Hepatic Cell News Volume 3.03 | Feb 1 2019

TOP STORY

Nuclear Lipid Droplets Derive from a Lipoprotein Precursor and Regulate Phosphatidylcholine Synthesis

The authors showed that nuclear lipid droplets (LDs) in hepatocytes are derived from apolipoprotein B-free lumenal LDs, a precursor to very low-density lipoproprotein generated in the ER lumen by microsomal triglyceride transfer protein. [Nat Commun] Full Article

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Dual RNA-Seq Identifies Human Mucosal Immunity Protein Mucin-13 as a Hallmark of Plasmodium Exoerythrocytic Infection

Scientists confirmed mucin-13 (MUC13) transcript increased in hepatoma cell lines and primary hepatocytes. In immunofluorescence assays, host MUC13 protein expression distinguished infected cells from adjacent uninfected cells and showed similar colocalization with parasite biomarkers such as UIS4 and HSP70. [Nat Commun] Full Article

FBXW5 Mediates the Ubiquitination of ASK1 and Exacerbates Nonalcoholic Steatohepatitis

An in vivo study showed that hepatocyte-specific overexpression of protein F-box/WD repeat-containing protein 5 (FBXW5) exacerbated diet-induced systemic and hepatic metabolic disorders, as well as the activation of apoptosis signal-regulating kinase 1 (ASK1)-related MAPK signaling in the liver. Conversely, hepatocyte-specific deletion of FBXW5 significantly prevented the progression of these abnormalities. [Hepatology] Abstract

Lymphoid Enhancer-Binding Factor-1 Promotes Stemness and Poor Differentiation of Hepatocellular Carcinoma by Directly Activating the Notch Pathway

Researchers found the lymphoid enhancer-binding factor-1, a transcriptional factor, was frequently overexpressed in hepatocellular carcinoma cells, which was significantly associated with poor prognosis and tumor cell differentiation. [Oncogene] Abstract

Tobacco Smoke Induced Hepatic Cancer Stem Cell-Like Properties through IL-33/p38 Pathway

Investigators showed that p38 MAPK modulated tobacco smoke (TS)-stimulated hepatic cancer stem cells (CSC)-like properties, as evidenced by the findings that long term TS exposure activated p38, and that TS-induced stemness was abolished by p38 inhibition. Data from in vitro model showed that similar to cigarette smoke extract, IL-33 treatment promoted the activation of p38, increased the levels of liver CSCs markers expression and epithelial-to mesenchymal transition-like changes. [J Exp Clin Cancer Res] Full Article

Scutellarin Inhibits Proliferation and Invasion of Hepatocellular Carcinoma Cells via Down-Regulation of JAK2/STAT3 Pathway

Scientists showed that scutellarin potentially suppresses invasiveness of HepG2 and MHCC97-H cells in vitro by remodelling their cytoskeleton. The molecular mechanism behind it might be the inhibition of the epithelial-to mesenchymal transition process, which could be attributed to the down-regulation of the JAK2/STAT3 pathway. [J Cell Mol Med] Full Article

Knockout of α-Calcitonin Gene-Related Peptide Attenuates Cholestatic Liver Injury by Differentially Regulating Cellular Senescence of Hepatic Stellate Cells and Cholangiocytes

Cholangiocyte supernatant from bile duct ligation (BDL) α-Calcitonin gene-related peptide ^-/- mice inhibited the activation and increased cellular senescence of cultured human HSCs (HHSCs) compared to HHSCs stimulated with BDL cholangiocyte supernatant. [Lab Invest] Abstract

Impaired Mitophagy Triggers NLRP3 Inflammasome Activation during the Progression from Nonalcoholic Fatty Liver to Nonalcoholic Steatohepatitis

Primary rat hepatocytes were treated with palmitic acid for various periods of time. Mitophagy was measured by protein levels of LC3II and P62. NLRP3, caspase-1, interleukin (IL)-18, and IL-1β at mRNA and protein levels were used as indicators of inflammasome activation. [Lab Invest] Abstract

