NOX1 is essential for TNFα-induced intestinal epithelial ROS secretion and inhibits M cell signatures.

Objective: Loss-of-function mutations in genes generating reactive oxygen species (ROS), such as , are associated with IBD. Mechanisms whereby loss of ROS drive IBD are incompletely defined.

Design: ROS measurements and single-cell transcriptomics were performed on colonoids stratified by genotype and TNFα stimulation.

Single-cell transcriptomics reveals conserved cell identities and fibrogenic phenotypes in zebrafish and human liver.

The mechanisms underlying liver fibrosis are multifaceted and remain elusive with no approved antifibrotic treatments available. The adult zebrafish has been an underutilized tool to study liver fibrosis. We aimed to characterize the single-cell transcriptome of the adult zebrafish liver to determine its utility as a model for studying liver fibrosis.

From single-target to cellular niche targeting in Crohn's disease: intercepting bad communications.

The mainstay of moderate to severe Crohn's disease (CD), anti-TNF treatment, shows no clinical benefit in ∼40% of patients, likely due to incomplete cellular targeting and delayed treatment institution. While single-target therapeutics have been highly effective for some CD patients, substantial limitations with respect to safety, efficacy, and long-term, complete remission remain. Deconvolution of the cellular and molecular circuitry of tissue lesions underscores the importance of combinatorial strategies targeting cellular niches.

A Role for CXCR3 Ligands as Biomarkers of Post-Operative Crohn's Disease Recurrence.

Background And Aims: Crohn's disease [CD] recurrence following ileocolic resection [ICR] is common. We sought to identify blood-based biomarkers associated with CD recurrence.

Methods: CD patients undergoing ICR were recruited across six centres.

A myeloid-stromal niche and gp130 rescue in NOD2-driven Crohn's disease.

Crohn's disease is a chronic inflammatory intestinal disease that is frequently accompanied by aberrant healing and stricturing complications. Crosstalk between activated myeloid and stromal cells is critical in the pathogenicity of Crohn's disease, and increases in intravasating monocytes are correlated with a lack of response to anti-TNF treatment. The risk alleles with the highest effect on Crohn's disease are loss-of-function mutations in NOD2, which increase the risk of stricturing.

Inflamed Ulcerative Colitis Regions Associated With MRGPRX2-Mediated Mast Cell Degranulation and Cell Activation Modules, Defining a New Therapeutic Target.

Background & Aims: Recent literature has implicated a key role for mast cells in murine models of colonic inflammation, but their role in human ulcerative colitis (UC) is not well established. A major advance has been the identification of mrgprb2 (human orthologue, MRGPX2) as mediating IgE-independent mast cell activation. We sought to define mechanisms of mast cell activation and MRGPRX2 in human UC.

Machine learning identifies novel blood protein predictors of penetrating and stricturing complications in newly diagnosed paediatric Crohn's disease.

Background: There is a need for improved risk stratification in Crohn's disease.

Aim: To identify novel blood protein biomarkers associated with future Crohn's disease complications METHODS: We performed a case-cohort study utilising a paediatric inception cohort, the Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's disease (RISK) study. All patients had inflammatory disease (B1) at baseline.

Glycemic Index of Wheat and Rice are Similar When Consumed as Part of a North Indian Mixed Meal.

Introduction: Wheat is preferable over rice due to its lower glycemic index (GI). It is not known if the same is true when these staples are a part of mixed meals, hence we compared the Glycemic responses of wheat/rice containing mixed meals.

Materials And Methods: Glycemic responses of 2 mixed meals were compared with reference meal (glucose) where each was designed to provide a total of 50 g of available carbohydrate (AvCHO), in 10 healthy adult volunteers as per recent recommendations.

Single-Cell Analysis of Crohn's Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy.

Clinical benefits of cytokine blockade in ileal Crohn's disease (iCD) are limited to a subset of patients. Here, we applied single-cell technologies to iCD lesions to address whether cellular heterogeneity contributes to treatment resistance. We found that a subset of patients expressed a unique cellular module in inflamed tissues that consisted of IgG plasma cells, inflammatory mononuclear phagocytes, activated T cells, and stromal cells, which we named the GIMATS module.

Zebrafish modeling of intestinal injury, bacterial exposures and medications defines epithelial responses relevant to human inflammatory bowel disease.

Genome-wide association studies have identified over 200 genomic loci associated with inflammatory bowel disease (IBD). High-effect risk alleles define key roles for genes involved in bacterial response and innate defense. More high-throughput systems are required to rapidly evaluate therapeutic agents.

MPI depletion enhances O-GlcNAcylation of p53 and suppresses the Warburg effect.

Rapid cellular proliferation in early development and cancer depends on glucose metabolism to fuel macromolecule biosynthesis. Metabolic enzymes are presumed regulators of this glycolysis-driven metabolic program, known as the Warburg effect; however, few have been identified. We uncover a previously unappreciated role for Mannose phosphate isomerase (MPI) as a metabolic enzyme required to maintain Warburg metabolism in zebrafish embryos and in both primary and malignant mammalian cells.

trappc11 is required for protein glycosylation in zebrafish and humans.

Activation of the unfolded protein response (UPR) can be either adaptive or pathological. We term the pathological UPR that causes fatty liver disease a "stressed UPR." Here we investigate the mechanism of stressed UPR activation in zebrafish bearing a mutation in thetrappc11gene, which encodes a component of the transport protein particle (TRAPP) complex.