The homeostasis of the gastrointestinal epithelium relies on cell regeneration and differentiation into distinct lineages organised inside glands and crypts. Regeneration depends on WNT/β-Catenin pathway activation, but to understand homeostasis […]» Read more
Approach to the management of recently diagnosed inflammatory bowel disease patients: a user’s guide for adult and pediatric gastroenterologists.
Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic, progressive, immune-mediated disease of adults and children that has no cure. IBD can cause significant […]» Read more
Genetic alterations affecting transforming growth factor β (TGF-β) signaling are exceptionally common in diseases and cancers of the gastrointestinal (GI) system. As a regulator of tissue renewal, TGF-β signaling and […]» Read more
Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder associated with an elevated risk of colorectal cancer (CRC). IBD-associated CRC (IBD-CRC) may represent a distinct pathway of tumorigenesis compared […]» Read more
TET2 drives 5hmc marking of GATA6 and epigenetically defines pancreatic ductal adenocarcinoma transcriptional subtypes.
Pancreatic ductal adenocarcinoma (PDAC) is characterised by advanced disease stage at presentation, aggressive disease biology and resistance to therapy resulting in extremely poor five-year survival <10%. PDAC is classified into […]» Read more
MondoA-TXNIP axis maintains regulatory T cell identity and function in colorectal cancer microenvironment.
The metabolic features and function of intratumoral Tregs are ambiguous in colorectal cancer. Tumor-infiltrating Tregs are reprogrammed to exhibit high glucose-depleting properties and adapt to the glucose-restricted microenvironment. The glucose-responsive […]» Read more
A diffusion-like process accommodates new crypts during clonal expansion in human colonic epithelium.
Colorectal cancer (CRC) is thought to arise when the cumulative mutational burden within colonic crypts exceeds a certain threshold that leads to clonal expansion and ultimately neoplastic transformation. Therefore, quantification […]» Read more
Colonic Motility is Improved by the Activation of 5-HT2B Receptors on Interstitial Cells of Cajal in Diabetic Mice.
Constipation is commonly associated with diabetes. Serotonin (5-HT), produced predominantly by enterochromaffin (EC) cells via tryptophan hydroxylase 1 (TPH1), is a key modulator of gastrointestinal (GI) motility. However, the role […]» Read more
Non-food prebiotic, probiotic, and synbiotic use has increased in U.S. adults and children from 1999 to 2018.
Public interest in pre- , pro-, and synbiotic products is increasing because of interactions between gut microbiota and human health. Our aim was to describe non-food (from dietary supplements or […]» Read more
Tumor secreted extracellular vesicles regulate T-cell costimulation and can be manipulated to induce tumor specific T-cell responses.
Colorectal Cancer is a major cause of cancer-related deaths worldwide. Immune checkpoint blockade therapies are effective in 30-60% of the microsatellite instable-high subtype. Unfortunately, most colorectal cancer patients (>85%) have […]» Read more
Development and Validation of Test for “Leaky Gut” Small Intestinal and Colonic Permeability Using Sugars in Healthy Adults.
Oral monosaccharides and disaccharides are used to measure in vivo human gut permeability through urinary excretion.1. To obtain normative data on small intestinal and colonic permeability; 2. To assess variance […]» Read more
Hypothalamic melanocortin 4 receptors (MC4R) are a key regulator of energy homeostasis. Brain-penetrant MC4R agonists have failed, as concentrations required to suppress food intake also increase blood pressure. However, peripherally […]» Read more
Crohn’s Disease (CD) and ulcerative colitis (UC) are characterized by dysregulated adaptive immune responses to the microbiota in genetically susceptible individuals, but the specificity of these responses remains largely undefined. […]» Read more
Fecal microbiota transplantation for recurrent Clostridioides difficile infection associates with functional alterations in circulating microRNAs.
The molecular mechanisms underlying successful fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (rCDI) remain poorly understood. The primary objective of this study was to characterize alterations in microRNAs […]» Read more
Lynch syndrome is associated with pathogenic variants in 4 mismatch repair (MMR) genes that increase lifetime risk of colorectal cancer (CRC). Guidelines recommend intensive CRC surveillance with colonoscopy every 1-2 […]» Read more
Comparative Effectiveness of Multiple Different First-Line Treatment Regimens for Helicobacter pylori Infection: a Network Meta-Analysis.
