Hepatic Cell News Volume 1.05 | Feb 24 2017

TOP STORY

Targeting CASP8 and FADD-Like Apoptosis Regulator Ameliorates Nonalcoholic Steatohepatitis in Mice and Nonhuman Primates

Scientists report that CASP8 and FADD-like apoptosis regulator (CFLAR) is a key suppressor of steatohepatitis and its metabolic disorders. They provide mechanistic evidence that CFLAR directly targeted the kinase MAP3K5 and interrupted its N-terminus-mediated dimerization, thereby blocking signaling involving ASK1 and the kinase MAPK8. [Nat Med] Abstract

(Ranked by impact factor of the journal)

Transcriptional Activation of Lipogenesis by Insulin Requires Phosphorylation of MED17 by CK2

Investigators showed that USF1, a key transcription factor for fatty acid synthase (FASN) activation, directly interacted with the mediator subunit MED17 at the FASN promoter. They showed that MED17 was phosphorylated at Ser⁵³ by casein kinase 2 (CK2) in the livers of fed mice or insulin-stimulated hepatocytes, but not in the livers of fasted mice or untreated hepatocytes. [Sci Signal] Abstract

Nutritional Modulation of Mouse and Human Liver Bud Growth through a Branched-Amino Acid Metabolism

Transcriptome analyses showed progenitors of mouse and human liver bud growth stage specifically expressed branched chain aminotransferase1 gene, a known breakdown enzyme of branched-chain amino acid (BCAA) for energy generation. Global metabolome analysis confirmed the active consumption of BCAA in the growing liver bud, but not in the later fetal or adult liver. [Development] Full Article

Simvastatin-Induced Cell Cycle Arrest through Inhibition of STAT3/SKP2 Axis and Activation of AMPK to Promote p27 and p21 Accumulation in Hepatocellular Carcinoma Cells

Scientists demonstrated simvastatin-induced G0/G1 arrest by inducing p21 and p27 accumulation in HepG2 and Hep3B cells. Simvastatin also promoted AMP-activated protein kinase (AMPK) activation, which induced p21 upregulation by increasing its transcription. [Cell Death Dis] Full Article

NGS-Based Transcriptome Profiling Reveals Biomarkers for Companion Diagnostics of the TGF-β Receptor Blocker Galunisertib in HCC

The small molecule kinase inhibitor galunisertib, targeting the transforming growth factor-beta (TGF-β) receptor I, blocks hepatocellular carcinoma (HCC) progression in preclinical models and shows promising effects in ongoing clinical trials. As the drug is not similarly effective in all patients, researchers aimed to identify new companion diagnostics biomarkers for patient stratification. [Cell Death Dis] Full Article

Hyodeoxycholic Acid Derivatives as Liver X Receptor α and G-Protein-Coupled Bile Acid Receptor Agonists

Bile acids are extensively investigated for their potential in the treatment of human disorders. The authors report a library of hyodeoxycholic acid derivatives endowed with modulatory activity on the two receptors. [Sci Rep] Full Article

Type I Neuregulin1α Is a Novel Local Mediator to Suppress Hepatic Gluconeogenesis in Mice

Investigators showed that type I isoform of neuregulin1 with an α-type epidermal growth factor-like domain (Nrg1α) is the major isoform in mouse liver and regulates hepatic glucose production. Forced expression of Nrg1α in mouse liver enhanced systemic glucose disposal and decreased hepatic glucose production with reduced fasting blood glucose levels. [Sci Rep] Full Article

Chronic Alcohol Feeding Potentiates Hormone-Induced Calcium Signaling in Hepatocytes

Data indicated that chronic alcohol feeding induces a leftward shift in the dose-response for Ca²⁺-mobilizing hormones resulting in more sustained and prolonged increases in both cultured hepatocytes and hepatocytes within the intact perfused liver. Ca²⁺ increases were initiated at lower hormone concentrations, and intercellular calcium wave propagation rates were faster in alcoholics compared to controls. [J Physiol] Abstract

MiRNA Expression Profiles Reveal the Involvement of miR-26a, miR-548l and miR-34a in Hepatocellular Carcinoma Progression through Regulation of ST3GAL5

