Hepatic Cell News Volume 3.08 | Mar 8 2019

TOP STORY

Hepatocytes Direct the Formation of a Pro-Metastatic Niche in the Liver

Researchers showed that hepatocytes coordinate myeloid cell accumulation and fibrosis within the liver and, in doing so, increased the susceptibility of the liver to metastatic seeding and outgrowth. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Improving Drug Discovery by Nucleic Acid Delivery in Engineered Human Microlivers

The authors applied a new modality to a previously established, functionally stable, multi-well bioengineered microliver-fabricated from primary human hepatocytes and supportive stromal cells—in order to advance both small molecule and nucleic acid therapeutic pipelines. [Cell Metab] Full Article | Press Release | Graphical Asbtract

MITA1, a Novel Energy Stress-Inducible lncRNA, Promotes Hepatocellular Carcinoma Metastasis

Scientists identifed a novel long non-coding RNAs (lncRNA), termed metabolism-induced tumor activator 1 (MITA1), which is upregulated in hepatocellular carcinoma and contributed to metastasis. MITA1, a chromatin-enriched lncRNA discovered by nuclear RNA sequencing, is significantly induced by energy stress. [Hepatology] Abstract

Stabilized Peptide HDAC Inhibitors Derived from HDAC1 Substrate H3K56 for the Treatment of Cancer Stem-Like Cells In Vivo

Investigators showed designed peptides exerted superior anti-proliferation effects on cancer stem-like cells with minimal toxicity to normal cells compared to the small molecular inhibitor SAHA, which showed nonspecific toxicity to normal and cancer cells. These peptide inhibitors also inactivated cellular HDAC1 and HDAC6, and disrupted the formation of the HDAC1, LSD1, and CoREST complex. [Cancer Res] Full Article

Amplification of SMYD3 Promotes Tumorigenicity and Intrahepatic Metastasis of Hepatocellular Carcinoma via Upregulation of CDK2 and MMP2

Researchers results showed that overexpression of SMYD3 increased, while silencing of SMYD3 inhibited, cell proliferation, invasiveness and tumorigenicity both in vitro and in vivo. SMYD3 also promotes intrahepatic metastasis of hepatocellular carcinoma cells. [Oncogene] Abstract

Targeting c-MET by Tivantinib through Synergistic Activation of JNK/c-Jun Pathway in Cholangiocarcinoma

The inhibition of aberrant c-MET expression in human cholangiocarcinoma cell lines was achieved by blocking the phosphorylation of c-MET with tivantinib. Notable losses in cell viability and colony-forming capability were detected. [Cell Death Dis] Full Article

Extensive Reprogramming of the Nascent Transcriptome during iPSC to Hepatocyte Differentiation

Investigators demonstrated that a large fraction of hepatocyte-specific genes are regulated at transcriptional level and identify hundreds of differentially expressed non-coding RNAs, including primary miRNAs and long non-coding RNAs. They also identified sets of transcriptional regulators that might drive transcriptional changes during hepatocyte differentiation. [Sci Rep] Full Article

FGF Signal Is Not Required for Hepatoblast Differentiation of Human iPS Cells

The authors examined the roles of bone morphogenetic proteins and fibroblast growth factors (FGFs) in the hepatoblast differentiation from human induced pluripotent stem (iPS) cells . The gene expression levels of hepatoblast markers were upregulated by the removal of FGFs. In addition, the percentages of hepatoblast markers-positive cells were increased by the removal of FGFs. [Sci Rep] Full Article

Small Molecule IVQ, as a Prodrug of Gluconeogenesis Inhibitor QVO, Efficiently Ameliorates Glucose Homeostasis in Type 2 Diabetic Mice

4-[2-(1H-indol-3-yl)vinyl]quinoline (IVQ) did not inhibit the hepatic glucose production in primary hepatocytes in vitro. Pharmacokinetic studies demonstrated that (E)-3-(2-(quinoline-4-yl)vinyl)-1H-indol-6-ol (IVQ) was quickly converted to QVO in mice and rats following administration. [Acta Pharmacol Sin] Abstract

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Cholangiocyte Pathobiology

The authors highlight advances in cholangiocyte research, especially their role in development and liver regeneration, their functional and biochemical heterogeneity, their activation and involvement in inflammation and fibrosis and their engagement with the immune system. [Nat Rev Gastroenterol Hepatol] Abstract

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Alnylam Reports Positive Topline Results from Envision Phase III Study of Givosiran in Acute Hepatic Porphyria

Alnylam Pharmaceuticals, Inc. announced that the ENVISION Phase III study of givosiran, an investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 in development for the treatment of acute hepatic porphyria, met its primary efficacy endpoint and the majority of secondary endpoints. [Alnylam Pharmaceuticals, Inc.] Press Release

MYR Pharma Announces Grant of Promising Innovative Medicine (PIM) Designation by British MHRA for Bulevirtide (Myrcludex), the First-in-Class Entry Inhibitor for Treatment of Chronic Hepatitis D Infections

MYR Pharma announced that the British Medicines and Healthcare products Regulatory Agency has issued the Promising Innovative Medicine designation for MYR’s lead compound bulevirtide. [MYR Pharma (PR Newswire Association LLC)] Press Release

Study Finds Gender Imbalances in First-Time NIH Awards

Women receiving their first research grant from the National Institutes of Health are awarded an average of $39,000 less than men, according to an analysis published in JAMA. [The Scientist] Editorial

Head of US Food and Drug Agency Resigns

Scott Gottlieb, the head of the US FDA, resigned on 5 March and will depart the agency in one month. [Nature News] Editorial | Opinion

NEW NAFLD Summit 2019
September 26, 2019
Sevilla, Spain

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

NEW Postdoctoral Position – Hepatitis C Virus Vaccine Research (TWINCORE – Centre for Experimental and Clinical Infection Research)

Postdoctoral Position – Non-Alcoholic Fatty Liver Disease (University of California, San Diego)

Assistant Professor – Computational Biology/Stem Cell Biology (University of Illinois at Chicago)

Postdoctoral Research Associate – Liver DIseases (University of Illinois at Chicago)

Senior Research Scientist – Nonalcoholic Steatohepatitis (Gilead Sciences, Inc)

Postdoctoral Position – Non-Alcoholic Fatty Liver Disease (London Foundation for Liver Research)

Postdoctoral Research Scientist – Cancer Biology (The Beatson Institute for Cancer Research)

Assistant/Associate Professor – Cancer Biology (Virginia Commonwealth University)

Postdoctoral Researcher – Cancer Biology (University of California, San Francisco)

Postdoctoral Positions – Development & Progression of Cancer (Rutgers Cancer Institute of New Jersey)

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