Intestinal Cell News Volume 5.13 | Apr 12 2019

TOP STORY

Potent and Selective Caspase-2 Inhibitor Prevents MDM-2 Cleavage in Reversine-Treated Colon Cancer Cells

Researchers used their hybrid combinatorial substrate library approach to broadly profile caspase-2 substrate specificity using peptide scanning libraries. This screen uncovered previously unknown caspase-2 peptidyl substrate preferences, which were further used to develop caspase-2 selective fluorogenic substrates and covalent, irreversible AOMK inhibitors. [Cell Death Differ] Abstract

(Ranked by impact factor of the journal)

TNFα Promotes Mucosal Wound Repair through Enhanced Platelet Activating Factor Receptor Signaling in the Epithelium

Investigators showed that TNFα promoted intestinal mucosal repair through upregulation of the GPCR platelet activating factor receptor (PAFR) in the intestinal epithelium. Platelet activating factor was increased in healing mucosal wounds and its engagement with epithelial PAFR leads to activation of epidermal growth factor receptor, Src and Rac1 signaling to promote wound closure. [Mucosal Immunol] Full Article

Division of Labor: Roles of Groucho and CtBP in Notch-Mediated Lateral Inhibition That Controls Intestinal Stem Cell Differentiation in Drosophila

Investigators showed that the establishment of lateral inhibition between intestinal stem cell-differentiating enteroblasts required two evolutionarily conserved transcriptional co-repressors Groucho and C-terminal binding protein that acted differently. [Stem Cell Reports] Full Article

B7-H3 Promotes Aerobic Glycolysis and Chemoresistance in Colorectal Cancer Cells by Regulating HK2

The authors found that overexpression of B7-H3 effectively increased the rate of glucose consumption and lactate production, whereas knockdown of B7-H3 had the opposite effect. Furthermore, they showed that B7-H3 increased glucose consumption and lactate production by promoting hexokinase 2 (HK2) expression in colorectal cancer (CRC) cells, and they also found that HK2 was a key mediator of B7-H3-induced CRC chemoresistance. [Cell Death Dis] Full Article

Chemotherapeutic and Antiangiogenic Drugs beyond Tumor Progression in Colon Cancer: Evaluation of the Effects of Switched Schedules and Related Pharmacodynamics

Proliferation assays were achieved in vitro on different colon cancer cell lines exposed to SN-38 and sunitinib alone or in combination. ABCG2 gene expression was performed with real-time PCR and SN-38 intracellular concentrations were measured. [Biochem Pharmacol] Abstract | Graphical Abstract

Polymeric Lids for Microcontainers for Oral Protein Delivery

Lysozyme was chosen as model protein and loaded into microcontainers with the permeation enhancer sodium decanoate. The loaded microcontainers were sealed and functionalized by applying polymeric lids onto the cavity of the devices. The first lid was poly(lactic-co-glycolic) acid and on top of this either polyethylene glycol or chitosan was applied. [Macromol Biosci] Abstract

Unique Gene Expression Signatures in the Intestinal Mucosa and Organoids Derived from Germ-Free and Monoassociated Mice

Scientists used cDNA microarrays to determine the gene expression signature of mucosa isolated from the small intestine and colon of germ-free (GF) mice and animals monoassociated with two E. coli strains. The results were compared to the expression data obtained in conventionally reared (CR) mice. In addition, they analyzed gene expression in colon organoids derived from CR, GF, and monoassociated animals. [Int J Mol Sci] Full Article

Anticancer Profile of Newly Synthesized BRAF Inhibitors Possess 5-(Pyrimidin-4-yl)imidazo[2,1-B]thiazole Scaffold

The pyrimidine ring containing either amide or sulphonamide moiety attached to a linker (ethyl or propyl) at position 2 of the pyrimidine ring. The final compounds were selected by NCI for in vitro cytotoxicity screening. Most derivatives showed cytotoxic activity against colon cancer and melanoma cell lines. [Bioorg Med Chem] Abstract | Graphical Abstract

Phenotypic Heterogeneity of 2D Organoid Reflects Clinical Tumor Characteristics

The authors established primary cultured organoid in 2D culture (2D organoid; 2DO) in a reproducible manner and with clinical phenotypic heterogeneity. The 2DO contained cancer stem cells (CSCs) expressing CD44 and CD133. The addition of basic fibroblast growth factor and transforming growth factor-β as niche factors was necessary to establish the 2DO and maintain the CSC population. [Biochem Biophys Res Commun] Abstract

Dimethyl Sulfoxide Extract of Dianthus carmelitarumInduces S Phase Arrest and Apoptosis in Human Colon Cancer Cells

Researchers evaluated the phenolic characterization and the cytotoxic effect of D. carmelitarum on human colon cancer cells and the possible mechanisms involved. Total polyphenolic contents and phenolic characterization of the extract were evaluated using the Folin-Cioceltau method and reversed-phase high performance liquid chromatography, respectively. [Nutr Cancer] Abstract

