Hepatic Cell News Volume 3.34 | Sep 13 2019

TOP STORY

CPAP Promotes Angiogenesis and Metastasis by Enhancing STAT3 Activity

Mechanical investigation showed that the expression level of centrosomal P4.1-associated protein (CPAP) was positively correlated with activated STAT3 in hepatocellular carcinoma. CPAP acted as a transcriptional coactivator of STAT3 by directly binding with STAT3. Interrupting the interaction between CPAP and STAT3 attenuated STAT3-mediated tumor growth and angiogenesis. [Cell Death Differ] Full Article

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Role of Regulatory T Cells and Effector T Cell Exhaustion in Liver-Mediated Transgene Tolerance in Muscle

Scientists characterized liver-induced transgene tolerance after simultaneous transduction of liver and muscle. A clinically relevant transgene, α-sarcoglycan, mutated in limb-girdle muscular dystrophy type 2D, was fused with the SIINFEKL epitope and expressed with adeno-associated virus vectors (AAV-hSGCA-SIIN). Intramuscular delivery of AAV-hSGCA-SIIN resulted in a strong inflammatory response, which could be prevented and reversed by concomitant liver expression of the same antigen. [Mol Ther Methods Clin Dev] Abstract | Full Article

SREBP-1 Inhibitor Betulin Enhances the Antitumor Effect of Sorafenib on Hepatocellular Carcinoma via Restricting Cellular Glycolytic Activity

Mechanistical studies revealed that the inhibition of SREBP-1 via its inhibitor Betulin suppressed cellular glucose metabolism. In addition to the reduced glycolytic activity, a thwarted metastatic potential was observed in hepatacelluar carcinoma cells upon Betulin administration. [Cell Death Dis] Full Article

High Throughput circRNA Sequencing Analysis Reveals Novel Insights into the Mechanism of Nitidine Chloride against Hepatocellular Carcinoma

In vitro experiments showed that two circRNAs inhibited the malignant biological behaviour of hepatocellular carcinoma cells (HCC), suggesting that they may play important roles in the development of HCC. To elucidate whether the two circRNAs functioned as “miRNA sponges” in HCC, scientists identified circRNA-miRNA and miRNA-mRNA interactions by using CircInteractome and miRwalk, respectively. [Cell Death Dis] Full Article

Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling

Investigators generated and characterized a hepatic organoid (eHEPO) culture system using human induced pluripotent stem cell-derived EpCAM-positive endodermal cells as an intermediate. eHEPOs could be produced within two weeks and expanded long term without any loss of differentiation capacity to mature hepatocytes. [Stem Cell Reports] Full Article | Graphical Abstract

miR-146a Deficiency Accelerates Hepatic Inflammation without Influencing Diet-Induced Obesity in Mice

Adipocyte apoptosis, adipose tissue collagen and macrophage accumulation as detected by TUNEL, Picro Sirius and F4/80 immunostaining, respectively, were comparable between two groups of mice. Although miR-146a deficiency had no influence on high fat diet-induced hepatic lipid accumulation, interestingly, it significantly increased obesity-induced inflammatory responses in liver tissue. [Sci Rep] Full Article

Liver Sinusoidal Endothelial Cell ICAM-1 Mediated Tumor/Endothelial Crosstalk Drives the Development of Liver Metastasis by Initiating Inflammatory and Angiogenic Responses

Investigators performed in vitro co-cultures and an in vivo model of liver metastasis of colorectal cancer. ICAM-1 blockade in liver sinusoidal endothelial cells (LSECs) decreased the adhesion and transmigration of tumor cells through an LSEC in vitro and vivo. Co-cultures of C26 cells and LSECs contained higher amounts of IL-1β, IL-6, PGE-2, TNF-α and ICAM-1 than monocultures. [Sci Rep] Abstract

Leptin-Derived Peptides Block Leptin-Induced Proliferation by Reducing Expression of Pro-Inflammatory Genes in Hepatocellular Carcinoma Cells

The authors examined the effects of OB3 and [D-Leu-4]-OB3 on cell proliferation and gene expressions in human hepatacelluar carcinoma cells cell cultures. In contrast to what was reported for leptin, OB3 and [D-Leu-4]-OB3 reduced cell proliferation in hepatomas. [Food Chem Toxicol] Abstract

LncRNA NEAT1 Promotes Hepatic Lipid Accumulation via Regulating miR-146a-5p/ROCK1 in Nonalcoholic Fatty Liver Disease