The authors investigated the microRNA (miRNA) expressional profiles in the highly invasive human hepatocellular carcinoma cell line MHCC97-H and MHCC97-L with lower metastatic potential using miRNA microarrays. Thirteen differentially expressed miRNAs were identified between MHCC97-H and MHCC97-L cells; and the same results were found in clinical samples. [Lab Invest] Abstract

Platelets Prime Hematopoietic–Vascular Niche to Drive Angiocrine-Mediated Liver Regeneration

How liver regeneration is initiated after mass loss remains to be defined. Researchers reported that following liver injury, activated platelets deploy SDF-1 and VEGF-A to stimulate CXCR7⁺ liver sinusoidal endothelial cell and VEGFR1⁺ myeloid cell, orchestrating hepatic regeneration. [Signal Transduct Target Ther] Full Article

Non-Alcoholic Fatty Liver Disease: An Emerging Driving Force in Chronic Kidney Disease

It is now increasingly clear that non-alcoholic fatty liver disease not only affects the liver but can also increase the risk of developing extra-hepatic diseases, including type 2 diabetes mellitus, cardiovascular disease and chronic kidney disease, which have a considerable impact on health-care resources. [Nat Rev Nephrol] Abstract

New Advances in Polycystic Liver Diseases

The authors summarize the key aspects of polycystic liver disease etiology, pathogenesis, and therapy, highlighting the most recent advances and future research directions. [Semin Liver Dis] Abstract

Visit our reviews page to see a complete list of reviews in the hepatic cell research field.

Zydus Receives Approval from USFDA to Initiate Phase II Clinical Studies of Saroglitazar Magnesium in Patients with Primary Biliary Cholangitis (PBC)

Zydus Cadila announced that the USFDA has approved the group’s plans to initiate a Phase II clinical trial of Saroglitazar Magnesium in patients with PBC of the liver. [Zydus Cadila] Press Release

NeuroVive Appoints Recognized Scientific Advisors and Enters Research Agreements in NASH and Hepatocellular Carcinoma

NeuroVive Pharmaceutical AB announced two new research agreements and the appointment of Professor Philippe Gallay, PhD, and Professor Massimo Pinzani, MD, PhD, FRCP, as scientific advisors. The aim of the agreements is to further explore NeuroVive’s new drug compounds in development for the treatment of NASH and hepatocellular carcinoma. [NeuroVive Pharmaceutical AB] Press Release

Updated: Will They or Won’t They? What Science Groups Are Saying About Joining the March for Science

The March for Science is creating a buzz in the scientific community. The march arose as a grassroots reaction to concerns about the conduct of science under President Donald Trump. And it has spurred debate over whether it will help boost public support for research, or make scientists look like another special-interest group, adding to political polarization. [ScienceInsider] Editorial

More Groups Sue to Force USDA to Restore Online Animal Welfare Records

The U.S. Department of Agriculture (USDA) restored some of the tens of thousands of animal welfare documents that it removed from its website early this month. [ScienceInsider] Editorial

NEW American Hepato-Pancreato-Biliary Association 2017 Annual Meeting
March 29-April 2, 2017
Miami, United States

NEW AACR Annual Meeting 2017
April 1-5, 2017
Washington, D.C., United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Fellow – Non-Alcoholic Steatohepatitis (AstraZeneca)

Postdoctoral Position – Liver Fibrosis (Massachusetts General Hospital)

Postdoctoral Fellow or Research Scientist – Diabetes (Novo Nordisk)

Postdoctoral Research Fellow – Liver Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Non-Alcoholic Fatty Liver Disease (University of Gothenburg)

PhD Studentship – Hepatocytes (KU Leuven, Stem Cell Institute)

PhD Position – Pathogens Infecting Liver (Helmholtz Association)

PhD Studentships – Liver Organ Growing (Downstate Medical Center)

Senior Scientist – Oncology (Genentech Research)

Training Fellowship – Clinical Research (University of Oxford)

Postdoctoral Associate – Cancer Biology (University of Florida)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

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