Hepatic Cell News Volume 1.06 | Mar 3 2017

TOP STORY

Human ES Cell-Derived Hepatoblasts Are an Optimal Lineage Stage for HCV Infection

Scientists investigated the susceptibility to HCV at multiple stages comprising human embryonic stem cells, definitive endodermal cells, hepatic stem cells (hHpSCs), hepatoblasts (hHBs) and mature hepatocytes. Susceptibility to infection occurred initially at the stage of hHpSC, however, hHBs proved to have the highest permissiveness and infectivity compared with all other stages. [Hepatology] Abstract

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Nur77 Suppresses Hepatocellular Carcinoma via Switching Glucose Metabolism toward Gluconeogenesis through Attenuating Phosphoenolpyruvate Carboxykinase Sumoylation

Investigators showed that the nuclear receptor Nur77 is a tumor suppressor for hepatocellular carcinoma (HCC) that regulates gluconeogenesis. Low Nur77 expression in clinical HCC samples correlated with poor prognosis, and a Nur77 deficiency in mice promoted HCC development. [Nat Commun] Full Article

Melatonin Protects against Lipid-Induced Mitochondrial Dysfunction in Hepatocytes and Inhibits Stellate Cell Activation during Hepatic Fibrosis in Mice

Melatonin, a potent antioxidant, protects against lipid-mediated mitochondrial reactive oxygen species generation. The melatonin-mediated protection against mitochondrial dysfunction was observed in high fat diet (HFD)-fed mice through restoration of enzymatic activities associated with respiratory chain and TCA cycle. Subsequently, melatonin reduced hepatic fat deposition and inflammation in HFD-fed mice. [J Pineal Res] Abstract

Hepatic Activation of the FAM3C-HSF1-CaM Pathway Attenuates Hyperglycemia of Obese Diabetic Mice

FAM3C is a member of family with sequence similarity 3 (FAM3) gene family, and the authors determined its role and mechanism in regulation of hepatic glucose/lipid metabolism. In obese diabetic mice, FAM3C expression was reduced in the liver, and hepatic FAM3C restoration improved insulin resistance, hyperglycemia and fatty liver. [Diabetes] Abstract

Inhibition of Kupffer Cell Autophagy Abrogates Nanoparticle-Induced Liver Injury

Using upconversion nanoparticles (UCNs) as a model engineered nanomaterial, researchers uncovered a critical role for Kupffer cells in nanomaterial-induced liver toxicity, as depletion of Kupffer cells significantly exacerbates UCN-induced liver injury. [Adv Healthc Mater] Abstract

Acquired Resistance with Epigenetic Alterations under Long-Term Anti-Angiogenic Therapy for Hepatocellular Carcinoma

Investigators established in vivo drug-tolerant subclones of human hepatocellular carcinoma cells by long-term treatment with vascular endothelial growth factor receptor inhibitor and serial transplantation in immunocompromised mice, and then compared them with the parental cells in molecular and biological features. [Mol Cancer Ther] Abstract

Transcriptome-Based Repurposing of Apigenin as a Potential Anti-Fibrotic Agent Targeting Hepatic Stellate Cells

The authors used a computational approach to identify anti-fibrotic therapies by querying a transcriptome. The flavonoid apigenin was among nine top-ranked compounds predicted to have anti-fibrotic activity; indeed, apigenin dose-dependently reduced collagen I in the human hepatic stellate cell line, TWNT-4. [Sci Rep] Full Article

Salvianolic Acid B Inhibits Mitochondrial Dysfunction by Up-Regulating Mortalin

Researchers verified that Salvianolic acid B efficiently blocked mitochondrial deformation and dysfunction induced by H₂O₂ in the human hepatocyte cell line HL7702. They found that Salvianolic acid B significantly up-regulated mortalin protein expression levels. [Sci Rep] Full Article

IL-1β Induced and p38^MAPK-Dependent Activation of the Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinase (MK) 2 in Hepatocytes: Signal Transduction with Robust and Concentration-Independent Signal Amplification

