Hepatic Cell News Volume 2.20 | Jun 1 2018

TOP STORY

The Histone Demethylase Phf2 Acts as a Molecular Checkpoint to Prevent NAFLD Progression during Obesity

Researchers established a downstream epigenetic checkpoint, whereby plant homeodomain finger 2 (Phf2), through facilitating H3K9me2 demethylation at specific gene promoters, protects liver from the pathogenesis progression of non alcoholic fatty liver disease (NAFLD). [Nat Commun] Full Article

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Production of Elastin-Derived Peptides Contribute to the Development of Non-Alcoholic Steatohepatitis

Scientists studied the effects of elastin-derived peptides (EDPs), biomarkers of aging, on the non-alcoholic fatty liver disease progression. They evaluated the consequences of EDP accumulation in mice and of elastin receptor complex activation on the lipid storage in hepatocytes, inflammation, and fibrosis development. [Diabetes] Abstract

DNase II Activated by the Mitochondrial Apoptotic Pathway Regulates RIP1-Dependent Non-Apoptotic Hepatocyte Death via the TLR9/IFN-Β Signaling Pathway

Without DNase II, apoptotic stimulation on hepatocytes induced TLR9-dependent interferon (IFN)-β production and RIP1-dependent non-apoptotic cell death originating from mitochondrial DNA. In fatty livers, DNase II activity was suppressed in contrast to simple inactivation of Bcl-xL or Mcl-1, and both apoptotic and non-apoptotic hepatocyte death could develop, leading to the progression of liver fibrosis. [Cell Death Differ] Abstract

HBx-Induced S100A9 in NF-κB Dependent Manner Promotes Growth and Metastasis of Hepatocellular Carcinoma Cells

Investigators found that all expression levels of myeloid-specific S100 proteins were elevated in serum and tissue samples from hepatocellular carcinoma (HCC) patients. Hepatitis B virus (HBx) was shown to facilitate translocation of NF-κB from the cytoplasm to the nucleus, and NF-κB bound to the promoter of S100A9 to enhance its transcription. [Cell Death Dis] Full Article

CD24 Regulates Sorafenib Resistance via Activating Autophagy in Hepatocellular Carcinoma

Researchers found that CD24-related sorafenib resistance was accompanied by the activation of autophagy and can be blocked by the inhibition of autophagy using either pharmacological inhibitors or essential autophagy gene knockdown. [Cell Death Dis] Full Article

Galactose Derivative-Modified Nanoparticles for Efficient siRNA Delivery to Hepatocellular Carcinoma

Galactose residues recognized by the asialoglycoprotein receptor can serve as potent targeting moieties for hepatocellular carcinoma (HCC) cells. To achieve more efficient siRNA delivery in HCC, scientists synthesized various galactoside derivatives and investigated the siRNA delivery capability of nanoparticles modified with those galactoside derivatives. [Biomacromolecules] Abstract | Graphical Abstract

Aldehyde Dehydrogenase 2 Activation Ameliorates CCl₄-Induced Chronic Liver Fibrosis in Mice by Up-Regulating Nrf2/HO-1 Antioxidant Pathway

Aldehyde dehydrogenase 2 (ALDH2) deficiency aggravated carbon tetrachloride (CCl4) -induced hepatic fibrosis through ROS overproduction, increased apoptosis and mitochondrial damage, whereas ALDH2 activation through Alda-1 administration alleviated hepatic fibrosis partly through activation of the Nrf2/HO-1 antioxidant pathway and Parkin-related mitophagy [J Cell Mol Med] Abstract | Full Article

Taraxasterol Suppresses the Growth of Human Liver Cancer by Upregulating Hint1 Expression

Researchers report that taraxasterol treatment significantly suppressed cell proliferation and induced cell cycle arrest at G0/G1 phase and apoptosis in liver cancer cells, but not in non-tumor hepatocytes. Taraxasterol upregulated histidine triad nucleotide-binding protein 1 (Hint1) and Bax, but downregulated Bcl2 and cyclin D1 expression, accompanied by promoting the demethylation in the Hint1 promoter region in liver cancer cells. [J Mol Med (Berl)] Abstract

