Hepatic Cell News Volume 2.24 | Jun 29 2018

TOP STORY

Generation of Hepatic Stellate Cells from Human Pluripotent Stem Cells Enables In Vitro Modeling of Liver Fibrosis

Researchers report efficient differentiation of human pluripotent stem cells into hepatic stellate cell-like cells (iPSC-HSCs). When maintained as 3D spheroids with HepaRG hepatocytes, iPSC-HSCs exhibited a quiescent phenotype but mounted a fibrogenic response and secreted pro-collagen in response to known stimuli and hepatocyte toxicity. [Cell Stem Cell] Abstract | Graphical Abstract

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Hepatocyte SHP Deficiency Protects Mice from Acetaminophen-Evoked Liver Injury in a JNK-Signaling Regulation and GADD45β-Dependent Manner

Small heterodimer partner (SHP)-deficient primary mouse hepatocytes showed decreased cell death and inhibition of sustained c-Jun N-terminal kinase (JNK) phosphorylation following toxic acetaminophen (APAP) treatment. The ameliorative effects of SHP deficiency on APAP-induced liver injury were abolished in Shp^-/-growth arrest and DNA damage-inducible 45 beta (GADD45β)^-/- mice. [Arch Toxicol] Abstract

PRMT1 Promoted HCC Growth and Metastasis In Vitro and In Vivo via Activating the STAT3 Signaling Pathway

Cell proliferation, colony formation and migration in vitro were enhanced by protein arginine methyltransferase 1 (PRMT1) upregulation and decreased by PRMT1 downregulation in hepatocellular carcinoma (HCC) cell lines. Cryptotanshinone, a STAT3 inhibitor, inhibited STAT3 phosphorylation and reversed the HCC phenotype of PRMT1 expression. [Cell Physiol Biochem] Full Article

High-Mobility Group Box 1 Induces Endoplasmic Reticulum Stress and Activates Hepatic Stellate Cells

Scientists demonstrated that high-mobility group box 1 (HMGB1) can be released from hepatocytes and the released HMGB1 activates the hepatic stellate cells via endoplasmic reticulum (ER) stress at the transcriptional level which was dependent on the activation of both the TLR4 and RAGE signaling pathways rather than the TLR2 signaling pathway. [Lab Invest] Abstract

Frataxin-Mediated PINK1-Parkin-Dependent Mitophagy in Hepatic Steatosis: The Protective Effects of Quercetin

Lentivirus-mediated stable knockdown of frataxin in HepG2 inhibited PINK1- Parkin-associated mitophagy and resulted in lipid accumulation. Frataxin was further decreased by free fatty acids in knockdown cells concomitantly with depressed PINK1-Parkin-associated mitophagy, which was partially normalized by quercetin. [Mol Nutr Food Res] Abstract

Prolonged Inhibition of Class I PI3K Promotes Liver Cancer Stem Cell Expansion by Augmenting SGK3/GSK-3β/Β-Catenin Signaling

Serum and glucocorticoid-regulated kinase 3 (SGK3) promoted β-catenin accumulation by suppressing GSK-3β-mediated β-catenin degradation in liver cancer stem cells (CSCs), and then promoting the expansion of liver CSCs. Prolonged treatment of human hepatocarcinoma cells with class I phosphoinositide 3-kinase (PI3K) inhibitors lead to activation of SGK3 and expansion of liver CSCs. [J Exp Clin Cancer Res] Full Article

Sodium Orthovanadate Overcomes Sorafenib Resistance of Hepatocellular Carcinoma Cells by Inhibiting Na⁺/K⁺-ATPase Activity and Hypoxia-Inducible Pathways

Researchers demonstrated that sodium orthovanadate was able to overcome sorafenib resistance and strengthened sorafenib in suppressing sorafenib-resistant hepatocellular carcinoma cells in vitro and in animal models. [Sci Rep] Full Article

Periostin Promotes Liver Fibrogenesis by Activating Lysyl Oxidase in Hepatic Stellate Cells

