Hepatic Cell News Volume 3.46 | Dec 6 2019

TOP STORY

Type 1 Innate Lymphoid Cells Protect Mice from Acute Liver Injury via Interferon-γ Secretion for Upregulating Bcl-XL Expression in Hepatocytes

The authors demonstrated that carbon tetrachloride injection into mice activated type 1 innate lymphoid cells (ILC1s), but not natural killer cells, in the liver. Activated ILC1s produced interferon-γ and protected mice from CCl 4-induced acute liver injury. IFN-γ released from activated ILC1s promoted the survival of hepatocytes through upregulation of Bcl-xL. [Immunity] Abstract | Graphical Abstract

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Maintenance of Primary Hepatocyte Functions In Vitro by Inhibiting Mechanical Tension-Induced YAP Activation

Researchers found that mechanical tension-induced yes-associated protein activation triggers hepatocyte dedifferentiation. Alleviation of mechanical tension by confining cell spreading is sufficient to inhibit hepatocyte dedifferentiation. [Cell Rep] Full Article | Graphical Abstract

Quantitative In Vivo Proteomics of Metformin Response in Liver Reveals AMPK-Dependent and -Independent Signaling Networks

Despite significant effort, the molecular basis for metformin response remains poorly understood, with a limited number of specific biochemical pathways studied to date. To broaden our understanding of hepatic metformin response, they combined phospho-protein enrichment in tissue from genetically engineered mice with a quantitative proteomics platform to enable the discovery and quantification of basophilic kinase substrates in vivo. [Cell Rep] Abstract | Graphical Abstract

3D Bioprinting of Liver Spheroids Derived from Human Induced Pluripotent Stem Cells Sustain Liver Function and Viability In Vitro

Investigators evaluated the impacts of using single cell dispersion of iPS-derived parenchymal versus using induced-pluriptent derived hepatocyte-like cells spheroids, both in combination with non-parenchymal cells, into final liver tissue functionality. Single cell constructs showed reduced cell survival and hepatic function and unbalanced protein/amino acid metabolism when compared to spheroid printed constructs after 18 days in culture. [Biofabrication] Full Article

SPIN1 Triggers Abnormal Lipid Metabolism and Enhances Tumor Growth in Liver Cancer

Tissue microarray showed that 75% of hepatocellular carcinoma (HCC) tissues were positive for SPIN1, which was highly expressed in clinical HCC samples and positively associated with malignancy of HCC. Strikingly, SPIN1 could modulate abnormal lipid metabolism by increasing intracellular triglycerides, cholesterols, and lipid droplets in hepatoma cells, which could remarkably enhance the proliferation of hepatoma cells. [Cancer Lett] Abstract

STMN1 Upregulation Mediates HCC and Hepatic Stellate Cells Crosstalk to Aggravate Cancer through Triggering MET Pathway

The authors analyzed STMN1 expression and the related clinical significance in hepatocellular carcinoma (HCC) by using well-established Protein Atlas, TCGA and GEO cancer databases. The analysis indicated that STMN1 was highly expressed in HCC and closely associated with vascular invasion, higher histological grade, advanced clinical grade and shorter survival time in HCC patients. [Cancer Sci] Abstract

Lotus Seedpod Extracts Reduced Lipid Accumulation and Lipotoxicity in Hepatocytes

Oleic acid (OA), an unsaturated fatty acid, was used to induce the phenotype of NAFLD in human hepatocytes, HepG2 cells. LSE dose-dependently improved the OA-induced viability loss of HepG2 cells. [Nutrients] Full Article

Inhibition of Proprotein Convertase Subtilisin/Kexin Type 9 Ameliorates Liver Fibrosis via Mitigation of Intestinal Endotoxemia

Researchers found that Proprotein convertase subtilisin/kexin type 9 (PCSK9) increased significantly in human and BDL mouse injured liver tissues, so did hepatocyte nuclear factor-1 alpha and SREBP2. No significant difference of plasma PCSK9 was observed. Inhibited PCSK9 using CRISPR-PCSK9 adeno-associated virus in BDL mice ameliorated liver inflammation and fibrosis, with LPS decrease in serum, without any change in intestinal wall integrity. [Inflammation] Abstract

