Intestinal Cell News Volume 5.21 | Jun 14 2019

TOP STORY

A Comprehensive Structure-Function Study of Neurogenin3 Disease-Causing Alleles during Human Pancreas and Intestinal Organoid Development

Investigators utilized human tissue differentiated from NEUROG3^−/− pluripotent stem cells for functional analyses. Most disease-associated alleles had hypomorphic or null phenotype in both tissues, whereas the S171fsX68 mutation had reduced activity in the pancreas but largely null in the intestine. [Dev Cell] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

Lineage Tracing and Targeting of IL17RB⁺ Tuft Cell-Like Human Colorectal Cancer Stem Cells

Based on the analysis of mouse Dclk1⁺ tumor cells, the authors identified a cancer stem cell-specific cell surface marker in human colorectal cancers and validated the therapeutic effect of targeting it. IL17RB was distinctively expressed by Dclk1⁺ mouse intestinal tumor cells. Using Il17rb-CreERT2-IRES-EGFP mice, they showed that IL17RB marked intestinal tumor stem cells in an IL13-dependent manner. [Proc Natl Acad Sci USA] Abstract

GLI2 Modulated by SUFU and SPOP Induces Intestinal Stem Cell Niche Signals in Development and Tumorigenesis

Researchers investigated Hedgehog (Hh)-mediated mechanisms by analyzing mice deleted for key negative regulators of Hh signaling, Sufu and/or Spop, in the gut mesenchyme, and demonstrated their dosage-dependent roles. Although these mutants exhibited abnormal mesenchymal cell growth and functionally defective muscle layers, villification was completed with proper mesenchymal clustering, implying a permissive role for Hh signaling. [Cell Rep] Full Article | Graphical Abstract

SARI Attenuates Colon Inflammation by Promoting STAT1 Degradation in Intestinal Epithelial Cells

Bone marrow reconstitution experiments demonstrated that disease susceptibility was not dependent on the deficiency of SARI in the immune compartment but on the protective role of SARI in the intestinal epithelial cells. Furthermore, SARI deficiency enhanced chemokine ligand 2 production and knockout of CCR2 blocked the promoting role of SARI deficiency on colitis. [Mucosal Immunol] Abstract

A Novel YAP1/SLC35B4 Regulatory Axis Contributes to Proliferation and Progression of Gastric Carcinoma

Using the complementary DNA arrays, promoter reporter assays, and chromatin immunoprecipitation assays, scientists demonstrated that Solute carrier family 35 member B4 (SLC35B4) was directly transactivated by YAP1-TEADs complex in gastric cancer (GC) cells. CCK-8, plate colony formation and soft agar assays revealed that SLC35B4 was essential for survival and proliferation in GC cells and nude mice models. [Cell Death Dis] Full Article

Activation of PTEN by Inhibition of TRPV4 Suppresses Colon Cancer Development

Researchers demonstrated that transient receptor potential vanilloid type 4 (TRPV4) was upregulated in colon cancer and associated with poor prognosis. Contrary to the reported cell death-promoting activity of TRPV4 in certain cancer cells, TRPV4 positively regulated cell survival in human colon cancer in vitro and in vivo. [Cell Death Dis] Full Article

Development of a Novel Ex-Vivo 3D Model to Screen Amoebicidal Activity on Infected Tissue

The three chemically synthetized compounds T-001, T-011, and T-016, which act as amoebicides in vitro, were active in infected tissues, as they decreased the number of trophozoites, and provoked death by disintegration of the amoeba, similar to metronidazole. However, compound T-011 induced signs of cytotoxicity to liver slices. [Sci Rep] Full Article

Progesterone Decreases Gut Permeability through Upregulating Occludin Expression in Primary Human Gut Tissues and Caco-2 Cells

Progesterone treatment increased intestinal trans-epithelial electrical resistance in primary human colon tissues and Caco-2 cells in vitro through upregulating tight junction protein occludin expression. Furthermore, progesterone exhibited an inhibitory effect on nuclear factor kappa B activation following lipopolysaccharide stimulation in Caco-2 cells. [Sci Rep] Full Article

LINC00261 Suppresses Human Colon Cancer Progression via Sponging miR-324-3p and Inactivating the Wnt/β-Catenin Pathway

Investigators found LINC00261 was reduced in colon cancer cells. Meanwhile, overexpressed LINC00261 repressed colon cancer cell viability and proliferation capacity. In addition, colony cancer cell colony formation was inhibited and apoptosis was enhanced by upregulation of LINC00261. [J Cell Physiol] Abstract

Sirtuin 3 Silencing Impairs Mitochondrial Biogenesis and Metabolism in Colon Cancer Cells

The authors analyzed whether sirtuin 3 (SIRT3) silencing in colon cancer cells could affect mitochondrial biogenesis and impair mitochondrial function. For this purpose, metastatic colon cancer cell line SW620 was transfected with a specific shRNA against SIRT3 to obtain a stable knockdown. [Am J Physiol Cell Physiol] Abstract

Octreotide Remits Endoplasmic Reticulum Stress to Reduce Autophagy of Intestinal Epithelial Cell Line Caco-2 via Upregulation of miR-101

