Hepatic Cell News Volume 2.12 | Apr 6 2018

TOP STORY

Telomerase-Expressing Liver Cells Regenerate the Organ

A subset of liver cells with high levels of telomerase renews the organ during normal cell turnover and after injury, according to Stanford researchers. The cells may also give rise to liver cancer. [Press release from Stanford Medicine discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

Blocking H1/H2 Histamine Receptors Inhibits Damage/Fibrosis in Mdr2^-/- Mice and Human Cholangiocarcinoma Tumorigenesis

Investigators examined the effects of chronic treatment with H1/H2HR antagonists on primary sclerosing cholangitis (PSC) and cholangiocarcinoma (CCA). H1/H2HR and mast cell presence increased in human PSC and CCA. [Hepatology] Abstract

Ubiquitin-Specific Protease 4 Is an Endogenous Negative Regulator of Metabolic Dysfunctions in Nonalcoholic Fatty Liver Disease

The authors report that ubiquitin specific protease 4 (USP4) expression was dramatically downregulated in the livers from nonalcoholic fatty liver disease (NAFLD) patients and different NAFLD mouse models induced by a high fat diet (HFD) or a genetic deficiency as well as in palmitate‐treated hepatocytes. Hepatocyte‐specific USP4 depletion exacerbated hepatic steatosis, insulin resistance and inflammatory response in HFD‐induced NAFLD mice. [Hepatology] Abstract

Inhibition of Enhancer of Zeste Homolog 2 (EZH2) Induces Natural Killer Cell-Mediated Eradication of Hepatocellular Carcinoma Cells

Scientists determined that hepatocellular carcinoma cells exhibit transcriptional down-regulation of natural killer (NK) group 2D ligands and are largely resistant to NK cell-mediated eradication. [Proc Natl Acad Sci USA] Abstract

Direct Conversion of Mouse Fibroblasts into Cholangiocyte Progenitor Cells

It has been shown that the combination of Hnf1β and Foxa3 could directly convert mouse fibroblasts into bipotential hepatic stem cell-like cells, termed iHepSCs. The authors describe that the expression of Hnf1β and Foxa3 dramatically facilitated the robust generation of iHepSCs. [Stem Cell Reports] Full Article | Graphical Abstract

Hepatocellular Carcinoma Cell-Secreted Exosomal MicroRNA-210 Promotes Angiogenesis In Vitro and In Vivo

Researchers evaluated whether miRNAs were secreted by hepatocellular carcinoma (HCC) cells and contributed to tumor angiogenesis. High level of miR-210-3p was detected in the exosomes isolated from the sera of HCC patients and the conditioned media of hepatoma cells. [Mol Ther Nucleic Acids] Full Article

Integrated Transcriptomic and Proteomic Analyses Reveal ɑ-Lipoic Acid-Regulated Cell Proliferation via Grb2-Mediated Signaling in Hepatic Cancer Cells

Investigators provide a novel mechanism through which alpha lipoic acid regulates cell proliferation via the down‐regulation of growth factor‐stimulated Grb2 signaling. [J Cell Mol Med] Full Article

NEFA-Induced ROS Impaired Insulin Signaling through the JNK and p38MAPK Pathways in Non-Alcoholic Steatohepatitis

Scientists investigated the changes in hepatic oxidative phosphorylation complexes in patients and cows with non-alcoholic steatohepatitis and investigated the mechanism that links mitochondrial dysfunction and hepatic insulin resistance induced by non-esterified fatty acids. [J Cell Mol Med] Full Article

Silencing Retinoid X Receptor Alpha Expression Enhances Early-Stage Hepatitis B Virus Infection in Cell Cultures

Researchers report that retinoid X receptor alpha (RXRα) negatively regulates hepatitis B virus (HBV) infection at an early stage in cell cultures. The RXR-specific agonist bexarotene inhibited HBV in HepG2 cells expressing the sodium taurocholate cotransporting polypeptide, HepaRG cells, and primary tupaia hepatocytes; reducing RXRα expression significantly enhanced HBV infection in the cells. [J Virol] Abstract

Direct Antiviral Properties of TLR Ligands against HBV Replication in Immune-Competent Hepatocytes

Scientists explored the direct anti-hepatitis B virus (HBV) effect of toll-like-receptors (TLR) agonists in hepatocytes. HBV-infected primary human hepatocytes or differentiated HepaRG cells were treated with various TLR agonists. [Sci Rep] Abstract

Three-Dimensional Co-Culture of Primary Hepatocytes and Stellate Cells in Silk Scaffold Improves Hepatic Morphology and Functionality In Vitro

An improved 3D co‐culture system of hepatocytes was established in which rat primary hepatocytes were co‐cultured with hepatic stellate cells in silk porous scaffolds. Silk scaffolds with incorporated extracellular matrix provided a suitable microenvironment for maintaining the viability, morphology and gene expression of the primary hepatocyte in vitro. [J Biomed Mater Res A] Abstract

Extracellular Adenosine: A Critical Signal in Liver Fibrosis

The authors examine the current lines of evidence on adenosinergic regulation of liver fibrosis and myofibroblasts, identify unanswered research questions, and propose important future areas of investigation. [Am J Physiol Gastrointest Liver Physiol] Abstract

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Arrowhead Pharmaceuticals Announces Multiple Presentations

Arrowhead Pharmaceuticals Inc. announced that it will present clinical and pre-clinical data on the company’s investigational medicines for the treatment of chronic hepatitis B infection and liver disease. [Press release from Arrowhead Pharmaceuticals Inc. discussing research to be presented at the Annual Meeting of the European Association for the Study of the Liver (EASL) 2018, Paris] Press Release

