Introduction The pathogenesis of inflammatory bowel disease (IBD) has not yet been clarified and is closely related to several pro‐inflammatory factors. MicroRNA‐233 (miR‐223) might be involved in the development of IBD; however, the mechanism underlying its pathogenesis is unclear. In this study, we attempted to determine the role of miR‐223 in dextran sodium sulfate (DSS)‐induced colitis and explore the involvement of the IL‐6/STAT3 pathway in the development of intestinal mucosal inflammation. Materials and Methods Except control (WT) group, male C57BL/6 mice were provided DSS, then treated for with miR‐223 agomir or antagomir including DSS group, DSS + miR‐223 agomir (DSS + A) group, and DSS + miR‐223 antagomir (DSS + AN) group. The colitis symptoms were observed, the disease activity index (DAI) score were recorded daily, and colonic inflammation was evaluated by histopathological scoring. The expression of myeloperoxidase (MPO), cytokines and IL‐6/STAT3 pathway‐related proteins were measured. Results miR‐223 expression in the terminal ileum and colon was increased in the DSS group compared with the WT group. Colitis symptoms were significantly alleviated in the DSS + A group and exacerbated in the DSS + AN group after administration of the miR‐223 agomir and antagomir, respectively. MPO, tumor necrosis factor‐α, IL‐6, and IL‐17 were decreased and IL‐10 was increased in the DSS + A group, but these changes were reversed in the DSS + AN group. Gp130, p‐STAT3, Bcl‐2, and Bcl‐xl in the colon declined in the DSS + A group, but these levels increased in the DSS + AN group. Conclusions The upregulation of miR‐223 by agomir administration alleviated colonic inflammation in a DSS‐induced colitis model, which was likely mediated by inhibiting the production of pro‐inflammatory cytokines via the IL‐6/STAT3 signaling pathway. These findings provide evidence that miR‐223 might have potential therapeutic implications in IBD.
Background: Few reports have focused on single-balloon enteroscopy (SBE) for evaluation of small bowel Crohn disease (CD) strictures. The aim of this study was to analyze the relationships between peripheral blood inflammatory markers and small bowel CD strictures observed by SBE.Materials and Methods: CD patients who underwent SBE between January 2016 and December 2020 were enrolled. The clinical characteristics and peripheral blood inflammatory markers were collected and analyzed to screen for predictive factors significantly associated with small bowel CD strictures.Results: A total of 221 CD patients underwent SBE. The lymphocyte (LC) counts in peripheral blood were significantly lower in the active group (n = 178) than in the inactive group (n = 43) according to the simple endoscopic score for CD (SES-CD), P = 0.011, and was correlated with the SES-CD (r = −0.134, P = 0.047). The LC levels were significantly lower in the stricture group (n = 116) than in the nonstricture group (n = 105) based on whether small bowel strictures developed, P = 0.000, and LC was a risk factor for strictures in the multivariate analysis [hazard ratio (HR), 2.332; 95% CI, 1.102-4.937; P = 0.027]. In the subgroup analysis, LC levels notably decreased after stricture aggravation (P = 0.000). Forty-seven patients who underwent small bowel resection underwent SBE at 6 to 12 months after surgery. The LC level was significantly lower in the postoperative patients with strictures (P = 0.025), and LC (HR, 4.444; 95% CI, 1.265-15.617; P = 0.020) was a risk of postoperative strictures by univariate analysis, but the age at diagnosis (HR, 6.462; 95% CI,; P = 0.022) was an independent risk factor by multivariate analysis. Conclusion:Peripheral blood LC levels were correlated with SES-CD and gradually decreased as the intestinal stricture increased in small bowel CD patients. The LC level was also significantly lower in the postoperative CD patients with strictures. The level of LC was a risk factor for small bowel strictures. These results suggest that peripheral blood LC could be a novel marker of small bowel CD strictures to guide CD diagnosis and therapy.
