Hepatic Cell News Volume 3.31 | Aug 22 2019

TOP STORY

Development of the First Low Nanomolar Liver Receptor Homolog-1 Agonist through Structure-Guided Design

Scientists exploited a newly-discovered polar interaction to lock agonists in a consistent orientation. This enabled the discovery of the first low nanomolar liver receptor homolog-1 agonist, one hundred times more potent than the best previous modulator. [J Med Chem] Abstract

(Ranked by impact factor of the journal)

Protopanaxadiol Inhibits Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma by Targeting STAT3 Pathway

The anti-tumor effects of several derivatives, including protopanaxadiol (PPD), Rg5, Rg3, Rh2, and Rh3, were evaluated in five different cancer cell lines. PPD demonstrated the best inhibitory effects on the proliferation and migration of the five cancer cell lines, especially the hepatocellular carcinoma cell lines. [Cell Death Dis] Abstract

Therapeutic Effects of a Small Molecule Agonist of the Relaxin Receptor ML290 in Liver Fibrosis

RNA sequencing analysis of TGF-β1-activated LX-2 cells showed that ML290 treatment primarily affected extracellular matrix remodeling and cytokine signaling, with expression profiles indicating an antifibrotic effect of ML290. ML290 treatment in human liver organoids with LPS-induced fibrotic phenotype resulted in a significant reduction of type I collagen. [FASEB J] Abstract

Adult and iPS-Derived Non-Parenchymal Cells Regulate Liver Organoid Development through Differential Modulation of Wnt and TGF-β

Researchers evaluated the influence of isogenic versus heterogenic non-parenchymal cells, using induced pluripotent stem cell (iPS)-derived or adult primary cell lines, in the liver organoid development. They tested four groups comprised of all different combinations of non-parenchymal cells for the liver functionality in vitro. [Stem Cell Res Ther] Full Article

Ablation of Serum Response Factor in Hepatic Stellate Cells Attenuates Liver Fibrosis

Scientists investigated the effect of hepatic stellate cell (HSC)-specific ablation of serum response factor (SRF) on liver fibrosis in vivo and the underlying mechanism. They report that SRF bound to the promoter regions of pro-fibrogenic genes, including collagen type I and alpha smooth muscle actin, with greater affinity in activated HSCs compared to quiescent HSCs. [J Mol Med] Abstract

RORα Suppresses Interleukin-6-Mediated Hepatic Acute Phase Response

IL-6-mediated activation of STAT3 was repressed after RORα activation by either adenoviral infusion of RORα or JC1-40 treatment in primary hepatocytes. Activation of RORα decreased transcriptional expression of IL-6 receptor α, an upstream activator of STAT3, both in vitro and in vivo. [Sci Rep] Full Article

G9a and HDACs Are Crucial for Snail2-Mediated E-Cadherin Repression and Metastasis in Hepatocellular Carcinoma

Investigators showed that Snail2 was upregulated in primary hepatocellular carcinoma, and significantly increased during TGF-β-induced liver cell epithelial-to-mesenchymal transition (EMT). Snail2 overexpressing and knock-down cell lines were established to determine its function in EMT in hepatocellular carcinoma. [Cancer Sci] Abstract

Long-Term Maintenance of Functional Primary Human Hepatocytes Using Small Molecules

The authors found that YPAC allows primary human hepatocytes to retain enzymatic activities of cytochrome P450 (CYP)1A2, CYP2B6 and CYP3A4 even after 40 days of culture, and that inducibility of CYP3A4 activity in response to the prototypical inducers rifampicin and phenobarbital was also maintained. [FEBS Lett] Abstract

Docosahexaenoic Acid Inhibits Hepatic Stellate Cell Activation to Attenuate Liver Fibrosis in a PPARγ-Dependent Manner

Docosahexaenoic acid (DHA) was found to inhibit hepatic stellate cell (HSC)-LX2 cell viability and downregulate marker proteins of HSC activation. Furthermore, DHA induced cell cycle arrest at G1 phase in HSCs. [Int Immunopharmacol] Abstract

