Intestinal antigen uptake is enhanced in inflammatory bowel disease. We analyzed transcellular transport routes of antigens in different compartments of normal enterocytes and atypical intestinal epithelial cells called "rapid antigen uptake into the cytosol enterocytes" (RACE cells). These cells constitute a recently described population of enterocyte-derived cells, which are increased in inflammatory bowel disease. Mucosa of freshly resected specimens were incubated with the antigens ovalbumin or horseradish peroxidase. Ultrastructural labeling patterns of differentiation-dependent proteins, the brush-border enzyme sucrase-isomaltase and the cytoskeleton proteins villin and actin, were determined in enterocytes. Apoptosis was investigated biochemically and ultrastructurally by cleavage of caspase-3. Both antigens were transported to late endosomes and to trans-Golgi vesicles of enterocytes in inflammatory bowel disease and control specimens. Quantitative evaluation revealed a significantly increased transepithelial antigen transport in both compartments of RACE relative to normal enterocytes. Labeling densities for sucrase-isomaltase, villin, and actin were decreased in RACE relative to normal enterocytes. Caspase-3 was not increased in RACE cells relative to controls. RACE cells are characterized by increased antigen transport to late endosomes and the trans-Golgi network, a disassembled cytoskeleton and lower concentrations of proteins that are markers of cell differentiation.
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http://dx.doi.org/10.1016/S0002-9440(10)63308-1 | DOI Listing |
Trends Pharmacol Sci
December 2024
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA; Texas Children's Microbiome Center, Department of Pathology, Texas Children's Hospital, Houston, TX, USA. Electronic address:
The human microbiome consists of diverse microorganisms that inhabit various body sites. As these microbes are increasingly recognized as key determinants of health, there is significant interest in leveraging individual microbiome profiles for early disease detection, prevention, and drug efficacy prediction. However, the complexity of microbiome data, coupled with conflicting study outcomes, has hindered its integration into clinical practice.
View Article and Find Full Text PDFBr J Ophthalmol
December 2024
Department of Ophthalmology and Medical Research Center, Oulu University Hospital; Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland.
Background/aims: The purpose of this study is to define genetic factors associated with anterior uveitis through genome-wide association study (GWAS).
Methods: In this GWAS meta-analysis, we combined data from the FinnGen, Estonian Biobank and UK Biobank with a total of 12 205 anterior uveitis cases and 917 145 controls. We performed a phenome-wide association study (PheWAS) to investigate associations across phenotypes and traits.
Clin Gastroenterol Hepatol
December 2024
Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California, USA; Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla, California, USA. Electronic address:
Background And Aims: We sought to ascertain how prior exposure to TNF antagonists impacts treatment response with various classes of advanced therapies in patients with ulcerative colitis (UC), through a systematic review and meta-analysis.
Methods: Through a systematic review of multiple databases through June 30, 2024, we identified 17 RCTs in 8871 adults with moderate-severe UC who were treated with different advanced therapies vs. placebo, and reported efficacy in induction of clinical remission, stratified by prior exposure to TNF antagonists.
J Adv Res
December 2024
Department of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Inflammatory Bowel Disease Research Center, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Division of Gastroenterology and Hepatology, Baoshan Branch, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address:
Introduction: In Crohn's disease (CD), lesions are mainly distributed in a segmental manner, with the primary sites of involvement being the ileum and colon. Heterogeneity in colon and ileum results in location-specific clinical presentations and therapeutic responses. Mucosal healing tends to be more readily and quickly achieved in the colon than in the ileum, where lesions are more likely to develop into complex behaviors.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 510006, China. Electronic address:
Ulcerative colitis (UC) is an inflammatory bowel disease marked by gut inflammation and microbial dysbiosis. Exopolysaccharides (EPS) from probiotic bacteria have been shown to regulate microbial composition and metabolism, but their role in promoting probiotic growth and alleviating inflammation in UC remains unclear. Here, we investigate BLEPS-1, a novel EPS derived from Bifidobacterium longum subsp.
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