Hepatic Cell News Volume 3.28 | Aug 2 2019

TOP STORY

A Pharmacogenomic Landscape in Human Liver Cancers

To characterize the landscape of pharmacogenomic interactions in liver cancers, scientists developed a protocol to establish human liver cancer cell models at a success rate of around 50% and generated the Liver Cancer Model Repository (LIMORE) with 81 cell models. LIMORE represented genomic and transcriptomic heterogeneity of primary cancers. [Cancer Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

ECM1 Prevents Activation of Transforming Growth Factor Beta, Hepatic Stellate Cells, and Fibrogenesis in Mice

Livers were collected from mice and analyzed by histology, immunohistochemistry, in situ hybridization, and immunofluorescence analyses. Hepatocytes and hepatic stellate cells were isolated from livers of mice and incubated with extracellular matrix protein 1; production of cytokines and activation of reporter genes were quantified. [Gastroenterology] Abstract

ER-Residential Nogo-B Accelerates NAFLD-Associated HCC Mediated by Metabolic Reprogramming of oxLDL Lipophagy

Researchers discovered an endoplasmic reticulum (ER)-residential protein, Nogo-B, as a highly expressed metabolic modulator in both murine and human non-alcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC), which accelerated high-fat, high-carbohydrate diet-induced metabolic dysfunction and tumorigenicity. [Nat Commun] Full Article

The Molecular Mechanism of LncRNA34a-Mediated Regulation of Bone Metastasis in Hepatocellular Carcinoma

Investigators found that LncRNA34a (Lnc34a) was significantly overexpressed in hepatocellular cancer (HCC) tissues and associated with bone metastasis. Both in vitro and in vivo experiments indicated that the restoration or knockdown of Lnc34a expression in HCC cells had a marked effect on cellular migration, invasion, and metastasis. [Mol Cancer] Full Article

Hepatitis C Virus Infection Induces Hepatic Expression of NF-κB-Inducing Kinase and Lipogenesis by Downregulating miR-122

The authors manipulated NF-κB-inducing kinase (NIK) expression in Huh7.5.1 cells through loss- and gain-of-function approaches and examined the effects on IκB kinase α (IKK-α) activation, cellular lipid metabolism, and viral assembly. They demonstrated that NIK interacted with IKK-α to form a kinase complex in association with the stress granules, in which IKK-α was phosphorylated upon hepatitis C virus infection. [MBio] Full Article

3-D Culture and Endothelial Cells Improve Maturity of Human Pluripotent Stem Cell-Derived Hepatocytes

Scientists describe a serum-free, chemically defined 3D in vitro model using human-induced pluripotent stem cell-derived hepatocytes (iHEP cells), which was compatible with automation and conventional assay plates. The iHEP cells cultured in this model formed polarized aggregates with functional bile canaliculi and strongly increased expression of albumin, urea and genes encoding Phase I and II drug metabolism enzymes and bile transporters. [Acta Biomater] Abstract | Graphical Abstract

S-1-Propenylmercaptocysteine Protects Murine Hepatocytes against Oxidative Stress via Persulfidation of Keap1 and Activation of Nrf2

Pretreatment of cells with l-buthionine-S,R-sulfoximine confirmed that S-1-propenylmercaptocysteine (CySSPe) increased de novo synthesis of glutathione (GSH) by upregulating expression of the GSH-synthesizing enzyme GCL. Treatment of cells with CySSPe elevated hydrogen sulfide production. [Free Radic Biol Med] Abstract | Graphical Abstract

The RNA-Binding Protein SORBS2 Suppresses Hepatocellular Carcinoma Tumorigenesis and Metastasis by Stabilizing RORA mRNA

Expression of sorbin and SH3 domain‐containing 2 (SORBS2) in hepatocellular carcinoma (HCC) was detected by qRT-PCR, immunohistochemistry assay and Western blot assay. Proliferation, migration, invasion and cell cycle progression of HCC cells were measured by MTT assay, colony-forming assay, Transwell assay and flow cytometry assay, respectively. [Liver Int] Abstract

Viramidine-Loaded Galactosylated Nanoparticles Induce Hepatic Cancer Cell Apoptosis and Inhibit Angiogenesis

Viramidine, 5-fluorouracil, and paclitaxel-loaded galactosyl-terminating solid lipid nanoparticles (Gal-SLNs) were characterized inside cells. Cytotoxicities of free-drug, nano-void, and drug-loaded Gal-SLN were evaluated using HepG2 cells; over three days, cell viability was measured. [Appl Biochem Biotechnol] Abstract

