Hepatic Cell News Volume 2.45 | Nov 23 2018

TOP STORY

Hepatocyte Notch Activation Induces Liver Fibrosis in Nonalcoholic Steatohepatitis

Researchers report that hepatocyte Notch activity tracks with disease severity and treatment response in patients with nonalcoholic steatohepatitis (NASH) and is similarly increased in a mouse model of diet-induced NASH and liver fibrosis. [Sci Transl Med] Abstract

(Ranked by impact factor of the journal)

Autophagy Is a Gatekeeper of Hepatic Differentiation and Carcinogenesis by Controlling the Degradation of Yap

Investigators showed that Yap is an autophagy substrate and mediator of tissue remodeling and hepatocarcinogenesis independent of the p62/Sqstm1-Nrf2 axis. Hepatocyte-specific deletion of Atg7 promoted liver size, fibrosis, progenitor cell expansion, and hepatocarcinogenesis, which was rescued by concurrent deletion of Yap. [Nat Commun] Full Article

Prolonged PM2.5 Exposure Elevates Risk of Oxidative Stress-Driven Nonalcoholic Fatty Liver Disease by Triggering Increase of Dyslipidemia

Researchers confirmed increases in insulin resistance, glucose tolerance, peripheral inflammation and dysarteriotony in PM2.5-induced mice. Oxidative stress and inflammatory response in the liver caused by PM2.5 inhalation contributed to abnormal hepatic function, further promoting lipid accumulation in the liver. [Free Radic Biol Med] Abstract

Methyl Helicterate Inhibits Hepatic Stellate Cell Activation through Modulation of Apoptosis and Autophagy

Hepatic stellate cell (HSC)-T6 cells were treated with various concentration of methyl helicterate (MH) and autophagy was inhibited by 3-methyl adenine (3-MA) or RNA interference. MH significantly inhibited HSC activation, as evidenced by the inhibition of cell viability, colony formation and the expression of α-SMA and collagen I. [Cell Physiol Biochem] Full Article

Long Non-Coding RNA H19 Inhibition Promotes Hyperglycemia in Mice by Upregulating Hepatic FoxO1 Levels and Promoting Gluconeogenesis

H19 inhibition in HepG2 cells increased the levels of FoxO1, its overexpression led to significant inhibition in FoxO1 levels, thereby identifying H19 as an important regulator of FoxO1. In vivo silencing of H19 in normal mice caused hyperglycemia, hyperinsulinemia and impaired glucose, insulin, and pyruvate tolerance. Serum triglyceride and cholesterol levels, however, did not show any change. [J Mol Med (Berl)] Abstract

miR-330-5p Targets SPRY2 to Promote Hepatocellular Carcinoma Progression via Mapk/Erk Signaling

Scientists report that miR-330-5p expression was upregulated in hepatocellular carcinoma (HCC) tissues and cell lines, and was associated with tumor size, tumor nodule number, capsule formation and tumor node metastasis stage in HCC patients. Overexpression of miR-330-5p promoted proliferation and growth of HCC cells in vitro and in vivo, while miR-330-5p knockdown had the inverse effect. [Oncogenesis] Full Article

Hypoxia Induced δ-Catenin to Enhance Mice Hepatocellular Carcinoma Progression via Wnt Signaling

The authors found that the hypoxia-inducible transcriptional factor, HIF1α, directly upregulated the expression of the gene Ctnnd2, which codes the protein δ-Catenin. δ-Catenin stabilized β-Catenin by disrupting the destruction complex, which led to the activation of Wnt signaling. As a result, δ-Catenin promoted the proliferation and migration of HCC cells in vitro, further enhance mice HCC tumorigenesis in vivo. [Exp Cell Res] Abstract

Ellagic Acid Ameliorates Oxidative Stress and Insulin Resistance in High Glucose-Treated HepG2 Cells via miR-223/keap1-Nrf2 Pathway

Ellagic acid (EA) upregulated glucose consumption, IRS1, Akt and ERK phosphorylation under insulin stimulation, reduced ROS and O2− production and MDA level, and increased SOD activity in high glucose-exposed HepG2 cells. In addition, EA elevated miR-223 expression level, downregulated mRNA and protein levels of keap1, and upregulated Nrf2, HO-1, SOD1 and SOD2 protein levels in the cell model. [Biomed Pharmacother] Full Article | Graphical Abstract

