Hepatic Cell News Volume 1.46 | Dec 15 2017

TOP STORY

The Deubiquitinating Enzyme TNFAIP3 Mediates Inactivation of Hepatic ASK1 and Ameliorates Nonalcoholic Steatohepatitis

In screening for proteins that interact with apoptosis signal-regulating kinase 1 (ASK1) in the context of nonalcoholic steatohepatitis, the authors identified the deubiquitinase tumor necrosis factor alpha–induced protein 3 (TNFAIP3) as a key endogenous suppressor of ASK1 activation, and we found that TNFAIP3 directly interacts with and deubiquitinates ASK1 in hepatocytes. [Nat Med] Abstract

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Functional Hepatocyte Clusters on Bioactive Blend Silk Matrices towards Generating Bioartificial Liver Constructs

The authors investigated the potential of novel blend (BA) silk scaffold fabricated by blending mulberry (BM) silk fibroin with cell adhesion motif rich non-mulberry (AA) silk fibroin in generating a functional liver construct. Three-dimensional porous silk scaffolds (BM, AA and BA) were physico-chemically characterized and functionally evaluated using human hepatocarcinoma cells and primary neonatal rat hepatocytes. [Acta Biomater] Abstract | Graphical Abstract

Snail Mediates Crosstalk between TGFβ and LXRα in Hepatocellular Carcinoma

Scientists demonstrated that stimulation of the nuclear liver X receptor α (LXRα) receptor system by physiological and clinically useful agonists controls the hepatocellular carcinoma response to transforming growth factor β (TGFβ). [Cell Death Differ] Full Article

Hepatocyte Toll-Like Receptor 4 Mediates Lipopolysaccharide-Induced Hepcidin Expression

Researchers showed that lipopolysaccharide (LPS) can directly induce the mRNA expression and secretion of hepcidin by hepatocytes via toll-like receptor 4 (TLR4) activation. Using hepatocytes deficient in TLR4, myeloid differentiation factor 88 and TIR domain-containing adaptor inducing interferon-β, they demonstrated that LPS-induced hepcidin expression by hepatocytes is regulated by its specific receptor, TLR4, via a MyD88-dependent signaling pathway. [Exp Mol Med] Full Article

Human Fetal Liver Cultures Support Multiple Cell Lineages that Can Engraft Immunodeficient Mice

The authors tested if maturation of fetal hepatocytes in short-term cultures supported by epidermal growth factor and oncostatin M could improve their ability to engraft immunodeficient mice. [Open Biol] Full Article

Role of IL-6-Mediated Expression of NS5ATP9 in Autophagy of Liver Cancer Cells

Scientists demonstrated that human interleukin-6 (IL-6) recombinant protein induced autophagy of HepG2 cells. Autophagy decreased after IL-6 was silenced or neutralized with monoclonal antibody against human IL-6. [J Cell Physiol] Abstract

Decellularized Human Liver Extracellular Matrix Mediated Hepatic Differentiation of Human Induced Pluripotent Stem Cells

Human induced pluripotent cells were differentiated on the decellularized human liver matrix (hDLM) scaffolds using an established hepatic differentiation protocol. Investigators demonstrated that using hDLM leads to upregulation of functional hepatic markers when compared to standard differentiation conditions. [J Tissue Eng Regen Med] Abstract

Hepatic Progenitor Cells in Metastatic Liver Carcinomas

Hybrid structures composed of hepatic progenitor cells and metastatic adenocarcinoma cells were recognized and confirmed by double immunostaining. Carcinoma cells were also observed singly or in groups within the epithelium of interlobular bile ducts and/or ductules in portal tracts without evidence of carcinomatous infiltration and at a distance from the metastatic foci. [Histopathology] Abstract

Quantitative Expression of Hepatobiliary Transporters and Functional Uptake of Substrates in Hepatic 2D Sandwich-Cultures: A Comparative Evaluation of Upcyte and Primary Human Hepatocytes

Investigators quantified mRNA and protein levels of key hepatobiliary transporters and assessed associated uptake activity in short- and long-term cultures of upcyte human hepatocytes, in comparison to cryopreserved primary human hepatocytes. [Drug Metab Dispos] Full Article

LncRNA XIST Functions as a Molecular Sponge of miR-194-5p to Regulate MAPK1 Expression in Hepatocellular Carcinoma Cell

