Hepatic Cell News Volume 2.36 | Sep 21 2018

TOP STORY

Small Molecule-Mediated Reprogramming of Human Hepatocytes into Bipotent Progenitor Cells

Scientists developed a robust culture system for generating human chemically derived hepatic progenitors (hCdHs) with therapeutic potential. hCdHs expressed hepatic progenitor markers and could self-renew for at least ten passages while retaining normal karyotype and potential to differentiate into functional hepatocytes and biliary epithelial cells in vitro. [J Hepatol] Abstract

(Ranked by impact factor of the journal)

CARM1 Methylates GAPDH to Regulate Glucose Metabolism and Is Suppressed in Liver Cancer

Coactivator-associated arginine methyltransferase 1 (CARM1) signaled glucose availability to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and suppressed glycolysis in liver cancer cells. CARM1 methylated GAPDH at arginine 234 (R234), inhibiting its catalytic activity. R234 methylation delayed tumor cell proliferation in vitro and in vivo. [Cell Rep] Full Article | Graphical Abstract

Sorafenib and Carfilzomib Synergistically Inhibit the Proliferation, Survival and Metastasis of Hepatocellular Carcinoma

Researchers found that carfilzomib had moderate anticancer activity toward liver cancer cells, but strongly enhanced the ability of sorafenib to suppress hepatocellular carcinoma cell growth, proliferation, migration, invasion and survival. The drug combination exhibited even more potent antitumor activity when tested in animal tumor models. [Mol Cancer Ther] Abstract

linc-SCRG1 Accelerates Liver Fibrosis by Decreasing RNA-Binding Protein Tristetraprolin

linc-SCRG1 increased along with liver fibrosis progression in human tissues and in activated LX2 cells induced by TGF-β1. Knock-down of linc-SCRG1 significantly reversed the effects of TGF-β1 on LX2, including inhibiting activation, promoting apoptosis, reducing proliferation, lessening invasion, and down-regulating genes. Tristetraprolin mRNA had negative relevance with linc-SCRG1 and was gradually reduced during human liver fibrosis progression. [FASEB J] Abstract

CPEB1 Mediates Hepatocellular Carcinoma Cancer Stemness and Chemoresistance

Cytoplasmic polyadenylation element-binding protein 1 (CPEB1) was downregulated in hepatocellular carcinoma (HCC). Overexpression of CPEB1 dramatically reduced HCC cell stemness, whereas silencing CPEB1 enhanced it. [Cell Death Dis] Full Article

Idelalisib Promotes Bim-Dependent Apoptosis through AKT/FoxO3a in Hepatocellular Carcinoma

Idelalisib treatment promoted Bim induction in hepatocellular carcinoma (HCC) via the FoxO3a pathway following PI3K/AKT inactivation. Bim was required for idelalisib-mediated apoptosis in HCC. A xenograft experiment revealed that the Bim deficiency abolished apoptosis and antitumor effects of idelalisib in vivo. [Cell Death Dis] Full Article

Robust Human and Murine Hepatocyte Culture Models of Hepatitis B Virus Infection and Replication

Scientists constructedd stable sodium taurocholate cotransporting polypeptide (NTCP)-expressing HepG2 and AML12 cell lines and found that hepatitis B virus (HBV) permissiveness was correlated with NTCP expression. They developed robust HBV cell culture models by treating the HBV-infected cells with dimethyl sulfoxide and hydrocortisone, which significantly promoted HBV replication and production. [J Virol] Abstract

Molecular Hydrogen Protects against Ischemia-Reperfusion Injury in a Mouse Fatty Liver Model via Regulating HO-1 and Sirt1 Expression

Methionine and choline-deficient plus high fat ischemia-reperfusion mice showed higher levels of AST and ALT in serum, TUNEL-positive apoptotic cells, F4/80 immunopositive cells, mRNA levels of inflammatory cytokines, constituents of the signaling pathway, pro-apoptotic molecules in liver, and Kupffer cells and/or primary hepatocytes, compared to the control group. In contrast, hydrogen treatment significantly suppressed the signs of I/R injury in fatty liver. [Sci Rep] Full Article

LncRNA CRNDE Promotes Hepatocellular Carcinoma Cell Proliferation, Invasion, and Migration through Regulating miR-203/ BCAT1 Axis

