Hepatic Cell News 3.20 June 7, 2019 | |
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TOP STORYAryl hydrocarbon receptor (AHR) was expressed at high levels in quiescent hepatic stellate cells (HSCs), but the expression decreased with HSC activation. Activation of HSCs from AHR-knockout mice was accelerated, compared to HSCs from wild-type mice. In contrast, TCDD or ITE inhibited spontaneous and transforming growth factor beta-induced activation of HSCs. [Gastroenterology] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)APOBEC3B Interaction with PRC2 Modulates Microenvironment to Promote HCC Progression APOBEC3B (A3B) promoter luciferase reporter and other techniques were applied to elucidate mechanisms of A3B upregulation in hepatocellular carcinoma (HCC). A3B overexpression and knockdown cell models, immunocompetent and immune-deficient mouse HCC model were conducted to investigate the influence of A3B on HCC progression. [Gut] Abstract GDNF was confined mainly to hepatic stellate cells (HSCs) and contributed to HSC activation through activin receptor-like kinase 5 (ALK5) at His39 and Asp76 and through downstream signaling via Smad2/3, but not through GDNF family receptor alpha-1. GDNF, ALK5 and α-smooth muscle actin colocalized in human and mouse HSCs, as demonstrated by confocal microscopy. [Gut] Full Article CHML Promotes Liver Cancer Metastasis by Facilitating Rab14 Recycle Investigators report that expression of choroideremia-like (CHML) was increased in hepatocellular carcinoma (HCC), associated with poor survival, early recurrence and more satellite nodules in HCC patients. CHML promoted migration, invasion and metastasis of HCC cells, in a Rab14-dependent manner. They revealed that CHML facilitated constant recycling of Rab14 by escorting Rab14 to the membrane. [Nat Commun] Full Article Scientists report that c-Myc was significantly upregulated by TRAF6, an E3 ubiquitin ligase, in hepatocarcinogenesis. Mechanistically, TRAF6 interacted with and ubiquitinated histone deacetylase 3 (HDAC3) with K63-linked ubiquitin chains, which led to the dissociation of HDAC3 from the c-Myc promoter and subsequent acetylation of histone H3 at K9, thereby epigenetically enhancing the mRNA expression of c-Myc. [Hepatology] Abstract Liver ASK1 Protects from Non-Alcoholic Fatty Liver Disease and Fibrosis Researchers identified apoptosis signal-regulating kinase 1 (ASK1) as a suppressor of non-alcoholic steatohepatitis and fibrosis formation. High-fat diet-fed and aged chow-fed liver-specific ASK1-knockout mice developed a higher degree of hepatic steatosis, inflammation, and fibrosis compared to controls. [EMBO Mol Med] Full Article | Graphical Abstract Reduced expression of circular tripartite motif containing 33-12 (circTRIM33-12) in hepatocellular carcinoma (HCC) cells increased tumor proliferation, migration, invasion and immune evasion. Mechanistically, the authors demonstrated that circTRIM33-12 upregulated TET1 expression by sponging miR-191, resulting in significantly reduced 5-hydroxymethylcytosine levels in HCC cells. [Mol Cancer] Full Article The correlation between hepatic glucagon response and mitochondrial pyruvate carrier 1 (MPC1) induction was investigated in fasted mice and primary hepatocytes. The effects of ginsenoside Rb1 on MPC1 function were observed. Glucagon challenge raised blood glucose with hepatic MPC1 induction and inhibition of MPC induction coincided with a reduced rise in blood glucose. [Br J Pharmacol] Abstract Sanguinarine (SG) significantly inhibited hepatocellular carcinoma cell proliferation in a p53-dependent manner by inducing cell cycle arrest and reactive oxygen species-associated apoptosis. Silencing miR-16 by treatment with anti-miR16 miRNA inhibitors rescued the cell viability repression effect caused by SG. [Cancer Lett] Abstract Long non-coding RNA (lncRNA) distal-less homeobox 6 antisense 1 (DLX6-AS1) was upregulated in hepatocellular carcinoma. The silencing of lncRNA DLX6-AS1 was shown to reduce and inhibit spheroid formation, colony formation, proliferation, and tumor formation abilities, as well as attenuated CD133, CD13, OCT-4, SOX2, and Nanog expression in liver cancer stem cells. [J Exp Clin Cancer Res] Full Article Subscribe to one of our other 19 science newsletters such as Intestinal Cell News & Pancreatic Cell News. | |
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REVIEWSPathobiology of Inherited Biliary Diseases: A Roadmap to Understand Acquired Liver Diseases New knowledge has been steadily acquired about genetic and congenital cholangiopathies, and this has led to a better understanding of the mechanisms of acquired cholangiopathies. The authors focus on findings from studies on Alagille syndrome, polycystic liver diseases, fibropolycystic liver diseases and cystic fibrosis-related liver disease. [Nat Rev Gastroenterol Hepatol] Abstract Visit our reviews page to see a complete list of reviews in the hepatic cell research field. | |