Enanta Pharmaceuticals Announces Data Presentations

Enanta Pharmaceuticals, Inc. announced that data from Enanta’s wholly-owned development programs, including EP-027367, one of Enanta’s novel core inhibitors in preclinical testing for hepatitis B virus, and EDP-305, an FXR agonist in development for non-alcoholic steatohepatitis and primary biliary cholangitis, have been accepted for presentation. [Press release from Enanta Pharmaceuticals, Inc. discussing research to be presented at the Annual Meeting of the European Association for the Study of the Liver (EASL) 2018, Paris] Press Release

MYR Pharma Announces Multiple Presentations

MYR Pharma GmbH, focused on the development of Myrcludex B, a novel drug for the treatment of hepatitis B and delta, announced a number of oral and poster presentations. [Press release from MYR Pharma GmbH (PR Newswire Association LLC.) discussing research to be presented at the Annual Meeting of the European Association for the Study of the Liver (EASL) 2018, Paris] Press Release

CPRIT Awards UT Southwestern Investigators $16 Million for Cancer Therapy Research

More than a dozen UT Southwestern Simmons Cancer Center researchers received awards from the Cancer Prevention and Research Institute of Texas (CPRIT) for research into breast, prostate, brain, kidney, liver, and pediatric cancers. [The University of Texas Southwestern Medical Center] Press Release

Lilly Announces CYRAMZA^® (Ramucirumab) Phase III REACH-2 Study in Second-Line Hepatocellular Carcinoma Patients Met Overall Survival Endpoint

Eli Lilly and Company announced top-line results from its Phase III REACH-2 study of CYRAMZA^® as a single agent in the second-line treatment of people with hepatocellular carcinoma, also known as liver cancer. [Eli Lilly and Company] Press Release

Conatus Pharmaceuticals Announces Top-Line Results from Phase IIb POLT-HCV-SVR Clinical Trial

Conatus Pharmaceuticals Inc. announced top-line results from the company’s exploratory Phase IIb POLT-HCV-SVR proof-of-concept clinical trial in liver transplant patients with fibrosis or cirrhosis. [Conatus Pharmaceuticals Inc.] Press Release

Cocrystal Pharma Receives FDA Clearance to Initiate Phase IIa Clinical Study Evaluating CC-31244 for the Treatment of Hepatitis C Virus

Cocrystal Pharma, Inc. announced that its Investigational New Drug application to the FDA is now open and the company is cleared to initiate its Phase IIa clinical study evaluating CC-31244 for the treatment of hepatitis C virus infected individuals. [Cocrystal Pharma, Inc.] Press Release

MediciNova Announces Phase II Trial of MN-001 (Tipelukast) in NASH / NAFLD will be Terminated Early Based on Significant Positive Results from Interim Analysis

MediciNova, Inc. announced that it will terminate the Phase II clinical trial of MN-001 in non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD) with hypertriglyceridemia early based on the significant positive results from an interim analysis. [MediciNova, Inc.] Press Release

Arrowhead Begins Dosing in Phase I/II Study of ARO-HBV for Treatment of Chronic Hepatitis B

Arrowhead Pharmaceuticals Inc. announced that it has dosed the first subjects in a Phase I/II clinical study of ARO-HBV, which is being developed as a potentially curative therapy for patients with chronic hepatitis B virus. [Arrowhead Pharmaceuticals Inc.] Press Release

Unnecessary Exclusions Shut Patients out of Clinical Trials

The FDA will hold a public meeting in Washington to discuss issues related to clinical trial eligibility criteria. Researchers, study sponsors, patients, and the general public will have an opportunity to share their experiences and tell our regulators why it’s time to revisit the guidelines. [STAT News] Editorial

Why The Ohio State University Decided to Go Public about Misconduct

In an unusual move, The Ohio State University in Columbus released a detailed account of the scientific misbehavior of one of its former faculty members. The 75-page report was damning: It concluded that cancer researcher Ching-Shih Chen—once lauded as an “Innovator of the Year” and the winner of millions of dollars in federal funding—had committed misconduct in eight papers. [ScienceInsider] Editorial

2018 March for Science Will Be Far More than Street Protests

The March for Science has matured. It may even have outgrown its name. [ScienceInsider] Editorial

NEW LabRoots: 2^nd Annual Cell Biology Virtual Event
September 26-27, 2018
Online

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

NEW Postdoctoral Fellow – Alcoholic Liver Disease (University of North Carolina at Greensboro)

NEW Postdoctoral Position – Inflammation and Metabolism (Sanford Burnham Prebys Medical Discovery Institute)

Assistant/Associate Professor – Virology (Saint Louis University School of Medicine)

Postdoctoral Position – Cancer, Immunotherapy, and Fibrosis (University of Alabama at Birmingham)

Postdoctoral Research Fellow – Liver Cancer Pathogenesis and Immunobiology (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Human Liver Function (Karolinska Institutet)

Postdoctoral Research Associate – Hepatitis B Virology (Imperial College London)

Postdoctoral Scientist – Viral Vectored Vaccines for Hepatitis Infections (University of Oxford)

Postdoctoral Research Associate – Liver Diseases (University of Illinois at Chicago)

Postdoctoral Scientist – Acute-on-Chronic Liver Failure (Foundation for Liver Research)

Lectureship – Stem Cell Biology and Regenerative Medicine (University of Edinburgh)

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