Hepatic Cell News Volume 3.15 | May 3 2019

TOP STORY

Long-Term Functional Maintenance of Primary Human Hepatocytes In Vitro

Scientists demonstrated the long-term in vitro maintenance of primary human hepatocytes (PHHs) by modulating cell signaling pathways with a combination of five chemicals (5C). 5C-cultured PHHs showed global gene expression profiles and hepatocyte-specific functions resembling those of freshly isolated counterparts. [Science] Abstract

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Dexamethasone-Induced Krüppel-Like Factor 9 Expression Promotes Hepatic Gluconeogenesis and Hyperglycemia

Researchers showed that hepatic Krüppel-like factor 9 (Klf9) gene expression was induced by dexamethasone and fasting. The overexpression of Klf9 in primary hepatocytes strongly stimulated Pgc1a gene expression through direct binding to its promoter, thereby activating the gluconeogenic program. [J Clin Invest] Full Article | Graphical Abstract

Translation of the Circular RNA Circβ-Catenin Promotes Liver Cancer Cell Growth through Activation of the Wnt Pathway

Silencing of circβ-catenin significantly suppressed malignant phenotypes in vitro and in vivo, and knockdown of this circRNA reduced the protein level of β-catenin without affecting its mRNA level. [Genome Biol] Full Article

Liver-Target Nanotechnology Facilitates Berberine to Ameliorate Cardio-Metabolic Diseases

A rational designed micelle consisting of an α-tocopheryl hydrophobic core and an on-site detachable polyethylene glycol-thiol shell was developed for effective liver deposition of berberine (BBR). The bio-distribution analysis proved that the accumulation of BBR in the liver was increased by 248.8% assisted by micelles. Up-regulation of a range of energy-related genes was detectable in the HepG2 cells and in vivo. [Nat Commun] Full Article

A Novel LncRNA IHS Promotes Tumor Proliferation and Metastasis in Hepatocellular Carcinoma by Regulating ERK and Akt/GSK-3β Signaling Pathway

Long noncoding RNA (lncRNA) IHS (lncIHS) was overexpressed in hepatocellular carcinoma (HCC) and decreased the survival rate of HCC patients. Knockdown of lncIHS inhibited HCC cell migration, invasion and proliferation, and vice versa. Further study showed that lncIHS positively regulated the expression of EMT-related markers, c-Myc and Cyclin D1, as well as the activation of the ERK and Akt signaling pathway. [Mol Ther Nucleic Acids] Abstract | Full Article

Molecular Genetic and Immune Functional Responses Distinguish Bone Marrow Mesenchymal Stromal Cells from Hepatic Stellate Cells

Investigators showed that culture-adapted hepatic stellate cells (HeSCs) expressed substantially higher levels of hepatocyte growth factor, matrix metalloproteinase-1 and chemokine (C-C motif) ligand 2 than bone marrow mesenchymal stromal cells (BM-MSCs). Both human BM-MSCs and HeSCs inhibited T cell proliferation by a shared indoleamine, 2,3 dioxygenase-dependent mechanism. [Stem Cells] Abstract

Nobiletin Ameliorates Hepatic Ischemia and Reperfusion Injury through the Activation of SIRT-1/FOXO3a-Mediated Autophagy and Mitochondrial Biogenesis

Hepatic ischemia and reperfusion increased hepatocellular oxidative damage, inflammation, and cell death, but these changes were alleviated upon nobiletin treatment. Nobiletin increased the expression of proteins that controlled autophagy, mitochondrial dynamics, and biogenesis. [Exp Mol Med] Full Article

A High Throughput Imaging Database of Toxicological Effects of Nanomaterials Tested on HepaRG Cells

Researchers present a dataset including data based on a maximum of 14 different read outs of the human hepatoma HepaRG cell line treated with a large set of nanomaterials, coatings and supernatants at different concentrations. [Sci Data] Full Article

UPF1 Inhibits the Hepatocellular Carcinoma Progression by Targeting Long Non-Coding RNA UCA1

Scientists revealed that knockdown of up-frameshift protein 1 (UPF1) promoted hepatocellular carcinoma cell growth and invasion. Furthermore, they found that UPF1 could bind to long non-coding RNA urothelial cancer associated 1 (UCA1) and was negatively correlated with UCA1. UCA1 expression also affected HCC growth and invasion. [Sci Rep] Full Article

Paracrine Effects of CCN3 from Non-Cancerous Hepatic Cells Increase Signaling and Progression of Hepatocellular Carcinoma

Compared with conditioned media from wild-type LO2 cells, conditioned media from hepatic cell line LO2 activated by LX2 (aLO2-CM) induced CCN3 expression and hepatocellular carcinoma (HCC) cell proliferation and metastasis. Further, aLO2-CM activated MAPK signaling and epithelial-mesenchymal transition in HCC cells. [BMC Cancer] Full Article

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Technological Advancements for the Development of Stem Cell-Based Models for Hepatotoxicity Testing

The authors highlight the most recent cell culture systems, including scaffold-free and scaffold-based 3D technologies and microfluidics that can be employed for culture and hepatic differentiation of stem cells intended for hepatotoxicity testing. [Arch Toxicol] Abstract

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Innovate Biopharmaceuticals Shows Larazotide Is the First Drug, with Its Novel Mechanism of Action of Re-Normalizing the Intestinal Barrier, to Demonstrate Improvements in Validated NASH Biomarkers and Endpoints in Synergy with Obeticholic Acid, an FXR ag

Innovate Biopharmaceuticals, Inc. announced that larazotide acetate, a new class of medicine based on gut-restricted peptides which re-normalize the intestinal epithelial barrier and gut-liver axis, is the first drug with this novel mechanism to shown improvements in validated NASH biomarkers and endpoints. [Press release from Innovate Biopharmaceuticals, Inc. discussing research to be presented at the Digestive Disease Week (DDW) Conference, San Diego] Press Release

