group of 13-14 years, and 2. 50-4. 64 for the age group of 15 years.


Input: The reference range for FT4 (ng/dL) was 1. 12-1. 67, 1. 07-1. 61, 0. 96-1. 60, 1. 02-1. 52, 0. 96-1. 52, 0. 95-1. 53.


Input: The reference range for TSH (mu U/mL) was 0. 62-4. 90, 0. 53-5. 16, 0. 67-4. 52, 0. 62-3. 36, 0. 54-2. 78, 0. 32-3. 00.


Input: Serum FT3, FT4 and TSH levels in children differ from those in adults.


Input: It is, therefore, of importance to perform evaluation of thyroid function in children using reference values appropriate for the chronological ages, because misdiagnosis of hypothyroidism or inappropriate secretion of TSH (SITSH) and oversight of mild subclinical hypothyroidism could occur if the diagnosis is made using reference values for adults.


Input: Polybetaine modification of PDMS microfluidic devices to resist thrombus formation in whole blood.

PDMS


Input: Assembled polydimethylsiloxane microfluidic devices were modified with a sulfobetaine polymer through continuous " tip-to-tip " modification, significantly reducing blood clotting and extending device patency under blood flow.

polydimethylsiloxane

sulfobetaine


Input: This technology can be designed to enable the development of devices that can continuously work in whole blood, especially in an extracorporeal or in vivo environment.


Input: Assessing triclosan-induced ecological and trans-generational effects in natural phytoplankton communities: a trait-based field method.

triclosan


Input: We exposed replicated phytoplankton communities confined in semi-permeable membrane-based mesocosms to 0, 0. 1, 1 and 10 mu g L (-1) triclosan (TCS) and placed them back in their original environment to investigate the occurrence of trans-generational responses at individual, population and community levels.

triclosan

TCS


Input: TCS diffused out of mesocosms with a half-life of less than 8 h, so that only the parental generation was directly stressed.

TCS


Input: At the beginning of the experiment and after 7 days (approximately 2 generations) we analysed responses in the phytoplankton using scanning flow-cytometry.


Input: We acquired information on several individually expressed phenotypic traits, such as size, biovolume, pigment fluorescence and packaging, for thousands of individuals per replicated population and derived population and community aggregated traits.


Input: We found significant changes in community functioning (increased productivity in terms of biovolume and total fluorescence), with maximal effects at 1 mu g L (-1) TCS.

TCS


Input: We detected significant and dose-dependent responses on population traits, such as changes in abundance for several populations, increased average size and fluorescence of cells, and strong changes in within-population trait mean and variance (suggesting micro-evolutionary effects).


Input: We applied the Price equation approach to partition community effects (changes in biovolume or fluorescence) in their physiological and ecological components, and quantified the residual component (including also evolutionary responses).


Input: Our results suggested that evolutionary or inheritable phenotypic plasticity responses may represent a significant component of the total observed change following exposure and over relatively small temporal scales.


Input: Radiolabeled Heterobivalent Peptidic Ligands: an Approach with High Future Potential for in vivo Imaging and Therapy of Malignant Diseases.


Input: Two-pronged synergism: We review the recently developed approach of using heterobivalent peptide ligands that interact concomitantly with different receptors on tumor cells.


Input: These ligands exhibit highly favorable tumor-targeting properties and pave the way for the development of drugs for specific, sensitive, and noninvasive tumor imaging and therapy.


Input: Metabolic response demonstrated by 18F-FDG-PET/CT in metastatic medullary thyroid carcinoma under sorafenib therapy.

sorafenib


Input: A 51-year-old woman with a medullary thyroid carcinoma (MTC) presented with a palpable nodule in the right breast.


Input: Serum calcitonin was 1, 453 pg/ml and carcinoembryonic antigen was 201 ng/ml.


Input: Cervical ultrasound and bone scintigraphy were normal.


Input: Computed tomography (CT) showed nodules in the right breast and anterior thoracic wall and a hypodense lesion in the right hepatic lobe.


Input: Histology of the breast nodule confirmed metastasis from MTC.


Input: To evaluate the metabolic activity of these lesions, 18F-fluorodeoxiglucose positron emission tomography-CT (FDG-PET/CT) scan was requested.

FDG


Input: Axial fused images revealed high FDG uptake by the breast and thoracic wall nodules and the right hepatic lobe.

FDG


Input: FDG-PET/CT also showed uptake in sacrum and right iliac bone, undetected by CT and bone scintigraphy.

FDG


Input: After seven cycles of sorafenib PET/CT became negative.

sorafenib


Input: Calcitonin decreased to 82. 5.


Input: A PET/CT performed 6 months later remained negative.


Input: This is the first published image of the complete metabolic response of MTC to sorafenib therapy using FDG-PET/CT.

sorafenib

FDG


Input: Detection of Statin Cytotoxicity Is Increased in Cells Expressing the OATP1B1 Transporter.


Input: Cytotoxicity of a compound is determined by the intracellular concentration mediated both by passive permeability and active uptake through drug transporters.


Input: However, the major liver uptake transporters were either absent or expressed at significantly lower levels in human liver cell lines than in human liver.


Input: When comparing cytotoxicity of five statins, the organic anion transporting polypeptide 1B1 (OATP1B1) expressing HEK cells showed a significantly higher sensitivity than the wild-type HEK cells.


Input: The IC50 shifts ranged from 9-to > 100-fold, and the potency shifts collapsed in the presence of rifampicin, the inhibitor for OATPs.

rifampicin


Input: The extent of the IC50 shift correlated with the permeability of the statins with high permeable compounds having smaller shifts and low permeable compounds having larger shifts.


Input: The changes in statin potency in transporter transfected cells reflect the active uptake of statins into the cells and the increased intracellular drug concentration lead to increased toxicity.


Input: The data suggested that uptake transporters have a significant impact on the outcomes of a cell-based assay and should be considered during the early stages of compound toxicity screening in drug discovery.


Input: For compounds with low permeability which are likely to undergo transporter-mediated uptake, it is important to test them in transporter-competent cell models.


Input: Expression of a novel mRNA transcript for human microsomal epoxide hydrolase (EPHX1) is regulated by short open reading frames within its 5'-untranslated region.

epoxide


Input: Microsomal epoxide hydrolase (mEH, EPHX1) is a critical xenobiotic-metabolizing enzyme, catalyzing both detoxification and bioactivation reactions that direct the disposition of chemical epoxides, including the carcinogenic metabolites of several polycyclic aromatic hydrocarbons.

epoxide

epoxides

polycyclic aromatic hydrocarbons


Input: Recently, we discovered that a previously unrecognized and primate-specific EPHX1 transcript, termed E1-b, was actually the predominant driver of EPHX1 expression in all human tissues.


Input: In this study, we identify another human EPHX1 transcript, designated as E1-b'.


Input: Unusually, both the E1-b and E1-b' mRNA transcripts are generated from the use of a far upstream gene promoter, localized ~ 18. 5 kb 5'-upstream of the EPHX1 protein-coding region.


Input: Although expressed at comparatively lower levels than E1-b, the novel E1-b' transcript is readily detected in all tissues examined, with highest levels maintained in human ovary.


Input: The E1-b' mRNA possesses unusual functional features in its 5'-untranslated region, including a GC-rich leader sequence and two upstream AUGs that encode for short peptides of 26 and 17 amino acids in length, respectively.


Input: Results from in vitro transcription/translation assays and direct transfection in mammalian cells of either the E1-b' transcript or the encoded peptides demonstrated that the E1-b' upstream open reading frames (uORFs) are functional, with their presence markedly inhibiting the translation of EPHX1 protein, both in cis and in trans configurations.


Input: These unique uORF peptides exhibit no homology to any other known uORF sequences but likely function to mediate post-transcription regulation of EPHX1 and perhaps more broadly as translational regulators in human cells.


Input: Effects of Intraduodenal Glutamine on Incretin Hormone and Insulin Release, the Glycemic Response to an Intraduodenal Glucose Infusion, and Antropyloroduodenal Motility in Health and Type 2 Diabetes.

Glutamine

Glucose


Input: OBJECTIVEGlutamine reduces postprandial glycemia when given before oral glucose.

OBJECTIVEGlutamine

glucose


Input: We evaluated whether this is mediated by stimulation of insulin and/or slowing of gastric emptying. RESEARCH DESIGN AND METHODSTen healthy subjects were studied during intraduodenal (ID) infusion of glutamine (7. 5 or 15 g) or saline over 30 min, followed by glucose (75 g over 100 min), while recording antropyloroduodenal pressures.

glutamine

glucose


Input: Ten patients with type 2 diabetes mellitus (T2DM) were also studied with 15 g glutamine or saline. RESULTSID glutamine stimulated glucagon-like peptide 1 (GLP-1; healthy: P < 0. 05; T2DM: P < 0. 05), glucose-dependent insulinotropic polypeptide (GIP; P = 0. 098; P < 0. 05), glucagon (P < 0. 01; P < 0. 001), insulin (P = 0. 05; P < 0. 01), and phasic pyloric pressures (P < 0. 05; P < 0. 05), but did not lower blood glucose (P = 0. 077; P = 0. 5). CONCLUSIONSGlutamine does not lower glycemia after ID glucose, despite stimulating GLP-1, GIP, and insulin, probably due to increased glucagon.

glutamine

glutamine

glucose

glucose

CONCLUSIONSGlutamine

glucose


Input: Its capacity for pyloric stimulation suggests that delayed gastric emptying is a major mechanism for lowering glycemia when glutamine is given before oral glucose.

glutamine

glucose


Input: Low-Carbohydrate Diet for the Treatment of Gestational Diabetes: A randomized controlled trial.

Carbohydrate


Input: OBJECTIVEMedical nutrition therapy based on the control of the amount and distribution of carbohydrates (CHO) is the initial treatment for gestational diabetes mellitus (GDM), but there is a need for randomized controlled trials comparing different dietary strategies.

carbohydrates

CHO


Input: The purpose of this study was to test the hypothesis that a low-CHO diet for the treatment of GDM would lead to a lower rate of insulin treatment with similar pregnancy outcomes compared with a control diet. RESEARCH DESIGN AND METHODSA total of 152 women with GDM were included in this open, randomized controlled trial and assigned to follow either a diet with low-CHO content (40% of the total diet energy content as CHO) or a control diet (55% of the total diet energy content as CHO).

CHO

CHO

CHO

CHO


Input: CHO intake was assessed by 3-day food records.

CHO


Input: The main pregnancy outcomes were also assessed. RESULTSThe rate of women requiring insulin was not significantly different between the treatment groups (low CHO 54. 7% vs. control 54. 7%; P = 1).

