Metabolic pathways of decabromodiphenyl ether (BDE209) in rainbow trout (Oncorhynchus mykiss) via intraperitoneal injection.

Decabromodiphenyl ether (BDE209) was of great concern due to its biotransformation in different organisms. However, most studies devoted to the metabolic intermediates of BDE209, less has been done on the metabolic pathways in vivo, especially on the relationships among debrominated-BDEs, OH-BDEs and MeO-BDEs. In this study, the metabolic pathways and intermediates of BDE209 in rainbow trout (Oncorhynchus mykiss) were investigated, and the time-dependent transformations of the metabolites were also examined.

Drug-drug interaction profile of the all-oral anti-hepatitis C virus regimen of paritaprevir/ritonavir, ombitasvir, and dasabuvir.

Background & Aims: Paritaprevir (administered with ritonavir, PTV/r), ombitasvir (OBV), and dasabuvir (DSV) are direct-acting antiviral agents (DAAs) for the treatment of chronic hepatitis C virus (HCV) infection. Thirteen studies were conducted to characterize drug-drug interactions for the 3D regimen of OBV, PTV/r, and DSV and various medications in healthy volunteers to inform dosing recommendations in HCV-infected patients.

Methods: Mechanism-based drug-drug interactions were evaluated for gemfibrozil, ketoconazole, carbamazepine, warfarin, omeprazole, digoxin, pravastatin, and rosuvastatin.

The optimal corepressor function of nuclear receptor corepressor (NCoR) for peroxisome proliferator-activated receptor γ requires G protein pathway suppressor 2.

Repression of peroxisome proliferator-activated receptor γ (PPARγ)-dependent transcription by the nuclear receptor corepressor (NCoR) is important for homeostatic expression of PPARγ target genes in vivo. The current model states that NCoR-mediated repression requires its direct interaction with PPARγ in the repressive conformation. Previous studies, however, have shown that DNA-bound PPARγ is incompatible with a direct, high-affinity association with NCoR because of the inherent ability of PPARγ to adopt the active conformation.

Ultrasonication assisted preparation of carbonaceous nanoparticles modified polyurethane foam with good conductivity and high oil absorption properties.

In this work, we report a facile, low cost and time-saving method for the fabrication of compressible, electrically conductive, oil absorptive, cost-effective and flexible polyurethane (PU) foam through ultrasonication induced carbonaceous nanoparticles (CNP) onto flexible PU foam (CNP-PU foam). SEM images showed that the CNP could be firmly anchored onto the PU foam, and made the PU foam surface much rougher. Zero-dimensional carbonaceous nanoparticles were easier to anchor onto the PU foam surface than one-dimensional nanoparticles (e.

Effects of fluoxetine on behavior, antioxidant enzyme systems, and multixenobiotic resistance in the Asian clam Corbicula fluminea.

Fluoxetine (FLX), a selective serotonin reuptake inhibitor, is widespread in aquatic environments. Despite its reported effects on behavior and reproduction in aquatic species, little is known about the effects of FLX on cellular detoxification and defense system in bivalves. Here, the adult Asian clam (Corbicula fluminea) was exposed to 0.

Glucocorticoids transcriptionally regulate miR-27b expression promoting body fat accumulation via suppressing the browning of white adipose tissue.

Long-term glucocorticoid (GC) treatment induces central fat accumulation and metabolic dysfunction. We demonstrate that microRNA-27b (miR-27b) plays a central role in the pathogenesis of GC-induced central fat accumulation. Overexpression of miR-27b had the same effects as dexamethasone (DEX) treatment on the inhibition of brown adipose differentiation and the energy expenditure of primary adipocytes.

Butachlor causes disruption of HPG and HPT axes in adult female rare minnow (Gobiocypris rarus).

Butachlor is a chloroacetamide herbicide widely used in Asia, and may enter the aquatic environment through agricultural application. In this study, plasma VTG and hormone levels (E2, 11-KT, T3 and T4) were determined after the female rare minnow (Gobiocypris rarus) was exposed to butachlor at environmental relevant concentrations (0, 0.1, 1, and 10μg/L) for 40days.

Thin layer terahertz sensing using two-channel parallel-plate waveguides.

We report on the highly sensitive terahertz measurement of a thin, dielectric layer using two channels formed by inserting a single slit sheet in the parallel-plate waveguides (PPWGs). When a thin layer is applied to coat the upper surface of the channel, the single resonance frequency caused by the two-channel PPWGs is shifted as a result of the layer's properties, including length, thickness, and refractive index. The measured frequency tuning sensitivities (FTS) throughout the 20-mm layer length are 2.

