Hepatic Cell News Volume 4.00 | Jan 10 2020

TOP STORY

Expansion, In Vivo-Ex Vivo Cycling, and Genetic Manipulation of Primary Human Hepatocytes

Investigators showed that the pyrrolizidine alkaloid retrorsine improved primary human hepatocyte repopulation of chimeric mice on average 10-fold and rescued the ability of even poorly plateable donor hepatocytes to provide cells for subsequent ex vivo cultures. [Proc Natl Acad Sci USA] Abstract

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Robust Hepatitis E Virus Infection and Transcriptional Response in Human Hepatocytes

Researchers established a protocol based on the hepatitis E virus (HEV) genotype 3 p6 and the human hepatoma cell lines HepG2 and HepG2/C3A with different media conditions to produce intracellular HEV cell culture-derived particles with viral titers between 105 and 106 FFU/mL. [Proc Natl Acad Sci USA] Abstract

Intracellular XBP1-IL-24 Axis Dismantles Cytotoxic Unfolded Protein Response in the Liver

Interleukin-24 (IL-24) was previously found to promote ER stress-mediated cell death, and yet its expression and function in the liver remained elusive. Scientists identified an antiapoptotic role of IL-24, which transiently accumulated within ER-stressed hepatocytes in a X-box binding protein 1 (XBP1)-dependent manner. [Cell Death Dis] Full Article

Conditional Loss of Geranylgeranyl Diphosphate Synthase Alleviates Acute Obstructive Cholestatic Liver Injury by Regulating Hepatic Bile Acid Metabolism

When Ggps1 was conditionally deleted in the liver, amelioration of liver injury, as shown by downregulation of the hepatic inflammatory response and decreased hepatocellular apoptosis, was found after ligation of the common bile duct and cholecystectomy. [FEBS J] Abstract

The Correlation and Role Analysis of COL4A1 and COL4A2 in Hepatocarcinogenesis

The authors found that COL4A1/2 expressions were significantly correlated with hepatocarcinogenesis, progression, and prognosis. The expressions of COL4A1/2 were significantly upregulated in the preneoplastic and hepatocellular carcinoma tissues compared with normal tissues. [Aging (Albany NY)] Full Article

Exogenous 8-Hydroxydeoxyguanosine Ameliorates Liver Fibrosis through the Inhibition of Rac1-NADPH Oxidase Signaling

In vitro, hepatic stellate cell line LX-2 and HHSteC cells were stimulated by angiotensin-II. The ROS production was measured by confocal microsopy. The expressions of NOX1, NOX2, α-SMA, transforming growth factor-β1, and collagen Iα were analyzed by quantitative real-time polymerase chain reaction or immunoblotting. [J Gastroenterol Hepatol] Abstract

Investigating Fibrosis and Inflammation in an Ex Vivo NASH Murine Model

Investigators aimed to develop an ex vivo model of inflammation and fibrosis in steatotic murine precision-cut liver slices. Nonalcoholic steatohepatitis (NASH) was induced in C57Bl/6 mice using amylin and choline-deficient L-amino acid-defined diet. [Am J Physiol Gastrointest Liver Physiol] Abstract

UBQLN4 Promotes Progression of HCC via Activating Wnt-β-Catenin Pathway and Is Regulated by miR-370

Immunochemistry, real-time PCR, and western blotting were used to evaluate the expression levels of UBQLN4 in cancer tissues. Univariate, Cox-regression, and Kaplan-Meier analyses were performed to determine the association between UBQLN4 expression and HCC prognosis. [Cancer Cell Int] Full Article

The Metabolic Reprogramming Profiles in the Liver Fibrosis of Mice Infected with Schistosoma japonicum

Scientists characterized the metabolic profiles and the involvement of PTEN in the hepatic fibrosis induced by Schistosoma japonicum to provide a novel clue for metabolism-targeted treatment. [Inflammation] Abstract