CHO


Input: Daily food records confirmed a difference in the amount of CHO consumed between the groups (P = 0. 0001).

CHO


Input: No differences were found in the obstetric and perinatal outcomes between the treatment groups. CONCLUSIONSTreatment of women with GDM using a low-CHO diet did not reduce the number of women needing insulin and produced similar pregnancy outcomes.

CHO


Input: In GDM, CHO amount (40 vs. 55% of calories) did not influence insulin need or pregnancy outcomes.

CHO


Input: Expansion of the Homeostasis Model Assessment of beta-Cell Function and Insulin Resistance to Enable Clinical Trial Outcome Modeling Through the Interactive Adjustment of Physiology and Treatment Effects--iHOMA2.


Input: OBJECTIVETo describe and make available an interactive, 24-variable homeostasis model assessment (iHOMA2) that extends the HOMA2 model, enabling the modeling of physiology and treatment effects, to present equations of the HOMA2 and iHOMA2 models, and to exemplify iHOMA2 in two widely differing scenarios: changes in insulin sensitivity with thiazolidinediones and changes in renal threshold with sodium glucose transporter (SGLT2) inhibition. RESEARCH DESIGN AND METHODSiHOMA2 enables a user of the available software to examine and modify the mathematical functions describing the organs and tissues involved in the glucose and hormonal compartments.

thiazolidinediones

sodium glucose

glucose


Input: We exemplify this with SGLT2 inhibition modeling (by changing the renal threshold parameters) using published data of renal effect, showing that the modeled effect is concordant with the effects on fasting glucose from independent data. RESULTSiHOMA2 modeling of thiazolidinediones effect suggested that changes in insulin sensitivity in the fasting state are predominantly hepatic.

glucose

thiazolidinediones


Input: SGLT2 inhibition modeled by iHOMA2 resulted in a decrease in mean glucose of 1. 1 mmol/L.

glucose


Input: Observed data showed a decrease in glucose of 0. 9 mmol/L.

glucose


Input: There was no significant difference between the model and the independent data.


Input: Manipulation of iHOMA2s renal excretion threshold variable suggested that a decrease of 17% was required to obtain a 0. 9 mmol/L decrease in mean glucose. CONCLUSIONSiHOMA2 is an extended mathematical model for the assessment of insulin resistance and beta-cell function.

glucose


Input: The model can be used to evaluate therapeutic agents and predict effects on fasting glucose and insulin and on beta-cell function and insulin sensitivity.

glucose


Input: The C-terminus of Botulinum A Protease Has Profound and Unanticipated Kinetic Consequences Upon the Catalytic Cleft.


Input: Botulinum neurotoxins (BoNTs) are among the most deadly poisons known though ironically, they also are of great therapeutic utility.


Input: A number of research programs have been initiated to discover small molecule inhibitors of BoNTs metalloprotease activity.


Input: Many, though not all of these programs have screened against a truncated and more stable form of the enzyme, that possess comparable catalytic properties to the full length enzyme.


Input: Interestingly, several classes of inhibitors notably the hydroxamates, display a large shift in potency between the two enzyme forms.

hydroxamates


Input: In this report we compare the kinetics of active-site, alpha-exosite and beta-exosite inhibitors versus truncated and full length enzyme.


Input: Molecular dynamics simulations conducted with the truncated and homology models of the fully length BoNT LC/A indicate the flexibility of the C-terminus of the full length enzyme is responsible for the potency shifts of active-site proximally binding inhibitors while distal binding (alpha-exosite) inhibitors remain equipotent.


Input: Human Precision-Cut Liver Slices as an ex Vivo Model to Study Idiosyncratic Drug-Induced Liver Injury.


Input: Idiosyncratic drug-induced liver injury (IDILI) is a major problem during drug development and has caused drug withdrawal and black-box warnings.


Input: Because of the low concordance of the hepatotoxicity of drugs in animals and humans, robust screening methods using human tissue are needed to predict IDILI in humans.


Input: According to the inflammatory stress hypothesis, the effects of inflammation interact with the effects of a drug or its reactive metabolite, precipitating toxic reactions in the liver.


Input: As a follow-up to our recently published mouse precision-cut liver slices model, an ex vivo model involving human precision-cut liver slices (hPCLS), co-incubated for 24 h with IDILI-related drugs and lipopolysaccharide (LPS), was developed to study IDILI mechanisms related to inflammatory stress in humans and to detect potential biomarkers.


Input: LPS exacerbated the effects of ketoconazole and clozapine toxicity but not those of their non-IDILI-related comparators, voriconazole and olanzapine.

ketoconazole

clozapine

voriconazole

olanzapine


Input: However, the IDILI-related drugs diclofenac, carbamazepine, and troglitazone did not show synergistic toxicity with LPS after incubation for 24 h.

diclofenac

carbamazepine

troglitazone


Input: Co-incubation of ketoconazole and clozapine with LPS decreased the levels of glutathione in hPCLS, but this was not seen for the other drugs.

ketoconazole

clozapine

glutathione


Input: All drugs affected LPS-induced cytokine release, but interestingly, only ketoconazole and clozapine increased the level of LPS-induced TNF release.

ketoconazole

clozapine


Input: Decreased levels of glutathione and cysteine conjugates of clozapine were detected in IDILI-responding livers following cotreatment with LPS.

glutathione

cysteine

clozapine


Input: In conclusion, we identified ketoconazole and clozapine as drugs that exhibited synergistic toxicity with LPS, while glutathione and TNF were found to be potential biomarkers for IDILI-inducing drugs mediated by inflammatory stress.

ketoconazole

clozapine

glutathione


Input: hPCLS appear to be suitable for further unraveling the mechanisms of inflammatory stress-associated IDILI.


Input: Controlling the Effective Surface Area and Pore Size Distribution of sp (2) Carbon Materials and Their Impact on the Capacitance Performance of These Materials.

Carbon


Input: A series of sp (2) carbon materials with different specific surface area (SSA) and controlled pore size distribution (PSD) were synthesized at large scale through a facile and low-cost method.

carbon


Input: The SSA and PSD of these carbon materials were controlled by using different carbon sources and preparation methods.

carbon

carbon


Input: With different total and effective SSA (E-SSA) and PSD, the impacts on their capacitance performance were investigated thoroughly, which demonstrated that both E-SSA and PSD played the most important roles in their capacitance performance.


Input: Furthermore, theoretical modeling was performed, and the results are in agreement with the experimental results for the influence of E-SSA and PSD on their capacitance performance.


Input: Based on these, a general model using the slit/cylindrical NL-DFT approach is proposed for the estimation of the specific capacitance of sp (2) carbon materials, which offers a simple but reliable method to predict the capacitance performance of these materials, thus speeding up the design and screening of the materials for high-performance supercapacitor and other surface area related devices.

carbon


Input: Approach to dark spin cooling in a diamond nanocrystal.

diamond


Input: Using a Hartman-Hahn protocol, we demonstrate spin polarization transfer from a single, optically polarized nitrogen-vacancy (NV) center to the ensemble of paramagnetic defects hosted by an individual diamond nanocrystal.

nitrogen

diamond


Input: Owing to the strong NV-bath coupling, the transfer takes place on a short, microsecond time scale.


Input: Upon fast repetition of the pulse sequence, we observe strong polarization transfer blockade, which we interpret as an indication of spin bath cooling.


Input: Numerical simulations indicate that the spin bath polarization is nonuniform throughout the nanoparticle, averaging approximately 5% over the crystal volume, but reaching up to 25% in the immediate vicinity of the NV.


Input: These observations may prove relevant to the planning of future bath-assisted magnetometry tests.


Input: The role of intracrine androgen metabolism, androgen receptor and apoptosis in the survival and recurrence of prostate cancer during androgen deprivation therapy.

androgen

androgen

androgen


Input: Prostate cancer (CaP) is the most frequently diagnosed cancer and leading cause of cancer death in American men.


Input: Almost all men present with advanced CaP and some men who fail potentially curative therapy are treated with androgen deprivation therapy (ADT).

androgen


Input: ADT is not curative and CaP recurs as the lethal phenotype.


Input: The goal of this review is to apply our current understanding of CaP and castration-recurrent CaP (CR-CaP) to earlier studies that characterized ADT and the molecular mechanisms that facilitate the transition from androgen-stimulated CaP to CR-CaP.

androgen


Input: Reexamination of earlier studies also may provide a better understanding of how more newly recognized mechanisms, such as intracrine metabolism, may be involved with the early events that allow CaP survival after initiation of ADT and subsequent development of CR-CaP.


Input: Real-time evaluation of binding mechanisms in multivalent interactions: a surface plasmon resonance kinetic approach.


Input: Multivalency is a key, ubiquitous phenomenon in nature characterized by a complex combination of binding mechanisms, with special relevance in carbohydrate-lectin recognition.

carbohydrate


Input: Herein we introduce an original surface plasmon resonance kinetic approach to analyze multivalent interactions that has been validated with dendrimers as monodisperse multivalent analytes binding to lectin clusters.


Input: The method, based on the analysis of early association and late dissociation phases of the sensorgrams provides robust information of the glycoconjugate binding efficiency and real-time structural data of the binding events under the complex scenario of the glyco-cluster effect.


Input: Notably, it reveals the dynamic nature of the interaction and offers experimental evidence on the contribution of binding mechanisms.


Input: Enhancing Catalytic Performance of Palladium in Gold and Palladium Alloy Nanoparticles for Organic Synthesis Reactions through Visible Light Irradiation at Ambient Temperatures.

Palladium

Palladium


Input: The intrinsic catalytic activity of palladium (Pd) is significantly enhanced in gold (Au)-Pd alloy nanoparticles (NPs) under visible light irradiation at ambient temperatures.

palladium

Pd

Au

Pd


Input: The alloy NPs strongly absorb light and efficiently enhance the conversion of several reactions, including Suzuki-Miyaura cross coupling, oxidative addition of benzylamine, selective oxidation of aromatic alcohols to corresponding aldehydes and ketones, and phenol oxidation.

benzylamine

aromatic alcohols

aldehydes

ketones

phenol


Input: The Au/Pd molar ratio of the alloy NPs has an important impact on performance of the catalysts since it determines both the electronic heterogeneity and the distribution of Pd sites at the NP surface, with these two factors playing key roles in the catalytic activity.

Au

Pd

Pd


Input: Irradiating with light produces an even more profound enhancement in the catalytic performance of the NPs.