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Emerging Roles of Bile Acids in Mucosal Immunity and Inflammation

The authors discuss the three-dimensional interplay between bile acids, the microbiota, and the mucosal immune system, focusing on the mechanisms that regulate intestinal homeostasis and inflammation. Although the functions of bile acids in mucosal immune regulation are only beginning to be appreciated, targeting bile acids and their cellular receptors has already proven an important area of new drug discovery. [Mucosal Immunol] Full Article

Mucus and Mucins in Diseases of the Intestinal and Respiratory Tracts

The inner of the two mucus layers of colon is normally impenetrable to bacteria, keeping the commensals away from and protecting the epithelium. This impenetrable property is dependent on the bacterial composition and the host diet, observations that can explain the increased incidence of inflammatory bowel diseases in the western world as bacteria reach the epithelial cells in active ulcerative colitis. [J Intern Med] Abstract | Full Article

ILC3 Function as a Double-Edged Sword in Inflammatory Bowel Diseases

Investigators feature the group 3 innate lymphoid cells’ (ILC3) development, biological function, maintenance of gut homeostasis, mediation of IBD occurrence, and potential application to IBD therapy. [Cell Death Dis] Full Article

Visit our reviews page to see a complete list of reviews in the intestinal cell research field.

Innovate Biopharmaceuticals Presents Oral Poster Demonstrating Positive Effect of Larazotide on Reduced Intestinal Permeability in a NASH Preclinical Study

Innovate Biopharmaceuticals, Inc. announced that data demonstrating proof-of-concept in an established model of nonalcoholic steatohepatitis (NASH) will be presented. There are currently no treatments for nonalcoholic fatty liver disease or NASH approved by the FDA. [Press release from Innovate Biopharmaceuticals, Inc. discussing research presented at the International Liver Congress™ 2019, Vienna] Press Release

Dr. James Wells presents his group’s work on hPSC-derived GI organoids and their use for studying disease. Watch Now

Fe3 Medical Completes First Human Study of Electric Transdermal Iron Patch

Fe3 Medical is moving forward with its wearable patch that uses electrical current to deliver iron directly through the skin to treat one of the world’s most common deficiencies. For many people with Crohn’s disease, IBD or gastric bypass operations, it can be hard to maintain sufficient levels of iron in the bloodstream. [FierceBiotech] Press Release

Signum Surgical Receives €3.6 Million in Grant Funding to Support Launch of Therapy for Patients with a Common Colorectal Disease

Signum Surgical announced the company has secured €3.6 million ($4 million) through two grant funding awards. The grants include €2.3 million from the European Union Horizon 2020 SME Instrument, and €1.3 million from Ireland’s Disruptive Technologies Innovation Fund. [Signum Surgical (Business Wire, Inc.)] Press Release

ImmunogenX Receives Major Grant from the National Institutes of Health (NIH) to Conduct a Clinical Trial for Latiglutenase

The NIH’s National Institute of Allergy and Infectious Diseases has awarded a grant to ImmunogenX to conduct a Phase II trial for latiglutenase, an investigational drug for celiac disease. The study will be conducted at multiple study centers including the Mayo Clinic and Columbia University. [ImmunogenX, LLC.] Press Release

Impact Factors Are Still Widely Used in Academic Evaluations

About 40% of institutes with a strong focus on research mention impact factors in documents used in the review, promotion and tenure process, according to the analysis, which examined more than 800 documents across 129 institutions in the United States and Canada. [Nature News] Editorial

FDA, New York Attorney General Go After Stem Cell Clinics

On April 3, the FDA sent letters to 20 companies providing stem cell treatments, reports The New York Times, reminding them that they may require FDA approval and should take action to comply. The agency also issued a warning to a stem cell company for violating good manufacturing practices. [The Scientist] Editorial

NEW World Congress on Gastrointestinal Cancer
July 3-6, 2019
Barcelona, Spain

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

NEW Postdoctoral Position – Functional Genomics of IBS (Wellcome Sanger Institute)

NEW Postdoctoral Position – Intestinal Epithelial Barrier in Autoimmune Diseases (BioMed X Innovation Center)

NEW Postdoctoral Position – Oesophago-Gastric Cancer Research (University of Cambridge)

Postdoctoral Position – IBS and Autoimmune Disease (National Research Council of Canada)

Postdoctoral Position – Animal Genomics & IBD (University of Liège)

Graduate Student Position – Breast & Colorectal Cancer Research (Dalhousie University)

Postdoctoral Fellow – Inflammatory Bowel Disease Research (University of Toronto)

Postdoctoral Fellow – Functional Genomics & IBD (Wellcome Sanger Institute)

Postdoctoral & Research Associate Positions – Biology of Intestinal & Colon Stem Cells & Gastrointestinal Cancer (Johns Hopkins University)

Associate Professor – Oncology (University of California, Davis)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

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