Hepatic Cell News Volume 3.45 | Nov 29 2019

TOP STORY

Loss of Histone MacroH2A1 in Hepatocellular Carcinoma Cells Promotes Paracrine-Mediated Chemoresistance and CD4⁺CD25⁺FoxP3⁺ Regulatory T Cells Activation

Researchers screened aggressive human hepatocellular carcinoma (HCC) for macroH2A1 and CD44 cancer stem cell marker expression. They also knocked down macroH2A1 in HCC cells, and performed integrated transcriptomic and secretomic analyses. [Theranostics] Full Article

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HBsAg-Specific CD8⁺ T Cells as an Indispensable Trigger to Induce Murine Hepatocellular Carcinoma

Recipient hepatocytes mice exhibited persistent HBsAg expression with chronic hepatitis and eventually developed hepatocellular carcinoma (HCC) with a prevalence of 100%. HBsAg-specific CD8⁺ T cells were generated and specifically and continuously induced hepatocyte apoptosis with progressive chronic inflammation, and the depletion of CD8⁺ T cells or their deficiency prevented HCC, which could then be reproduced by the transfer of HBsAg-specific CD8⁺ T cells. [Cell Mol Immunol] Abstract

DNMT3b/OCT4 Expression Confers Sorafenib Resistance and Poor Prognosis of Hepatocellular Carcinoma through IL-6/STAT3 Regulation

Hepatocellular carcinoma tissue samples were used to examine the association between DNMTs/OCT4 expression levels and clinical prognosis. Serum levels of IL-6 were detected using ELISA assays. Gain- and loss-of-function experiments were performed in cell lines and mouse xenograft models to determine the underlying mechanism in vitro and in vivo. [J Exp Clin Cancer Res] Full Article

Forkhead Box (FOX) G1 Promotes Hepatocellular Carcinoma Epithelial-Mesenchymal Transition by Activating Wnt Signal through Forming T-Cell Factor-4/Beta-Catenin/FOXG1 Complex

Levels of FOXG1 were determined by immunohistochemical and real-time PCR analysis in hepatocellular carcinoma (HCC) cell lines and human HCC samples. The effect of FOXG1 on cancer cell invasion and metastasis was investigated in vitro and in vivo in either FOXG1-silenced or overexpressing human HCC cell lines. [J Exp Clin Cancer Res] Full Article

MKL1 Promotes Endothelial-to-Mesenchymal Transition and Liver Fibrosis by Activating TWIST1 Transcription

Mechanistically, MKL1 was recruited to the promoter region of TWIST1, a master regulator of endothelial-mesenchymal transition, and activated TWIST1 transcription in a STAT3-dependent manner. A small-molecule STAT3 inhibitor alleviated EndMT in cultured cells and bile duct ligation induced liver fibrosis in mice. [Cell Death Dis] Full Article

CircRNA-5692 Inhibits the Progression of Hepatocellular Carcinoma by Sponging miR-328-5p to Enhance DAB2IP Expression

CircRNA expression profile was analyzed by a microarray. Regulatory gene targets were predicted by bioinformatics analysis and validated by luciferase assay. Their expression was determined by qRT-PCR and Western blotting. [Cell Death Dis] Full Article

Glutamine/Glutamate Metabolism Rewiring in Reprogrammed Human Hepatocyte-Like Cells

The authors report, using stable isotope-resolved metabolic analysis in combination with metabolomic-lipidomic approaches, that hepatocyte-like (HEP-L) cells mirrored glutamine/glutamate metabolism in primary cultured human hepatocytes that was very different from parental human fibroblasts. HEP-L cells diverged glutamine from multiple metabolic pathways into deamidation and glutamate secretion, just like periportal hepatocytes did. [Sci Rep] Full Article

The Protein Tyrosine Kinase SYK Regulates the Alternative p38 Activation in Liver during Acute Liver Inflammation

Researchers found that a mutation of alternative p38 in mice augmented the severity of acute liver inflammation. Moreover, TNF-induced hepatocyte death was augmented by a mutation of alternative p38, suggesting that alternative p38 signaling in hepatocytes contributed more significantly to the pathology of acute liver injury. [Sci Rep] Full Article

6-C-(E-Phenylethenyl)naringenin Attenuates the Stemness of Hepatocellular Carcinoma Cells by Suppressing Wnt/β-Catenin Signaling