Rapid Generation of Functional Hepatocyte-Like Cells from Human Minor Salivary Gland-Derived Stem Cells

Investigators explored a three-step protocol to rapidly induce human minor salivary gland mesenchymal stem cells into hepatocytes in vitro, and finally obtained hepatocyte-like cells within six days. After a series of relevant detection from gene, protein and functional levels, they confirmed that the finally induced cells were mature hepatocyte-like cells with certain hepatocyte functions to some extent. [Biochem Biophys Res Commun] Abstract

Platyconic Acid A, Platycodi Radix-Derived Saponin, Suppresses TGF-1-Induced Activation of Hepatic Stellate Cells via Blocking SMAD and Activating the PPAR Signaling Pathway

Researchers investigated the inhibitory effects of platyconic acid A (PA) on TGF-1-induced activation of hepatic stellate cells (HSCs). PA inhibited TGF-1-enhanced cell proliferation, as well as expression of -SMA and collagen 1 in HSC-T6 cells. PA suppressed TGF-1-induced smad2/3 phosphorylation and smad binding elements 4 luciferase activity. [Cells] Abstract | Download Full Article

Dickkopf-1 Contributes to Hepatocellular Carcinoma Tumorigenesis by Activating the Wnt/β-Catenin Signaling Pathway

Scientists investigated the clinical significance and biological functions of DKK1 in hepatocellular carcinoma (HCC). The expression of DKK1 was examined in cirrhotic and HCC tissues by immunohistochemistry and quantitative real-time PCR. DKK1 was silenced or overexpressed in HCC cell lines, and in vitro and in vivo studies were performed. [Signal Transduct Target Ther] Full Article

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Tumor Evolution in Hepatocellular Carcinoma

Studies using next-generation sequencing of multiple regions of the same tumor nodule suggest different patterns of HCC evolution and confirm the high molecular heterogeneity in a subset of patients. Different hypotheses have been proposed to explain tumor evolution, including clonal selection or neutral and punctuated acquisition of genetic alterations. [Nat Rev Gastroenterol Hepatol] Press Release

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Tetra Bio-Pharma Receives FDA Orphan Drug Designation for Hepatocellular Carcinoma

Tetra Bio-Pharma Inc. announced it has received FDA Orphan Drug Designation for delta-9-tetrahydrocannabinol in the treatment of hepatocellular carcinoma. [Tetra Bio-Pharma Inc.] Press Release

Cold Spring Harbor Lab Wins Grant for Cancer Research

Cold Spring Harbor Laboratory has won a $750,000 grant from TD Bank to support its new cancer research facility. The award is part of the TD Ready Challenge, an initiative to provide financial support to organizations that have developed solutions to improve detection and intervention of diseases. [Sacred Heart University] Press Release

Science Publishers Review Ethics of Research on Chinese Minority Groups

Two science publishers are reviewing the ethics of research papers in which scientists backed by China’s government used DNA or facial-recognition technology to study minority groups in the country, such as the predominantly Muslim Uyghur population. [Nature News] Editorial

What the United Kingdom’s ‘Brexit Election’ Means for Science

The United Kingdom’s three main political parties have each pledged to increase spending on science, ahead of a general election overshadowed by the country’s vote three and a half years ago to leave the European Union. [Nature News] Editorial

NEW Advances in Liquid Biopsies
January 13-16, 2020
Miami, Florida, United States

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NEW Postdoctoral Fellow – Liver Pathology (University of Illinois at Chicago)

NEW Professor – Hepatology (Jena University Hospital)

Postdoctoral Researcher – HIV and the Liver (Seattle’s Children’s Hospital)

Postdoctoral Researcher – High Throughput Microfluidic Drug Screening (National University of Ireland Galway)

Postdoctoral Researcher – Oncogenic Pathways (University of Liège)

Faculty Member – Pathogen-Associated Malignancies (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Drug-Induced Liver Injury (Johnson & Johnson)

Postdoctoral Researcher – Liver Disease Treatment (University of Southern Denmark)

Postdoctoral Researcher – Personalized Medicine (Mayo Clinic Center for Individualized Medicine)

Postdoctoral Scientist – RAS Cancer Biology (Genetech, Inc.)

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