Hepatic Cell News Volume 4.04 | Feb 7 2020

TOP STORY

A Positive Feedback Loop of TET3 and TGF-β1 Promotes Liver Fibrosis

The authors demonstrated that in human hepatic stellate cells, TET3 promoted pro-fibrotic gene expression by up-regulation of multiple key TGF-β pathway genes, including TGFB1. TET3 bound to target gene promoters, inducing demethylation, which in turn facilitated chromatin remodeling and transcription. [Cell Rep] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

Hepatocyte Caveolin-1 Modulates Metabolic Gene Profiles and Functions in Non-Alcoholic Fatty Liver Disease

Microarray analysis showed strong differences in gene expression profiles of livers from HepCAV1ko mice compared those of global Cav1 knockout animals. Pathway enrichment analysis identified that metabolic alterations were sex-dimorphically regulated by hepatocyte-specific CAV1. In male HepCAV1ko mice, metabolic pathways were suppressed in non-alcoholic fatty liver disease (NAFLD), whereas in female knockout mice induced. [Cell Death Dis] Full Article

Oncogene-Dependent Function of BRG1 in Hepatocarcinogenesis

Investigators analyzed BRG1 in human HCC samples as well as in mouse models. They found that BRG1 is overexpressed in most of human HCC samples, especially in those associated with poorer prognosis. [Cell Death Dis] Full Article

Obeticholic Acid and INT-767 Modulate Collagen Deposition in a NASH In Vitro Model

Co-cultures of human hepatoma and hepatic stellate (HSCs) cells were exposed to free fatty acids alone or in combination with obeticholic acid or INT-767. mRNA expression of HSCs activation markers and FXR engagement were evaluated at 24, 96 and 144-hours. [Sci Rep] Full Article

Targeting of miR-96-5p by Catalpol Ameliorates Oxidative Stress and Hepatic Steatosis in LDLr^-/- Mice via p66shc/Cytochrome C Cascade

Researchers found that the increased expression of p66shc was observed in non-alcoholic fattly liver disease (NAFLD) models and catalpol could inhibit p66shc expression to ameliorate NAFLD effectively. However, the underlying mechanisms remained unknown. The aim of the present study was to investigate the p66shc-targeting miRNAs in regulating oxidative stress and hepatic steatosis, also the mechanisms of catalpol inhibiting NAFLD. [Aging (Albany NY)] Full Article

TBBPA Regulates Calcium-Mediated Lysosomal Exocytosis and Thereby Promotes Invasion and Migration in Hepatocellular Carcinoma

The authors investigated the potential effects of tetrabromobisphenol A (TBBPA) on a metastatic phenotype of hepatocellular carcinoma cell line-HepG2. Results revealed that TBBPA significantly promoted the migration and invasion via affecting the number and distribution of lysosomes in HepG2 cells in a dose-dependent manner. [Ecotoxicol Environ Saf] Abstract | Graphical Abstract

Long Noncoding RNA DUXAP8 Contributes to the Progression of Hepatocellular Carcinoma via Regulating miR-422a/PDK2 Axis

Expression levels of double homeobox A pseudogene 8 (DUXAP8) in hepatocellular carcinoma (HCC) tissue samples were measured using qRT-PCR. The association between pathological indexes and the expression of DUXAP8 was also analyzed. Human HCC cell lines SMMC‐7721 and QSG‐7701 were used in in vitro studies. CCK‐8 assay was used to assess the effect of DUXAP8 on HCC cell line proliferation. [Cancer Med] Full Article

Acetaminophen-Induced Hepatotoxicity of Cultured Hepatocytes Depends on Timing of Isolation From Light-Cycle Controlled Mice

The sensitivity toward acetaminophen-induced hepatotoxicity depended on the circadian rhythm of the expression of acetaminophen-metabolizing genes and intracellular glutathione levels in primary cultured hepatocytes. These results obtained from cultured cells corresponded to those in mice, suggesting that the timing of hepatocyte isolation was important when investigating drug metabolism and toxicity tests in culture. [Genes Cells] Abstract

A Comparative Investigation of the Ability of Various Aptamer-Functionalized Drug Nanocarriers to Induce Selective Apoptosis in Neoplastic Hepatocytes: In Vitro and In Vivo Outcome

Scientists investigated the comparative potential of L5 with some other previously reported liver cancer cell-specific aptamers, conjugated on the surface of drug-nanocarriers. Various in vitro studies such as cytotoxicity, in vitro cellular uptake, cell cycle analysis, and investigations related to apoptosis were performed. [AAPS PharmSciTech] Abstract

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New Landscapes and Horizons in Hepatocellular Carcinoma Therapy

The authors discuss further advances beyond sorafenib that target additional signaling pathways and immune checkpoint proteins. The scenario of possible systemic therapies for patients with advanced HCC has changed dramatically in recent years. [Aging (Albany NY)] Abstract

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Three U of T Researchers Win Polanyi Prize for Work in Astronomy, English and Medicine

Mamatha Bhat became fascinated with the liver as a resident in gastroenterology at McGill University during her hepatology rotation. Now, her research focuses on how to ensure the long-term health of patients after they undergo a liver transplant. [University of Toronto] Press Release

Feds Fund Innovative Health Research Happening at DAL, NSHA and IWK

Dalhousie University is home to four of the newest recipients of funding from the Government of Canada for their innovative health research. The $1,159,527 in funding is provided by the Canadian Institutes of Health Research (CIHR) Project Grants, which help researchers gather the kind of information they need to make real improvements to clinical practice, health service delivery, and public health policy. [Dalhousie University] Press Release

Why Did a Chinese University Hire Charles Lieber to Do Battery Research?

Among the ongoing mysteries surrounding last week’s arrest of Harvard University nanoscientist Charles Lieber is the precise nature of the research program Lieber was conducting in his cooperation with Chinese researchers. [ScienceInsider] Editorial

Cash from Cannabis Companies Creates Conflicted Researchers

Imagine that scientists charged with doing research on tobacco’s health implications were funded by tobacco companies. In fact, the tobacco industry used this tactic for decades to cast doubt on the adverse health effects of smoking. But today it would be an outrageous conflict of interest – research on addictive drugs shouldn’t be paid for by people who stand to profit from selling them. Yet this is exactly what is happening with cannabis. [STAT News] Editorial

NEW Asthma: Making New Discoveries into Better Therapies
April 2-6, 2020
Snowbird, Utah, United States

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NEW Postdoctoral Fellow – Fatty Liver Dieases (University of Kansas Medical Center)

Postdoctoral Fellow – Diabetes and Fatty Liver Disease (NIH National Heart, Lung, and Blood Institute)

Postdoctoral Position – Culturing ‘Foie Gras’ (KU Leuven)

Team Leader – Cholangiocytes (Miromatrix Medical)

Postdoctoral Fellow – Cell Therapy for Liver Repair (University of Edinburgh)

Program Leader – Propionic Acidemia Research (None)

Postdoctoral Fellow – Metabolic Dysfunction (Lewis Katz School of Medicine)

Postdoctoral Researchers – MicroRNAs in NAFLD (Weill Cornell Medicine)

Postdoctoral Fellow – Translational Cancer Research (University of New Mexico Comprehensive Cancer Center)

Research Associate – Liver Damage (University of Colorado Denver)

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