Investigators established a mathematical model for interleukin (IL)-1β induced activation of the p38^MAPK/MK2 pathway in hepatocytes that was calibrated to quantitative data on time- and IL-1β concentration-dependent phosphorylation of p38^MAPK and MK2 in primary mouse hepatocytes. The analysis showed that in hepatocytes signal transduction from IL-1β via p38^MAPK to MK2 is characterized by strong signal amplification. [J Biol Chem] Full Article

Folate Protects Hepatocytes of Hyperhomocysteinemia Mice from Apoptosis via Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Activated Endoplasmic Reticulum Stress

Scientists employed a high homocysteine-induced liver injury model of Apolipoprotein E-deficient mice fed high-methionine diet and found that high homocysteine induced endoplasmic reticulum stress and liver cell apoptosis by downregulation of CFTR expression; observations that were attenuated with supplementation of dietary folate. [J Cell Biochem] Abstract

Non-Alcoholic Fatty Liver Disease

The author briefly summarizes the most recent data on the pathophysiology, diagnosis, and treatment of non-alcoholic fatty liver disease. [BMC Med] Full Article

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

New Preclinical Data Show Can-Fite’s Namodenoson (CF102) Prevents Progression of Liver Fibrosis

Can-Fite BioPharma Ltd. announced new data that show its liver disease drug candidate CF102 prevented liver (hepatic) fibrosis progression in preclinical studies. [Can-Fite BioPharma Ltd.] Press Release

Enanta Announces CHMP Grants Positive Opinion for an Eight-Week Treatment Option with Abbvie’s VIEKIRAX^® (Ombitasvir/Paritaprevir/Ritonavir Tablets) + EXVIERA^® (Dasabuvir Tablets) for Patients with Genotype 1b Chronic Hepatitis C

Enanta Pharmaceuticals, Inc. announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has granted a positive opinion for an eight-week treatment regimen of AbbVie’s VIEKIRAX^® + EXVIERA^® as an option for previously untreated adult patients with genotype 1b chronic hepatitis C virus infection and minimal to moderate fibrosis. [Enanta Pharmaceuticals, Inc.] Press Release

How the Fallout from Trump’s Travel Ban Is Reshaping Science

Many foreign-born scientists say they are reconsidering plans to work or study in the United States, even though federal courts have indefinitely blocked US President Donald Trump’s travel ban. The policy, which Trump signed on 27 January, sought to deny entry to citizens of seven Muslim-majority nations for 90 days — including those with valid US visas. [Nature News] Editorial

Senior Republican Lawmaker Has Some Advice for U.S. Science Marchers

The chairman of a congressional spending panel that oversees a wide swath of U.S. science agencies has some unusual advice for scientists planning to march on 22 April: Don’t talk about research. Instead, demand that Congress find a way to cut mandatory spending programs. [ScienceInsider] Editorial

NEW Stem Cells and Regenerative Medicine 2^nd International Congress
April 19-21, 2017
Mashhad, Iran

NEW The Biology of Regenerative Medicine
April 25-27, 2017
Hinxton, United Kingdom

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

NEW Research Fellow – Hepatocytes (National University of Singapore)

NEW Academic Pathologist – Liver/GI (University of Texas Southwestern Medical Center)

NEW Associate or Full Professor – Gastroenterology (University of Washington)

Postdoctoral Fellow – Non-Alcoholic Steatohepatitis (AstraZeneca)

Postdoctoral Position – Liver Fibrosis (Massachusetts General Hospital)

Postdoctoral Research Fellow – Liver Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Non-Alcoholic Fatty Liver Disease (University of Gothenburg)

PhD Studentship – Hepatocytes (KU Leuven, Stem Cell Institute)

Senior Scientist – Oncology (Genentech Research)

Training Fellowship – Clinical Research (University of Oxford)

Postdoctoral Associate – Cancer Biology (University of Florida)

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