Psoralen Induces Hepatic Toxicity through PERK and ATF6 Related ER Stress Pathways in HepG2 Cells

HepG2 cells were treated with psoralen for 6, 12, 24, or 48 hours, and an endoplasmic reticulum (ER) stress specific inhibitor, 4-PBA, was employed to investigate the mechanism of psoralen on ER stress and unfolded protein response. Cell viability was tested by MTT assay, ATP assay, and cell death by LDH. [Toxicol Mech Methods] Abstract

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Immunomodulatory TGF-β Signaling in Hepatocellular Carcinoma

The authors dissect the genetic landscape of the transforming growth factor beta (TGF-β) superfamily genes in hepatocellular carcinoma (HCC) and discuss the essential effects of this pathway on the tumor immune micro-environment. They highlight the TGF-β signature as a potential biomarker for identifying individualized immunotherapeutic approaches in HCC. [Trends Mol Med] Full Article

Reversal of NASH Fibrosis with Pharmacotherapy

A number of compounds targeting multiple pathways involved in the progression of NAFLD are currently in Phase II–III trials. Investigators briefly discuss the epidemiology, the pathogenesis and the current status of treatment of NAFLD. [Hepatol Int] Abstract

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

Algernon Pharmaceuticals Announces Russian Athletic Performance Enhancing Drugs Bemethyl (NP-135) and Bromantane (NP-160) Exhibited Potent Anti-Fibrotic Activity in NASH and CKD Studies

Algernon Pharmaceuticals Inc. report that its lead drugs for non-alcoholic steatohepatitis (NASH) and chronic kidney disease (CKD) are Bemethyl and Bromantane. They are representative of a class of drugs called “actoprotectors” developed during the Soviet Union era to improve performance of their military, cosmonauts and national athletes under extreme physical conditions. [Algernon Pharmaceuticals (GlobeNewswire, Inc.)] Press Release

Hepion Pharmaceuticals Receives FDA Authorization to Proceed with IND Opening Study of CRV431 for NASH

Hepion Pharmaceuticals, Inc. announced that the FDA has reviewed its Investigational New Drug (IND) application for CRV431 for the treatment of NASH and has authorized that the company proceed with its planned IND opening study. This IND for non-alcoholic steatohepatitis (NASH) is in addition to the company’s current open IND for hepatitis B virus. [Hepion Pharmaceuticals, Inc.] Press Release

‘Tropical Trump’ Sparks Unprecedented Crisis for Brazilian Science

Since Bolsonaro took office in January, Brazil’s researchers have faced funding cuts and repeated attempts by the administration to roll back protections for the environment and Indigenous populations. [Nature News] Editorial

‘No One Is Immune’: Alaska’s Scientists Despair over Plan to Shrink State Universities

The University of Alaska’s governing board plans to consolidate campuses to cope with a 40% cut in state funding. [Nature News] Editorial

China’s Scientists Alarmed, Bewildered by Growing Anti-Chinese Sentiment in the United States

Scientists in China are concerned about what they see as growing anti-Chinese sentiment in the United States. They dismiss claims of a vast conspiracy to steal US intellectual property and worry that new visa restrictions, scrutiny of export of scientific devices, and US investigations of Chinese and Chinese American scientists will hinder international collaborations. That could harm both countries’ research efforts as well as global scientific progress, many say. [ScienceInsider] Editorial

NEW 13^th Annual Conference of the International Liver Cancer Association (ILCA)
September 20-22, 2019
Chicago, Illinois, United States

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

NEW Postdoctoral Researcher – Liver Pathogenesis (Washington University)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Associate Scientist – In Vitro ADME Research (Gilead Sciences)

Researcher – Cell Biologist and Bioengineer (3D BioLabs, LLC)

Postdoctoral Fellow – Hepatitis C Virus (The Research Institute at Nationwide Children’s Hospital)

Postdoctoral Fellow – Inflammatory Liver Disease (The University of Kansas Medical Center)

Project Leader – Chronic Liver Disease Drug Discovery (Inserm Institute for Viral and Liver Disease)

Research Associate – System Level Analysis of Human Organogenesis (The University of Manchester)

Postdoctoral Position – Human Liver Microphysiology Systems (University of Pittsburgh Drug Discover Institute)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

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