Hepatic Cell News Volume 2.04 | Feb 2 2018

TOP STORY

Non-Parenchymal TREM-2 Protects the Liver from Immune-Mediated Hepatocellular Damage

Scientists hypothesized that the anti-inflammatory effects of triggering receptor expressed on myeloid cells 2 (TREM-2) on toll-like receptor signaling may limit hepatic injury. TREM-2 was expressed on non-parenchymal hepatic cells and induced during liver injury in mice and man. Liver damage in Trem–2^-/- mice following chronic injury and acetaminophen challenge was associated with elevated hepatic lipid peroxidation and macrophage content. [Gut] Abstract

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Circular RNA cSMARCA5 Inhibits Growth and Metastasis in Hepatocellular Carcinoma

The role of cSMARCA5 in hepatocellular carcinoma progression was assessed both in vitro and in vivo. Mechanistically, the authors found that cSMARCA5 could promote the expression of TIMP3, a well-known tumor suppressor, by sponging miR-17-3p and miR-181b-5p. [J Hepatol] Abstract

Hepatocyte-Specific Deletion of IL1-RI Attenuates Liver Injury by Blocking IL-1 Driven Autoinflammation

Interleukin-1 receptor type 1 (IL-1RI) during acute liver failure (ALF) was investigated using a novel transgenic mouse model exhibiting deletion of all signaling-capable IL-1R isoforms in hepatocytes. IL-1RI in hepatocytes played a pivotal role in an IL-1-driven auto-amplification of cell death and inflammation in the onset of ALF. [J Hepatol] Abstract

Hexokinase-2 Depletion Inhibits Glycolysis and Induces Oxidative Phosphorylation in Hepatocellular Carcinoma and Sensitizes to Metformin

Hepatic hexokinase (HK2) deletion inhibited tumor incidence in a mouse model of hepatocarcinogenesis. Silencing HK2 in human hepatocellular carcinoma cells inhibited tumorigenesis and increased cell death, which could not be restored by glucokinase or mitochondrial binding deficient HK2. [Nat Commun] Full Article | Press Release

Tumor Progression Locus 2 in Hepatocytes Potentiates Both Liver and Systemic Metabolic Disorders

Researchers report that tumor progression locus 2 (TPL2) protein expression was significantly increased in fatty liver from diverse species, including humans, monkeys and mice. Further investigations revealed that compared to wild-type littermates, hepatocyte-specific TPL2 knockout mice exhibited improved lipid and glucose imbalance, reserved insulin sensitivity and alleviated inflammation in response to high-fat diet feeding. [Hepatology] Abstract

Targeting Pin1 by Inhibitor API-1 Regulates MicroRNA Biogenesis and Suppresses Hepatocellular Carcinoma Development

Investigators present in vivo evidence that Pin1 overexpression is directly linked to the development of hepatocellular carcinoma (HCC). Administration with Pin1 inhibitor API-1, a novel and specific small molecule targeting Pin1 PPIase domain and inhibiting Pin1 cis–trans isomerizing activity, suppressed in vitro cell proliferation and migration of HCC cells. [Hepatology] Abstract

Upregulation of Kinesin Family Member 4A Enhanced Cell Proliferation via Activation of Akt Signaling and Predicted a Poor Prognosis in Hepatocellular Carcinoma

The authors found that KIF4A expression was upregulated in hepatocellular carcinoma (HCC) based on a meta-analysis of Oncomine database. They further confirmed that both KIF4A mRNA and protein expressions were overexpressed in human HCC tumor tissues as well as cancer cell lines. [Cell Death Dis] Full Article

Ubiquitin-Specific Protease 4 Promotes Hepatocellular Carcinoma Progression via Cyclophilin a Stabilization and Deubiquitination

Using in vitro and in vivo assays, scientists demonstrated that ubiquitin-specific protease 4 (USP4) overexpression enhanced hepatocellular carcinoma (HCC) cell growth, migration, and invasion. Mechanistically, cyclophilin A was identified as an important molecule for USP4-mediated oncogenic activity in HCC. [Cell Death Dis] Full Article

Implication of trans-11,trans-13 Conjugated Linoleic Acid in the Development of Hepatic Steatosis

In mice with depleted n-3 polyunsaturated fatty acids, researchers observed an accumulation of trans-11,trans-13 CLA and cis-9,cis-11 conjugated linoleic acids in the liver tissue that were associated with an increased triglyceride content and expression of lipogenic genes. They used an in vitro model to evaluate the impact of these two conjugated linoleic acids on hepatic lipid metabolism. [PLoS One] Full Article

The Immunology of Hepatocellular Carcinoma

The authors summarize the roles of specific immune cell subsets in chronic liver disease, with a focus on non-alcoholic steatohepatitis and hepatocellular carcinoma . [Nat Immunol] Abstract

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First John W. Walsh Translational Research Award Granted

The Alpha-1 Foundation celebrated the first granting of the John W. Walsh Translational Research Award in Alpha-1 Antitrypsin Deficiency. The award was granted to Joseph Kaserman, MD, instructor of medicine at Boston University School of Medicine and a physician in Pulmonary, Allergy, Sleep and Critical Care Medicine at Boston Medical Center. [Alpha-1 Foundation] Press Release

Varian Signs Agreement to Acquire Sirtex

Varian Medical Systems announced it has signed an agreement to acquire all the outstanding shares of Sirtex Medical Limited, an Australia-based global life sciences company focused on interventional oncology therapies. [Varian Medical Systems] Press Release

Bulgaria in the Cold as European Union Freezes Its Funding

European Union science ministers are due to meet in their bloc’s poorest member state — Bulgaria — to discuss future EU research policy. For the host nation, it was supposed to be a chance to showcase its ambitious plans to boost economic growth by attracting international research institutes to the country. [Nature News] Editorial

UK Doctors Select First Women to Have ‘Three-Person Babies’

Doctors in Newcastle have been granted permission to create Britain’s first “three-person babies” for two women who are at risk of passing on devastating and incurable genetic diseases to their children. [The Guardian] Editorial

Kid Co-Authors in South Korea Spur Government Probe

The South Korean government is expanding an investigation into researchers who named their children as co-authors on papers. The extended probe comes after a government report identified 82 academic papers on which authors had named their children or relatives — many of them in middle or high school — as co-authors on the publications. [Nature News] Editorial

NEW Stem Cells in Disease Modelling and Drug Discovery (SCDMDD) 2018
June 17-18, 2018
Melbourne, Australia

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NEW PhD Student – Hepatic Endothelial Heterogeneity (German Cancer Research Center)

Postdoctoral Fellow – Liver Cancer Research (University of California, San Francisco)

Locum Chief Editor – Nature Reviews Gastroenterology & Hepatology (Nature Research)

Postdoctoral Position – Liver Diseases (University of Illinois)

Part-Time Postdoctoral Scientist – HCV Vaccine Model Development (University of Oxford)

Postdoctoral Research Fellow – Liver Cancer Pathogenesis and Immunobiology (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Liver Cancer (University Health Network)

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

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

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