Intestinal Cell News 4.38 October 5, 2018 | |
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TOP STORYEpithelial RNase H2 Maintains Genome Integrity and Prevents Intestinal Tumorigenesis in Mice Scientists investigated whether intestinal epithelial proliferation required RNase H2 function and whether RNase H2 activity was disrupted during intestinal carcinogenesis. They isolated epithelial cells, generated intestinal organoids, and performed RNA sequence analyses. [Gastroenterology] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)ATG16L1 Orchestrates Interleukin-22 Signaling in the Intestinal Epithelium via cGAS–STING IL-22 stimulation physiologically led to transient endoplasmic reticulum stress and subsequent activation of STING-dependent type I interferon (IFN-I) signaling, which was augmented in Atg16l1ΔIEC intestinal organoids. IFN-I signals amplified epithelial TNF production downstream of IL-22 and contributed to necroptotic cell death. [J Exp Med] Full Article | Press Release | Graphical Abstract X-linked inhibitor of apoptosis protein (XIAP) functioned as an ubiquitination E3 ligase towards p62 and suppressed p62 expression through ubiquitin-proteasomal degradation. Furthermore, XIAP enhanced cancer cell proliferation, viability, and colony formation in vitro via suppression of p62. [Oncogene] Abstract Succinate Receptor Mediates Intestinal Inflammation and Fibrosis In human isolated fibroblasts from Crohn’s disease patients succinate receptor (SUCNR1) expression was higher than in those from controls and treatment with succinate increased SUCNR1 expression, fibrotic markers and inflammatory cytokines through SUCNR1. [Mucosal Immunol] Abstract Researchers found that the combination of TNFα and IL-17 induced a dramatic upregulation of NOXO1 expression that was dependent on the activation of p38MAPK and JNK1/2, and resulted into an increase of NOX1 activity and reactive oxygen species (ROS) production. NOX1-derived ROS drove the expression of lipocalin-2 (LCN-2) by controlling the expression of IκBζ, a master inducer of LCN-2. [Mucosal Immunol] Abstract ATXII, a mycotoxin produced by the food contaminant fungus Alternaria alternata was studied in HT-29 intestinal adenocarcinoma cells and in non-transformed intestinal epithelial cells, HCEC. ATXII reduced the migratory potential of HCEC as well as their membrane fluidity, but had no respective impact on HT-29 cells. [Arch Toxicol] Full Article Grapefruit-derived nanovectors loaded with aptamer increased doxorubicin (Dox) accumulation in multidrug resistance LoVo cells, an effect that was abolished by pretreatment with DNase. The LA1 aptamer effectively promoted nanovector internalization into cells at 4°C and increased the targeted delivery of Dox to tumors. [Cell Physiol Biochem] Full Article The authors showed that loss of dual-specificity phosphatase 6 (DUSP6) increased crypt depth and epithelial cell proliferation without altering colonic architecture. Crypt regeneration capacity was also enhanced, as revealed by ex vivo Dusp6 knockout organoid cultures. Loss of Dusp6 induced goblet cell expansion without affecting enteroendocrine and absorptive cell differentiation. [J Cell Physiol] Abstract The silencing of serine and arginine rich splicing factor 3 (SRSF3) in human colon cancer cells induced a marked growth inhibition in both in vitro and in vivo experiments and caused an increase in the pyruvate kinase muscle 1 (PKM1)/PKM2 ratio, thus resulting in a metabolic shift from glycolysis to oxidative phosphorylation. [Int J Mol Sci] Full Article Treating Caco-2 cells with sodium butyrate led to a significant increase in carrier-mediated riboflavin (RF) uptake. This increase was associated with a significant induction in the level of expression of the hRFVT3 protein, mRNA, and heterogenous nuclear RNA. [Dig Dis Sci] Abstract Homoectoine Protects against Colitis by Preventing a Claudin Switch in Epithelial Tight Junctions Only homoectoine ameliorated the drop in transepithelial electrical resistance induced by IFN-γ and TNF-α in Caco-2 cells. Both ectoines inhibited loss of ZO-1 and occludin and prevented IFN-γ/TNF-α-induced increased paracellular flux of 4 kDa FITC-dextran in vitro. [Dig Dis Sci] Abstract Scientists revealed that the expression of miR-145 was significantly downregulated in colon adenocarcinoma cells and the ectopic expression of miR-145 in colon cancer inhibited proliferation by promoting the apoptosis of SW480 primary colon adenocarcinoma cells. [Int J Mol Med] Full Article Subscribe to one of our other 19 science newsletters such as Pulmonary Cell News & ESC & iPSC News. | |
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REVIEWSCountries with early and high uptake rates of effective screening have exhibited major declines in colorectal cancer (CRC) incidence and mortality, in contrast to most other countries. Increasing evidence shows that the prognosis and quality of life of CRC patients can be substantially improved by tertiary prevention measures, such as the administration of low-dose aspirin and the promotion of physical activity. [Br J Cancer] Abstract Recent Progress in Organoid Culture to Model Intestinal Epithelial Barrier Functions In the past decade, significant progress has been made in the development of culture technologies to maintain intestinal epithelial cells as various forms of intestinal organoids. The author showcases recent work that have utilized intestinal organoids to study various aspects of intestinal epithelial barrier functions. [Int Immunol] Full Article Visit our reviews page to see a complete list of reviews in the intestinal cell research field. | |