Input: For example, the best conversion rate achieved thermally at 30 degrees C for Suzuki-Miyaura cross coupling was 37% at a Au/Pd ratio of 1: 1. 86, while under light illumination the yield increased to 96% under the same conditions.

Au

Pd


Input: The catalytic activity of the alloy NPs depends on the intensity and wavelength of incident light.


Input: Light absorption due to the Localized Surface Plasmon Resonance of gold nanocrystals plays an important role in enhancing catalyst performance.


Input: We believe that the conduction electrons of the NPs gain the light absorbed energy producing energetic electrons at the surface Pd sites, which enhances the sites' intrinsic catalytic ability.

Pd


Input: These findings provide useful guidelines for designing efficient catalysts composed of alloys of a plasmonic metal and a catalytically active transition metal for various organic syntheses driven by sunlight.

transition metal


Input: Effects of Curcumin on Apoptosis and Oxidoinflammatory Regulation in a Rat Model of Acetic Acid-Induced Colitis: The Roles of c-Jun N-Terminal Kinase and p38 Mitogen-Activated Protein Kinase.

Curcumin

Acetic Acid

N


Input: Abstract The present study evaluated the effects of curcumin on epithelial cell apoptosis, the immunoreactivity of the phospho-c-Jun N-terminal kinase (JNK) and phospho-p38 mitogen-activated protein kinases (MAPKs) in inflamed colon mucosa, and oxidative stress in a rat model of ulcerative colitis induced by acetic acid.

curcumin

N

acetic acid


Input: Rats were randomly divided into three groups: control, acetic acid, and acetic acid + curcumin.

acetic acid

acetic acid

curcumin


Input: Curcumin (100 mg/kg per day, intragastrically) was administered 10 days before the induction of colitis and was continued for two additional days.

Curcumin


Input: Acetic acid-induced colitis caused a significant increase in the macroscopic and microscopic tissue ranking scores as well as an elevation in colonic myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels, and the number of apoptotic epithelial cells in colon tissue compared to controls.

Acetic acid

malondialdehyde

MDA


Input: In the rat colon, immunoreactivity of phospho-p38 MAPK was increased, whereas the phospho-JNK activity was decreased following the induction of colitis.


Input: Curcumin treatment was associated with amelioration of macroscopic and microscopic colitis sores, decreased MPO activity, and decreased MDA levels in acetic acid-induced colitis.

Curcumin

MDA

acetic acid


Input: Furthermore, oral curcumin supplementation clearly prevented programmed cell death and restored immunreactivity of MAPKs in the colons of colitic rats.

curcumin


Input: The results of this study suggest that oral curcumin treatment decreases colon injury and is associated with decreased inflammatory reactions, lipid peroxidation, apoptotic cell death, and modulating p38-and JNK-MAPK pathways.

curcumin


Input: Oligonol supplementation attenuates body temperature and the circulating levels of prostaglandin e2 and cyclooxygenase-2 after heat stress in humans.

prostaglandin e2


Input: Abstract Oligonol, a phenolic production from lychee, has been reported to exhibit anti-oxidative and anti-inflammatory effects.

phenolic


Input: This study investigated the effect of Oligonol supplementation on circulating levels of prostaglandin E2 (PGE2) and cyclooxygenase (COX)-2, as well as body temperature, after heat stress in 17 healthy human male volunteers (age, 21. 6 +/- 2. 1 years).

prostaglandin E2


Input: All experiments were performed in an automated climate chamber (26. 0 degrees C +/- 0. 5 degrees C, relative humidity 60% +/- 3. 0%, air velocity less than 1 m/sec) between 2 and 5 p. m.


Input: Subjects ingested an Oligonol (100 mg)-containing beverage or placebo beverage before half-body immersion into hot water (42 degrees C +/- 0. 5 degrees C for 30 min).


Input: Tympanic and skin temperatures were measured and mean body temperatures were calculated.


Input: Serum concentrations of PGE2 and COX-2 were analyzed before, immediately after, and 60 min after immersion.


Input: Oligonol intake significantly prevented elevation of tympanic (temperature difference: 0. 17 degrees C at Post, P <. 05; 0. 17 degrees C at Re-60, P <. 05) and mean body temperatures (temperature difference: 0. 18 degrees C at Post, P <. 05; 0. 15 degrees C at Re-60, P <. 05), and lowered concentrations of serum PGE2 (increased by 13. 3% vs. 29. 6% at Post, P <. 05) and COX-2 (increased by 15. 6% vs. 21. 8% at Post, P <. 05), compared to placebo beverage.


Input: Our result suggests that Oligonol has the potential to suppress increases in body temperature under heat stress, and this is associated with decreases in serum levels of PGE2 and COX-2.


Input: Flaxseed-derived enterolactone is inversely associated with tumor cell proliferation in men with localized prostate cancer.

enterolactone


Input: Abstract Enterolactone and enterodiol, mammalian lignans derived from dietary sources such as flaxseed, sesame seeds, kale, broccoli, and apricots, may impede tumor proliferation by inhibiting activation of nuclear factor kappa B (NF kappa B) and vascular endothelial growth factor (VEGF).

Enterolactone

enterodiol

lignans


Input: We examined the associations between urinary enterolactone and enterodiol with prostatic tumor expression of NF kappa B, VEGF, and Ki67 among 147 patients with prostate cancer who participated in a presurgical trial of flaxseed supplementation (30 g/day) for ~ 30 days.

enterolactone

enterodiol


Input: Urinary enterolignans and tissue biomarkers were determined by high-performance liquid chromatography and immunohistochemistry, respectively.

enterolignans


Input: After supplementation, we observed significant correlations between intakes of plant lignan and urinary concentrations of total enterolignans (rho = 0. 677, P <. 0001), enterolactone (rho = 0. 676, P <. 0001), and enterodiol (rho = 0. 628, P <. 0001).

lignan

enterolignans

enterolactone

enterodiol


Input: Importantly, we observed that total urinary enterolignans and enterolactone were significantly and inversely correlated with Ki67 in the tumor tissue (rho =-0. 217, P =. 011, and rho =-0. 230, P =. 007, respectively), and a near-significant inverse association was observed for enterodiol (rho =-0. 159, P =. 064).

enterolignans

enterolactone

enterodiol


Input: An inverse association was observed between enterolactone and VEGF (rho =-0. 143, P =. 141), although this did not reach statistical significance.

enterolactone


Input: We did not observe an association between enterolignans and NF kappa B.

enterolignans


Input: In conclusion, flaxseed-derived enterolignans may hinder cancer cell proliferation via VEGF-associated pathways.

enterolignans


Input: Synthesis and structure-activity relationships of 2-amino-3-carboxy-4-phenylthiophenes as novel atypical protein kinase C inhibitors.


Input: Recent evidence suggests atypical protein kinase C (aPKC) isoforms are required for both TNF-and VEGF-induced breakdown of the blood-retinal barrier (BRB) and endothelial permeability to 70kDa dextran or albumin.

retinal


Input: A chemical library screen revealed a series of novel small molecule phenylthiophene based inhibitors of aPKC isoforms that effectively block permeability in cell culture and in vivo.

phenylthiophene


Input: In an effort to further elucidate the structural requirements of this series of inhibitors, we detail in this study a structure-activity relationship (SAR) built on screening hit 1, which expands on our initial pharmacophore model.


Input: The biological activity of our analogues was evaluated in models of bona fide aPKC-dependent signaling including NF kappa B driven-gene transcription as a marker for an inflammatory response and VEGF/TNF-induced vascular endothelial permeability.


Input: The EC50 for the most efficacious inhibitors (6, 32) was in the low nanomolar range in these two cellular assays.


Input: Our study demonstrates the key structural elements that confer inhibitory activity and highlights the requirement for electron-donating moieties off the C-4 aryl moiety of the 2-amino-3-carboxy-4-phenylthiophene backbone.


Input: These studies suggest that this class has potential for further development into small molecule aPKC inhibitors with therapeutic efficacy in a host of diseases involving increased vascular permeability and inflammation.


Input: Synthesis, cytotoxicity and topoisomerase II inhibitory activity of lomefloxacin derivatives.

lomefloxacin


Input: A novel series of amide derivatives of lomefloxacin were synthesized and evaluated for their topoisomerase I and II inhibitory activity as well as cytotoxicity against a panel of five human cancer cell lines.

amide

lomefloxacin


Input: Of the compounds prepared compounds 9d and 9g exhibited strong inhibition against topoisomerase II at 100 mu M.


Input: In addition, docking studies were performed to predict the inhibition mode.


Input: Tomatidine inhibits invasion of human lung adenocarcinoma cell A549 by reducing matrix metalloproteinases expression.

Tomatidine


Input: Tomatidine is an aglycone of glycoalkaloid tomatine in tomato.

Tomatidine

tomatine


Input: Tomatidine is found to possess anti-inflammatory properties and may serve as a chemosensitizer in multidrug-resistant tumor cells.

Tomatidine


Input: However, the effect of tomatidine on cancer cell metastasis remains unclear.

tomatidine


Input: This study examines the effect of tomatidine on the migration and invasion of human lung adenocarcinoma A549 cell in vitro.

tomatidine


Input: The data demonstrates that tomatidine does not effectively inhibit the viability of A549 cells.

tomatidine


Input: When treated with non-toxic doses of tomatidine, cell invasion is markedly suppressed by Boyden chamber invasion assay, while cell migration is not affected.

tomatidine


Input: Tomatidine reduces the mRNA level of matrix metalloproteinase-2 (MMP-2), MMP-9 and increases the expression of reversion-inducing cysteine-rich protein with kazal motifs (RECK), as well as tissue inhibitor of metalloproteinase-1 (TIMP-1).

Tomatidine

cysteine


Input: The immunoblotting assays indicate that tomatidine is very effective in suppressing the phosphorylation of Akt and extracellular signal regulating kinase (ERK).

tomatidine


Input: In addition, tomatidine significantly decreases the nuclear level of nuclear factor kappa B (NF-kappa B), which suggests that tomatidine inhibits NF-kappa B activity.

tomatidine

tomatidine


Input: Furthermore, the treatment of inhibitors specific for PI3K/Akt (LY294002), ERK (U0126), or NF-kappa B (pyrrolidine dithiocarbamate) to A549 cells reduced cell invasion and MMP-2/9 expression.

pyrrolidine dithiocarbamate


Input: The results suggest that tomatidine inhibits the invasion of A549 cells by reducing the expression of MMPs.

tomatidine


Input: It also inhibits ERK and Akt signaling pathways and NF-kappa B activity.