Protein associated with endoplasmic reticulum stress and autophagy was detected by western blot. microRNA (miR)-101 was examined by qRT-PCR. Besides, miR-101 or G protein-coupled receptor 78-silenced Caco-2 cells were established by transfection. [Life Sci] Abstract

The Response of Five Intestinal Cell Lines to Anoxic Conditions In Vitro

Scientists characterized the cellular response of commonly used cell cultures for the study of intestinal epithelial processes and colon cancer development under conventional normoxic conditions and in an anoxicenvironment generated in an anaerobic chamber. Anoxic conditions led to lower levels of oxidative stress, a reduction in GSH/GSSG ratio, the shift of the redox status to oxidized glutathione levels, reduced cell proliferation, decreased barrier function and higher glycolysis rates at the expense of oxidative respiration. [Biol Cell] Abstract

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Fecal Microbiota Transplantation as a New Therapy: From Clostridioides Difficile Infection to Inflammatory Bowel Disease, Irritable Bowel Syndrome, and Colon Cancer

Following newfound appreciation for the role of the gut microbiome in both health and disease and owing to fecal microbiota transplantation’s (FMT’s) unique mechanism/s of action, FMT is rapidly advancing as an effective treatment for a number of conditions in which the gastrointestinal microbiome is thought to play a role. Investigators review the role of FMT from its beginnings in Clostridioides difficile infection to its expansion into inflammatory bowel disease, irritable bowel syndrome, and colon cancer. [Curr Opin Pharmacol] Abstract

Capturing the Biologic Onset of Inflammatory Bowel Diseases: Impact on Translational and Clinical Science

The authors discuss what is known about the biologic onset and pre-clinical Crohn’s disease with an emphasis on studies conducted in patients’ first degree relatives. They then review the possible strategies to diagnose IBD very early in time including screening, available disease markers and imaging, and the possible clinical implications of treating these conditions at or close to their biologic onset. [Cells] Full Article

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

Innovate Biopharmaceuticals Announces the Start of the First Phase III Clinical Trial in Celiac Disease

Innovate Biopharmaceuticals, Inc. announced the start of the first Phase III clinical trial in celiac disease. Innovate expects to provide further updates as screening and enrollment proceed over the next few months. [Innovate Biopharmaceuticals, Inc.] Press Release

RedHill Biopharma Receives Allowance for New US Patent Covering RHB-104 for Crohn’s Disease and RHB-204 for NTM Infections

RedHill Biopharma Ltd. announced that it has received a Notice of Allowance from the US Patent and Trademark Office for a new patent covering RHB-104 for Crohn’s disease and RHB-204 for Mycobacterium avium complex disease, the most common cause of pulmonary nontuberculous mycobacteria infections. [RedHill Biopharma] Press Release

Xynomic Completes Pre-IND Meeting with US FDA for XP-102, a Novel Pan-RAF Inhibitor against Colorectal Cancer and Lung Cancer

Xynomic Pharmaceuticals Holdings, Inc. announced that it recently held a pre-IND meeting with the FDA for its pan-PAF inhibitor XP-102 for the treatment of cancers. The FDA addressed Xynomic’s questions related to CMC, nonclinical and clinical protocol, and provided valuable advice on overall clinical development plan to advance this drug candidate. Xynomic is on track to file this Investigational New Drug application in the second half of 2019. [Xynomic Pharmaceuticals Holdings, Inc. (GlobeNewswire, Inc.)] Press Release

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

Harassment Common for National Institutes of Health Employees

More than one-fifth of people who work for the National Institutes of Health and who responded to a survey by the agency have experienced some form of harassment during the last year, according to an interim report the agency published on June 12. Of nearly 16,000 respondents, 10 percent reported that they had experienced unwanted sexual attention, while 18 percent said they had been subject to gender harassment. [The Scientist] Editorial

China Announces Hefty Fines for Unauthorized Collection of DNA

China announced a new law restricting the collection and use of genetic resources from people in the country — including biological samples that yield DNA, such as blood, and data gleaned from sequencing them. There will be hefty fines for unauthorized collection or use of genetic material. [Nature News] Editorial

NEW Keystone Symposia: Cancer Stem Cells: Advances in Biology & Clinical Translation
October 13-17, 2019
Hong Kong, China

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NEW Professor – Microbiomes of the Human Body (The University of South Florida)

Postdoctoral Research – Lipoproteins in IBD (University of Connecticut)

Postdoctoral Fellow – Immunometabolism of IBD (Luxembourg Institute of Health)

Postdoctoral Researcher – Genetics in IBD (Kennedy Institute of Rheumatology)

Principle Investigator – Gut Physiology (Nestlé Research Center)

Postdoctoral Researcher – Mucosal Immunology and Inflammation (Gilead Sciences, Inc.)

Postdoctoral Fellow – Intestinal and Pulmonary Stem Cell Biology (Stanford School of Medicine)

Postdoctoral Researcher – Intestinal Immunology (KU Leuven)

Associate Professor – Oncology (University of California, Davis)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

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