The effect of a novel semi-natural derivative of naringenin, 6-C-(E-phenylethenyl)naringenin (6-CEPN) on hepatocellular carcinoma (HCC) stemness was evaluated both in vitro and in vivo. 6-CEPN reduced HCC cell viability, inhibited sphere formation, cell migration and invasion, and blocked epithelial-mesenchymal-transition. [J Agric Food Chem] Abstract

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The Regulatory Role of MicroRNA in Hepatitis-B Virus-Associated Hepatocellular Carcinoma (HBV-HCC) Pathogenesis

The authors collate evidence of the regulatory role of miRNA in each stage of the HBV-HCC continuum. This includes the regulatory role of miRNA in early HBV infection, chronic inflammation, fibrosis/cirrhosis, and the onset of HCC. [Cells] Full Article | Graphical Abstract

The Many Roles of Cell Adhesion Molecules in Hepatic Fibrosis

Investigators focus on selectins, cadherins, integrins and members of the immunoglobulin superfamily of adhesion molecules as well as some non-classical cell adhesion molecules in the context of hepatic fibrosis. They describe their liver-specific contributions to leukocyte recruitment, cell differentiation and survival, matrix remodeling or angiogenesis and touch on their suitability as targets in antifibrotic therapies. [Cells] Full Article

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GENFIT: Positive 42-Month DSMB Recommendation for Continuation of Phase III RESOLVE-IT Study of Elafibranor in NASH

GENFIT announced that the Data Safety Monitoring Board (DSMB) issued a positive recommendation for the continuation, without any modifications, of the RESOLVE-IT Phase III trial evaluating elafibranor in NASH. [GENFIT] Press Release

Algernon Pharmaceuticals Provides Update on Its Planned Phase II Clinical Trial

Algernon Pharmaceuticals Inc. has acquired the capital resources required to launch its first Phase II clinical trial using one of its lead drug compounds in one of its four identified key disease areas being non-alcoholic steatohepatitis, chronic kidney disease, inflammatory bowel disease and idiopathic pulmonary fibrosis. [Algernon Pharmaceuticals Inc. (GlobeNewswire, Inc.)] Press Release

FDA Accepts Intercept’s NDA for OCA for the Treatment of Liver Fibrosis Due to NASH and Grants Priority Review

Intercept Pharmaceuticals, Inc. announced that the FDA has accepted Intercept’s New Drug Application (NDA) for obeticholic acid (OCA) seeking accelerated approval for the treatment of fibrosis due to nonalcoholic steatohepatitis (NASH) and granted priority review. [Intercept Pharmaceuticals, Inc.] Press Release

PhD Students in China Report Misery and Hope

In a Nature survey, only 55% of the Chinese students who responded to the survey said that they were at least partially satisfied with their PhD experience. For the 5,630 respondents outside China, the satisfaction rate was 72%. [Nature News] Editorial

Chinese Ministry Investigates Duplications in Papers by University President

The Chinese education ministry is investigating scientific articles authored by high-profile immunologist and university president Cao Xuetao, following suggestions that dozens of papers contain potentially problematic images. Four journals also say they are examining papers from Cao. [Nature News] Editorial

Stark Party Differences in ‘Brexit Election’ Could Shape Future of UK Science

When representatives of each party took to a stage last week at the Royal Society in London, they all promised increased funding and easier immigration for scientists. But Brexit loomed over the discussion, says Sarah Main, director of the Campaign for Science and Engineering, an advocacy group in London. [ScienceInsider] Editorial

NEW Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies
January 9-12, 2020
San Diego, California, United States

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NEW Postdoctoral Researcher – HIV and the Liver (Seattle’s Children’s Hospital)

Postdoctoral Researcher – High Throughput Microfluidic Drug Screening (National University of Ireland Galway)

Postdoctoral Researcher – Oncogenic Pathways (University of Liège)

Faculty Member – Pathogen-Associated Malignancies (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Drug-Induced Liver Injury (Johnson & Johnson)

Postdoctoral Researcher – Liver Disease Treatment (University of Southern Denmark)

Postdoctoral Researcher – Personalized Medicine (Mayo Clinic Center for Individualized Medicine)

Postdoctoral Researcher – Liver Plasticity (University of Southern Denmark)

Postdoctoral Scientist – RAS Cancer Biology (Genetech, Inc.)

Assistant Professor – Liver Research (The University of Hong Kong)

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