Input: These findings demonstrate a new therapeutic potential for tomatidine in anti-metastatic therapy.

tomatidine


Input: Phylogenetic relationship among genera of Polymorphidae (Acanthocephala), inferred from nuclear and mitochondrial gene sequences.


Input: Acanthocephalans of the family Polymorphidae Meyer, 1931 are obligate endoparasites with complex life cycles.


Input: These worms use vertebrates (marine mammals, fish-eating birds and waterfowl) as definitive hosts and invertebrates (amphipods, decapods and euphausiids) as intermediate hosts to complete their life cycle.


Input: Polymorphidae has a wordwide distribution, containing 12 genera, with approximately 127 species.


Input: The family is diagnosed by having a spinose trunk, bulbose proboscis, double-walled proboscis receptacle, and usually four to eight tubular cement glands.


Input: To conduct a phylogenetic analysis, in the current study sequences of the small (18S) and large-subunit (28S) ribosomal RNA, and cytochrome c oxidase subunit 1 (cox 1) were generated for 27 taxa representing 10 of 12 genera of Polymorphidae, plus three additional species of acanthocephalans that were used as outgroups.


Input: Maximum likelihood (ML), maximum parsimony (MP), and Bayesian analyses were conducted on a combined nuclear rRNA (18S + 28S) data set and on a concatenated dataset of nuclear plus one mitochondrial gene (18S + 28S + cox 1).


Input: Phylogenetic analyses inferred with the concatenated dataset of three genes support the monophyly of nine genera (Andracantha, Corynosoma, Bolbosoma, Profilicollis, Pseudocorynosoma, Southwellina, Arhythmorhynchus, Hexaglandula and Ibirhynchus).


Input: However, the four sampled species of Polymorphus were nested within several clades, indicating that these species do not share a common ancestor, requiring further taxonomic revision using phylogenetic systematics, and reexamination of morphological and ecological data.


Input: By mapping definitive and intermediate host association onto the resulting cladogram, we observe that aquatic birds were the ancestral definitive hosts for the family with a secondary colonization and diversification to marine mammals.


Input: Whereas amphipods were ancestral intermediate hosts and that the association with decapods represent episodes of secondary colonization that arose several times during the evolutionary history of the family.


Input: Our results are useful to start testing hypothesis about the evolutionary history of this highly diverse family of acanthocephalans.


Input: The influence of Bauhinia forficata Link subsp. pruinosa tea on lipid peroxidation and non-protein SH groups in human erythrocytes exposed to high glucose concentrations.

SH

glucose


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Bauhinia forficata (BF) has been traditionally used as tea in folk medicine of Brazil for treatment of Diabetes mellitus (DM).


Input: AIM OF THE STUDY: To evaluate the effects of BF leaf tea on markers of oxidative damage and antioxidant levels in an experimental model of hyperglycemia in human erythrocytes in vitro.


Input: MATERIALS AND METHODS: Human erythrocytes were incubated with high glucose concentrations or glucose and BF tea for 24h and 48h.

glucose

glucose


Input: After incubation lipid peroxidation and non-protein SH levels were analyzed.

SH


Input: Moreover, quantification of polyphenols and flavonoids, iron chelating property, scavenging of DPPH, and prevention of lipid peroxidation in isolated lipids were also assessed.

polyphenols

flavonoids

iron

DPPH


Input: RESULTS: A significant amount of polyphenols and flavonoids was observed.

polyphenols

flavonoids


Input: The main components found by LC-MS analysis were quercetin-3-O-(2-rhamnosyl) rutinoside, kaempferol-3-O-(2-rhamnosyl) rutinoside, quercetin-3-O-rutinoside and kaempferol-3-O-rutinoside.

quercetin-3-O-(2-rhamnosyl) rutinoside

kaempferol-3-O-(2-rhamnosyl) rutinoside


Input: BF tea presents important antioxidant and chelating properties.


Input: Moreover, BF tea was effective to increase non-protein SH levels and reduce lipid peroxidation induced by high glucose concentrations in human erythrocytes.

SH

glucose


Input: CONCLUSION: The antioxidant effects of BF tea could be related to the presence of different phenolic and flavonoids components.

phenolic

flavonoids


Input: We believe that these components can be responsible to protect human erythrocytes exposed to high glucose concentrations against oxidative damage.

glucose


Input: In vitro and in vivo anti-diabetic activity of Swertia kouitchensis extract.


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Swertia kouitchensis has long been used as a folk medicine to treat hepatitis and diabetes in central-western China.


Input: Therefore, this study was aimed to evaluate the anti-diabetic activity of the plant ethanol extract.

ethanol


Input: MATERIALS AND METHODS: Firstly, the extract was tested for its inhibitory activity on alpha-amylase and alpha-glucosidase in vitro.


Input: Following that, insulin secretion test in NIT-1cell was performed.


Input: Then, oral sucrose or starch tolerance test of the extract were carried out in normal mice.


Input: After that, acute effect of the extract was executed in normal and streptozotocin-induced (60mg/kg) diabetic mice.

streptozotocin


Input: Eventually, long term effect of the extract was performed in diabetic mice for 4 weeks.


Input: Oral glucose tolerance test and biochemical parameters were estimated at the end of the study.

glucose


Input: RESULTS: Swertia kouitchensis extract could remarkably inhibit the activity of alpha-amylase and alpha-glucosidase and stimulate insulin secretion in vitro.


Input: And also the extract displayed anti-hyperglycemic activity, improved antioxidant capacity, ameliorated the hyperlipidemia and carbohydrate metabolism in diabetic mice.

carbohydrate


Input: CONCLUSIONS: Swertia kouitchensis exhibits considerable anti-diabetic activity and metabolic alterations in diabetic mice.


Input: These results provide a rationale for the use of Swertia kouitchensis to treat diabetes mellitus.


Input: Safety assessment of the standardized extract of Carissa edulis root bark in rats.


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Preparations of Carissa edulis (Vahl) have been used in the Nigerian traditional medicine for the management of fever, sickle cell disease, epilepsy, pain and inflammation for many years and their efficacy is widely acclaimed among the Hausa communities of northern Nigeria.


Input: AIM OF THE STUDY: The present studies aimed at evaluating the toxicological properties of the standardized ethanol extract of C. edulis root bark in rats, in order to determine its safety and to complement earlier efficacy studies on this widely used medicinal plant.

ethanol


Input: MATERIALS AND METHODS: High performance liquid chromatography (HPLC) and preliminary phytochemical analysis of the extract were conducted and its oral median lethal dose (LD50) determined.


Input: Signs of toxicity, body weight changes, relative organs weight, feed and water consumption were monitored following 28 days of daily oral administration of graded doses of the extract in rats.


Input: Effects of the extract on sex hormones, low-and high-density lipids, hematological and biochemical parameters were examined and pathological changes of the vital organs after treatment with the extract were also investigated.


Input: RESULTS: The oral LD50 of the extract was estimated to be > 5000mg/kg.


Input: The body weights of treated rats increased progressively, but the changes were not significantly different from the control groups.


Input: The extract neither produces significant changes in feed and water consumption nor affected the relative organs weight.


Input: Although some variations were observed in hormonal and lipid profiles hematological and biochemical indices, these important parameters were normal and within acceptable limits.


Input: No lesions or pathological changes of the organs attributable to treatment with the extract were observed from the pathological examinations.


Input: The HPLC fingerprint of the extract shows a spectrum profile characteristic of C. edulis, while the preliminary phytochemical screening revealed the presence of saponins, flavonoids, tannins, anthraquinones and cardiac glycosides.

saponins

flavonoids

tannins

anthraquinones


Input: CONCLUSION: Our results provided evidence that short-term administration of the standardized ethanol extract of C. edulis root bark at doses lower than 1000mg/kg is safe in rats and may not exert severe toxic effects.

ethanol


Input: Identification of microcystins in a Lake Victoria cyanobacterial bloom using LC-MS with thiol derivatization.

microcystins

thiol


Input: Microcystins are cyclic heptapeptides from cyanobacteria which are responsible for poisonings of livestock and humans.

Microcystins

cyclic heptapeptides


Input: Cyanobacteria also produce a range of peptides and other compounds that can result in complex chromatograms when samples are analysed by LC-MS.


Input: Thiol derivatization of the alpha, beta-unsaturated amide present in most microcystins was recently shown to simplify analysis of LC-MS chromatograms of a Microcystis culture, making it easier to identify peaks corresponding to microcystins in complex mixtures.

Thiol

alpha, beta-unsaturated amide

microcystins

microcystins


Input: This method was applied to analysis of extracts taken from a natural cyanobacteria bloom in Mwanza Gulf, Lake Victoria, Tanzania, in 2010, revealing the presence of numerous putative microcystin analogues in the sample.

microcystin


Input: Results were verified using LC-MS (2), LC-MS/MS with precursor-ion scanning, and LC-HRMS, leading to identification of 8 major and 17 minor microcystins in the sample, including analogues of microcystin-RY,-RL and-RA.

microcystins

microcystin-RY,-RL and-RA


Input: Microcystin-YR (2),-RR (3), and-RY (9) were isolated from bloom material from Lake Victoria, and the structure of 9 was confirmed by NMR spectroscopic analysis and NMR spectral comparison with 2 and 3.

Microcystin-YR (2),-RR (3), and-RY (9)


Input: Confirmation of the structure of MC-RY (9) facilitated detailed analysis of its MS (2) spectrum, thereby supporting the structures of related analogues tentatively established on the basis of MS analyses.

MC-RY


Input: Intra-articular drug delivery from an optimized topical patch containing teriflunomide and lornoxicam for rheumatoid arthritis treatment: Does the topical patch really enhance a local treatment?

teriflunomide

lornoxicam


Input: Patients with rheumatoid arthritis (RA) often bear joint destruction and symptomatic pain.


Input: The aim of this work is to develop a compound transdermal patch containing teriflunomide (TEF) and lornoxicam (LOX) to transport these drugs across the skin with the isochronous permeation rates for RA therapy and investigate intra-articular delivery of TEF and LOX following transdermal patches applied topically.

teriflunomide

TEF

lornoxicam

LOX

TEF

LOX


Input: The salts of TEF and LOX with organic amines diethylamine (DEtA), triethylamine (TEtA), diethanolamine (DEA), triethanolamine (TEA) and N-(2'-hydroxy-ethanol)-piperdine (NP) were prepared to improve the skin permeation of the parent drug.

TEF

LOX

organic amines diethylamine

DEtA

triethylamine

TEtA

diethanolamine

DEA

triethanolamine

TEA


Input: The optimized patch formulation is obtained from a 3-factor, 2-level central composite design.


