Hepatic Cell News Volume 3.10 | Mar 22 2019

TOP STORY

Alterations in Phosphorylation of Hepatocyte Ribosomal Protein S6 Control Plasmodium Liver Stage Infection

Infected hepatocytes exhibited elevated levels of phosphorylated ribosomal protein S6 (p-RPS6) while simultaneously abrogating the induction of phosphorylation of RPS6 in response to insulin stimulation. This is in contrast with the regulation of p-RPS6 by Toxoplasma gondii, which elevated levels of p-RPS6 after infection but did not alter the response to insulin. [Cell Rep] Full Article | Graphical Abstract

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Perilipin 5 and Lipocalin 2 Expression in Hepatocellular Carcinoma

Investigators showed in humans and mice that lipocalin 2 (LCN2) was secreted into the serum from liver cancer tissue. They also showed that α-fetoprotein-positive hepatocytes represented the main source for the massive expression of LCN2 in tumoral tissue. [Cancers] Full Article

rSJYB1 Inhibits Collagen Type I Protein Expression in Hepatic Stellate Cells via Down-Regulating Activity of Collagen α1 (I) Promoter

Recombinant SJYB1 (rSJYB1) protein was expressed in a bacterial system and purified by Ni-NTA His·Bind Resin. A human hepatic stellate cell line, the LX-2 cell line, was cultured and treated with rSJYB1. The role of rSJYB1 on LX-2 cells was then analyzed by Western blot and luciferase assay. [J Cell Mol Med] Full Article

GDF11 Exhibits Tumor Suppressive Properties in Hepatocellular Carcinoma Cells by Restricting Clonal Expansion and Invasion

Growth differentiation factor 11 (GDF11) treatment significantly reduced proliferation, colony and spheroid formation in hepatocellular carcinoma cell lines. Consistently, down-regulation of CDK6, cyclin D1, cyclin A, and concomitant upregulation of p27 was observed after 24 hours of treatment. Interestingly, cell viability was unchanged, but cell functionality was compromised. [Biochim Biophys Acta Mol Basis Dis] Abstract

Effect of Spheroidal Age on Sorafenib Diffusivity and Toxicity in a 3D HepG2 Spheroid Model

HepG2 spheroids were generated and maintained on a self-assembled ultra-low attachment nanobiointerface and characterized regarding time-dependent changes in morphology, functionality as well as anti-cancer drug resistance. [Sci Rep] Full Article

Function and Immunogenicity of Gene-Corrected iPSC-Derived Hepatocyte-Like Cells in Restoring Low Density Lipoprotein Uptake in Homozygous Familial Hypercholesterolemia

From a patient’s induced pluripotent stem cells (iPSCs), one homozygous gene-corrected homozygous familial hypercholesterolemia-iPSC clone and two heterozygous clones were generated using the CRISPR/Cas9 method. Both types of iPSC-derived hepatocyte-like cells showed recovery of the function of low-density lipoprotein uptake in immunofluorescence staining analysis. [Sci Rep] Full Article

Hypomethylation-Mediated Activation of Cancer/Testis Antigen KK-LC-1 Facilitates Hepatocellular Carcinoma Progression through Activating the Notch1/Hes1 Signaling

Kita-Kyushu lung cancer antigen-1 (KK-LC-1) promoted cell growth, migration, invasion and epithelial-mesenchymal transition in vitro and in vivo. KK-LC-1 modulated the Notch1/Hes1 pathway to exacerbate hepatocellular carcinoma (HCC) progression through physically interacting with presenilin-1. Upregulation of KK-LC-1 in HCC was attributed to hypomethylated CpG islands. [Cell Prolif] Full Article

HBV-Regulated Growth of Liver Cancer Cells Occurs through the miR-340-5p-ATF7-HSPA1B Axis

Scientists demonstrated that miR-340-5p played an important role during hepatitis B (HBV) infection and hepatocellular carcinoma development. Specifically, this miRNA directly bound to the mRNA encoding activating transcription factor 7 (ATF7), a protein that both promoted cell proliferation and suppressed apoptosis through its interaction with heat shock protein A member 1B (HSPA1B). [Cancer Sci] Abstract