The expression levels of the long noncoding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) and BCAT1 were upregulated in hepatocellular cancer (HCC) tissues and cells, whereas miR-203 was downregulated in HCC. Knockdown of CRNDE or miR-203 overexpression inhibited HCC cell propagation and metastasis, and induced cell apoptosis. [J Cell Physiol] Abstract

Prolonged Inhibition of Hepatocellular Carcinoma Cell Proliferation by Combinatorial Expression of Defined Transcription Factors

Investigators found that combinatorial transduction of three hepatic transcription factors (TFs), HNF4A, HNF1A, and FOXA3, suppressed hepatocellular carcinoma (HCC) cell proliferation more stably than single transduction of these TFs. Combined transduction of the three TFs facilitated hepatic differentiation of HCC cell lines. [Cancer Sci] Abstract

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Non-Coding RNA in Drug Resistance of Hepatocellular Carcinoma

The authors overview up-to-date findings regarding miRNAs and long non-coding RNAs in drug resistance of hepatocellular carcinoma (HCC), summarize specific mechanisms that they use to modulate chemoresistance of HCC, and discuss their potential clinical application in overcoming the obstacle of HCC chemoresistance in the future. [Biosci Rep] Abstract | Full Article

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

MiNA Therapeutics Announces Findings from MTL-CEBPA Clinical Trial in Patients with Advanced Liver Cancer

MiNA Therapeutics provided an update from the ongoing Phase I study of small activating RNA candidate MTL-CEBPA in advanced liver cancer patients. [Press release from MiNA Therapeutics Limited discussing research presented at the International Liver Cancer Association Conference, London] Press Release

Take a look at hepatic organoids, their culture and applications. Learn More

Aspect Biosystems Announces Liver Tissue Collaboration with JSR

Aspect Biosystems announced a new collaboration to develop human liver tissue with JSR Corporation. Through this collaboration, Aspect’s proprietary Lab-on-a-Printer^™ 3D bioprinting platform and JSR’s advanced materials technology will be used to develop vascularized human liver lobules. [Aspect Biosystems (Business Wire, Inc.)] Press Release

Viking Therapeutics Announces Positive Top-Line Results from Phase II Study of VK2809 in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD) and Elevated LDL-Cholesterol

Viking Therapeutics, Inc. announced positive top-line results from a 12-week Phase II study of VK2809, its novel liver-selective thyroid receptor beta agonist, in patients with NAFLD and elevated low-density lipoprotein (LDL) cholesterol. [Viking Therapeutics, Inc.] Press Release

Cocrystal Pharma Completes Patient Enrollment in Phase IIa Study Evaluating CC-31244 for Ultra-Short Treatment of Hepatitis C

Cocrystal Pharma, Inc. announced the completion of patient enrollment in its Phase IIa clinical study evaluating CC-31244 for the ultra-short treatment of hepatitis C virus-infected individuals. [Cocrystal Pharma, Inc.] Press Release

ContraVir Pharmaceuticals Announces Completion of Phase I with CRV431

ContraVir Pharmaceuticals, Inc. announced that the primary endpoints of safety and tolerability were met in a single ascending dose study of CRV431 conducted in the United States. [ContraVir Pharmaceuticals Inc.] Press Release

Researchers Take Action to End Airlines’ Restrictions on Lab Animals

In a recently filed complaint to the US Department of Transportation, the National Association for Biomedical Research accused four major airlines of illegally discriminating against customers wishing to fly animals destined for the lab. [The Scientist] Editorial

This Research Groups Seeks to Expose Weaknesses in Science—and They’ll Step on Some Toes If They Have To

Metaresearchers investigate how scientists operate, and how they can slip off the rails. Their main focus is questionable research practices, such as massaging data and selective reporting of statistical tests. [ScienceInsider] Editorial

NEW The International Liver Congress^™ 2019
April 10-14, 2019
Vienna, Austria

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

NEW Scientist – In Vitro Pharmacology (Gubra)

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

NEW Project Manager – Translational Research and Fundraising (University of Strasbourg)

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

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

Post-Doctoral Biomedical Engineer – Human Liver Microphysiology Systems (University of Pittsburgh Drug Discovery Institute)

Assistant Professor – Basic and Translational Cancer Research (Texas Tech University Health Sciences Center)

Postdoctoral Fellow Positions – Metabolic Disorders (Temple University School of Medicine)

Research Faculty Position in Diabetes, Obesity, and Metabolism (University of Pittsburgh)

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

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