Activated Hepatic Stellate Cells Promote Progression of Post-Heat Residual Hepatocellular Carcinoma from Autophagic Survival to Proliferation

Hepatocellular carcinoma (HCC) cells were exposed to sublethal heat treatment and co-cultured with conditioned media from activated HSCs. Changes of cell proliferation, parameters of cell autophagy and activation of signaling pathways in heat-treated residual HCC cells were analyzed. [Int J Hyperthermia] Full Article

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Noncoding RNAs in Alcoholic Liver Disease

The authors cover the roles of noncoding RNAs in alcoholic liver disease, and the potential uses as markers for diagnosis and therapeutic options. [J Cell Physiol] Abstract

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Dicerna Announces Dosing of First Volunteer in Phase I Clinical Trial of DCR-HBVS Designed for the Treatment of Chronic Hepatitis B Virus

Dicerna Pharmaceuticals, Inc. announced the dosing of the first human volunteer in its Phase I clinical trial of DCR-HBVS, the company’s investigational GalXC^TM-based therapy for the treatment of chronic hepatitis B virus (HBV) infection in adults. The company anticipates human proof-of-concept data from the Phase I trial, which is known as DCR-HBVS-101, in the second half of 2019. [Dicerna Pharmaceuticals, Inc] Press Release

Eureka Therapeutics Announces US FDA Clearance of IND Application for Phase I/II Trial of ET140202 Artemis T-Cell Therapy, for the Treatment of Liver Cancer

Eureka Therapeutics, Inc. announced that the U.S. FDA has cleared its investigational new drug application for ET140202 ARTEMIS^™ T-cell therapy in AFP-positive patients with advanced hepatocellular carcinoma, the most common type of liver cancer. [Eureka Therapeutics, Inc] Press Release

Genetic Immunity Expands JSC Pharmadis Partnership by Granting 20 Cancer Vaccine Licenses for Russia and Commonwealth of Independent States

Genetic Immunity announced that it is expanding its collaboration with JSC Pharmadis by granting licenses to twenty cancer indications of its trans-dermally delivered pDNA-based vaccine technology. [Genetic Immunity (PR Newswire Association LLC.)] Press Release

Merck Family Foundation Makes the Largest Donation Ever to the Gulbenkian Institute of Science for Science Education in Africa

The pharmaceutical Merck, through the Merck Family Foundation, will support the Science for Development program of the Gulbenkian Institute of Science with a donation of about 350 thousand euros. [IGC – Instituto Gulbenkian de Ciência] Press Release

Macedonia Name Change Paves Way for Science Cooperation with Greece

A political agreement between Greece and its smaller northern neighbour, the Republic of Macedonia, ends a longstanding dispute over the republic’s name and sets the stage for renewed cross-border collaboration in research and higher education. [Nature News] Editorial

A 25% Pay Raise? That’s Not Nearly Enough, Young Indian Scientists Say

In response to months of protests and marches, the Indian government announced yesterday that it will give early-career scientists raises of up to 25%. But leaders of the protest movement, who had asked for an 80% hike, immediately rejected the offer. [ScienceInsider] Editorial

NEW Cell Symposia: Hallmarks of Cancer
November 17-19, 2019
Seattle, Washington, United States

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NEW Postdoctoral Research Scientist – Cancer Biology (The Beatson Institute for Cancer Research)

NEW Assistant/Associate Professor – Cancer Biology (Virginia Commonwealth University)

Postdoctoral Researcher – Cancer Biology (University of California, San Francisco)

Senior Scientific Officer – Cancer Biology (Cancer Research UK Beatson Institute)

Postdoctoral Researcher – Cancer Biology (University of Pennsylvania – Perelman School of Medicine)

Postdoctoral Position – Nonalcoholic Steatohepatitis (University of Southern Denmark)

Senior Scientific Officer – Tumor Microenvironment & Cancer Metabolism (Cancer Research UK Beatson Institute)

Postdoctoral Positions – Development & Progression of Cancer (Rutgers Cancer Institute of New Jersey)

Postdoctoral Scholar – Liver Disease (Pennsylvania State University)

Postdoctoral Position – Liver Disease (University of Illinois)

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