Hepatic Cell News Volume 2.41 | Oct 26 2018

TOP STORY

Obesity Drives STAT-1-Dependent NASH and STAT-3-Dependent HCC

Scientists showed that the oxidative hepatic environment in obesity inactivated STAT-1 and STAT-3 phosphatase T cell protein tyrosine phosphatase (TCPTP) and increased STAT-1 and STAT-3 signaling. TCPTP deletion in hepatocytes promoted T cell recruitment and ensuing non-alcoholic steatohepatitis (NASH) and fibrosis as well as hepatocellular carcinoma (HCC) in obese C57BL/6 mice that normally do not develop NASH and fibrosis or HCC. [Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

Expansion and Differentiation of Human Hepatocyte-Derived Liver Progenitor-Like Cells and Their Use for the Study of Hepatotropic Pathogens

Investigators described a protocol that achieved efficient conversion of human primary hepatocytes into liver progenitor-like cells (HepLPCs) through delivery of developmentally relevant cues, including NAD⁺-dependent deacetylase SIRT1 signaling. Under three-dimensional culture conditions, differentiated cells generated from HepLPCs regained the ability to support infection or reactivation of hepatitis B virus. [Cell Res] Full Article

Mastocytosis-Derived Extracellular Vesicles Exhibit a Mast Cell Signature, Transfer KIT to Stellate Cells, and Promote Their Activation

Researchers found that KIT was transferred from systemic mastocytosis (SM)-extracellular vesicles into a hepatic stellate cell line eliciting proliferation, cytokine production, and differentiation, processes that have been associated with liver pathology. These effects were reduced by KIT inhibition or neutralization and recapitulated by enforced expression of KIT or constitutively active D816V-KIT, a gain-of-function variant associated with SM. [Proc Natl Acad Sci USA] Abstract

Forcing ATGL Expression in Hepatocarcinoma Cells Imposes Glycolytic Rewiring through PPAR-α/p300-Mediated Acetylation of p53

The authors identified metabolic rewiring as a major outcome of adipose triglyceride lipase (ATGL) overexpression in hepatocellular carcinoma-derived cell lines. ATGL slackened both glucose uptake/utilization and cell proliferation in parallel with increased oxidative metabolism of fatty acids and enhanced mitochondria capacity. [Oncogene] Full Article

In Situ Differentiation and Generation of Functional Liver Organoids from Human iPSCs in a 3D Perfusable Chip System

The generated liver organoids exhibited favorable growth and differentiation of hepatocytes and cholangiocytes, recapitulating the key features of human liver formation with cellular heterogeneity. The liver organoids in perfused cultures displayed improved cell viability and higher expression of endodermal genes and mature hepatic genes under perfused culture conditions. [Lab Chip] Abstract

CircRNA_104075 Stimulates YAP-Dependent Tumorigenesis through the Regulation of HNF4a and May Serve as a Diagnostic Marker in Hepatocellular Carcinoma

HNF4a bound to the −1409 to −1401 region of the circRNA_104075 (circ_104075) promoter to stimulate the expression of circ_104075. Circ_104075 acted as a ceRNA to upregulate YAP expression by absorbing miR-582-3p. [Cell Death Dis] Full Article

Suitability of Hepatocyte Cell Lines HepG2, AML12 and THLE-2 for Investigation of Insulin Signaling and Hepatokine Gene Expression

Insulin responsiveness of AML12 and THLE-2 cells was impaired when cells were cultured in the recommended growth medium, but comparable with HepG2 cells by using insulin-deficient medium. THLE-2 cells showed low abundance of insulin receptor, while protein levels in HepG2 and AML12 were comparable. AML12 and THLE-2 cells showed only low or non-detectable transcript levels of G6PC and PCK1. [Open Biol] Full Article

Mechanisms of Concanavalin A-Induced Cytokine Synthesis by Hepatic Stellate Cells: Distinct Roles of Interferon Regulatory Factor-1 in Liver Injury

Specific binding of concanavalin A (ConA) to hepatic stellate cells (HSCs) induced rapid activation of JAK2 and STAT1. ConA-induced expression of interferon regulatory factor 1 (IRF1), IFNβ, TNFα and CXCL1 was abrogated by selective inhibition of JAK2 and STAT1. Despite activating JAK2/STAT1, ConA failed to stimulate expression of inflammatory cytokines in HSCs from IRF1-knockout mice. [J Biol Chem] Abstract | Full Article

14-3-3ζ Binds to Hepatitis B Virus Protein X and Maintains Its Protein Stability in Hepatocellular Carcinoma Cells

14-3-3ζ silencing augmented hepatitis B virus protein X (HBx) ubiquitination and decreased its expression in cancer cells and xenograft tumor. The migratory and invasive abilities of CSQT-2 cells were inhibited upon 14-3-3ζ silencing, whereas partly restored by HBx overexpression. [Cancer Med] Full Article

Long Non-Coding RNA THOR Promotes Liver Cancer Stem Cells Expansion via β-Catenin Pathway