Researchers investigated the functional role of XIST in hepatocellular carcinoma (HCC) initiation and progression. They first detected that XIST was significantly upregulated in HCC tissues and associated with tumor size and vascular invasion. Gain- and loss-of-function of XIST further presented that XIST promoted the progression of HCC cells, including proliferation, migration, and invasion. [J Cell Biochem] Abstract

Methylation Mediated Gadd45β Enhanced the Chemosensitivity of Hepatocellular Carcinoma by Inhibiting the Stemness of Liver Cancer Cells

Scientists confirmed the decreased expression of growth arrest DNA damage-inducible gene 45β (Gadd45β) in human liver cancer tissues and human liver cancer cell lines, when compared to the peri-tumor liver tissue and normal liver cells. They found that Gadd45β could inhibit the stemness of liver cancer cells, enhancing the apoptosis of cancer cells induced by chemotherapy. [Cell Biosci] Full Article

Current and Future Therapeutic Regimens for Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH)

In order to have approved regimens for treatment of NASH/NAFLD, a number of issues must be addressed. [Hepatology] Abstract

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

Tiziana Life Sciences Announces Safety of Milciclib in a Phase IIa Trial in Unresectable or Metastatic Hepatocellular Carcinoma (HCC) Patients

Tiziana Life Sciences plc announced that the independent data monitor committee completed interim analysis of the safety and pharmacokinetic data from the first six patients and concluded that treatment with Milciclib was safe and well-tolerated with no drug-related serious adverse events in patients with unresectable or metastatic HCC. [Tiziana Life Sciences plc] Press Release

Women in Cell Biology Early Career Medal Winner 2018: Meritxell Huch

Awarded by the British Society for Cell Biology, the annual Women in Cell Biology Medal honours the most promising early career female researchers, to serve as inspiring role models for the next generation. Dr. Meritxell Huch is a Group Leader at the Gurdon Institute, University of Cambridge. [University of Cambridge] Press Release

Would You Advise Trump on Science? Survey Examines Attitudes of U.S. Researchers

The policies of President Donald Trump have soured U.S. scientists on working with the federal government and his administration. An informal survey by Science of 66 prominent scientists and engineers suggests a more nuanced reaction to Trump’s first year in office. [ScienceInsider] Editorial

French Researchers Hope New Chief Will Revitalize Troubled Funding Agency

French scientists are hopeful that the newly appointed chief of a major research-funding agency will revive an organization suffering from squeezed budgets and staff discontent. [Nature News] Editorial

Brexit ‘Breakthrough’ Raises Hope — and Questions

British science is expected to benefit from a deal that would allow EU nationals to remain in the country once it leaves the union. [Nature News] Editorial

Nine Researchers Sue University of Rochester over Sexual-Harassment Allegations

Nine researchers filed a federal lawsuit against the University of Rochester in New York, its president Joel Seligman and its provost Robert Clark over their handling of alleged sexual harassment by a professor there. [Nature News] Editorial

NEW Basic to Translational: Current Concepts of Liver Immunology
February 22, 2018
London, United Kingdom

NEW The London Stem Cell Network Symposium 2018
February 26, 2018
London, United Kingdom

NEW 16^th International Symposium on Viral Hepatitis and Liver Disease (ISVHLD)
June 14-17, 2018
Toronto, Ontario, Canada

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

NEW Postdoctoral Scholar Position – Cancer & Stem Cell Epigenomics (University of California, Davis)

Postdoctoral Fellow – Liver Tissue Engineering (Massachusetts General Hospital and Harvard Medical School)

Research Associate – Non-Alcoholic Fatty Liver Disease (Newcastle University)

Assistant, Associate or Full Professor – Hepatology (University of California, San Diego)

Research Fellow – Hepatitis B Virology (National University of Singapore)

Research Scientist – Chronic Fibrotic and Metabolic Diseases (Gilead Sciences Inc.)

Postdoctoral Fellow – Liver-Like Organoids (KU Leuven)

Faculty Positions – Liver Health and Disease (University of Pittsburgh)

Postdoctoral Position – Liver Disease (University of Illinois)

Biomedical Scientist – Molecular and Cellular Gastroenterology (Mayo Clinic)

Faculty Position – Cancer Experimental Therapeutics (University of New Mexico)

Postdoctoral Research Fellow – Liver Tissue Engineering (Massachusetts General Hospital)

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