Endocrine disrupting effects of benzotriazole in rare minnow (Gobiocypris rarus) in a sex-dependent manner.

Benzotriazole (BT), an anticorrosive agent, is widely used in industrial applications and household dishwashing agents. Despite its reported toxicity to aquatic organisms, little is known about its endocrine disrupting effects. In this study, adult Chinese rare minnows (Gobiocypris rarus) were exposed to 0.

Effects of the human antiepileptic drug carbamazepine on the behavior, biomarkers, and heat shock proteins in the Asian clam Corbicula fluminea.

Carbamazepine (CBZ), an anticonvulsant and mood-stabilizing pharmaceutical, is a widespread contaminant in aquatic environments. In this study, the effects of chronic exposure to environmentally relevant CBZ concentrations were investigated in freshwater clams Corbicula fluminea. Adult C.

Disulfiram targeting lymphoid malignant cell lines via ROS-JNK activation as well as Nrf2 and NF-kB pathway inhibition.

Background: Disulfiram (DS), an anti-alcoholism drug, demonstrates strong antitumor activity in a copper (Cu)-dependent manner. This study investigates the cytotoxicity of DS/Cu complex in lymphoid malignant cell lines in vitro and in vivo.

Method: Raji cells were subjected to different treatments and thereafter MTT assay, flow cytometry were used to determine IC50 and apoptotic status.

Low MDR1 and BAALC expression identifies a new subgroup of intermediate cytogenetic risk acute myeloid leukemia with a favorable outcome.

Treatment optimization in acute myeloid leukemia requires the accurate assignment of patients at diagnosis to specific risk groups to guide subsequent risk-adapted treatment stratification. In this study, we have evaluated the impact of expression of the gene BAALC in conjunction with MDR1 in AML with intermediate cytogenetic risk group to more precisely define risk assessment. Low MDR1/high BAALC, high MDR1/low BAALC, and high MDR1/high BAALC expressers demonstrated a similar clinical outcome with CR rate being 68.

A novel anti-PcrV antibody providing enhanced protection against Pseudomonas aeruginosa in multiple animal infection models.

Pseudomonas aeruginosa is a major cause of hospital-acquired infections, particularly in mechanically ventilated patients, and it is the leading cause of death in cystic fibrosis patients. A key virulence factor associated with disease severity is the P. aeruginosa type III secretion system (T3SS), which injects bacterial toxins directly into the cytoplasm of host cells.

Basal and benzo[a]pyrene-induced expression profile of phase I and II enzymes and ABC transporter mRNA in the early life stage of Chinese rare minnows (Gobiocypris rarus).

ATP-binding cassette (ABC) transporters together with phase I and II detoxification enzymes have been considered as included in a cellular detoxification system. Previous studies have highlighted the involvement of aryl hydrocarbon receptor (AHR) and Cyp1a in PAH-induced embryo toxicity. However, the response of other xenobiotic enzymes/transporters in PAH-mediated embryo toxicity is not fully characterized.

Establishment of reference range for thyroid hormones in normal pregnant women in China's coastal area.

Purpose: The current study aims to establish reference ranges for thyroid hormones in normal pregnant women during their pregnancy period.

Materials And Methods: A one-time cross-sectional survey was conducted on 490 normal pregnant women and 51 nonpregnant women (control). The serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free tetraiodothyronine (FT4) levels were measured.

Transcriptional expression analysis of ABC efflux transporters and xenobiotic-metabolizing enzymes in the Chinese rare minnow.

In the present study, the cDNA fragments of five ABC transporter genes (ABCB1, ABCB11, ABCC1, ABCC2, and ABCG2) in the rare minnow were cloned, and their tissue-specific expression patterns were evaluated across eight rare minnow tissues (liver, gill, intestine, kidney, spleen, brain, skin, and muscle). Furthermore, the transcriptional effects on these ABC transporter genes and five xenobiotic-metabolizing enzyme genes (CYP1A, GSTm, GSTp1, GCLC, and UGT1a) were determined in the rare minnow liver after 12 days of pyrene exposure. Basal expression analysis showed that the tissues with high expression of the ABC transporters included the liver, kidney, and intestine.

Chronic thoracic spinal cord injury impairs CD8+ T-cell function by up-regulating programmed cell death-1 expression.

Background: Chronic spinal cord injury (SCI) induces immune depression in patients, which contributes to their higher risk of developing infections. While defects in humoral immunity have been reported, complications in T-cell immunity during the chronic phase of SCI have not yet been explored.