Input: After topical application of the optimized compound patch to only one knee joint in rabbit, intra-articular delivery of TEF and LOX on the application site was compared with that on the non-application site.

TEF

LOX


Input: Anti-inflammatory and analgesic effects of the optimized compound patch were evaluated using the adjuvant arthritis model and the pain model induced by acetic acid, respectively.

acetic acid


Input: The in vitro experiment results showed that the amine salts of TEF and LOX, especially TEF-TEtA and LOX-TEtA, enhanced the skin permeation of TEF and LOX from the transdermal patch system.

amine salts

TEF

LOX

TEF-TEtA

LOX-TEtA

TEF

LOX


Input: The optimal formulation successfully displayed isochronous permeation rates for TEF and LOX across rabbit skin, and was defined with 5% of TEF-TEtA, 10% of LOX-TEtA and 15% of azone.

TEF

LOX

TEF-TEtA

LOX-TEtA


Input: The in vivo study showed that TEF and LOX from transdermal patches were transferred into skin, ligament and fat pad on the application site by direct diffusion and on the non-application site by the redistribution of systemic blood supply, while local absorption of TEF and LOX in synovial fluid originated from the systemic blood supply rather than direct diffusion.

TEF

LOX

TEF

LOX


Input: In the RA rat model, the results of swelling inhibition on primary arthritis of bilateral hind paws further confirmed the above-mentioned point.


Input: The optimal formulation displayed a double response on joint inflammation and symptomatic pain.


Input: In conclusion, although transdermal administration applied topically can provide a local enhanced drug delivery for the superficial joint tissues by direct diffusion, it seemed unlikely to do that for the deeper tissue synovial fluid.


Input: Inhibition of UVB-induced skin phototoxicity by a grape seed extract as modulator of nitrosative stress, ERK/NF-kB signaling pathway and apoptosis, in SKH-1 mice.


Input: Molecular mechanisms concerning the modulation of nitrosative stress, signal transduction and proliferation/apoptosis by a grape seed extract, Burgund Mare variety (BM), in SKH-1 mice exposed to UVB, were investigated.


Input: The animals were irradiated with single and multiple doses of UVB in 10 consecutive days.


Input: In each experiment were used five groups of animals: control, vehicle, UVB irradiated, vehicle + UVB, BM + UVB.


Input: The extract was applied topically, 30min before each UVB exposure, in a dose of 4mg total polyphenols/cm (2).

polyphenols


Input: BM remarkably inhibited UVB-induced activation of inducible nitric oxide synthase (iNOS) and therefore generation of nitric oxide (NO) and nitrotyrosine, in a UVB single dose regimen.

nitric oxide

nitric oxide

NO

nitrotyrosine


Input: BM also suppressed NF-kB activation by UVB but did not affect the activity of total ERK 1/2.


Input: In multiple UVB irradiations, BM increased NO formation and total ERK 1/2 activity and reduced iNOS activity and nitrotyrosine levels, inhibited cell proliferation, diminished p53 and caspase-3 immunoreactivities and increased the percentage of Bcl-2 positive cells.

NO

nitrotyrosine


Input: We concluded that BM modulates the apoptotic response of SKH-1 mice skin in UVB irradiation by the inhibition of p53, caspase-3, Bax/Bcl-2 and proliferating cell nuclear antigen expressions, as well as by reducing the activation of iNOS and NF-kB.


Input: Neonatal exposure to lipopolysaccharide enhances accumulation of alpha-synuclein aggregation and dopamine transporter protein expression in the substantia nigra in responses to rotenone challenge in later life.

dopamine

rotenone


Input: Brain inflammation in early life may enhance adult susceptibility to develop neurodegenerative disorders triggered by environmental toxins.


Input: Our previous studies show that perinatal lipopolysaccharide (LPS) exposure enhances adult susceptibility to rotenone-induced injury to the dopaminergic system in the substantia nigra (SN) of the adult rat brain.

rotenone


Input: To further investigate the enhanced adult susceptibility by neonatal LPS exposure to rotenone neurotoxicity, we used our neonatal rat model of LPS exposure (1mg/kg, intracerebral injection in postnatal day 5, P5, neonatal rats) to examine the protein levels of alpha-synuclein and dopamine transporters (DAT) in the adult rat.

rotenone

dopamine


Input: By P70, rats from the saline-or LPS-exposed group were challenged with rotenone, a commonly used pesticide, through subcutaneous mini-pump infusion at a dose of 1. 25mg/kg/day for 14 days.

rotenone


Input: The accumulation of alpha-synuclein aggregation and increment of DAT protein content were found in the SN of LPS-exposed rats.


Input: Neonatal LPS exposure enhanced rotenone-stimulated accumulation of alpha-synuclein aggregation and increment in DAT protein expression in the cytoplasmic compartment of the SN, and in the synaptosomal compartment of the striatum of adult rats.

rotenone


Input: Rotenone treatment also resulted in reduction of [(3) H] dopamine uptake and mitochondrial complex I activity in the striatum of rats with neonatal LPS exposure, but not in those without this exposure.

Rotenone

[(3) H] dopamine


Input: The current study suggests possible roles of alpha-synuclein aggregate and DAT distribution in the cytoplasm and synaptosome triggered by environmental toxins in later life in the development of neurodegenerative disorders.


Input: Our model may be useful in studying mechanisms involved in the pathogenesis of nonfamilial Parkinson' s disease and for developing potential therapeutic treatments for this disease.


Input: Lyophilization of a triply unsaturated phospholipid: Effects of trace metal contaminants.


Input: As liquid liposomal formulations are prone to chemical degradation and aggregation, these formulations often require freeze drying (e. g., lyophilization) to achieve sufficient shelf-life.


Input: However, liposomal formulations may undergo oxidation during lyophilization and/or during prolonged storage.


Input: The goal of the current study was to characterize the degradation of 1, 2-dilinolenoyl-sn-glycero-3-phosphocholine (DLPC) during lyophilization and to also probe the influence of metal contaminants in promoting the observed degradation.

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

DLPC


Input: Aqueous sugar formulations containing DLPC (0. 01mg/ml) were lyophilized, and DLPC degradation was monitored using HPLC/UV and GC/MS methods.

sugar

DLPC

DLPC


Input: The effect of ferrous ion and sucrose concentration, as well as lyophilization stage promoting lipid degradation, was investigated.

ferrous

sucrose


Input: DLPC degradation increased with higher levels of ferrous ion.

DLPC

ferrous


Input: After lyophilization, 103. 1 +/- 1. 1%, 66. 9 +/- 0. 8%, and 28. 7 +/- 0. 7% DLPC remained in the sucrose samples spiked with 0. 0ppm, 0. 2ppm, and 1. 0ppm ferrous ion, respectively.

DLPC

sucrose

ferrous


Input: Lipid degradation predominantly occurs during the freezing stage of lyophilization.


Input: Sugar concentration and buffer ionic strength also influence the extent of lipid degradation, and DLPC loss correlated with degradation product formation.

Sugar

DLPC


Input: We conclude that DLPC oxidation during the freezing stage of lyophilization dramatically compromises the stability of lipid-based formulations.

DLPC


Input: In addition, we demonstrate that metal contaminants in sugars can become highly active when lyophilized in the presence of a reducing agent.

sugars


Input: The cyclin D1 (CCND1) rs9344 G > A polymorphism predicts clinical outcome in colon cancer patients treated with adjuvant 5-FU-based chemotherapy.


Input: Recent evidence indicates a potential prognostic and predictive value for germline polymorphisms in genes involved in cell cycle control.


Input: We investigated the effect of cyclin D1 (CCND1) rs9344 G > A in stage II/III colon cancer patients and validated the findings in an independent study cohort.


Input: For evaluation and validation set, a total of 264 and 234 patients were included.


Input: Patients treated with 5-fluorouracil-based chemotherapy, carrying the CCND1 rs9344 A/A genotype had significantly decreased time-to-tumor recurrence (TTR) in univariate analysis and multivariate analysis (hazard ratio (HR) 2. 47; 95% confidence interval (CI) 1. 16-5. 29; P = 0. 019).


Input: There was no significant association between CCND1 rs9344 G > A and TTR in patients with curative surgery alone.


Input: In the validation set, the A allele of CCND1 rs9344 G > A remained significantly associated with decreased TTR in univariate and multivariate analyses (HR 1. 94; 95% CI 1. 05-3. 58; P = 0. 035).


Input: CCND1 rs9344 G > A may be a predictive and/or prognostic biomarker in stage II/III colon cancer patients, however, prospective trials are warranted to confirm our findings. The Pharmacogenomics Journal advance online publication, 9 April 2013; doi: 10. 1038/tpj. 2013. 15.


Input: DNA-binding, photocleavage, cytotoxicity in vitro, apoptosis and cell cycle arrest studies of symmetric ruthenium (II) complexes.

ruthenium (II)


Input: Two novel ruthenium (II) complexes [Ru (dmb) 2 (addppn)] (ClO4) 2 (1) and [Ru (bpy) 2 (addppn)] (ClO4) 2 (2) were synthesized.

ruthenium (II)

[Ru (dmb) 2 (addppn)] (ClO4) 2

[Ru (bpy) 2 (addppn)] (ClO4) 2


Input: The DNA-binding constants of complexes 1 and 2 were determined to be 4. 78 (+/- 0. 49) x 10 (5) and 7. 42 (+/- 0. 53) x 10 (5) M (-1).


Input: The results indicate that complexes 1 and 2 interact with CT DNA through intercalative mode.


Input: The cytotoxicity in vitro of the complexes toward BEL-7402, HeLa, MG-63 and SKBR-3 cells was assessed by MTT assay.

MTT


Input: The apoptosis was carried out with Hoechst 33258 staining method and flow cytometry.

Hoechst 33258


Input: The cellular uptake was observed under fluorescence microscope.


Input: The cell cycle arrest shows that the antiproliferative mechanism induced by complexes 1 and 2 on BEL-7402 cells is G0/G1 phase arrest.


Input: Synthesis of novel 1, 3, 4-trisubstituted pyrazoles as anti-inflammatory and analgesic agents.

1, 3, 4-trisubstituted pyrazoles


Input: Some novel 1, 3, 4-trisubstituted pyrazoles were synthesized and screened for their anti-inflammatory and analgesic activities as well as their ulcerogenic liability.

1, 3, 4-trisubstituted pyrazoles


Input: They showed anti-inflammatory and analgesic activities with better GIT tolerance than the standard drug phenylbutazone.

phenylbutazone


Input: In addition, IC50 values for 5e and 8e were recorded.


