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Top five promising drugs Phase I (November 2013) Research

03:49 EDT 20th June 2018 | BioPortfolio

GPCR kinase 2-interacting protein-1 protects against ischemia-reperfusion injury of the spinal cord by modulating ASK1/JNK/p38 signaling.

GPCR kinase 2-interacting protein-1 (GIT1) is a scaffold protein that plays an important role in cell adaptation, proliferation, migration, and differentiation; however, the role of GIT1 in the regulation of neuronal death after spinal cord injury remains obscure. Here, we demonstrate that GIT1 deficiency remarkably increased neuronal apoptosis and enhanced JNK/p38 signaling, which resulted in str...

MicroRNA-141-3p/200a-3p target and may be involved in post-transcriptional repression of RNA decapping enzyme Dcp2 during renal development.

The RNA decapping enzyme Dcp2 is a crucial enzyme involved in the process of RNA turnover, which can post-transcriptionally regulate gene expression. Dcp2 has been found to be highly expressed in embryonic, but not adult, kidneys. Here we showed that Dcp2 mRNA was expressed, but Dcp2 proteins were absent, in mouse kidneys after postnatal day 10 (P10). In kidneys of adult Dcp2-IRES-EGFP knock-in mi...

Hyperlipidemia and Nonalcoholic Steatohepatitis Predispose to Hepatocellular Carcinoma Development Without Cirrhosis.

Hepatocellular carcinoma (HCC) accounts for 90% of primary hepatic malignancies. With the exception of chronic hepatitis B (CHB), other etiologies of chronic liver disease require progression to cirrhosis before HCC development. Case reports have described HCC in noncirrhotic patients with hepatitis C (HCV) and nonalcoholic fatty liver disease.

Real-World Study on Sofosbuvir-based Therapies in Asian Americans With Chronic Hepatitis C.

Limited data exist with regard to treatment outcomes in Asian Americans with chronic hepatitis C (CHC). We evaluated sofosbuvir (SOF)-based regimens in a national cohort of Asian Americans.

Inadequate Hepatocellular Carcinoma Screening in Patients With Nonalcoholic Steatohepatitis Cirrhosis.

Nonalcoholic steatohepatitis (NASH) is a common cause of liver disease which can progress to cirrhosis and hepatocellular carcinoma (HCC). American Association for the Study of Liver Diseases (AASLD) guidelines recommend abdominal ultrasound, with or without serum alpha-fetoprotein, every 6 months for HCC surveillance in cirrhotic patients.

Clinical Utility of Fluorescence In Situ Hybridization (FISH) for Deletion of Chromosome 3p in the Work-up of Renal Masses.

Chromosome 3p deletion is a well-established genetic aberration in clear cell renal cell carcinoma (RCC). We aimed to evaluate the clinical utility of 3p fluorescence in situ hybridization (FISH) on formalin-fixed paraffin-embedded tissue in surgical pathology specimens. 3p:3q

Prevalence estimates of HIV, syphilis, hepatitis B and C among female sex workers (FSW) in Brazil, 2016.

Female sex workers (FSW) bear a high burden of sexually transmitted infections (STI). In this paper, we estimate the prevalence of human immunodeficiency virus (HIV), HBV = hepatitis B virus (HBV), HCV = hepatitis C virus (HCV), syphilis and co-infections in the second Biological and Behavioral Surveillance Survey among FSW in Brazil.

Hepatitis C virus notification rates in Australia are highest in socioeconomically disadvantaged areas.

Poor access to health services is a significant barrier to achieving the World Health Organization's hepatitis C virus (HCV) elimination targets. We demonstrate how geospatial analysis can be performed with commonly available data to identify areas with the greatest unmet demand for HCV services.

Enhancement of bradykinin-induced relaxation by focal brain ischemia in the rat middle cerebral artery: Receptor expression upregulation and activation of multiple pathways.

Focal brain ischemia markedly affects cerebrovascular reactivity. So far, these changes have mainly been related to alterations in the level of smooth muscle cell function while alterations of the endothelial lining have not yet been studied in detail. We have, therefore, investigated the effects of ischemia/reperfusion injury on bradykinin (BK)-induced relaxation since BK is an important mediator...

Tongxinluo attenuates reperfusion injury in diabetic hearts by angiopoietin-like 4-mediated protection of endothelial barrier integrity via PPAR-α pathway.

Endothelial barrier function in the onset and Tongxinluo (TXL) protection of myocardial ischemia/reperfusion (I/R) injury, and TXL can induce the secretion of Angiopoietin-like 4 (Angptl4) in human cardiac microvascular endothelial cells during hypoxia/reoxygenation. We intend to demonstrate whether TXL can attenuate myocardial I/R injury in diabetes, characterized with microvascular endothelial b...

Antifibrotic role of PGC-1α-siRNA against TGF-β1-induced renal interstitial fibrosis.

