Hepatic Cell News Volume 4.13 | Apr 17 2020

TOP STORY

Cholesterol Stabilizes TAZ in Hepatocytes to Promote Experimental Non-Alcoholic Steatohepatitis

Scientists showed that the cholesterol-TAZ pathway was present in primary human hepatocytes, and associations among liver cholesterol, TAZ, and RhoA in human non-alcoholic steatohepatitis (NASH) liver were consistent with the pathway. Thus, hepatocyte cholesterol contributed to fibrotic NASH by increasing TAZ, suggesting new targets for therapeutic intervention. [Cell Metab] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Stem Cell-Derived Polarized Hepatocytes

The authors provided proof-of-concept that polarized hepatocyte-like cells can be used for pharmacokinetic and drug-drug interaction studies. This novel system provided a powerful tool to study hepatocyte biology, disease mechanisms, genetic variation, and drug metabolism. [Nat Commun] Full Article

Loss of Thymine DNA Glycosylase Causes Dysregulation of Bile Acid Homeostasis and Hepatocellular Carcinoma

Researchers demonstrated that the conditional deletion of thymine DNA glycosylase (TDG) in adult mice resulted in a male-predominant onset of hepatocellular carcinoma. TDG loss led to a prediabetic state, as well as bile acid accumulation in the liver and serum of male mice. [Cell Rep] Full Article | Graphical Abstract

Zinc Finger Protein 703 Induces EMT and Sorafenib Resistance in Hepatocellular Carcinoma by Transactivating CLDN4 Expression

Scientists demonstrated that the overexpression of zinc finger protein 703 (ZNF703) in human hepatocellular carcinoma (HCC) tissue was correlated with tumor metastasis and recurrence, and it was also related with the prognosis and survival rate of patients. ZNF703 overexpression promoted HCC progression in vitro and in vivo, whereas ZNF703 knockdown had the opposite effect. [Cell Death Dis] Full Article

Imbalance in Mitochondrial Dynamics Induced by Low PGC-1α Expression Contributes to Hepatocyte EMT and Liver Fibrosis

Investigating the role of mitochondrial dynamics in hepatocyte epithelial mesenchymal transition (EMT) and liver fibrosis, researchers used an in vitro human hepatic cell line and an in vivo mouse model of liver fibrosis. They showed that oxidative stress-induced mitochondrial DNA damage was associated with abnormal mitochondrial fission and hepatocyte EMT. [Cell Death Dis] Full Article

Involvement of Ammonia Metabolism in the Improvement of Endurance Performance by Tea Catechins in Mice

Examining how ammonia affected endurance capacity and how green tea catechins affected ammonia metabolism in vivo in mice and in vitro in mouse skeletal muscle and liver, scientists found blood ammonia concentration was significantly negatively correlated with exercise endurance capacity. [Sci Rep] Full Article

Fabrication of Perfusable Vascular Channels and Capillaries in 3D Liver-Like Tissue

Investigators outlined a method which involved tube-shaped 3D liver-like tissue with large channels and capillary-like structures using a perfusion device. They described how this can be used to construct 3D tissues, which was useful for fields of in vitro tissue regeneration for drug development and regenerative medicine. [Sci Rep] Full Article

Synergistic Antitumor Activity of Sorafenib and Artesunate in Hepatocellular Carcinoma Cells

Scientists investigated the synergistic anticancer effect of combining sorafenib and artesunate, an anti-malaria drug derivative, against hepatocellular carcinoma (HCC) in vitro and in vivo. They demonstrated that a combination of sorafenib and artesunate exerted synergistic antiproliferation effect and induced synergistic apoptosis in HCC cell lines. [Acta Pharmacol Sin] Abstract

GPR50 Promotes Hepatocellular Carcinoma Progression via the Notch Signaling Pathway Through Direct Interaction with ADAM17

Investigators showed that G protein-coupled receptor 50 (GPR50) in hepatocellular carcinoma (HCC) was overexpressed and that GPR50 knockdown downregulated cancer cell progression through attenuation of the Notch signaling pathway. They found that GPR50 knockdown reduced HCC progression by inactivating Notch signaling in a ligand-independent manner through ADAM17, a proteolytic enzyme that cleaves the Notch receptor. [Mol Ther Oncolytics] Abstract | Full Article

