Search results for "S3"
showing 10 items of 95 documents
Downregulation of thioredoxin-1-dependent CD95 S-nitrosation by Sorafenib reduces liver cancer
2020
Hepatocellular carcinoma (HCC) represents 80% of the primary hepatic neoplasms. It is the sixth most frequent neoplasm, the fourth cause of cancer-related death, and 7% of registered malignancies. Sorafenib is the first line molecular targeted therapy for patients in advanced stage of HCC. The present study shows that Sorafenib exerts free radical scavenging properties associated with the downregulation of nuclear factor E2-related factor 2 (Nrf2)-regulated thioredoxin 1 (Trx1) expression in liver cancer cells. The experimental downregulation and/or overexpression strategies showed that Trx1 induced activation of nitric oxide synthase (NOS) type 3 (NOS3) and S-nitrosation (SNO) of CD95 rece…
Model Based Targeting of IL-6-Induced Inflammatory Responses in Cultured Primary Hepatocytes to Improve Application of the JAK Inhibitor Ruxolitinib
2017
IL-6 is a central mediator of the immediate induction of hepatic acute phase proteins (APP) in the liver during infection and after injury, but increased IL-6 activity has been associated with multiple pathological conditions. In hepatocytes, IL-6 activates JAK1-STAT3 signaling that induces the negative feedback regulator SOCS3 and expression of APPs. While different inhibitors of IL-6-induced JAK1-STAT3-signaling have been developed, understanding their precise impact on signaling dynamics requires a systems biology approach. Here we present a mathematical model of IL-6-induced JAK1-STAT3 signaling that quantitatively links physiological IL-6 concentrations to the dynamics of IL-6-induced …
Comprehensive Screening for Naturally Occurring Hepatitis C Virus Resistance to Direct-Acting Antivirals in the NS3, NS5A, and NS5B Genes in Worldwid…
2015
ABSTRACTThere is no comprehensive study available on the natural hepatitis C virus (HCV) polymorphism in sites associated with resistance including all viral genotypes which may present variable susceptibilities to particular direct-acting antivirals (DAAs). This study aimed to analyze the frequencies, genetic barriers, and evolutionary histories of naturally occurring resistance-associated variants (RAVs) in the six main HCV genotypes. A comprehensive analysis of up to 103 RAVs was performed in 2,901, 2,216, and 1,344 HCV isolates for the NS3, NS5A, and NS5B genes, respectively. We report significant intergenotypic differences in the frequencies of natural RAVs for these three HCV genes. I…
Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor α
2020
Plasticizers released from microplastic are increasingly viewed with concern. While adverse health effects induced by bisphenol A and its analogues on marine animals are well documented in the literature, the endocrine potential of bisphenolic compounds on human health remains elusive. We applied next generation sequencing (NGS) with the estrogen receptor α (ERα) positive human breast cancer cell line MCF-7 treated with 17-β-estradiol (E2), bisphenol A (BPA), bisphenol B (BPB), bisphenol Z (BPZ) and tetramethyl bisphenol A (4MeBPA). We used molecular docking, microscale thermophoresis, ERα activation assay, and cell cycle experiments on MCF-7 and ERα overexpressing HEK293 cells to verify th…
HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with differe…
2016
OBJECTIVES: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. METHODS: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. RESULTS: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype…
Differential PI3K signal transduction in obesity-associated cardiac hypertrophy and response to ischemia
2014
Objective Elevated insulin and inflammatory cytokine levels in obesity may chronically activate signaling pathways regulating cardiac growth and contractility. Our aim was to examine the effect of obesity on cardiac PI3K isoform and Akt activation during left ventricular (LV) hypertrophy and heart failure. Methods Wild-type mice were fed normal chow or high-fat diet (HFD) for 2, 4, or 6 months. A subset of mice was subjected to chronic myocardial ischemia (MI). Results Echocardiography revealed a progressive increase in LV mass, wall thickness, and diameters in obese mice. Systolic pump function was not impaired. Increased cardiac levels of PI3Kγ, phosphorylated Akt, GSK3β, and Epac were ob…
Influence of Centerline Intermetallic Stringers on Pitting Corrosion Resistance of Superduplex Stainless Steel
2021
Superduplex stainless steel UNS S32750 / EN 1.4410 is commonly used in marine environment, petrochemical, oil and gas, chemical and desalination industries, requiring materials with superior corrosion and mechanical properties. Very few residual intermetallic particles may be present under the form of centerline stringers whose effects on corrosion properties are not well documented. A previous study demonstrated the negligible influence of the intermetallic phases in centerline stringers (typically < 0.1% over thickness) on the hydrogen embrittlement susceptibility of superduplex stainless steel [1]. The present study aims at highlighting the impact of centerline intermetallic stringers on…
Sb2S3 nanovadu fotoelektriskās īpašības
2015
Perspektīvā nanovadus varēs izmantot sensoros, slēdžos, saules baterijās un citās optoelektriskajās ierīcēs, ņemot vērā to lielo virsmas un tilpuma attiecību. Pateicoties šai attiecībai, fizikālās īpašības nanoizmēros ir izteiktākas nekā makroskopiskos izmēros. Līdz šim nebija iespējams iegūt informāciju par Sb2S3 nanovadu fotoelektriskajām īpašībām. Darbā tika pētītas Sb2S3 nanovadu fotoelektriskās īpašības atkarībā no ierosinātās gaismas viļņu garuma, uzņemot I-V un fotostrāvas raksturlīknes. Darbā tika pētīta Sb2S3 nanovadu piemērotība dažādu optoelektrisko ierīču izstrādē. Anodētā alumīnija oksīda (AAO) matricā iekapsulēto nanovadu masīvu īpašības tika salīdzinātas ar individuālo nanova…
The European Regional Convergence Process, 1980-1995: Do Spatial Regimes and Spatial Dependence Matter?
2002
International audience; The authors show that spatial dependence and spatial heterogeneity matter in the estimation of the ß-convergence process among 138 European regions over the 1980 to 1995 period. Using spatial econometrics tools, the authors detect both spatial dependence and spatial heterogeneity in the form of structural instability across spatial convergence clubs. The estimation of the appropriate spatial regimes spatial error model shows that the convergence process is different across regimes. The authors also estimate a strongly significant spatial spillover effect: the average growth rate of per capita GDP of a given region is positively affected by the average growth rate of …
Trends for genetic variation of Hepatitis C Virus quasispecies in Human Immunodeficiency virus-1 coinfected patients
2007
Chronic infection by Hepatitis C Virus (HCV) causes liver fibrosis, which is accelerated by unknown mechanisms in patients with HIV-1 coinfection. The evolution of HCV quasispecies in this setting of coinfection is not fully understood. To compare HCV quasispecies between HIV-HCV coinfection and HCV monoinfection, we sequenced 340 HCV clones from the HVR-1 and NS3 regions at two different time points in two groups of treatment-naive patients with HCV-1a infection: (1) HIV-HCV positive (n=6); and (2) HIV negative-HCV positive (n=3). In HCV/HIV coinfection, we found a trend for reduced HCV genetic complexity and diversity, and a trend towards reduced dN/dS ratios in the HVR-1 region, especial…