ABSTRACT
Ulcerative colitis (UC) is a chronic inflammatory condition of the intestinal tract. Various programmed cell death pathways in the intestinal mucosa are crucial to the pathogenesis of UC. Disulfidptosis, a recently identified form of programmed cell death, has not been extensively reported in the context of UC. This study evaluated the expression of disulfidptosis-related genes (DRGs) in UC through public databases and assessed disulfide accumulation in the intestinal mucosal tissues of UC patients and dextran sulfate sodium (DSS)-induced colitis mice via targeted metabolomics. We utilized various bioinformatics techniques to identify UC-specific disulfidptosis signature genes, analyze their potential functions, and investigate their association with immune cell infiltration in UC. The mRNA and protein expression levels of these signature genes were confirmed in the intestinal mucosa of DSS-induced colitis mice and UC patients. A total of 24 DRGs showed differential expression in UC. Our findings underscore the role of disulfide stress in UC. Four UC-related disulfidptosis signature genes-SLC7A11, LRPPRC, NDUFS1, and CD2AP-were identified. Their relationships with immune infiltration in UC were analyzed using CIBERSORT, and their expression levels were validated by quantitative real-time PCR and western blotting. This study provides further insights into their potential functions and explores their links to immune infiltration in UC. In summary, disulfidptosis, as a type of programmed cell death, may significantly influence the pathogenesis of UC by modulating the homeostasis of the intestinal mucosal barrier.
Subject(s)
Colitis, Ulcerative , Intestinal Mucosa , Colitis, Ulcerative/genetics , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/metabolism , Colitis, Ulcerative/pathology , Animals , Humans , Mice , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Dextran Sulfate , Apoptosis/genetics , Male , Disease Models, Animal , Female , Gene Expression Profiling , Mice, Inbred C57BL , Computational Biology/methodsABSTRACT
Ulcerative colitis (UC) is a refractory inflammatory disease with imbalances in intestinal mucosal homeostasis. Cuproptosis serves as newly identified programmed cell death (PCD) form involved in UC. In the study, UC-related datasets were extracted from the Gene Expression Omnibus (GEO) database. A comparison of UC patients and healthy controls identified 11 differentially expressed cuproptosis-related genes (DE-CRGs), where FDX1, LIAS, and DLAT were differentially expressed in UC groups from the mouse models and clinical samples, with their expression correlating with disease severity. By comprehending weighted gene co-expression network analysis (WGCNA) and differential expression analysis, the key genes common to the module genes relevant to different cuproptosis-related clusters and differentially expressed genes (DEGs) both in different clusters and patients with and without UC were identified using several bioinformatic analysis. Furthermore, the mRNA levels of four characteristic genes with diagnostic potential demonstrated significant decrease in both mouse models and clinical UC samples. Our discoveries offer a theoretical foundation for cuproptosis effect in UC.
ABSTRACT
Monodispersed Au nanoparticles in ordered mesoporous carbon/silica (Au/OMCS) nanocomposites were prepared by the solvent evaporation induced self-assembly. Au/OMCS nanocomposites were characterized through XRD, BET, and TEM. The obtained nanocomposites exhibit uniform mesopores with the size of 18 ± 2 nm. And ultrafine Au nanoparticles with the size of 3~7 nm are well dispersed in the cavities. An ultrasensitive nanoenzyme sensor was fabricated based on a Au/OMCS-modified electrode. The Au/OMCS-modified electrode displays high xanthine oxidase-like catalytic activity evaluated through cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The DPV response currents are linearly dependent on concentrations of xanthine (Xa) in the range 0.10-20 µM, along with a high sensitivity of 6.84 µA µM-1 cm-2 and very low detection limit of 0.006 µM (S/N = 3) under the optimal working potential of 0.64 V vs. SCE. Interference experiments show that the nanoenzyme sensor has no obvious responses to most potentially interfering species at a potential of 0.64 V. The fabricated sensor has been applied to the determination of Xa in spiked urine samples with recoveries ranging from 98.26 to 101.4%. Graphical abstract.