HepG2 cells were treated by free fatty acids and C57BL/6J mice were treated by high-fat diet to establish nonalcoholic fatty liver disease in vitro and in vivo models, respectively. Cell transfection was applied to regulate the expression of NEAT1, ROCK1, and miR-146a-5p. [Life Sci] Abstract

Inflammatory Microenvironment Contributes to Stemness Properties and Metastatic Potential of Hepatocellular Carcinoma via NF-κB/miR-497/SALL4 Axis

Researchers discovered that miR-497 directly targeted SALL4 and negatively regulated its expression, and further inhibited the self-renewal and metastasis of hepatacelluar carcinoma cells (HCC); more importantly, inflammatory factor TNFα inhibited the expression of miR-497 via NF-kB mediated negative transcriptional regulation, and simultaneously up-regulated the expression of SALL4 and promoted self-renewal and metastasis phenotype of HCC cells. [Mol Ther Oncolytics] Abstract | Full Article

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Clinical Considerations for Capsid Choice in the Development of Liver-Targeted AAV-Based Gene Transfer

The authors examine the body of evidence across trials to determine the possible influences of serotype choice on key clinical outcomes such as safety, vector clearance, treatment eligibility, occurrence of transaminase elevations, activation of capsid-directed cytotoxic T-cell responses and clinical efficacy. [Mol Ther Oncolytics] Abstract | Full Article

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Tiziana Life Sciences Reports Positive Phase IIa Clinical Data Exhibiting Positive Clinical Activity with Milciclib Monotherapy in Advanced Sorafenib-Refractory or -Intolerant Patients with Unresectable or Metastatic Hepatocellular Carcinoma

Tiziana Life Sciences plc announced additional positive Phase IIa clinical data exhibiting impressive clinical activity of Milciclib monotherapy in patients with advanced Sorafenib-resistant or -intolerant patients with unresectable or metastatic hepatocellular carcinoma. [Tiziana Life Sciences plc] Press Release

Fractyl Announces Positive Topline Results in the Revita-2 Clinical Trial in Patients with Type 2 Diabetes and Nonalcoholic Fatty Liver Disease

Fractyl Laboratories Inc. announced positive topline results from Revita-2, the first randomized, double-blind, sham-controlled, multicenter clinical trial of Fractyl’s Revita™ DMR. Data from patients with type 2 diabetes with and without nonalcoholic fatty liver disease show that Revita DMR, a minimally invasive, outpatient procedural therapy that resurfaces the duodenal mucosa, is safe and effective relative to a sham procedure. [Fractyl Laboratories Inc.] Press Release

Science under Maximum Pressure in Iran

Research scientists Shahin Akhondzadeh received a novel reason why a journal was unable to publish his work: his nationality. Akhondzadeh is Iranian and works at the Tehran University of Medical Science. And for the US-based journal and its publisher, that made him a persona non grata. [The Scientist] Editorial

Clubby and ‘Disturbing’ Citation Behavior by Researchers in Italy Has Surged

The rate at which scientists in Italy cite themselves and their compatriots is rising faster than in ten other developed countries, according to a new study. The surge in Italy’s clubby citation behavior is likely the result of a 2010 law requiring productivity standards for academic recruitment or promotion, the study authors say. [ScienceInsider] Editorial

EU Research Commissioner Named, but Lacks ‘Research’ in Her Title

Mariya Gabriel, a conservative politician from Bulgaria, is slated to become the next European research chief- although her job title, unlike that of her predecessors, doesn’t include the words “research” or “science.” Some researchers and science policy experts worry the new job title could signal a reduced standing for science within von der Leyen’s proposed executive branch for the European Union, made up of 26 commissioners. [ScienceMagazine] Editorial

NEW Cancer Evolution and Combinatorial Cancer Therapies: Concepts and Challenges
January 19-23, 2020
Banff, Alberta, Canada

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NEW Postdoctoral Researcher – Liver Cell-Cell Interactions (Flanders Institute for Biotechnology)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Research Technologist – Intestinal Stem Cell Biology (STEMCELL Technologies Inc.)

Group Leader – Immunology (University Hospital Düsseldorf)

Postdoctoral Researcher – Liver Disease (Albert Einstein College of Medicine)

Senior Researcher – Inflammatory Diseases (Genentech, Inc.)

Postdoctoral Researcher – Microbiome in IBD (GIGA-Medical Genomics Unit)

Postdoctoral Fellow – Designer Probiotics (Massachusetts General Hospital)

Postdoctoral Researchers – Microbiota in Neonatal Immunity and Imprinting (Institut Pasteur)

Principal Researcher – Systems Disease Biology (Boehringer Ingelheim)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

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