In primary rat hepatic stellate cells (HSCs) in vitro, periostin significantly increased the expression levels and activities of lysyl oxidase and lysyl oxidase-like isoforms 1-3. Periostin also induced expression of intra- and extracellular collagen type 1 and fibronectin in HSCs. [J Biol Chem] Abstract | Full Article

Dual Effects of the Nrf2 Inhibitor for Inhibition of Hepatitis C Virus and Hepatic Cancer Cells

Brusatol suppressed the persistent hepatitis C virus (HCV) infection at both the RNA and protein levels in association with a reduction in nuclear factor E2-related factor 2 (Nrf2) protein in HPI cells. Combination of brusatol with an anticancer drug not only enhanced the anticancer effect but also, in the case of the combination with sorafenib, strongly suppressed HCV infection. [BMC Cancer] Full Article

Taurine Attenuates the Development of Hepatic Steatosis through the Inhibition of Oxidative Stress in a Model of Nonalcoholic Fatty Liver Disease In Vivo and In Vitro

In HepG2 cells, taurine suppressed the fatty acid-induced lipid accumulation, production of reactive oxygen species and thiobarbituric acid-reactive substances level, and amelioration of the fatty acid-induced disruption of the mitochondrial membrane potential. [Amino Acids] Abstract

Anti-Cancer Effect of Histone Deacetylase Inhibitor Scriptaid as a Single Agent on Hepatocellular Carcinoma

Investigators showed that histone deacetylase inhibitor scriptaid decreased hepatocellular carcinoma (HCC) cell proliferation and induced cell cycle G2/M phase arrest in a dose-dependent manner. Scriptaid triggered HCC cell death via transcriptional activation of p21 and subsequent elevated global H3Ac levels. [Biosci Rep] Abstract | Full Article

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Endoplasmic Reticulum Stress Signaling and the Pathogenesis of Non-Alcoholic Fatty Liver Disease

The authors provide an overview of the evidence linking endoplasmic reticulum stress to non-alcoholic fatty liver disease and discuss possible points of intervention. [J Hepatol] Abstract

Emerging Role and Therapeutic Implication of Wnt Signaling Pathways in Liver Fibrosis

Scientists describe the present knowledge about the Wnt signaling pathway, which significantly participates in liver fibrosis and hepatic stellate cell activation, and look ahead on new perspectives of Wnt signaling pathway research. They discuss the different interactions with Wnt signaling pathway-regulated liver fibrosis. [Gene] Abstract

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Prometic Presents New Data on NASH Drug Candidate PBI-4547

Prometic Life Sciences Inc. announced the presentation of four posters. The posters and data suggest that PBI-4547 offers the potential to successfully address significant unmet medical needs in liver fibrosis, nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease, obesity and diabetes. [Press release from Prometic Life Sciences Inc. discussing research presented at the American Diabetes Association’s 78^th Scientific Sessions, Orlando] Press Release

Fractyl Announces Presentation of Key Scientific Research Indicating that Modern Diets Durably Alter Duodenal Lining, Highlighting the Intestine’s Role in Type 2 Diabetes and NASH

Fractyl Laboratories Inc. announced the presentation of breakthrough research providing the first clear mechanistic link between modern diets and their causal effect on the pandemics of insulin resistance, obesity, and metabolic diseases. [Press release from Fractyl Laboratories, Inc. discussing research presented at the American Diabetes Association’s 78^th Scientific Sessions, Orlando] Press Release

Arrowhead Presents New Clinical Data on ARO-AAT at Alpha-1 National Education Conference

Arrowhead Pharmaceuticals Inc. will present preclinical and initial clinical data on 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 (AAT) deficiency. [Press release from Arrowhead Pharmaceuticals Inc. discussing research presented at the Alpha-1 National Education Conference, San Francisco] Press Release

Meet Dr. Caroline Lindemans and explore her work using organoids to study intestinal repair. Read the Full Profile

Revive Therapeutics Announces FDA Grants Orphan Drug Designation for Cannabidiol in the Treatment of Autoimmune Hepatitis