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Leveraging Human Genetics to Identify Potential New Treatments for Fatty Liver Disease

The authors focus on how human molecular genetics of fatty liver disease have highlighted defects in hepatic lipid handling as a major common mechanism of its pathology and how this insight could be leveraged to treat and prevent its more serious complications. [Cell Metab] Full Article

Liver-on-a-Chip Models of Fatty Liver Disease

Scientists discuss advances in modeling liver tissue and the latest developments in understanding disease etiology and treatment from the perspective of engineered in vitro models spanning from conventional planar, static monolayer cultures to those based on the more recently developed bioprinted and liver-on-a-chip platforms. [Hepatology] Abstract

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Axcella Announces Positive Interim Findings from Ongoing Clinical Study of AXA1125/AXA1957 in Subjects with NAFLD and Expected 2020 Milestones

Axcella has completed the enrollment of 102 adult subjects with non-alcoholic fatty liver disease (NAFLD) in an ongoing randomized, dose-ranging study in which subjects receive either AXA1125, one of two AXA1957 doses or placebo for 16 weeks. This study, which is being conducted at 18 US medical centers, is assessing the impact of AXA1125/AXA1957 on safety, tolerability and physiology, as measured by a comprehensive panel of imaging and soluble biomarkers related to metabolism, inflammation and fibrosis. [Axcella] Press Release

Promethera Announces Initiation of Phase IIb DHELIVER Study of HepaStem™ inPpatients with Acute-on-Chronic Liver Failure (ACLF)

Promethera^® Biosciences SA announced the initiation of a Phase IIb clinical trial to evaluate the efficacy and safety of HepaStem™, the company’s liver-derived stem cell therapy candidate, in patients with acute-on-chronic liver failure. [Promethera^® Biosciences SA] Press Release

Ultragenyx Announces Positive Topline Cohort III Results and Improved Longer-Term Cohort II Results from Phase I/II Study of DTX301 Gene Therapy in Ornithine Transcarbamylase (OTC) Deficiency

Ultragenyx Pharmaceutical Inc. announced topline positive safety and efficacy data from Cohort 3 and longer-term data from Cohort II of the ongoing Phase I/II study of DTX301, an investigational adeno-associated virus gene therapy for the treatment of OTC deficiency. [Ultragenyx Pharmaceutical Inc.] Press Release

Scripps Acquires Pfizer’s Massive Microbial Library

The East Coast campus of the research institute received shipments of freeze-dried or frozen samples of more than 210,000 microbial strains, which scientists plan to mine for potentially useful natural products. [The Scientist] Editorial

Government Call for Science ‘Weirdos’ Prompts Caution from Researchers

Researchers have reacted with surprise and caution to a bizarrely worded job advertisement posted by a senior UK government adviser. The notice calls for scientists, mathematicians and “super-talented weirdos” to work for the prime minister and to help make “rapid progress with long-term problems”, and cites several scientific papers. [Nature News] Editorial

NEW Lorne Cancer Conference
February 13-15, 2020
Lorne, Australia

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NEW Postdoctoral Fellow – Metabolic Dysfunction (Lewis Katz School of Medicine)

NEW Postdoctoral Researchers – MicroRNAs in NAFLD (Weill Cornell Medicine)

NEW Postdoctoral Fellow – Translational Cancer Research (University of New Mexico Comprehensive Cancer Center)

NEW Research Associate – Liver Damage (University of Colorado Denver)

NEW Postdoctoral Researcher – Cell Biology of the Liver (Max Planck Institute of Immunobiology and Epigenetics)

Postdoctoral Fellow – Liver Pathology (University of Illinois at Chicago)

Professor – Hepatology (Jena University Hospital)

Postdoctoral Researcher – HIV and the Liver (Seattle’s Children’s Hospital)

Postdoctoral Researcher – Oncogenic Pathways (University of Liège)

Faculty Member – Pathogen-Associated Malignancies (Fred Hutchinson Cancer Research Center)

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