Methods: To assess the impact of chronic SCI on peripheral T-cell number and function we used a mouse model of severe spinal cord contusion at thoracic level T9 and performed flow cytometry analysis on the spleen for T-cell markers along with intracellular cytokine staining.

Biomarker analyses from a placebo-controlled phase II study evaluating erlotinib±onartuzumab in advanced non-small cell lung cancer: MET expression levels are predictive of patient benefit.

Purpose: In a recent phase II study of onartuzumab (MetMAb), patients whose non-small cell lung cancer (NSCLC) tissue scored as positive for MET protein by immunohistochemistry (IHC) experienced a significant benefit with onartuzumab plus erlotinib (O+E) versus erlotinib. We describe development and validation of a standardized MET IHC assay and, retrospectively, evaluate multiple biomarkers as predictors of patient benefit.

Experimental Design: Biomarkers related to MET and/or EGF receptor (EGFR) signaling were measured by IHC, FISH, quantitative reverse transcription PCR, mutation detection techniques, and ELISA.

Uniform nomenclature for the mitochondrial contact site and cristae organizing system.

The mitochondrial inner membrane contains a large protein complex that functions in inner membrane organization and formation of membrane contact sites. The complex was variably named the mitochondrial contact site complex, mitochondrial inner membrane organizing system, mitochondrial organizing structure, or Mitofilin/Fcj1 complex. To facilitate future studies, we propose to unify the nomenclature and term the complex "mitochondrial contact site and cristae organizing system" and its subunits Mic10 to Mic60.

Pyruvate carboxylase as a sensitive protein biomarker for exogenous steroid chemicals.

Assessing protein responses to endocrine disrupting chemicals is critical for understanding the mechanisms of chemical action and for the assessment of hazards. In this study, the response of the liver proteome of male rare minnows (Gobiocypris rarus) treated with 17β-estradiol (E2) and females treated with 17α-methyltestosterone (MT) were analyzed. A total of 23 and 24 proteins were identified with differential expression in response to E2 and MT, respectively.

Sweat chloride as a biomarker of CFTR activity: proof of concept and ivacaftor clinical trial data.

Background: We examined data from a Phase 2 trial {NCT00457821} of ivacaftor, a CFTR potentiator, in cystic fibrosis (CF) patients with aG551D mutation to evaluate standardized approaches to sweat chloride measurement and to explore the use of sweat chloride and nasal potential difference (NPD) to estimate CFTR activity.

Methods: Sweat chloride and NPD were secondary endpoints in this placebo-controlled, multicenter trial. Standardization of sweat collection, processing,and analysis was employed for the first time.

Effects of dechlorane plus on the hepatic proteome of juvenile Chinese sturgeon (Acipenser sinensis).

Dechlorane Plus (DP), an alternative to decabromodiphenyl ether (BDE-209), is a widely used polychlorinated flame retardant that is frequently detected in aquatic ecosystems. While the mechanisms of toxicity of BDE-209 have been well documented, less is known about the toxicity of DP. In this study, juvenile Chinese sturgeon (Acipenser sinensis) were treated with DP at doses of 1, 10, and 100mg/kg wet weight for 14 days via a single intraperitoneal injection (i.

Dicamba affects sex steroid hormone level and mRNA expression of related genes in adult rare minnow (Gobiocypris rarus) at environmentally relevant concentrations.

Dicamba is a benzoic acid herbicide that has been detected in surface and ground water. The herbicide has been shown to have cytogeneic and DNA damaging effects and to cause organ damage in mammals; however, little is known about the endocrine disrupting effects of dicamba in fish. In this study, histological changes, plasma vitellogenin (VTG) and sex hormone levels, and mRNA expression of sex steroid hormone-related genes were determined in adult rare minnow exposed to environmentally relevant concentrations of dicamba (0, 0.

Chk1 inhibition in p53-deficient cell lines drives rapid chromosome fragmentation followed by caspase-independent cell death.

Activation of Checkpoint kinase 1 (Chk1) following DNA damage mediates cell cycle arrest to prevent cells with damaged DNA from entering mitosis. Here we provide a high-resolution analysis of cells as they undergo S- and G₂-checkpoint bypass in response to Chk1 inhibition with the selective Chk1 inhibitor GNE-783. Within 4-8 h of Chk1 inhibition following gemcitabine induced DNA damage, cells with both sub-4N and 4N DNA content prematurely enter mitosis.