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SCIENCE NEWSSynergy Pharmaceuticals to Present New Analyses of TRULANCE® (Plecanatide) Presentations include a poster detailing outcomes from a large post-hoc analysis evaluating the safety and tolerability of TRULANCE® in chronic idiopathic constipation and irritable bowel syndrome with constipation in patients aged 65 and older compared to those in a younger cohort. [Press release from Synergy Pharmaceuticals Inc. discussing research to be presented at the American College of Gastroenterology (ACG) Annual Scientific Meeting, Philadelphia] Press Release NOXXON Pharma N.V. announced that it is presenting top-line data of the ongoing clinical trial testing NOX-A12 alone and available safety data from the combination of NOX-A12 with Merck & Co./MSD’s Keytruda® in patients with metastatic, microsatellite-stable pancreatic and colorectal cancer. [Press release from NOXXON Pharma discussing research presented at the 4th CRI-CIMT-EATI-AACR International Cancer lmmunotherapy Conference, New York] Press Release | |
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INDUSTRY NEWSZealand Pharma A/S announced the enrollment of the first patient in a global Phase III trial evaluating the potential of glepaglutide as a novel short bowel syndrome treatment. [Zealand Pharma A/S] Press Release ImmusanT Announces First Patient Dosed in Phase II Trial of Therapeutic Vaccine for Celiac Disease ImmusanT, Inc. announced that the first patient has been dosed in its Phase II RESET CeD trial for the treatment of celiac disease. The trial will evaluate the safety and efficacy of Nexvax2®, the company’s lead investigational therapeutic vaccine in celiac disease patients who carry the immune recognition genes for HLA-DQ2.5, a subset that accounts for approximately 90% of those living with the disease. [ImmusanT, Inc.] Press Release ImmunogenX Completes CypCel Trial for Celiac Disease ImmunogenX and the Mayo Clinic announced the completion of a longitudinal study to further evaluate a disease management tool for monitoring the intestinal health of recovering celiac disease patients. [Immunogenics LLC] Press Release Allergan plc announced the initiation of two global clinical research programs for brazikumab, an investigational drug being studied for inflammatory bowel disease (IBD). INTREPID (Crohn’s disease) and EXPEDITION (ulcerative colitis), will evaluate the safety and efficacy of brazikumab and will investigate the role of biomarkers in determining a predictive response of brazikumab in patients with IBD. [Allergan] Press Release Determining Cell Fate and the Onset of Crohn’s Disease How cells talk to each other, and what they say, has long held fascination for Seema Khurana, professor of biology and biochemistry. Now with a new $2.3 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases, Khurana will continue monitoring cellular cross talk to find new targets for drug development that could push Crohn’s into remission. [University of Houston] Press Release | |
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POLICY NEWSMajor Publishers Sue ResearchGate over Copyright Infringement Two journal publishers have launched legal proceedings in the United States against academic-networking site ResearchGate for copyright infringement. [Nature News] Editorial Women Fare Well in This Year’s Crop of NIH High-Risk Awards Women did unusually well in this year’s round for two categories of awards: Half of this year’s 10 Pioneer Awards for established researchers went to women. And five of 11 EIA winners were women. In past years, the balance has skewed toward men. [ScienceInsider] Editorial Brazil’s Presidential Election Could Savage Its Science A populist surge from a right-wing presidential candidate in Brazil that is threatening to upend the country’s politics could have huge impacts on research budgets and environmental policies. [Nature News] Editorial
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EVENTSNEW Defence is the Best Attack: Immuno-Oncology Breakthroughs Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Research Associate – Gut Signaling and Metabolism (Imperial College London) NEW Postdoctoral Position – Dendritic Cell Biology & Antigen Presentation (Weill Cornell Medicine) Postdoctoral Position – Cancer Metabolism (IDIBELL) Group Leader – Organoid Modeling of Disease (European Molecular Biology Laboratory) Postdoctoral Position – Colon Cancer Research (Vanderbilt University Medical Center) Postdoctoral Scholar – Intestinal Research (Penn State College of Medicine) Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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