Patient-Derived Multicellular Tumor Spheroids towards Optimized Treatment for Patients with Hepatocellular Carcinoma

To monitor the effect of the interaction of cancer cells and stromal cells in multicellular tumor spheroids, the authors used a 3D co-culture model with patient-derived hepatocellular carcinoma cells and stromal cells from human hepatic stellate cells, human fibroblasts, and human umbilical vein endothelial cells to facilitate screening for optimized cancer therapy. [J Exp Clin Cancer Res] Full Article

Expansion of Human Primary Hepatocytes In Vitro through Their Amplification as Liver Progenitors in a 3D Organoid System

Investigators showed that adult human primary hepatocytes when grown in 3D organoids are easily amplified, providing a substantial source of functional hepatocytes ready for transplantation. Following their plating, differentiated human hepatocytes were amplified during a transient and reversible step as liver progenitors, and could subsequently be converted back to mature differentiated hepatocytes. [Sci Rep] Full Article

Interaction of Hepatic Stellate Cells with Neutrophils and Macrophages in the Liver following Oncogenic kras Activation in Transgenic Zebrafish

Activation of hepatic stellate cells (HSC) plays a crucial role in the liver disease progression from liver fibrosis/cirrhosis to cancer. By manipulating the numbers of neutrophils and macrophages through morpholino knockdown, researchers found that macrophages contributed to both HSC survival and activation while neutrophils appear to be only required for HSC activation. Activated HSCs promoted the pro-tumorigenesis functions of neutrophils and macrophages through secretion of Tgfb1. [Sci Rep] Full Article

Hepatitis Transactivator Protein X Promotes Extracellular Matrix Modification through HIF/LOX Pathway in Liver Cancer

Overexpression of transactivator protein X elevated the mRNA and protein expression of a family of hypoxia-inducible factor-1α (HIF-1α) target genes, the lysyl oxidase (LOX) family in hepatocellular carcinoma. [Oncogenesis] Full Article

Noninvasive Biomarkers in NAFLD and NASH — Current Progress and Future Promise

This article reviews current and potential biomarkers for different features of nonalcoholic fatty liver disease (NAFLD), namely, steatosis, necroinflammation and fibrosis. For each biomarker, the authors evaluate its accuracy, reproducibility, responsiveness, feasibility and limitations. [Nat Rev Gastroenterol Hepatol] Abstract

In Vitro and In Silico Liver Models: Current Trends, Challenges and Opportunities

Liver may be modeled using “liver on a chip” devices, which may include established cell lines, primary human cells, and stem cell-derived hepatocyte-like cells. The choice of biological material along with its processing and maintenance greatly influence both the device performance and the resultant toxicity predictions. [ALTEX] Full Article

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

Arrowhead Completes Enrollment in Single Dose Portion of Phase I/II Study of ARO-HBV

Arrowhead Pharmaceuticals Inc. announced that it has completed enrollment and dosing of all five planned cohorts of healthy adult volunteers in the single-ascending dose portion of its ongoing Phase I/II study of ARO-HBV, the company’s third generation subcutaneously administered RNA interference therapeutic being developed as a potentially curative therapy for patients with chronic hepatitis B virus (HBV) infection. The company intends to submit a late-breaking abstract with initial clinical data on ARO-HBV. [Press release from Arrowhead Pharmaceuticals, Inc. discussing research to be presented at American Association for the Study of Liver Disease (AASLD), San Francisco] Press Release

Take a look at hepatic organoids, their culture and applications. Learn More

Green Park Collaborative, the Forum for Collaborative Research, and the Obesity Action Coalition (OAC) Launch coreNASH to Develop Consensus on Critical Outcomes in Non-Alcoholic Steatohepatitis (NASH) Clinical Research