Baicalein and Baicalin Promote Antitumor Immunity by Suppressing PD-L1 Expression in Hepatocellular Carcinoma Cells

PD-L1 upregulation induced by interferon-γ was significantly inhibited by two flavonoids in vitro. Both baicalein and baicalin enhanced the cytotoxicity of T cells to eliminated tumor cells, which was abrogated after hepatocellular carcinoma cells were transfected with a PD-L1 overexpression plasmid or after T cells were pretreated with an anti-PD-1 blocking antibody. [Int Immunopharmacol] Abstract

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Drug-Induced Liver Injury

Drug-induced liver injury is an adverse reaction to drugs or other xenobiotics that occurs either as a predictable event when an individual is exposed to toxic doses of some compounds or as an unpredictable event with many drugs in common use. Drugs can be harmful to the liver in susceptible individuals owing to genetic and environmental risk factors. [Nat Rev Dis Primers] Abstract

A Global View of Hepatocellular Carcinoma: Trends, Risk, Prevention and Management

Risk factors for hepatocellular carcinoma (HCC) include chronic hepatitis B and hepatitis C, alcohol addiction, metabolic liver disease and exposure to dietary toxins such as aflatoxins and aristolochic acid. All these risk factors are potentially preventable, highlighting the considerable potential of risk prevention for decreasing the global burden of HCC. [Nat Rev Gastroenterol Hepatol] Abstract

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ChemomAb Ltd., Announces Data from Phase I Study of CM-101 Subcutaneous Formulation Demonstrating Comparable Exposure to the Intravenous CM-101 Formulation

ChemomAb Ltd. announced results from its Phase I single administration study evaluating the subcutaneous formulation of CM-101 in healthy volunteers. This study is the second phase I study conducted with CM-101, the first study was a single ascending dose study using the IV formulation. [ChemomAb Ltd. (Business Wire, Inc.)] Press Release

Baylor Awarded CPRIT Grants to Support Cancer Research

Baylor College of Medicine has been awarded more than $17.4 million by the Cancer Prevention & Research Institute of Texas (CPRIT) to support new cancer research and programs, core facilities and recruitment of new faculty. More than 70 grants were awarded to institutions across Texas, totaling close to $136 million to advance the fight against cancer, including nine grants to Baylor College of Medicine. [Baylor College of Medicine] Press Release

‘Paralysed by Anxiety’: Researchers Speak about Life in Troubled Ancient-DNA Lab

The University of Adelaide has suspended the leader and founder of its premier ancient-DNA centre, Alan Cooper, following an investigation into the ‘culture’ at the Australian centre. The university has not given a reason for its decision, but current and former co-workers of Cooper – an award-winning evolutionary biologist who specializes in human migration – have told Nature that he bullied them or that they watched him bully others. [Nature] Editorial

As Brexit Nears, Britain’s Drugs, Devices and Pricing Regulators Seek the Exit

Firm details on exactly how the UK will regulate new medicines is still to be decided after it leaves the EU later this year (caveats on timing abound), but we now know that the regulator won’t be run by Dr. Ian Hudson, who is stepping down after six years in charge. [FierceBiotech] Editorial

NEW Cell Death in Immunity and Inflammation
October 6-9, 2019
Crete, Greece

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NEW Postdoctoral Fellow – Natural Killer Cells in Liver Disease (Karolinska Institutet)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Postdoctroal Researcher – Human Liver Function and Disease (Karolinska Institutet)

Postdoctoral Fellow – Metabolism and Physiology of Liver Diseases (University of Connecticut)

Postdoctoral Fellow – Multi-Omics Data in the Gut-Liver Axis (Mayo Clinic Health System)

Postdoctoral Researcher – Liver Pathogenesis (Washington University)

Associate Scientist – In Vitro ADME Research (Gilead Sciences)

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

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

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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