A number of double, triple and quadruple therapies have been proposed as first line H. pylori infection empiric treatments. However, knowledge of their worldwide and regional comparative efficacy is lacking. […]» Read more
A Liquid Biopsy Assay for Noninvasive Identification of Lymph Node Metastases in T1 Colorectal Cancer.
We recently reported use of tissue-based transcriptomic biomarkers (miRNA or mRNA) for identification of lymph node metastasis (LNM) in patients with invasive submucosal colorectal cancers (T1 CRC). In this study, […]» Read more
The existence of different subtypes of pancreatic ductal adenocarcinoma (PDAC) and their correlation with patient outcome have shifted the emphasis on patient classification for better decision-making algorithms and personalized therapy. […]» Read more
In homeostasis, intestinal cell fate is controlled by balanced gradients of morphogen signalling. The Bone Morphogenetic Protein (BMP) pathway has a physiological, pro-differentiation role, predominantly inferred through previous experimental pathway […]» Read more
Limited understanding of pruritus mechanisms in cholestatic liver diseases hinders development of anti-pruritic treatments. Previous studies implicated lysophosphatidic acid (LPA) as a potential mediator of cholestatic pruritus.Pruritogenicity of LPC, LPA’s […]» Read more
Sulfation is a conjugation reaction essential for numerous biochemical and cellular functions in mammals. The 3′-phosphoadenosine 5′-phosphosulfate (PAPS) synthase 2 (PAPSS2) is the key enzyme to generate PAPS, which is […]» Read more
Outcomes of thermal ablation of the mucosal defect margin after endoscopic mucosal resection: A prospective, international, multi-centre trial of 1000 large non-pedunculated colorectal polyps.
Thermal ablation of the defect margin after endoscopic mucosal resection (EMR-T) for treating large (≥ 20mm) non-pedunculated colorectal polyps (LNPCPs) has shown efficacy in a randomized trial, with a four-fold […]» Read more
Familial burden and other clinical factors associated with various types of cancer in individuals with Lynch syndrome.
Lynch syndrome (LS) is associated with increased risks of various gastrointestinal, gynecologic, genitourinary, and other cancers. Many clinical practice guidelines recommend that LS carriers’ screening strategies be devised based on […]» Read more
Epigenetic Regulation of Intestinal Stem Cells and Disease: A Balancing Act of DNA and Histone Methylation.
Genetic mutations or regulatory failures underlie cellular malfunction in many diseases, including colorectal cancer and inflammatory bowel diseases. However, mutational defects alone fail to explain the complexity of such disorders. […]» Read more
Deleterious variants in ABCC12 are detected in idiopathic chronic cholestasis and cause intrahepatic bile duct loss in model organisms: ABCC12 pathogenic variants lead to cholestasis.
The etiology of cholestasis remains unknown in many children. We surveyed the genome of children with chronic cholestasis for variants in genes not previously associated with liver disease and validated […]» Read more
Neutrophils Alter DNA Repair Landscape to Impact Survival and Shape Distinct Therapeutic Phenotypes of Colorectal Cancer.
Tumor-infiltrating neutrophils (PMNs) are a prominent feature of colorectal cancer (CRC), where they can promote cytotoxicity or exacerbate disease outcomes. We recently showed that in acute colon injury, PMNs can […]» Read more
Simple sugar and sugar-sweetened beverage intake during adolescence and risk of colorectal cancer precursors: Adolescent sugar intake and colorectal polyp.
Recent increasing trends in early-onset colorectal cancer (CRC) strongly supports that early-life diet is involved in CRC development. However, data are lacking on the relationship with high sugar intake during […]» Read more
Sequential administration of XPO1 and ATR inhibitors enhances therapeutic response in TP53-mutated colorectal cancer.
Understanding the mechanisms by which tumors adapt to therapy is critical for developing effective combination therapeutic approaches to improve clinical outcomes for patients with cancer.To identify promising and clinically actionable […]» Read more
The long-term trend in gastric cancer rates has rarely been reported from a global perspective. We aimed to explore the past temporal trends (1988-2012) in gastric cancer incidence rates in […]» Read more
Paternal Exposure to Immunosuppressive and/or Biologic Agents and Birth Outcomes in Patients with Immune-Mediated Inflammatory Diseases.
We conducted a retrospective cohort study to inform the safety of exposure to immunosuppressive and/or biologic agents around conception in expectant fathers with immune-mediated inflammatory diseases (IMIDs) on birth outcomes.Using […]» Read more