Epigallocatechin Gallate Inhibits Hepatic Glucose Production in Primary Hepatocytes via Downregulating PKA Signaling Pathways and Transcriptional Factor FoxO1

Researchers showed the treatment of 10 μM epigallocatechin gallate (EGCG) for 6 hours decreased hepatic glucose production by 20 and 23% in wild-type and factor O-class member 1 (FoxO1) knock out primary hepatocytes, respectively. EGCG repressed both gluconeogenesis and glycogenolysis in primary hepatocytes, coupled with activating AMPK. In addition, EGCG decreased mitochondrial oxygen consumption. [J Agric Food Chem] Abstract | Graphical Abstract

Morin Enhances Auranofin Anticancer Activity by Up-Regulation of DR4 and DR5 and Modulation of Bcl-2 through Reactive Oxygen Species Generation in Hep3B Human Hepatocellular Carcinoma Cells

Morin enhanced the inhibitory effects on thioredoxin reductase activity of auranofin (AF) as well as reducing cell viability. Annexin V/PI double staining revealed that morin/AF cotreatment induced apoptotic cell death. Further, morin/AF cotreatment upregulated death receptor DR4/DR5, modulated Bcl-2 family members, and activated caspase-3, -8, and 9. [Phytother Res] Abstract

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Molecular Mechanisms Driving Progression of Liver Cirrhosis towards Hepatocellular Carcinoma in Chronic Hepatitis B and C Infections: A Review

The authors review recent knowledge concerning the molecular mechanisms of liver cirrhosis and its progression to hepatocellular carcinoma (HCC) from genetic and epigenomic points of view. Because ~70% of patients with HCC have hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection, they focus on HBV- and HCV-associated HCC. [Int J Mol Sci] Full Article

Biological Mechanisms and Related Natural Modulators of Liver X Receptor in Nonalcoholic Fatty Liver Disease

Investigators discuss the mechanisms of liver X receptor (LXR) in nonalcoholic steatohepatitis and summarize the natural products reported to modulate nonalcoholic fatty liver disease (NAFLD) via LXR or the LXR pathway, offering an alternative approach for LXR-related drug development in NAFLD. [Biomed Pharmacother] Abstract | Graphical Abstract

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

Takeda and HemoShear Therapeutics Extend Exclusive Drug Discovery Partnership in Liver Diseases

HemoShear Therapeutics, LLC announced an extension of its partnership with Takeda Pharmaceutical Company Limited to discover and develop additional novel therapeutics for liver diseases, including nonalcoholic steatohepatitis. [HemoShear Therapeutics, LLC] Press Release

Merck and NGM Bio Announce Extension of Broad, Multi-Year Strategic Collaboration to 2022

Merck and NGM Biopharmaceuticals, Inc. announced that Merck has exercised its option to extend the research phase of the companies’ broad, strategic collaboration for an additional two-year period from March 2020 to March 2022. [Merck & Co., Inc.] Press Release

Conatus Announces Top-Line Results from ENCORE-NF Phase IIb Clinical Trial in NASH Fibrosis

Conatus Pharmaceuticals Inc. announced top-line results from the company’s Phase IIb ENCORE-NF clinical trial in patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) and liver fibrosis. The trial’s primary endpoint was a ≥1 CRN fibrosis stage improvement with no worsening of steatohepatitis compared with placebo at week 72. [Conatus Pharmaceuticals Inc.] Press Release

Enanta Pharmaceuticals Completes Enrollment in Two Ongoing Phase II Studies

Enanta Pharmaceuticals, Inc. announced it has completed enrollment in two Phase II studies. The ARGON-1 study in non-alcoholic steatohepatitis (NASH) is a 12-week, randomized, double-blind, placebo-controlled Phase II study evaluating the safety, tolerability, pharmacokinetics and efficacy of EDP-305 in subjects with NASH. [Enanta Pharmaceuticals, Inc.] Press Release