Researchers observed high expression of testis-associated highly conserved oncogenic long non-coding RNA (THOR) in chemoresistant hepatocellular carcinomas (HCCs). Interference THOR suppressed liver cancer stem cell (CSC) expansion by inhibiting the dedifferentiation of hepatoma cells and decreasing the self-renewal ability of liver CSCs. [Gene] Abstract

Molecular Pathways of Nonalcoholic Fatty Liver Disease Development and Progression

The authors aim at integrating the overwhelming progress made in the characterization of the physiopathological mechanisms of nonalcoholic fatty liver disease at a molecular level, to better understand the factor influencing the initiation and progression of the disease. [Cell Mol Life Sci] Abstract

Chemical Induction of Hepatic Apoptosis in Rodents

Investigators address the mechanism by which hepatotoxicity is initiated in hepatocytes in different rodents aiding the researcher in choosing the right animal model for a better research outcome. [J Appl Toxicol] Abstract

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

Axcella To Present New Data

Axcella Health, announced that Manu Chakravarthy, M.D., Ph.D., Senior Vice President, Clinical Development and Chief Medical Officer, will be presenting new data on the company’s novel candidate AXA1125. [Press release from Axcella Health discussing research presented at the 2018 American Association for the Study of Liver Disease (AASLD) Meeting, San Francisco.] Press Release

Cirius Therapeutics Reports Positive Data for MSDC-0602K in Interim Analysis of Phase IIb Clinical Trial in NASH Patients with Fibrosis

Cirius Therapeutics announced positive results from an interim analysis of exploratory endpoints from its ongoing, fully enrolled Phase IIb clinical trial evaluating MSDC-0602K in 402 patients diagnosed with non-alcoholic steatohepatitis (NASH) with fibrosis. [Cirius Therapeutics (PR Newswire Association LLC)] Press Release

TaiwanJ Pharmaceuticals Announces Positive Top-Line Results from Phase II Study of JKB-122 on Non-Alcoholic Fatty Liver Disease (NAFLD)

TaiwanJ Pharmaceuticals, announced the results of Phase II clinical trial of JKB-122 for the treatment of NAFLD that demonstrated significant improvement on relevant diagnosis and biomarkers from the JKB-122 treated subjects after the completion of 12-week study. [TaiwanJ Pharmaceuticals (PR Newswire Association LLC)] Press Release

Endonovo Therapeutics Provides Update on Liver Study

Endonovo Therapeutics, Inc. announced results performed in a study to determine if Sofpulse^® could counteract the effects of nonalcoholic steatohepatitis in an animal model. [Endonovo] Press Release

MYR Pharma Announces Grant of Breakthrough Therapy Designation by US FDA for Myrcludex, the First-in-Class Entry Inhibitor for Treatment of Chronic Hepatitis B and D Infections

MYR Pharma announced that US FDA has granted the Breakthrough Therapy designation for its lead compound Myrcludex. The designation is granted in the indication chronic hepatitis delta infection. [MYR PHARMA (PR Newswire Association LLC)] Press Release

Dozens of Scientists Ran for U.S. Congress. on the Eve of the General Election, 18 Are Still Standing

A flood of candidates with scientific, technical, and health backgrounds decided to run this year for the U.S. House of Representatives. All but one is a Democrat, and many were reacting to the 2016 election of President Donald Trump and the policies of the Republican majority in Congress. [ScienceInsider] Editorial

What a Massive Database of Retracted Papers Reveals About Science Publishing’s ‘Death Penalty’

Nearly a decade ago, headlines highlighted a disturbing trend in science: The number of articles retracted by journals had increased 10-fold during the previous 10 years. Fraud accounted for some 60% of those retractions; one offender, anesthesiologist Joachim Boldt, had racked up almost 90 retractions after investigators concluded he had fabricated data and committed other ethical violations. [ScienceInsider] Editorial

NEW Global NASH Congress
February 25-26, 2019
London, United Kingdom

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

NEW Principal Investigator/Group Leader – Non-Alcoholic Fatty Liver Disease (Foundation for Liver Research)

NEW Postdoctoral Position – Liver Cancer Translational Research (August Pi i Sunyer Biomedical Research Institute)

NEW Postdoctoral Position – Molecular & Integrative Physiology (University of Michigan)

Principal Scientific Officer – Liver Regeneration & Cancer (Cancer Research UK Beatson Institute)

Postdoctoral Researcher – RNA-Targeting Therapeutics (Ionis Pharmaceuticals, Inc.)

Research Fellow – Antibody Engineering and Hepatitis B Virology (National University of Singapore)

Postdoctoral Fellow – Inflammation/Innate Immunity/Cell Signaling (University of Colorado Denver)

Group Leader – Organoid Modeling of Disease (European Molecular Biology Laboratory)

Faculty Position – Biochemistry and/or Biophysics (University of Kansas Medical Center)

Faculty Position – Cancer Biology (Children’s Research Institute at UT Southwestern)

Postdoctoral Scholarship – Diabetes and Non-Alcoholic Fatty Liver Disease (University of Gothenburg)

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