MicroRNA1124 Regulates Fatty Acid and Triglyceride Homeostasis

Scientists identified miR-124 as a regulator of triglyceride (TG) metabolism. Consistent with inhibition of TG and fatty acid catabolism, miR-124 expression promoted cellular TG accumulation. miR-124 inhibited the production of hepatitis C virus, a virus that hijacks lipid pathways during its lifecycle. [iScience] Abstract | Graphical Abstract

Wnt-β-Catenin Signalling in Liver Development, Health and Disease

In this review, the authors discuss the most relevant molecular mechanisms of action and regulation of Wnt-β-catenin signalling in liver development and pathophysiology. [Nat Rev Gastroenterol Hepatol] Abstract

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

Pliant Therapeutics Receives FDA Orphan Drug Designation for Lead Program Pln-74809 in Primary Sclerosing Cholangitis

Pliant Therapeutics, Inc announced that the U.S. FDA has granted orphan drug designation for the company’s anti-fibrotic lead compound, PLN-74809, for the treatment of primary sclerosing cholangitis. [Pliant Therapeutics, Inc] Press Release

China National Medical Products Administration Approves Gilead’s Vemlidy^® for Chronic Hepatitis B Virus Infection

Gilead Sciences, Inc. announced that the China National Medical Products Administration has approved Vemlidy^® for chronic hepatitis B in adults and adolescents. [Gilead] Press Release

Target PharmaSolutions^® to Advance Research in NASH and Hepatitis B through New Collaboration with Gilead Sciences

TARGET PharmaSolutions, Inc. announced that it has entered into a strategic partnership with Gilead Sciences for TARGET-NASH and TARGET-HBV. [TARGET PharmaSolutions, Inc.] Press Release

Ascletis and Roche Enter Exclusive Pegasys Partnership in China for Viral Hepatitis

Shanghai Roche Pharmaceuticals Ltd. and Ascletis BioScience Co., Ltd. jointly announced that starting from 1st Dec 2018, Ascletis and Roche will expand their partnership in viral Hepatitis. Following the first successful partnership and promising launch for Ganovo (Danoprevir), Ascletis and Roche have decided to embark on a Pegasys partnership. [Ascletis Pharma Inc.] Press Release

DURECT Announces Amendment to Accelerate Ongoing Phase IIa Trial of Dur-928 in Alcoholic Hepatitis (AH) by Allowing Dosing of Severe AH Patients in Parallel to Moderate AH Patients

DURECT Corporation announced it has amended its ongoing Phase IIa clinical trial of intravenously administered DUR-928 in patients with AH to accelerate the initiation of dosing of severe AH patents. The company recently completed dosing for the low-dose of Part A, and with this amendment in place, can now begin enrolling Part B, starting with the low dose, while it simultaneously continues enrolling Part A at the next higher dose. [DURECT Corporation] Press Release

Australian Funding Delay Creates Stress and Uncertainty for Scientists

A weeks-long delay in a major funding announcement is having a detrimental effect on Australian science, say researchers. [Nature News] Editorial

Stop Exploitation of Foreign Postdocs in the United States

A survey reveals some lab heads are using the need for visas to create unacceptable conditions for junior researchers. Some PIs are exploiting the fact that overseas scientists rely on them for continued visas. The responses suggest that senior scientists are using this reliance to force postdocs to work longer hours and endure unacceptable conditions. [Nature] Editorial

NEW 17^th World Congress of the International Pancreas & Islet Transplant Association (IPITA 2019)
July 2-5, 2019
Lyon, France

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

NEW Postdoctoral Position – Cancer Biology (Fox Chase Cancer Center)

NEW Postdoctoral Scholarships – Medicinal Chemistry, Experimental Biology & Systems Biology (KTH Royal Institute of Technology)

NEW Postdoctoral Researcher – Alcohol-Induced Liver Injury (Indiana University)

NEW PhD Position – Non-Alcoholic Fatty Liver Disease (Deutsche Diabetes Forschungsgesellschaft e. V)

NEW Postdoctoral Positions – Experimental and Computational Quantitative Single-Cell Biology (Max Planck Institute of Immunobiology and Epigenetics)

NEW Postdoctoral Research Fellow – 3D Organoid Development (University of Oslo)

Postdoctoral Researcher – Alcohol-Induced Liver Injury (Indiana University)

Postdoctoral Researcher – Gene Regulation in Obesity Related Liver Cancer (Umeå University)

Postdoctoral Training Fellow – Metabolic Reprograming in Liver Cancer (The Francis Crick Institute)

Post Doctoral Fellowship – Liver Biology and Pathophysiology (Johns Hopkins University)

Postdoctoral Fellow – Molecular Mechanisms of Alcoholic Liver Disease (Northeast Ohio Medical University)

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

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

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

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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