Genkyotex Reports Clinical Evidence of Anti-Fibrotic Activity by GKT831 in Liver Fibrosis Patients

Genkyotex announced top-line efficacy data for its NOX1/4 inhibitor GKT831 Phase II trial in primary biliary cholangitis. The top-line data provide a clinical proof of concept for GKT831 and highlight its potential as an anti-fibrotic therapy in the liver and other organs. [Genkyotex] Press Release

BioVie Achieves Primary Objectives in Phase IIa Clinical Trial of BIV201 in Refractory Ascites

BioVie Inc. announced top-line results for its Phase IIa clinical trial of BIV201 in six patients with refractory ascites due to advanced liver cirrhosis. The primary objectives of this initial open-label study were to assess the safety, tolerability, and steady state pharmacokinetics of terlipressin administered as a continuous infusion for 28 days to cirrhotic patients with refractory ascites. [BioVie Inc.] Press Release

3-V Biosciences Commences Dosing in Phase II Clinical Study of the FASN Inhibitor TVB-2640 in Patients with NASH

3-V Biosciences, Inc. and Ascletis Pharma Inc. announced that 3-V Biosciences has recently dosed its first patient in a Phase II clinical trial of the fatty acid synthase (FASN) inhibitor TVB-2640 in patients with non-alcoholic steatohepatitis (NASH). [3-V Biosciences, Inc.] Press Release

Oncology Venture Provides News on Its Clinical Development Projects Dovitinib, 2X-121 and LiPlaCis

Oncology Venture A/S provided news on Drug Response Predictor (DRP^®) based analyses of biopsies from clinical trials with dovitinib. In addition to renal, endometrial and GIST tumors Oncology Venture has now also shown in two new indications liver cancer and breast cancer that the DRP can predict the responding patients. [Oncology Venture A/S] Press Release

Orgenesis Announces Planned Study to Confirm Suitability of Liver Cells as a Source for Personalized Cell Replacement Therapy for Insulin-Dependent Diabetic Patients

Orgenesis Inc. announced it has received Institutional Review Board approval to collect liver biopsies from patients at Rambam Medical Center located in Haifa, Israel for a planned study to confirm the suitability of liver cells for personalized cell replacement therapy for patients with insulin-dependent diabetes resulting from total or partial pancreatectomy. [Orgenesis Inc.] Press Release

Dicerna™ Submits Updated IND Application for DCR-PHXC for Treatment of Primary Hyperoxaluria (PH) for the PHYOX™2 Pivotal Trial

Dicerna^™ Pharmaceuticals, Inc. announced the submission of an updated investigational new drug (IND) application to the FDA for DCR-PHXC, the company’s lead GalXC^™ product candidate for the treatment of all forms of PH. [Dicerna^™ Pharmaceuticals, Inc.] Press Release

China National Medical Products Administration Approves Sinovant’s Clinical Trial Application for Derazantinib

Sinovant Sciences announced that its Clinical Trial Application for derazantinib has been accepted by the Center for Drug Evaluation at the China National Medical Products Administration, enabling the initiation of a registrational clinical trial in patients with second-line intrahepatic cholangiocarcinoma in the second half of 2019. [Sinovant Sciences] Press Release

FDA Approves First Treatment for All Genotypes of Hepatitis C in Pediatric Patients

The FDA approved Mavyret tablets to treat all six genotypes of hepatitis C virus (HCV) in children ages 12 to 17. Mavyret was previously approved to treat HCV in adults in 2017. The safety and efficacy of Mavyret in pediatric patients was evaluated during clinical trials of 47 patients with genotype 1, 2, 3 or 4 HCV infection without cirrhosis or with mild cirrhosis. [The U.S. Food and Drug Administration] Press Release

Dova Pharmaceuticals Receives Positive Opinion from CHMP for DOPTELET^® (Avatrombopag) for the Treatment of Thrombocytopenia in Patients with Chronic Liver Disease

Dova Pharmaceuticals, Inc. announced the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion for the use of DOPTELET^® for the treatment of severe thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo an invasive procedure. [Dova Pharmaceuticals, Inc.] Press Release

German Research Promised a Decade of Budget Increases

German research organizations cheered a decision announced by state and federal ministers to increase research budgets by 3% a year for the next decade—a total boost of €17 billion over that time. [ScienceInsider] Editorial

Shake-Up at NIH: Term Limits for Important Positions Would Open New Opportunities for Women, Minorities

The NIH is aiming to shake up its intramural program, the largest collection of biomedical researchers in the world, by imposing term limits on midlevel leadership positions. Starting next year, the 272 lab and branch chiefs who oversee NIH’s intramural research will be limited to 12-year terms. [ScienceInsider] Editorial

NEW IDWeek 2019
October 2-6, 2019
Washington, D.C., United States

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NEW Tier I CIHR Canada Research Chair – Mechanisms of Health & Disease (Brock University)

Postdoctoral Fellow – Profiling Single Exosomes & Liver Metastasis Research (McGill University)

Postdoctoral Research Fellow – Organ on a Chip Organoid Development (Universtiy of Oslo)

Research Scientist – Head of the Human Liver Cell Isolation Lab (University of California, San Diego)

Postdoctoral Researcher – Liver Mutagenesis (IRSET)

Postdoctoral Fellow – Fatty Liver Disease Research (Northeast Ohio Medical Universtiy)

Staff Scientist – Liver Disease Research (National Institute of Diabetes and Digestive and Kidney Diseases)

Cell Biologist – Regenerative Medicine & Liver Disease (Hepatx Corporation)

Postdoctoral Research Scholarship – Liver Function & Disease (Karolinska Institutet)

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

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