Revive Therapeutics Ltd. announced that the FDA has granted orphan drug designation for cannabidiol in the treatment of autoimmune hepatitis to Revive. [Revive Therapeutics Ltd. (GlobeNewswire, Inc.)] Press Release

Arrowhead Receives Positive EMA Opinion on Orphan Designation for ARO-AAT for Treatment of Congenital Alpha-1 Antitrypsin Deficiency

Arrowhead Pharmaceuticals Inc. announced that the European Medicines Agency (EMA) Committee for Orphan Medicinal Products issued a positive opinion on Arrowhead’s application for orphan designation of its RNAi candidate, ARO-AAT, for the treatment of congenital alpha-1 antitrypsin deficiency. [Arrowhead Pharmaceuticals Inc.] Press Release

Cocrystal Pharma Commences Enrollment and Initiates Patient Dosing in Phase IIa Study Evaluating CC-31244 for the Treatment of HCV

Cocrystal Pharma, Inc. announced the commencement of enrollment and initiation of patient dosing in its Phase IIa clinical study evaluating CC-31244 for the treatment of hepatitis C virus (HCV)-infected individuals. [Cocrystal Pharma, Inc.] Press Release

ContraVir Pharmaceuticals Initiates Dosing of CRV431 in First In-Human Trial

ContraVir Pharmaceuticals, Inc. announced dosing of the first subject in its single ascending dose Phase I trial in the United States with cyclophilin inhibitor, CRV431. [ContraVir Pharmaceuticals, Inc.] Press Release

GENFIT: New Preclinical Data Shows Elafibranor Inhibits Development of NAFLD/NASH-Related Cancer

GENFIT announced new preclinical results which indicate that elafibranor has anti-tumor development activity in the context of NAFLD/NASH-induced hepatocellular carcinoma. [GENFIT] Press Release

U.S. Lawmakers Want NIH and CDC Foundations to Say More About Donors

A key congressional spending panel has fired a shot across the bow of two federally chartered medical foundations, warning that the way they disclose information about donors may not pass muster. [ScienceInsider] Editorial

In Nigeria, a Battle Against Academic Plagiarism Heats Up

Six years ago, Emmanuel Unuabonah, a chemist at Redeemer’s University in Ede, Nigeria, read a scientific paper that made him feel “betrayed.” A colleague from Germany had shown him the study, which was published in a Nigeria-based journal. In it, four Nigerian researchers presented data copied from a paper by the German researcher as their own. [ScienceInsider] Editorial

Top US Court Upholds Trump Travel Ban: Student Visas Already in Decline

President Donald Trump’s policy to ban travellers from five Muslim-majority countries is lawful, the US Supreme Court said on 26 June. The 5–4 ruling comes after several lower courts acted to limit or suspend the policy, which Trump introduced in January 2017. [Nature News] Editorial

NEW Keystone Symposia: Integrated Pathways of Disease in NASH and NAFLD
January 20-24, 2019
Santa Fe, New Mexico, United States

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NEW Postdoctoral Positions – Medicinal Chemistry, Cellular and Experimental Biology and Systems Biology (University of Gothenburg)

Postdoctoral Fellows – Translational Oncology (Baylor College of Medicine)

Postdoctoral Fellow – Liver Cancer (Loyola University Chicago)

Postdoctoral Research Fellow – Gene Regulatory Mechanisms (University of California, Berkeley)

Group Leader – Systems Biology (Center for Systems Biology Dresden)

Postdoctoral/Project Leader – Hepatitis B and D Virus Research (University of Strasbourg)

Postdoctoral Scholar – Cancer Biology (Penn State College of Medicine)

Postdoctoral Fellow – Liver Injury, Hepatocellular Carcinoma and Metabolic Liver Diseases (University of Rhode Island)

Postdoctoral Position – Necroptosis in Liver Diseases (Inserm)

EBPOD Fellowship – NAFLD/NASH (European Molecular Biology Laboratory)

Postdoctoral Position – Inflammation and Metabolism (Sanford Burnham Prebys Medical Discovery Institute)

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