ATP7B Variant c.1934T > G p.Met645Arg Causes Wilson Disease by Promoting Exon 6 Skipping

Researchers used a minigene system and gene-edited HepG2 cells to demonstrate that c.1934T>G caused ~70% skipping of exon 6. Exon 6 skipping resulted in frameshift and stop-gain, leading to pathogenic loss-of-function variants in the ATP7B gene & resulting in Wilson disease. [npj Genomic Med] Full Article

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Production of Human Pluripotent Stem Cell-Derived Hepatic Cell Lineages and Liver Organoids: Current Status and Potential Applications

Human liver-based platforms hold great potential for clinical applications. The authors assess the production of the different hepatic cell lineages from human pluripotent stem cells (hPSCs), including hepatocytes, as well as the emerging strategies to generate hPSC-derived liver organoids, while highlighting current biomedical applications. [Bioengineering] Full Article

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

Alnylam and Dicerna Form RNAi Therapeutics Collaboration on Alpha-1 Antitrypsin Deficiency-Associated Liver Disease and Complete Cross-License Agreement for Primary Hyperoxaluria Programs

Alnylam Pharmaceuticals, Inc. and Dicerna Pharmaceuticals, Inc. have announced the formation of a development and commercialization collaboration on investigational RNAi therapeutics for the treatment of alpha-1 antitrypsin deficiency-associated liver disease. [Alnylam Pharmaceuticals, Inc.] Press Release

Yiviva Announces Dosing of First Patient in Phase IIb Study of First-Line YIV-906 Plus Sorafenib Combination Therapy in the Treatment of Hepatocellular Carcinoma

Yiviva have announced that the first patient has been dosed in a Phase IIb study of YIV-906 in combination with sorafenib in the treatment of patients with hepatitis B-positive hepatocellular carcinoma. YIV-906 is a novel, proprietary therapeutic candidate based on molecular profiling of extracts identified from use in traditional botanical medicine. [Yiviva, Inc.] Press Release

Madrigal MAESTRO Phase III NASH Trials Continue without Protocol Modifications; New Data Demonstrate that Reductions in Liver Fat Achieved by Resmetirom Predict NASH Resolution and Fibrosis Reduction

Madrigal Pharmaceuticals, Inc. announced that in response to guidance from regulatory agencies, measures for COVID-19 at impacted sites have been put in place for its Phase III MAESTRO-NASH and MAESTRO-NAFLD-1 studies, allowing both studies to continue without changes to protocol. [Madrigal Pharmaceuticals, Inc.] Press Release

How Research Funders Are Tackling Coronavirus Disruption

While science is crucial to the fight against COVID-19, researchers confined to their homes and unable to carry on with grant-funded work are becoming increasingly concerned about how the coronavirus pandemic will affect their funding. [Nature News] Editorial

WHO’s Tedros, Expressing ‘Regret’ over Trump Move to Cut Funding, Says His Focus Is on ‘Saving Lives’

The head of the World Health Organization expressed “regret” that President Trump intends to cut off US funding to the agency over its handling of the coronavirus, but pointedly avoided criticizing the US move. [STAT News] Editorial

Ending Coronavirus Lockdowns Will Be a Dangerous Process of Trial and Error

After the novel coronavirus made its way from China around the world, one country after another adopted harsh measures to stop SARS-CoV-2 from spreading and overwhelming hospitals. They have hit the pause button on their economies and their citizens’ lives, stopping sports events, religious services, and other social gatherings. [ScienceInsider] Editorial

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NEW Senior Research Scientist – Liver Disease (Novo Nordisk)

NEW Scientist – Molecular & Cellular Biology (Deep Genomics, Inc.)

Postdoctoral Position – Gut-Liver Axis (University of California, Davis)

Postdoctoral Position – Liver Pathogenesis (Washington University in St.Louis)

Therapuetic Specialist – Inflammation (Gilead Sciences Inc.)

Postdoctoral Fellow – The Microbiome in Liver Disease (University of Oslo)

Postdoctoral Researcher – Liver Pathogenesis (Washington University in St. Louis)

Senior Postdoctoral Research Assistant – Liver Research (University of Dundee)

Team Leader – Cholangiocytes (Miromatrix Medical)

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