Input: Compound 5e was found to be the most active one as anti-inflammatory and analgesic agent.


Input: On the other hand, COX-1/COX-2 isozyme selectivity was also done which showed equal inhibition to both isoforms.


Input: Analysis of the antioxidant properties of differently substituted 2-and 3-indolyl carbohydrazides and related derivatives.

2-and 3-indolyl carbohydrazides


Input: Herein, we report the antioxidant properties of some selected substituted 2-indolyl carbohydrazides (JL34, JL40, JL71, JL87, JL317, JL432, JL436), the substituted 3-indolyl carbohydrazide JL344, 3-(3-hydrazinylpropyl)-1H-indole (JL72) and 3-(1H-indol-3-yl) propanehydrazide (JL418), throughout the assessment of their antioxidative potential using different antioxidant assays such as DPPH, lipid peroxidation in the APPH, or the DMSO method.

2-indolyl carbohydrazides

3-indolyl carbohydrazide JL344

3-(1H-indol-3-yl) propanehydrazide

DPPH

DMSO


Input: We conclude that these compounds are convenient templates for the design of useful drugs in to treat Alzheimer' s disease (AD), a pathology characterized by extensive oxidative stress and inflammation, thus essentially affected by reactive oxygen species (ROS).

oxygen


Input: Most of them are potent hydroxyl radical scavengers and inhibit in vitro lipid peroxidation.

hydroxyl


Input: Compounds JL40 and JL432 presenting higher lipoxygenase inhibitory activity among the tested derivatives, were found to present a promising anti-inflammatory in vivo result, as well as antioxidant and LOX inhibitory profile.


Input: These results in combination to their known AChE/BuChE inhibitory activities led us to propose these indolyl carbohydrazides as new multifunctional compounds against AD.

indolyl carbohydrazides


Input: Biological evaluation of bisbenzaldehydes against four Mycobacterium species.

bisbenzaldehydes


Input: A series of bisbenzaldehydes and structurally related analogs, conveniently synthesized via microwave-assisted reactions, were evaluated in vitro against drug susceptible and multi-drug resistant Mycobacterium tuberculosis, against virulent Mycobacterium bovis, against Mycobacterium ulcerans and against two Mycobacterium avium subspecies.

bisbenzaldehydes


Input: Among the 33 substances that were tested, compound 12, i. e. 4, 4'-[1, 12-dodecanediyl (oxy)] bisbenzaldehyde, emerged as the most promising hit.

4, 4'-[1, 12-dodecanediyl (oxy)] bisbenzaldehyde


Input: Its activity was further confirmed in an intracellular growth inhibition assay of M. tb in murine J774 A. 1 macrophages.


Input: None of the compounds showed significant cytotoxicity on human C3A hepatocytes in a neutral red dye uptake assay and no genotoxicity or mutagenicity was observed as demonstrated by a VITOTOX (TM) test and confirmed with a comet assay.

neutral red


Input: Small-molecule regulators of autophagy and their potential therapeutic applications.


Input: Autophagy is a highly conserved process in which damaged proteins and organelles are sequestered in double-membrane autophagosomes and delivered to lysosomes for degradation and recycling.


Input: As an efficient response to cellular stress, autophagy is essential for the maintenance of cellular homeostasis.


Input: Defective autophagy is associated with a variety of diseases, including cancer.


Input: This article summarizes current knowledge about the molecular mechanism of autophagy and its role in tumorigenesis.


Input: Particular focus is placed on the development of small-molecule regulators of autophagy and their potential application as anticancer therapeutic agents.


Input: Thin films: organic vapor passivation of silicon at room temperature (adv. Mater. 14/2013).

silicon


Input: Initiated chemical vapor deposition is used to achieve air-stable organic passivation of silicon, as reported by Karen K. Gleason and co-workers on page 2078.

silicon


Input: This layer also functions as an anti-reflection coating.


Input: Resistively heated wires produce reactive gas phase species, including methyl radicals, while the silicon surface below remains near room temperature.

methyl

silicon


Input: Photoshop enhanced image by Felice C. Frankel.


Input: Cyclic AMP responsive element binding protein-a vital link in embryonic hormonal adaptation.

Cyclic AMP


Input: The transcription factor cyclic AMP responsive element binding protein (CREB) and activating transcription factors (ATFs) are downstream components of the insulin/IGF cascade, playing crucial roles in maintaining cell viability and embryo survival.

cyclic AMP


Input: One of the CREB target genes is adiponectin which acts synergistically with insulin.


Input: We have studied the CREB-ATF-adiponectin network in rabbit preimplantation development in vivo and in vitro. From the blastocyst stage onwards CREB and ATF1, 3 and 4 are present with increasing expression for CREB, ATF1 and 3 during gastrulation and with a dominant expression in the embryoblast (EB).


Input: In vitro stimulation with insulin and IGF1 reduced CREB and ATF1 transcripts by approx. 50%, while CREB phosphorylation was increased.


Input: Activation of CREB was accompanied by subsequent reduction in adiponectin and adiponectin receptor 1 (adipoR1) expression. Under in vivo conditions of diabetes type 1, maternal adiponectin levels were up-regulated in serum and endometrium.


Input: Embryonic CREB expression was altered in a cell lineage-specific pattern.


Input: While in EB cells CREB localization did not change, it was translocated from the nucleus into the cytosol in trophoblast (TB) cells.


Input: In TB adiponectin expression was increased [diabetic 427. 8 +/- 59. 3 pg/ml versus normoinsulinaemic 143. 9 +/- 26. 5 pg/ml], while it was no longer measureable in the EB.


Input: Analysis of embryonic adiponectin receptors showed an increased expression of adipoR1 and no changes in adipoR2 transcription. We conclude that the transcription factors CREB and ATFs vitally participate in embryo-maternal crosstalk prior to implantation in a cell lineage-specific manner.


Input: Embryonic CREB/ATFs act as insulin/IGF sensors.


Input: Lack of insulin is compensated by a CREB-mediated adiponectin expression which may maintain glucose uptake in blastocysts grown in diabetic mothers.

glucose


Input: Highly Stretchable Patterned Gold Electrodes Made of Au Nanosheets.

Au


Input: Multilayered Au nanosheets are suggested as a novel class of material for fabricating stretchable electrodes suitable for organic-based electronic devices.

Au


Input: The electrodes show no difference in resistivity during repeated stretching cycles up to epsilon = 40%.


Input: Effect of Topical Application of Chlorogenic Acid on Excision Wound Healing in Rats.

Chlorogenic Acid


Input: This study was undertaken to evaluate the therapeutic effects of topical chlorogenic acid on excision wounds in Wistar rats.

chlorogenic acid


Input: A 1% (w/w) chlorogenic acid or silver sulfadiazine ointment was applied topically once a day for 15 days on full-thickness excision wounds created on rats.

chlorogenic acid

silver sulfadiazine


Input: The 1% (w/w) chlorogenic acid ointment had potent wound healing capacity as evident from the wound contraction on the 15th post-surgery day, which was similar to that produced by 1% (w/w) silver sulfadiazine ointment.

chlorogenic acid

silver sulfadiazine


Input: Increased rates of epithelialization were observed in the treated rats.


Input: It also improved cellular proliferation, increased tumor necrosis factor-alpha levels during the inflammatory phase (12 h, 24 h, 48 h, and 72 h post-wounding) of wound healing, upregulated transforming growth factor-beta 1 and elevated collagen IV synthesis in the chlorogenic acid-treated group.

chlorogenic acid


Input: The results also indicated that chlorogenic acid possesses potent antioxidant activity by increasing superoxide dismutase, catalase, and glutathione, and decreasing lipid peroxidation.

chlorogenic acid

superoxide

glutathione


Input: In conclusion, these results demonstrate that topical application of chlorogenic acid can accelerate the process of excision wound healing by its ability to increase collagen synthesis through upregulation of key players such as tumor necrosis factor-alpha and transforming growth factor-beta 1 in different phases of wound healing as well as by its antioxidant potential.

chlorogenic acid


Input: Signaling mechanism of tumor cell-induced up-regulation of E3 ubiquitin ligase UBR2.


Input: The N-end rule pathway contributes significantly to accelerated muscle proteolysis mediated by the ubiquitin-proteasome pathway in various catabolic conditions.

N


Input: UBR2 (aka E3 alpha-II) is the only known E3 ubiquitin ligase of the N-end rule pathway that is up-regulated by cachectic stimuli including proinflammatory cytokines and tumors.

N


Input: However, the signaling mechanism through which UBR2 is up-regulated remains undetermined.


Input: Here we identify a signaling pathway that mediates tumor cell-induced up-regulation of UBR2.


Input: UBR2 expression in C2C12 myotubes was up-regulated by conditioned medium from Lewis lung carcinoma cells or C26 colon adenocarcinoma cells, which was blocked by a pharmacological inhibitor of p38 alpha/beta mitogen-activated protein kinase (MAPK), SB202190.


Input: Similarly, SB202190 administration (i. p.) abolished UBR2 up-regulation in the tibialis anterior of LLC tumor-bearing mice.


Input: Genetic gain and loss of function assays in C2C12 myotubes indicated that tumor-induced activation of the p38 beta isoform is sufficient and necessary for UBR2 up-regulation.


Input: In addition, UBR2 up-regulation required p38 beta-mediated phosphorylation of CCAAT/enhancer binding protein (C/EBP)-beta Thr-188, which was critical to C/EBP beta binding to the UBR2 promoter.

Thr


Input: Furthermore, luciferase reporter assay revealed that the C/EBP beta binding motif in the UBR2 promoter is a functional C/EBP beta-responsive cis-element that enhances the promoter activity on activation by p38 beta.


Input: Finally, genetic ablation of C/EBP beta blocked UBR2 up-regulation in LLC tumor-bearing mice.


Input: These results suggest that UBR2 up-regulation in cachectic muscle is mediated by the p38 beta-C/EBP beta signaling pathway responsible for the bulk of tumor-induced muscle proteolysis.-Zhang, G., Lin, R.-K., Kwon, Y.


Input: T., Li, Y.-P.


Input: Signaling mechanism of tumor cell-induced up-regulation of E3 ubiquitin ligase UBR2.


Input: Minor Compensatory Changes in SAGE Mdr1a (P-gp), Bcrp, and Mrp2 Knockout Rats do not Detract from their General Utility in the Study of Transporter-mediated Pharmacokinetics.


