Intestinal Cell News Volume 5.31 | Aug 23 2019

TOP STORY

Ketone Body Signaling Mediates Intestinal Stem Cell Homeostasis and Adaptation to Diet

Mechanistically, beta-hydroxybutyrate (βOHB) acted by inhibiting HDACs to reinforce Notch signaling, instructing intestinal stem cell (ISC) self-renewal and lineage decisions. Notably, although a high-fat ketogenic diet elevated ISC function and post-injury regeneration through βOHB-mediated Notch signaling, a glucose-supplemented diet had the opposite effects. [Cell] Abstract | Graphical Abstract | Press Release

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MYC Promotes Tryptophan Uptake and Metabolism by the Kynurenine Pathway in Colon Cancer

Compared with normal human colonic epithelial cells, colon cancer cells were more sensitive to the depletion of tryptophan. Blocking enzymes in the kynurenine pathway caused preferential death of established colon cancer cells and transformed colonic organoids. [Genes Dev] Abstract

Lead Optimization Yields High Affinity Frizzled 7-Targeting Peptides That Modulate Clostridium difficile Toxin B Pathogenicity in Epithelial Cells

Researchers report the discovery of high affinity peptides that selectively bound to frizzled 7 (FZD7) receptors. They describe an integrated approach for lead optimization, utilizing structure-based rational design and directed evolution, to enhance the peptide binding affinity while still maintaining FZD7 receptor selectivity. This work yielded new peptide leads with picomolar binding constants to FZD7 as measured by biophysical methods. [J Med Chem] Abstract

Downregulation of Eukaryotic Translation Initiation Factor 3b Inhibited Proliferation and Metastasis of Gastric Cancer

Investigators found that the downregulation of eukaryotic translation initiation factor 3 (eIF3b) could inhibit the proliferation and metastasis of gastric cancer cells by regulating the expression of cancer-related genes. In addition, the expression of eIF3b correlated with the stage and progression of gastric cancer and was shown to be upregulated in human chronic gastritis and in gastric cancer tissues compared with the expression of eIF3b in normal gastric tissues. [Cell Death Dis] Full Article

Enteroids Expressing a Disease-Associated Mutant of EpCAM Are a Model for Congenital Tufting Enteropathy

Mutant enteroids had reduced budding potential as well as significantly decreased mRNA expression for epithelial lineage markers, proliferation marker Ki67 and secretory pathway transcription factors. Significantly decreased numbers of Paneth and goblet cells were confirmed by staining. [Am J Physiol Gastrointest Liver Physiol] Abstract

Injectable Pegylated Niclosamide (Polyethylene Glycol-Modified Niclosamide) for Cancer Therapy

The pegylated niclosamide was synthesized and the chemical structure was identified by FTIR and ¹H NMR spectra. The anti-tumor activity was evaluated in CT26 and HCT116 colon cancer cells in vitro and nude mouse xenograft model of CT26 cells in vivo. [J Biomed Mater Res A] Abstract

Porcine Milk Exosome MiRNAs Attenuate LPS-Induced Apoptosis through Inhibiting TLR4/NF-κB and p53 Pathways in Intestinal Epithelial Cells

In vitro, exosomes inhibited lipopolysaccharide (LPS)-induced intestinal epithelial cell apoptosis. Porcine milk exosomes also decreased the LPS-induced TLR4/NF-κB signaling pathway activation. Furthermore, exosome miR-4334 and miR-219 reduced LPS-induced inflammation through the NF-κB pathway and miR-338 inhibited the LPS-induced apoptosis via the p53 pathway. [J Agric Food Chem] Abstract

Overexpression of LINC01082 Suppresses the Proliferation, Migration and Invasion of Colon Cancer

RT-qPCR for LINC01082 expression in tissues and cells were performed. CCK-8 assay for proliferation of colon cancer, Transwell assay for migration and invasion were carried out in SW480 and SW620 cells. The results revealed that LINC01082 was significantly decreased in tissues and cell lines of colon cancer. [Mol Cell Biochem] Abstract

mTOR-Dependent Stimulation of IL20RA Orchestrates Immune Cell Trafficking through Lymphatic Endothelium in Patients with Crohn’s Disease

Scientists isolated human intestinal lymphatic endothelial cells (HILECs) from surgical specimens of patients undergoing resection for complicated Crohn’s disease and from a disease-free margin of surgical specimens of patients undergoing resection for cancer. Both cell types underwent transcriptomic profiling, and their barrier functionality was tested using a transwell-based co-culture system between HILEC and lamina propria mononuclear cells. [Cells] Full Article

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Multitasking Kinase RIPK1 Regulates Cell Death and Inflammation

The authors focus on which signaling pathways use receptor-interacting serine threonine kinase 1 (RIPK1), how activation of RIPK1 is regulated, and when activation of RIPK1 appears to be an important driver of inflammation. [Cold Spring Harb Perspect Biol] Abstract

Influence of Growth Hormone and Glutamine on Intestinal Stem Cells: A Narrative Review

Investigators summarize the evidence of the actions of growth hormone (GH) and/or glutamine (Gln) on crypt cells and intestinal stem cells (ISCs) in the literature. Overall, most studies demonstrated that GH and Gln in combination exert synergistic effects to activate the proliferation of crypt cells and ISCs and enhance crypt organoid formation and mucosal growth. [Nutrients] Full Article

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First Patient Enrolled in Abivax ABX464-103 Phase IIb Clinical Trial in Patients with Ulcerative Colitis

Abivax announced that the first patient was enrolled in its Phase IIb clinical trial of ABX464 with once a day convenient oral dosing for treatment of patients with moderate to severe active ulcerative colitis. In total, the clinical trial will be conducted in over 15 countries in Europe and in Canada. [Abivax] Press Release

LONSURF^® (Trifluridine/Tipiracil) Receives Positive Opinion from CHMP in the EU for Patients with Previously Treated Metastatic Gastric Cancer

Servier and its partner Taiho Pharmaceutical Co., Ltd announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has issued a positive opinion for LONSURF^® as monotherapy for the treatment of adult patients with metastatic gastric cancer including adenocarcinoma of the gastroesophageal junction, who have been previously treated with at least two prior systemic treatment regimens for advanced disease. [Servier (Business Wire, Inc.)] Press Release

Learn the basics of culturing mouse intestinal organoids with an instructional video series. Watch the Video Now

uBiome’s Underlying Data Tainted with Samples from Infants, Pets: Report

A report from Business Insider details how deficiencies in uBiome’s company’s database— including the presence of data from dozens of minors, infants and at least one animal in its analysis of collected fecal samples- could make the results of its clinical tests unreliable. [FierceBiotech] Editorial

As Brexit Nears, Britain’s Drugs, Devices and Pricing Regulators Seek the Exit

Firm details on exactly how the UK will regulate new medicines is still to be decided after it leaves the EU later this year (caveats on timing abound), but we now know that the regulator won’t be run by Dr. Ian Hudson, who is stepping down after six years in charge. [FierceBiotech] Editorial

NEW Cell Death in Immunity and Inflammation
October 6-9, 2019
Crete, Greece

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NEW Senior Researcher – Inflammatory Diseases (Genentech, Inc.)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

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

Research Assistant – Pathophysiology of Enteroviruses (University of Cambridge)

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

Postdoctoral Fellow – Quantifying Intra-tumour Heteregeneity with Multi-Omics Data (The Institute of Cancer Research)

Postdoctoral Fellow – Designer Probiotics (Massacheusetts General Hospital)

Postdoctoral Fellow – Multi-Omics in Intra-Tumor Heteregenity (The Institute of Cancer Research)

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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