The Green Park Collaborative, a major initiative of the Center for Medical Technology Policy, is partnering with The Forum for Collaborative Research and the OAC, to develop a core set of outcomes for non-alcoholic steatohepatitis. This initiative, coreNASH, will be conducted as a collaboration involving a multi-stakeholder team, including NASH patients, clinicians, payers, health technology assessment groups, regulators, life sciences companies and others, who will help establish a consistent and stakeholder-relevant baseline for evaluation of NASH therapies. [Center for Medical Technology Policy] Press Release

Exelixis Announces U.S. FDA Accepts Supplemental New Drug Application for CABOMETYX^® (Cabozantinib) in Previously Treated Advanced Hepatocellular Carcinoma

Exelixis, Inc. announced that the FDA has accepted for filing the company’s supplemental New Drug Application for CABOMETYX tablets as a treatment for patients with previously treated advanced hepatocellular carcinoma. [Exelixis, Inc.] Press Release

China Drug Administration Approves Epclusa^® (Sofosbuvir/Velpatasvir), Gilead’s Pan-Genotypic Treatment for Chronic Hepatitis C Virus Infection

Gilead Sciences, Inc. announced that the China Drug Administration has approved Epclusa^® for the treatment of adults with genotype 1-6 chronic hepatitis C virus infection. [Gilead Sciences, Inc.] Press Release

ContraVir Pharmaceuticals’ Cyclophilin Inhibitor, CRV431, Reduces Liver Fibrosis in a Preclinical Model

ContraVir Pharmaceuticals Inc. announced findings from a preclinical study of CRV431 indicating that the drug, a cyclophilin inhibitor, decreased the extent of fibrosis in an animal model by 46 percent compared to vehicle control. [ContraVir Pharmaceuticals Inc.] Press Release

ContraVir Pharmaceuticals’ Cyclophilin Inhibitor, CRV431, Reduces Development and Progression of Liver Tumors in Preclinical Hepatocellular Carcinoma Study

ContraVir Pharmaceuticals Inc. announced new findings confirming that CRV431, a cyclophilin inhibitor, reduces the number and size of liver tumors in a hepatocellular carcinoma mouse model. [ContraVir Pharmaceuticals Inc.] Press Release

‘Right-to-Try’ Law Intended to Weaken the FDA, Measure’s Sponsor Says in Blunt Remarks

Sen. Ron Johnson, the author of the federal “right-to-try” law signed by President Trump this week, wants to make one thing clear: His new law is meant to weaken the FDA. “This law intends to diminish the FDA’s power over people’s lives, not increase it,” he wrote in a letter to Commissioner Scott Gottlieb. [STAT News] Editorial

China to Crack Down on Fraud in Scandal-Hit Scientific Research amid ZTE Wrangle

China has issued the first national guidelines to enforce academic integrity in scientific research and vowed to punish academics and institutes for misconduct such as plagiarism and fabrication of data. [South China Morning Post Publishers Ltd] Editorial

Sweden Commits to Open Science with New Open-Access Publishing Deal

Swedish researchers can now publish their articles in Frontiers’ Open Access journals through a simplified process that covers publishing fees, thanks to a national agreement announced between Frontiers and the National Library of Sweden, on behalf of the organizations participating in the Bibsam Consortium. [EurekAlert] Editorial

NEW The Liver Meeting 2018
November 9-13, 2018
San Francisco, California, United States

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

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

Research Technologist – Liver Biology (STEMCELL Technologies Inc.)

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)

Academic Position – Cancer Research (Cedars-Sinai Medical Center)

Postdoctoral Research Associate – Liver Disease and Injury (University of Pittsburgh)

Research Fellow – Liver Tumorigenesis (Harvard School of Dental Medicine)

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

Postdoctoral Position – Cancer, Immunotherapy, and Fibrosis (University of Alabama at Birmingham)

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