Input: Mdr1a-, Bcrp-, and Mrp2-knockout rats are a more practical species for ADME studies than murine models and previously demonstrated expected alterations in pharmacokinetics of various probe substrates.


Input: At present, gene expression and pathology changes were systematically studied in small intestine, liver, kidney, and brain tissue from male SAGE Mdr1a-, Bcrp-, and Mrp2-knockout rats versus wild-type Sprague Dawley controls.


Input: Gene expression data supported the relevant knockout genotype.


Input: As expected, Mrp2-knockout rats were hyperbilirubinemic and exhibited upregulation of hepatic Mrp3.


Input: Overall, few alterations were observed within 112 ADME-relevant genes.


Input: The two potentially most consequential changes were upregulation of intestinal carboxylesterase in Mdr1a-knockouts and catechol-O-methyltransferase in all tissues of Bcrp-knockout rats.

catechol

O


Input: Previously reported upregulation of hepatic Mdr1b P-glycoprotein in proprietary Wistar Mdr1a-knockout rats was not observed in the SAGE counterpart investigated herein.


Input: Relative liver and kidney weights were 22-53% higher in all three knockouts, with microscopic increases in hepatocyte size in Mdr1a-and Mrp2-knockout rats, and glomerular size in Bcrp-and Mrp2-knockouts.


Input: Increased relative weight of clearing organs is quantitatively consistent with reported increases in clearance of drugs that are not substrates of the knocked-out transporter.


Input: Overall, SAGE knockout rats demonstrated modest compensatory changes, which do not preclude their general application to study transporter-mediated pharmacokinetics.


Input: However, until future studies elucidate the magnitude of functional change, caution is warranted in rare instances of extensive metabolism by catechol-O-methyltransferase in Bcrp-knockouts and intestinal carboxylesterase in Mdr1a-knockout rats, specifically for molecules with free catechol groups and esters subject to gut wall hydrolysis.

catechol

O

catechol


Input: Structural and functional characterization of a phosphatase domain within yeast general transcription factor TFIIIC.


Input: Saccharomyces cerevisiae tau 55, a subunit of the RNA polymerase III-specific general transcription factor TFIIIC, comprises an N-terminal histidine phosphatase domain (tau 55-HPD) whose catalytic activity and cellular function is poorly understood.

histidine


Input: We solved the crystal structures of tau 55-HPD and its closely related paralogue Huf and used in silico docking methods to identify phospho-serine and phospho-tyrosine containing peptides as possible substrates that were subsequently validated using in vitro phosphatase assays.

phospho-serine

phospho-tyrosine


Input: A comparative phospho-proteomic study identified additional phosphopeptides as possible targets, which show the involvement of these two phosphatases in the regulation of a variety of cellular functions.

phospho


Input: Our results identify tau 55-HPD and Huf as bona fide protein phosphatases, characterize their substrate specificities and provide a small set of regulated phosphosite targets in vivo.


Input: Adenine-DNA Adducts Derived from the Highly Tumorigenic Dibenzo [a, l] pyrene Are Resistant to Nucleotide Excision Repair while Guanine Adducts Are Not.

Adenine

Dibenzo [a, l] pyrene

Nucleotide

Guanine


Input: The structural origins of differences in susceptibilities of various DNA lesions to nucleotide excision repair (NER) are poorly understood.

nucleotide


Input: Here we compared, in the same sequence context, the relative NER dual incision efficiencies elicited by two stereochemically distinct pairs of guanine (N (2)-dG) and adenine (N (6)-dA) DNA lesions, derived from enantiomeric genotoxic diol epoxides of the highly tumorigenic fjord region polycyclic aromatic hydrocarbon dibenzo [a, l] pyrene (DB [a, l] P).

guanine

adenine

diol epoxides

dibenzo [a, l] pyrene

DB [a, l] P


Input: Remarkably, in cell-free HeLa cell extracts, the guanine adduct with R absolute chemistry at the N (2)-dG linkage site is ~ 35 times more susceptible to NER dual incisions than the stereochemically identical N (6)-dA adduct.

guanine


Input: For the guanine and adenine adducts with S stereochemistry, a similar but somewhat smaller effect (factor of ~ 15) is observed.

guanine

adenine


Input: The striking resistance of the bulky N (6)-dA in contrast to the modest to good susceptibilities of the N (2)-dG adducts to NER is interpreted in terms of the balance between lesion-induced DNA distorting and DNA stabilizing van der Waals interactions in their structures, that are partly reflected in the overall thermal stabilities of the modified duplexes.


Input: Our results are consistent with the hypothesis that the high genotoxic activity of DB [a, l] P is related to the formation of NER-resistant and persistent DB [a, l] P-derived adenine adducts in cellular DNA.

DB [a, l] P

DB [a, l] P

adenine


Input: Reactions of Hydrocarbon Radicals and Biradicals.

Hydrocarbon Radicals and Biradicals


Input: Experimental measurements of the rate coefficients for several types of gas phase radical reactions are reviewed.


Input: They include radical isomerization and dissociation, radical + radical association, and unimolecular reactions of peroxy radicals.

peroxy


Input: Some reactions of methylene in its lowest singlet state are also considered.

methylene


Input: The links to theories of chemical reaction rates and especially of capture rates for radical + radical reactions are examined.


Input: Many of the reactions involve formation of adducts, which can isomerize and dissociate.


Input: Such reactions frequently involve energy distributions of the adducts that are far from Boltzmann, and the interpretation of measurements requires the use of master equation techniques.


Input: The basis of these methods and the use of matrix diagonalization and eigenvector/eigenvalue analysis to extract phenomenological rate coefficients are discussed.


Input: The relevance of the measurements to applications in atmospheric chemistry and, especially, in combustion is briefly considered.


Input: Ion impacts on graphene/ir (111): interface channeling, vacancy funnels, and a nanomesh.

graphene

ir (111)


Input: By combining ion beam experiments and atomistic simulations we study the production of defects in graphene on Ir (111) under grazing incidence of low energy Xe ions.

graphene

Ir (111)

Xe


Input: We demonstrate that the ions are channeled in between graphene and the substrate, giving rise to chains of vacancy clusters with their edges bending down toward the substrate.

graphene


Input: These clusters self-organize to a graphene nanomesh via thermally activated diffusion as their formation energy varies within the graphene moir e supercell.

graphene

graphene


Input: A facile strategy to design zeolite L crystals with tunable morphology and surface architecture.

zeolite L


Input: Tailoring the anisotropic growth rates of materials to achieve desired structural outcomes is a pervasive challenge in synthetic crystallization.


Input: Here we discuss a method to selectively control the growth of zeolite crystals, which are used extensively in a wide range of industrial applications.

zeolite


Input: This facile method cooperatively tunes crystal properties, such as morphology and surface architecture, through the use of inexpensive, commercially available chemicals with specificity for binding to crystallographic surfaces and mediating anisotropic growth.


Input: We examined over 30 molecules as potential zeolite growth modifiers (ZGMs) of zeolite L (LTL type) crystallization.

zeolite

zeolite L


Input: ZGM efficacy was quantified through a combination of macroscopic (bulk) and microscopic (surface) investigations that identified modifiers capable of dramatically altering the cylindrical morphology of LTL crystals.


Input: We demonstrate an ability to tailor properties critical to zeolite performance, such as external porous surface area, crystal shape, and pore length, which can enhance sorbate accessibility to LTL pores, tune the supramolecular organization of guest-host composites, and minimize the diffusion path length, respectively.

zeolite

sorbate


Input: We report that a synergistic combination of ZGMs and the judicious adjustment of synthesis parameters produce LTL crystals with unique surface features, and a range of length-to-diameter aspect ratios spanning 3 orders of magnitude.


Input: A systematic examination of different ZGM structures and molecular compositions (i. e., hydrophobicity and binding moieties) reveal interesting physicochemical properties governing their efficacy and specificity.


Input: Results of this study suggest this versatile strategy may prove applicable for a host of framework types to produce unrivaled materials that have eluded more conventional techniques.


Input: Silver Nanoparticles Induced RNA Polymerase-Silver Binding and RNA Transcription Inhibition in Erythroid Progenitor Cells.

Silver

Silver


Input: Due to its antimicrobial activity, nanosilver (nAg) has become the most widely used nanomaterial.


Input: Thus far, the mechanisms responsible for nAg-induced antimicrobial properties and nAg-mediated toxicity to organisms have not been clearly recognized.


Input: Silver (Ag) ions certainly play a crucial role, and the form of nanoparticles can change the dissolution rate, bioavailability, biodistribution, and cellular uptake of Ag.

Silver

Ag

Ag


Input: However, whether nAg exerts direct " particle-specific " effects has been under debate.


Input: Here we demonstrated that nAg exhibited a robust inhibition on RNA polymerase activity and overall RNA transcription through direct Ag binding to RNA polymerase, which is separated from the cytotoxicity pathway induced by Ag ions.

Ag


Input: nAg treatment in vitro resulted in reduced hemoglobin concentration in erythroid cells; in vivo administration of nAg in mice caused profound reduction of hemoglobin content in embryonic erythrocytes, associated with anemia in the embryos.


Input: Embryonic anemia and general proliferation deficit due to the significant inhibition on RNA synthesis, at least partially, accounted for embryonic developmental retardation upon nAg administration.


Input: To date, there is no conclusive answer to the sources of nAg-mediated toxicity: Ag ions or " particle-specific " effects, or both.


Input: We here demonstrated that both Ag ions and nAg particles simultaneously existed inside cells, demonstrating the " Trojan horse " effects of nAg particles in posing biological impacts on erythroid cells.

Ag


Input: Moreover, our results suggested that " particle-specific " effects could be the predominant mediator in eliciting biological influences on erythroid cells under relatively low concentrations of nAg exposure.


Input: The combined data highlighted the inhibitory effect of nAg on RNA polymerase activity through a direct reciprocal interaction.


Input: New genetic associations in thiopurine-related bone marrow toxicity among inflammatory bowel disease patients.

thiopurine


Input: Background: The toxicity related to thiopurine drug therapy for inflammatory bowel disease (IBD) varies widely among patients.

thiopurine


Input: Almost 15-30% of patients with IBD develop side effects during treatment, often bone marrow suppression.


Input: Several factors have been implicated in determining this toxicity, mainly individual genetic variation related to formation of active thiopurine metabolites.

thiopurine


Input: The aim was to identify genes involved in thiopurine-related myelosuppression.

thiopurine


Input: Materials & methods: A two-stage investigation of 19, 217 coding SNPs (cSNPs) was performed in a Spanish (Inflammatory Bowel Disease Group of Galicia [EIGA]) cohort of 173 IBD patients, 15 with bone marrow suppression.