Background: The pathogenesis of inflammatory bowel disease (IBD) has not yet been clarified and is closely related to several proinflammatory factors. MicroRNA-233 (miR-223) might be involved in the development of IBD; however, the mechanism underlying its pathogenesis is unclear. In this study, we attempted to determine the role of miR-223 in dextran sodium sulfate (DSS)-induced colitis and explore the involvement of the IL-6/STAT3 pathway in the development of intestinal mucosal inflammation.Methods: Male C57BL/6 mice were divided into six groups: control (WT) group, DSS group, DSS+miR-223 agomir (DSS+A) group, DSS+miR-223 agomir negative control (DSS+A+NC) group, DSS+miR-223 antagomir (DSS+AN) group and DSS+miR-223 antagomir negative control (DSS+AN+NC) group. Body weight, stool consistency, fecal blood and the disease activity index (DAI) score were recorded daily. The length of each colon was measured, and colonic inflammation was evaluated with hematoxylin and eosin (H&E) staining and histopathological scoring. The expression of myeloperoxidase (MPO), TNF-α, IL-6, IL-10 and IL-17 in the colonic tissues was measured by Enzyme-linked Immunosorbent Assay (ELISA) and real-time quantitative polymerase chain reaction (RT-qPCR). The mRNA expression of gp130, Bcl-2 and Bcl-xl in the colon was measured using RT-qPCR. The colonic levels of STAT3 and p-STAT3 were determined by Western blotting.Results: MiR-223 expression in the terminal ileum and colon was increased in the DSS group compared with the WT group. Colitis symptoms were significantly alleviated in the DSS+A group and exacerbated in the DSS+AN group after administration of the miR-223 agomir and antagomir, respectively. MPO, TNF-α, IL-6 and IL-17 were decreased and IL-10 was increased in the DSS+A group, but these changes were reversed in the DSS+AN group. Gp130 mRNA, p-STAT3, Bcl-2 and Bcl-xl in the colon declined in the DSS+A group, but these levels increased in the DSS+AN group.Conclusion: The upregulation of miR-223 by agomir administration alleviated colonic inflammation in a DSS-induced colitis model, which was likely mediated by inhibiting the production of proinflammatory cytokines via the IL-6/STAT3 signaling pathway. These findings provide evidence that miR-223 might have potential therapeutic implications in IBD.
Background: Intestinal stricture is a complication of Crohn’s disease (CD) due to fibrosis, but there are no biomarkers for predicting intestinal strictures before clinical obstruction. It is reported that several types of lymphocytes (LC) are involved in the pathogenesis of intestinal fibrosis. However, few studies have focused on the peripheral blood LC in patients with CD associated stricture.Aim:To analyze the relationships between peripheral blood inflammatory markers especially LC and CD to provide evidence for CD diagnosis and therapy. Methods: A total of 158 CD patients who underwent single-balloon enteroscopy from January 2016 to June 2019 in Jinling Hospital were retrospectively enrolled. The Montreal classification, maintenance medicines, CD activity index (CDAI), simple endoscopic score for CD (SES-CD), full blood count and C-reactive protein (CRP) level were recorded. The relationships among peripheral blood inflammatory markers, disease activity and intestinal strictures were analyzed using SPSS 22.0. Results: After excluding 8 patients treated with azathioprine, which severely affects blood counts, 150 patients were divided into two groups: a stricture group (n=82) and non-stricture group (n=68). LC and the proportion of lymphocytes (LC%) were significantly lower in the stricture group than in the non-stricture group, p was 0.000 and 0.018, respectively, and LC was an independent risk factor of stricture lesion. In the subgroup analysis, 30 strictures without obstruction were classified as mild strictures, and 52 cases of obstruction were in the severe stricture group. LC notably decreased following stricture aggravation, p=0.000. The area under the curve (AUC) of LC predicting strictures was 0.711 with sensitivity of 73.5% and a specificity of 63.4% (cutoff: 1.245). Conclusion: LC gradually decreases as intestinal strictures aggravated and could be a new marker for predicting intestinal strictures in CD patients.
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