Arrowhead Pharmaceuticals Files IND for Pivotal Phase II/III Study of ARO-AAT for Treatment of Alpha-1 Liver Disease

Arrowhead Pharmaceuticals Inc. announced that it has submitted an Investigational New Drug (IND) application to the FDA for an adaptive Phase II/III trial with the potential to serve as a pivotal registrational study of ARO-AAT, the company’s second generation subcutaneously administered RNA interference therapeutic being developed as a treatment for a rare genetic liver disease associated with alpha-1 antitrypsin deficiency. [Arrowhead Pharmaceuticals Inc.] Press Release

Kaleido Biosciences Announces Initiation of Dosing in Non-IND Clinical Studies in Patients with Urea Cycle Disorders and Cirrhosis

Kaleido Biosciences, Inc. announced the initiation of dosing in two non-Investigational New Drug (non-IND) clinical studies evaluating KB195 in patients with urea cycle disorders and KB174 in patients with cirrhosis. A third non-IND clinical study evaluating various doses of KB174 in healthy subjects is also underway. [Kaleido Biosciences, Inc.] Press Release

Tiziana Submits IND Application for Oral Formulation of Foralumab for Treatment of NASH

Tiziana Life Sciences plc announced that it has submitted an Investigational New Drug application (IND) to the FDA to initiate a Phase I clinical trial of enteric-coated capsules of Foralumab in healthy volunteers. [Tiziana Life Sciences plc] Press Release

FA Therapeutics Wins Second Key U.S. Patent For Treatment of Chronic Liver Diseases

SFA Therapeutics announced approval of the second key U.S. patent derived from its research & development program, which utilizes microbiome-derived metabolite small molecules as drugs to modulate the body’s anti-inflammatory and immune systems. [SFA Therapeutics (Business Wire, Inc.)] Press Release

Get to know Dr. Meritxell Huch and her approach to studying liver disease with hepatic organoids. Read the Full Profile

Chinese-American Scientist Societies Fear Racial Profiling

In a strongly worded letter published in Science, a group of Chinese-American scientists voiced concern that recent proposals from the National Institutes of Health and FBI actions could lead to unjust targeting of ethnically Chinese scientists. [The Scientist] Editorial

Universities Spooked by Trump Order Tying Free Speech to Grants

US President Donald Trump is expected to issue an executive order on 21 March that would require universities to certify that they protect free speech or risk losing federal research funds. The order will apply to 12 research agencies, including the National Institutes of Health, the National Science Foundation, the Department of Energy and NASA, a White House official said. [Nature News] Editorial

US Researchers Hope Congress Will Dig NSF Out of a $1 Billion Budget Hole

For the second time in three years, President Donald Trump has recommended deep cuts to the National Science Foundation (NSF) in Alexandria, Virginia. And scientists are hoping Congress will again come to the agency’s rescue. [ScienceInsider] Editorial

NEW 5^th CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference
September 25-28, 2019
Paris, France

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

NEW Postdoctoral Research Fellow – Biology of Liver Cancer (Boston Children’s Hospital)

NEW Postdoctoral Fellow – Alcoholic Liver Disease Research (Northeast Ohio Medical University)

Professor/Associate Professor – Cancer Biology (Norwegian University of Science and Technology)

Postdoctoral Position – Stem Cell Biology (University of Zurich)

Postdoctoral Position – Hepatitis C Virus Vaccine Research (TWINCORE – Centre for Experimental and Clinical Infection Research)

Postdoctoral Position – Non-Alcoholic Fatty Liver Disease (University of California, San Diego)

Assistant Professor – Computational Biology/Stem Cell Biology (University of Illinois at Chicago)

Postdoctoral Research Associate – Liver DIseases (University of Illinois at Chicago)

Senior Research Scientist – Nonalcoholic Steatohepatitis (Gilead Sciences, Inc)

Postdoctoral Research Scientist – Cancer Biology (The Beatson Institute for Cancer Research)

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