RESUMO
Background: Ulcerative colitis is an emerging global health concern that poses a significant threat to human health and can progress to colorectal cancer if not diagnosed and treated promptly. Currently, the biomarkers used clinically for diagnosis and dynamic severity monitoring lack disease specificity. Methods: Mouse models induced with 2%, 2.5%, and 3% DSS were utilized to simulate human UC with varying severities of inflammation. Transcriptome sequencing technology was employed to identify differentially expressed genes (DEGs) between the control group and each treatment group. Functional enrichment analysis of the KEGG database was performed for shared DEGs among the three treatment groups. DEGs that were significantly and strongly correlated with DSS concentrations were identified using Spearman correlation analysis. Human homologous genes of the interested DEGs were searched in the HomoloGene database, and their regulation patterns in UC patients were validated using the GSE224758 dataset. These genes were then submitted to the DisGeNET database to identify their known associations with human diseases. Online tools, including SignalP 6.0 and DeepTMHMM 1.0, were used to predict signal peptides and transmembrane helices in the amino acid sequences of human genes homologous to the DEGs of interest. Results: A total of 1,230, 995, and 2,214 DEGs were identified in the 2%, 2.5%, and 3% DSS-induced groups, respectively, with 668 DEGs common across all three groups. These shared DEGs were primarily associated with signaling transport, pathogenesis, and immune response. Through extensive screening, LGI2 and PRSS22 were identified as potentially novel biomarkers with higher specificity and ease of detection for the early diagnosis and dynamic severity monitoring of human UC, respectively. Conclusion: We have identified two potentially novel biomarkers, LGI2 and PRSS22, which are easy of detection and more specific for human UC. These findings provide new insights into the accurate diagnosis and dynamic monitoring of this persistent disease.
RESUMO
Poison of intestinal induce severe health problems in human infants and young animals due to contaminating foods and feedstuffs. With the emergence of public health concerns and high-speed diffuse of drug-opposition of bacteria, the adoption of antimicrobial peptides as potential candidates in treating pathogen infections raised up. Nature Microcin J25 (MccJ25), a class of lasso peptides separated from a fecal strain of E. coli, has been replied to display powerful antimicrobial behavior. Herein, the study was to assess the usefulness of biogenic MccJ25 in the prophylaxis of ETEC K88 infection in IPEC-J2 cells. In vitro antimicrobial activity against ETEC K88 and cytotoxicity of biogenic MccJ25 were determined first. To further understand how biogenic MccJ25 mediates its impact, ETEC K88 adhesion in cells, membrane permeability [as indicated by reduced release of lactate dehydrogenase (LDH)], transepithelial electrical resistance (TEER), barrier function, and proinflammatory cytokines levels were determined in IPEC-J2 cells after treatment with biogenic MccJ25 and challenge with ETEC K88. Biogenic MccJ25 had a minimum inhibitory concentration of 0.25 µg/mL against ETEC K88, decreased ETEC K88 adhesion in cells and did not cause cytotoxicity toward cells. Furthermore, biogenic MccJ25 protects against ETEC-induced barrier dysfunction by increasing the TEER, decreasing the LDH and promoting tight junction proteins (TJPs) by promoting the assembly of occludin and claudin-1 in the tight junction complex. Biogenic MccJ25 was further found to relieve inflammation responses through modulation of interleukine-6, IL-8 and tumor necrosis factor-α levels via inhibition of mitogen-activated protein kinase (MAPK) and nuclear factor κB activation. In summary, biogenic MccJ25 can protects against ETEC K88-induced intestinal damage and inflammatory response, recommend the hidden adoption of biogenic MccJ25 as a novel prophylactic agent to reduce pathogen infection in animals, food or humans.