Input: The top 20 cSNPs identified in the first stage with p < 10 (-3) for allelic test association and SNPs that define the common TPMT alleles were replicated in a different Spanish (ENEIDA) cohort (87 patients, 29 with bone marrow suppression).


Input: Results: Several cSNPs showed a significant p-value in the allelic joint analysis (p-Cochran-Mantel-Haenszel test <= 2. 55 x 10 (-3)) despite no cSNP passing correction for multiple testing in the first cohort.


Input: Of note is rs3729961 in the gene IL6ST, a transducer signal chain shared by many cytokines including IL6 (p-value combined = 2. 36 x 10 (-4), odds ratio [95% CI]: 3. 41 [1. 71-6. 78]).


Input: In addition, we detected association with rs3749598 in the FSTL5 gene that appears to interact with metalloproteases at the extracellular matrix level (p-value combined = 4. 89 x 10 (-4)), odds ratio (95% CI): 3. 67 (1. 68-8. 01).


Input: Conclusion: We have identified IL6ST and FSLT5 as new bone marrow suppression susceptibility candidate genes after thiopurine treatment in IBD patients.

thiopurine


Input: This is the first report of variants associated with thiopurine-related myelosuppression that was identified by a genome-wide association study.

thiopurine


Input: Its validation awaits functional analyses and replication in additional studies.


Input: Original submitted 14 September 2012; Revision submitted 13 February 2013.


Input: Pharmacogenomics of bipolar disorder.


Input: Bipolar disorder (BD) is a lifelong severe psychiatric condition with high morbidity, disability and excess mortality.


Input: The longitudinal clinical trajectory of BD is significantly modified by pharmacological treatment (s), both in acute and in long-term stages.


Input: However, a large proportion of BD patients have inadequate response to pharmacological treatments.


Input: Pharmacogenomic research may lead to the identification of molecular predictors of treatment response.


Input: When integrated with clinical information, pharmacogenomic findings may be used in the future to determine the probability of response/nonresponse to treatment on an individual basis.


Input: Here we present a selective review of pharmacogenomic findings in BD.


Input: In light of the evidence suggesting a genetic effect of lithium reponse in BD, we focused particularly on the pharmacogenomic literature relevant to this trait.

lithium


Input: The article contributes a detailed overview of the current status of pharmacogenomics in BD and offers a perspective on the challenges that can hinder its transition to personalized healthcare.


Input: Adsorption of small organic molecules on graphene.

graphene


Input: We present a combined experimental and theoretical quantification of the adsorption enthalpies of seven organic molecules (acetone, acetonitrile, dichloromethane, ethanol, ethyl acetate, hexane, and toluene) on graphene.

acetone

acetonitrile

dichloromethane

ethanol

ethyl acetate

hexane

toluene

graphene


Input: Adsorption enthalpies were measured by inverse gas chromatography and ranged from-5. 9 kcal/mol for dichloromethane to-13. 5 kcal/mol for toluene.

dichloromethane

toluene


Input: The strength of interaction between graphene and the organic molecules was estimated by density functional theory (PBE, B97D, M06-2X, and optB88-vdW), wave function theory (MP2, SCS (MI)-MP2, MP2. 5, MP2. X, and CCSD (T)), and empirical calculations (OPLS-AA) using two graphene models: coronene and infinite graphene.

graphene

graphene

coronene

graphene


Input: Symmetry-adapted perturbation theory calculations indicated that the interactions were governed by London dispersive forces (amounting to ~ 60% of attractive interactions), even for the polar molecules.


Input: The results also showed that the adsorption enthalpies were largely controlled by the interaction energy.


Input: Adsorption enthalpies obtained from ab initio molecular dynamics employing non-local optB88-vdW functional were in excellent agreement with the experimental data, indicating that the functional can cover physical phenomena behind adsorption of organic molecules on graphene sufficiently well.

graphene


Input: Maps of open chromatin highlight cell type-restricted patterns of regulatory sequence variation at hematological trait loci.


Input: Nearly three-quarters of the 143 genetic signals associated with platelet and erythrocyte phenotypes identified by meta-analyses of genome-wide association (GWA) studies are located at non-protein coding regions.


Input: Here, we assessed the role of candidate regulatory variants associated with cell type-restricted, closely related hematological quantitative traits in biologically relevant hematopoietic cell types.


Input: We used formaldehyde-assisted isolation of regulatory elements followed by next-generation sequencing (FAIRE-seq) to map regions of open chromatin in three primary human blood cells of the myeloid lineage.

formaldehyde


Input: In the precursors of platelets and erythrocytes, as well as in monocytes, we found that open chromatin signatures reflect the corresponding hematopoietic lineages of the studied cell types, and associate with the cell type-specific gene expression patterns.


Input: Dependent on their signal strength, open chromatin regions showed correlation with promoter and enhancer histone marks, distance to the transcription start site and ontology classes of nearby genes.


Input: Cell type-restricted regions of open chromatin were enriched in sequence variants associated with hematological indices.


Input: The majority (63. 6%) of such candidate functional variants at platelet quantitative trait loci (QTLs) coincided with binding sites of five transcription factors key in regulating megakaryopoiesis.


Input: We experimentally tested 13 candidate regulatory variants at 10 platelet QTLs, and found that 10 (76. 9%) affected protein binding, suggesting that this is a frequent mechanism by which regulatory variants influence quantitative trait levels.


Input: Our findings demonstrate that combining large-scale GWA data with open chromatin profiles of relevant cell types can be a powerful means of dissecting the genetic architecture of closely related quantitative traits.


Input: Structure-activity relationship of potent antimicrobial peptide analogs of Ixosin-B amide.

amide


Input: There is a great urgency in developing a new generation of antibiotics and antimicrobial agents since the bacterial resistance to antibiotics have increased dramatically.


Input: A series of overlapped peptide fragments of Ixosin-B, an antimicrobial peptide with amino acid sequence of QLKVDLWGTRSGIQPEQHSSGKSDVRRWRSRY, was designed, synthesized and examined for their antimicrobial activities against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa.

amino acid


Input: A potent 11-mer peptide TSG-8-1, WWSYVRRWRSR-amide, was developed, which exhibited antimicrobial activity against E. coli and S. aureus while very little hemolytic activity in human erythrocytes was observed at high dose level.

amide


Input: This peptide could be further modified for the development of a potent antimicrobial agent in the future.


Input: Identification of miRNA modulators to PARP inhibitor response.


Input: Based on the principle of synthetic lethality, PARP inhibitors have been shown to be very effective in killing cells deficient in homologous recombination (HR), such as those bearing mutations in BRCA1/2.


Input: However, questions regarding their wider use persist and other determinants of responsiveness to PARP inhibitor remain to be fully explored.


Input: MicroRNAs (miRNAs) are small non-coding RNAs, which serve as post-transcriptional regulators of gene expression and are involved in a wide variety of cellular processes, including the DNA damage response (DDR).


Input: However, little is known about whether miRNAs might influence sensitivity to PARP inhibitors.


Input: To investigate this, we performed a high throughput miRNA mimetic screen, which identified several miRNAs whose over-expression results in sensitization to the clinical PARP inhibitor olaparib.


Input: In particular, our findings indicate that hsa-miR-107 and hsa-miR-222 regulate the DDR and sensitise tumour cells to olaparib by repressing expression of RAD51, thus impairing DSB repair by HR.


Input: Moreover, elevated expression of hsa-miR-107 has been observed in a subset of ovarian clear cell carcinomas, which correlates with PARP inhibitor sensitivity and reduced RAD51 expression.


Input: Taken together, these observations raise the possibility that these miRNAs could be used as biomarkers to identify patients that may benefit from treatment with PARP inhibitors.


Input: Pyranocycloartobiloxanthone A, a novel gastroprotective compound from Artocarpus obtusus Jarret, against ethanol-induced acute gastric ulcer in vivo.

Pyranocycloartobiloxanthone A

ethanol


Input: Pyranocycloartobiloxanthone A (PA), a xanthone derived from the Artocarpus obtusus Jarret, belongs to the Moraceae family which is native to the tropical forest of Malaysia.

Pyranocycloartobiloxanthone A

xanthone


Input: In this study, the efficacy of PA as a gastroprotective compound was examined against ethanol-induced ulcer model in rats.

ethanol


Input: The rats were pretreated with PA and subsequently exposed to acute gastric lesions induced by absolute ethanol.

ethanol


Input: The ulcer index, gastric juice acidity, mucus content, histological analysis, glutathione (GSH) levels, malondialdehyde level (MDA), nitric oxide (NO) and non-protein sulfhydryl group (NP-SH) contents were evaluated in vivo.

glutathione

GSH

malondialdehyde

MDA

nitric oxide

NO

sulfhydryl

SH


Input: The activities of PA as anti-Helicobacter pylori, cyclooxygenase-2 (COX-2) inhibitor and free radical scavenger were also investigated in vitro.


Input: The results showed that the oral administration of PA protects gastric mucosa from ethanol-induced gastric lesions.

ethanol


Input: PA pretreatment significantly (p < 0. 05) restored the depleted GSH, NP-SH and NO levels in the gastric homogenate.

GSH

SH

NO


Input: Moreover, PA significantly (p < 0. 05) reduced the elevated MDA level due to ethanol administration.

MDA

ethanol


Input: The gastroprotective effect of PA was associated with an over expression of HSP70 and suppression of Bax proteins in the ulcerated tissue.


Input: In addition, PA exhibited a potent FRAP value and significant COX-2 inhibition.


Input: It also showed a significant minimum inhibitory concentration (MIC) against H. pylori bacterium.


Input: The efficacy of PA was accomplished safely without the presence of any toxicological parameters.


Input: The results of the present study indicate that the gastroprotective effect of PA might contribute to the antioxidant and anti-inflammatory properties as well as the anti-apoptotic mechanism and antibacterial action against Helicobacter pylori.


Input: Plant High-Affinity Potassium (HKT) Transporters Involved in Salinity Tolerance: Structural Insights to Probe Differences in Ion Selectivity.

Potassium


Input: High-affinity Potassium Transporters (HKTs) belong to an important class of integral membrane proteins (IMPs) that facilitate cation transport across the plasma membranes of plant cells.

Potassium


Input: Some members of the HKT protein family have been shown to be critical for salinity tolerance in commercially important crop species, particularly in grains, through exclusion of Na + ions from sensitive shoot tissues in plants.

Na +


Input: However, given the number of different HKT proteins expressed in plants, it is likely that different members of this protein family perform in a range of functions.