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SCIENCE NEWSBristol-Myers Squibb Company announced first results from the opdivo plus yervoy cohort of the Phase I/II CheckMate-040 study, evaluating the immuno-oncology combination in patients with advanced hepatocellular carcinoma previously treated with sorafenib. [Press release from Bristol-Myers Squibb Company discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release Interim Data on Cirius Therapeutics’ MSDC-0602K to Be Presented Cirius Therapeutics announced that results from an interim analysis of exploratory endpoints from its Phase IIb EMMINENCE trial of MSDC-0602K will be presented. [Press release from Cirius Therapeutics (PR Newswire Association LLC.) discussing research to be presented at the American Diabetes Association (ADA) 79th Scientific Sessions, San Francisco] Press Release | |
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INDUSTRY NEWSGENFIT Launches a Phase II Trial Evaluating Elafibranor on Hepatic Lipid Composition for NAFL GENFIT announced the launch of a Phase II clinical trial evaluating elafibranor’s activity on liver fat quantity and – most importantly – fat composition in nonalcoholic fatty liver (NAFL) disease patients. The Phase II is a randomized, placebo-controlled, double-blind, cross-over study in sixteen patients with NAFL as identified with magnetic resonance spectroscopy. [GENFIT] Press Release CStone Pharmaceuticals announced that it has received approval to initiate clinical development in China of CS1001 in combination with BLU-554 in patients with locally advanced or metastatic hepatocellular carcinoma (HCC). The trial is a multi-center, open-label, and multi-dose Phase Ib/II study that aims to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor efficacy of the combination in advanced HCC. [CStone Pharmaceuticals (PR Newswire Association LLC.)] Press Release ContraVir Pharmaceuticals, Inc. announced findings from a preclinical study where CRV431, a novel cyclophilin inhibitor, significantly decreased the extent of fibrosis in a second animal model of liver fibrosis. [ContraVir Pharmaceuticals, Inc.] Press Release Alnylam Pharmaceuticals, Inc. announced the completion of the rolling submission of a New Drug Application to the FDA for givosiran, an investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 in development for the treatment of acute hepatic porphyria. [Alnylam Pharmaceuticals, Inc.] Press Release | |
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POLICY NEWSPowerful US Senator Calls for Vetting NIH Grantees at Hearing on Foreign Influences Research typically enjoys bipartisan support in the US Congress. But when it comes to the increasingly contentious topic of academic espionage by foreign governments, politics is never far from the surface. At a hearing of the Senate Committee on Finance, Chairman Chuck Grassley urged federal agencies to do more to thwart “real, aggressive, and ongoing” attempts by foreign entities to steal the fruits of US-funded research. [ScienceInsider] Editorial Hungarians Protest against Proposed Government Takeover of Science Thousands of scientists and their supporters marched through the streets of Budapest on 2 June to protest against a proposed law that would give the Hungarian government direct control of the country’s top research institutes. [Nature News] Editorial Brexit ‘May Bar UK Scientists from €100bn EU Research Fund’ The Horizon Europe program will fund €100bn in research projects, making it one of the largest science funds in the world. British researchers will be locked out unless the government negotiates an access deal in the coming months. [The Guardian] Editorial
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JOB OPPORTUNITIESPostdoctoral Position – Liver Disease (University of Illinois at Chicago) Research Assistant – Liver Immunology (Maynooth University) Postdoctoral Research Scientists – Hepatitis Virus Research (Ohio State University) Faculty Position/Director – Cancer Research (Lewis Katz School of Medicine at Temple University) Research Assistant – Liver Damage Research (University of Colorado Denver) Tier I CIHR Canada Research Chair – Mechanisms of Health & Disease (Brock University) Postdoctoral Fellow – Profiling Single Exosomes & Liver Metastasis Research (McGill University) Postdoctoral Researcher – Liver Mutagenesis (IRSET) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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