Peroxisome proliferator-activated receptor coactivator-1 alpha (PGC-1α) is a transcriptional coactivator that regulates energy metabolism and mitochondrial biogenesis. Recently, mitochondrial dysfunction has been indicated as an established risk factor for the development of renal fibrosis. However, whether PGC-1α is involved in the pathogenesis of renal fibrosis is unknown. In this study, we tr...

ABT-263-induced MCL1 upregulation depends on autophagy-mediated 4EBP1 downregulation in human leukemia cells.

The present study aimed to investigate the pathway related to MCL1 expression in ABT-263-treated human leukemia U937 cells. ABT-263 upregulated MCL1 protein expression but did not affect its mRNA level and protein stability. Notably, ABT-263 increased 4EBP1 mRNA decay and thus reduced 4EBP1 expression. Overexpression of 4EBP1 abrogated ABT-263-induced MCL1 upregulation. ABT-263-induced activation ...

Rates and Factors Associated With Placebo Response in Trials of Pharmacotherapies for Nonalcoholic Steatohepatitis: Systematic Review and Meta-analysis.

Understanding the extent of the placebo effect in randomized controlled trials of studying nonalcoholic steatohepatitis (NASH) is important for optimal trial design, including sample size calculations and treatment endpoint definition.

Is Granulocyte Colony Stimulating Factor a New Treatment for Alcoholic Hepatitis?

Emricasan Improves Liver Function in Patients With Cirrhosis and High Model for End-stage Liver Disease Scores Compared With Placebo.

Caspase-mediated apoptosis and inflammation contribute to progression of liver disease. Emricasan is a pan-caspase inhibitor that reduced serum markers of apoptosis and liver inflammation in patients with hepatitis C and non-alcoholic steatohepatitis (NASH).

Serum cystatin C concentration measured routinely is a prognostic marker for renal disease in dogs.

This study examined the predictive value of serum cystatin C (Cys-C) concentration, measured during routine periodic health examinations, in the renal prognosis of dogs. A cohort of 140 dogs weighing

Thymoquinone Attenuates Myocardial Ischemia/Reperfusion Injury Through Activation of SIRT1 Signaling.

Myocardial ischemia/reperfusion (MI/R) injury is a leading factor responsible for damage in myocardial infarction, resulting in additional injury to cardiac tissues involved in oxidative stress, inflammation, and apoptosis. Thymoquinone (TQ), the main constituent of Nigella sativa L. seeds, has been reported to possess various biological activities. However, few reports regarding myocardial protec...

Lipid Biomarkers in Acute Myocardial Infarction Before and After Percutaneous Coronary Intervention by Lipidomics Analysis.

BACKGROUND Reperfusion injury is one of the leading causes of myocardial cell death and heart failure. This study was performed to identify new candidate lipid biomarkers for the purpose of optimizing the diagnosis of myocardial ischemia reperfusion (I/R) injury, assessing the severity of myocardial I/R injury and trying to find the novel mechanism related to lipids. MATERIAL AND METHODS Forty pat...

Hepatitis B Vaccination, Screening, and Linkage to Care.

Hepatitis B Vaccination, Screening, and Linkage to Care.

Hepatitis B Vaccination, Screening, and Linkage to Care.

Myocardin-related transcription factor A (MRTF-A) contributes to acute kidney injury by regulating macrophage ROS production.

A host of pathogenic factors induce acute kidney injury (AKI) leading to insufficiencies of renal function. In the present study we evaluated the role of myocardin-related transcription factor A (MRTF-A) in the pathogenesis of AKI. We report that systemic deletion of MRTF-A or inhibition of MRTF-A activity with CCG-1423 significantly attenuated AKI in mice induced by either ischemia-reperfusion or...

IL-15 and IFN-γ signal through the ERK pathway to inhibit HCV replication, independent of type I IFN signaling.

Despite effective new treatments for Hepatitis C virus (HCV) infection, development of drug resistance, safety concerns and cost are remaining challenges. More importantly, there is no vaccine available against hepatitis C infection. Recent data suggest that there is a strong correlation between spontaneous HCV clearance and human NK cell function, particularly IFN-γ production. Further, IL-15 ha...

SGLT2 inhibitors and the kidney: Effects and mechanisms.

Numerous clinical trials have shown that sodium glucose cotransporter 2 (SGLT2) inhibitors exert a favorable effect on the indices of renal function (albuminuria, glomerular filtration rate decline over time) and the incidence of hard renal endpoints such as renal death or time to initiation of renal replacement therapy.

Adherence with and completion of recommended hepatitis vaccination schedules among adults in the United States.

Adult vaccination coverage rates in the US are well below national targets, leaving many adults at increased risk. Additionally, typical vaccination coverage calculations do not adequately approximate population immunity as they do not consider whether multidose vaccines were administered within the recommended schedules. As timely administration of each dose optimizes overall vaccine effectivenes...

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