Intestinal Cell News Volume 4.38 | Oct 5 2018

TOP STORY

Epithelial 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

(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 Atg16l1^ΔIEC 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

XIAP Facilitates Breast and Colon Carcinoma Growth via Promotion of p62 Depletion through Ubiquitination-Dependent Proteasomal Degradation

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

NOX1-Derived ROS Drive the Expression of Lipocalin-2 in Colonic Epithelial Cells in Inflammatory Conditions

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

Functional Impairment Triggered by Altertoxin II (ATXII) in Intestinal Cells In Vitro: Cross-Talk between Cytotoxicity and Mechanotransduction

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

Overcoming Drug Resistance in Colon Cancer by Aptamer-Mediated Targeted Co-Delivery of Drug and siRNA Using Grapefruit-Derived Nanovectors

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

Dual-Specificity Phosphatase 6 Deletion Protects the Colonic Epithelium against Inflammation and Promotes Both Proliferation and Tumorigenesis

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

SRSF3, a Splicer of the PKM Gene, Regulates Cell Growth and Maintenance of Cancer-Specific Energy Metabolism in Colon Cancer Cells

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

Sodium Butyrate Enhances Intestinal Riboflavin Uptake via Induction of Expression of Riboflavin Transporter-3 (RFVT3)

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

MicroRNA-145 Regulates the Proliferation, Migration and Invasion of Human Primary Colon Adenocarcinoma Cells by Targeting MAPK1

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.

The Colorectal Cancer Epidemic: Challenges and Opportunities for Primary, Secondary and Tertiary Prevention

Countries 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.

Synergy 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 Presents Top-Line Data From NOX-A12 Monotherapy Part of Ongoing Metastatic Colorectal and Pancreatic Cancer Trial

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 4^th CRI-CIMT-EATI-AACR International Cancer lmmunotherapy Conference, New York] Press Release

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

Zealand Pharma Enrolls First Patient in Phase III Trial with Glepaglutide for the Treatment of Short Bowel Syndrome

Zealand 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 Launches Personalized Study Approach for Clinical Research Programs in Inflammatory Bowel Disease

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

Major 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

NEW Defence is the Best Attack: Immuno-Oncology Breakthroughs
March 11-13, 2019
Barcelona, Spain

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

NEW Research Associate – Gut Signaling and Metabolism (Imperial College London)

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

NEW Postdoctoral Position – Dendritic Cell Biology & Antigen Presentation (Weill Cornell Medicine)

NEW Assistant Professor – Basic & Translational Cancer Research (Texas Tech University Health Sciences Center)

Postdoctoral Position – Cancer Metabolism (IDIBELL)

Postdoctoral Position – Molecular Biology/Signal Transduction/Cancer/Inflammation (Université de Liege)

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.

Have we missed an important article or publication in Intestinal Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.