Efficacy and safety of moxibustion for ulcerative colitis: protocol for a systematic review and meta-analysis.

INTRODUCTION: Ulcerative colitis (UC) is a global chronic inflammatory bowel disease, and the poor efficacy of currently available pharmacological regimens makes the management of UC a great challenge. Moxibustion has shown great potential in the management of UC. However, its effectiveness and safety are still controversial. The purpose of this study is to synthesise the latest evidence regarding the clinical efficacy and safety of moxibustion for UC. METHODS AND ANALYSIS: The Cochrane Library, PubMed, EMBASE, CNKI, Wanfang, VIP and SinoMed databases will be searched from inception to July 2023, to identify all randomised controlled trials with moxibustion for UC. The primary outcome will be clinical efficacy, as measured by validated scales. The serum inflammatory factor, colonoscopy results, quality of life, recurrence rate and adverse events will be the secondary outcomes. The Cochrane Risk of Bias 2.0 tool will be used to assess the methodological quality of each included trial. All data extraction will be carried out independently by two investigators. RevMan V.5.4 software will be used for data analysis and Cochran's Q statistic and I2 test will be used to assess heterogeneity between studies. In addition, we will perform subgroup analyses, sensitivity analyses and publication bias if the available data are sufficient. The strength of evidence will be graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. ETHICS AND DISSEMINATION: Ethics approval is not required for this review. Our findings will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023425481.

Astragalus Polysaccharide Alleviates Ulcerative Colitis by Regulating the Balance of mTh17/mTreg Cells through TIGIT/CD155 Signaling.

The balance between memory Th17 cells (mTh17) and memory Treg cells (mTreg) plays a key role in the pathogenesis of ulcerative colitis (UC), and TIGIT signaling is involved in the differentiation of mTh17/mTreg cells. Astragalus polysaccharide (APS) has good immunomodulatory and anti-inflammatory effects. Here, the regulatory effects and potential mechanisms of APS on mTh17/mTreg cells in UC are explored. A UC model was induced with dextran sulfate sodium (DSS) and treated simultaneously with APS (200 mg/kg/day) for 10 days. After APS treatment, the mice showed a significant increase in colonic length and a significant decrease in colonic weight, colonic weight index and colonic weight/colonic length, and more intact mucosa and lighter inflammatory cell infiltration. Notably, APS significantly down-regulated the percentages of Th17 (CD4+CCR6+), cmTh17 (CD4+CCR7+CCR6+) and emTh17 (CD4+CCR7-CCR6+) cells and significantly up-regulated the percentages of cmTreg (CD4+CCR7+Foxp3+) and emTreg (CD4+CCR7-Foxp3+) cells in the mesenteric lymph nodes of the colitis mice. Importantly, APS reversed the expression changes in the TIGIT molecule on mTh17/mTreg cells in the colitis mice with fewer CD4+CCR6+TIGIT+, CD4+CCR7-CCR6+TIGIT+ and CD4+CCR7-CCR6+TIGIT+ cells and more CD4+Foxp3+TIGIT+, CD4+CCR7-Foxp3+TIGIT+ and CD4+CCR7-Foxp3+TIGIT+ cells. Meanwhile, APS significantly inhibited the protein expression of the TIGIT ligands CD155, CD113 and CD112 and downstream proteins PI3K and AKT in the colon tissues of the colitis mice. In conclusion, APS effectively alleviated DSS-induced UC in mice by regulating the balance between mTh17/mTreg cells, which was mainly achieved through regulation of the TIGIT/CD155 signaling pathway.

Curcumin alleviated dextran sulfate sodium-induced colitis by recovering memory Th/Tfh subset balance.

BACKGROUND: Restoration of immune homeostasis by targeting the balance between memory T helper (mTh) cells and memory follicular T helper (mTfh) cells is a potential therapeutic strategy against ulcerative colitis (UC). Because of its anti-inflammatory and immunomodulatory properties, curcumin (Cur) is a promising drug for UC treatment. However, fewer studies have demonstrated whether Cur can modulate the mTh/mTfh subset balance in mice with colitis. AIM: To explore the potential mechanism underlying Cur-mediated alleviation of colitis induced by dextran sulfate sodium (DSS) in mice by regulating the mTh and mTfh immune homeostasis. METHODS: Balb/c mice were administered 3% and 2% DSS to establish the UC model and treated with Cur (200 mg/kg/d) by gavage on days 11-17. On the 18th d, all mice were anesthetized and euthanized, and the colonic length, colonic weight, and colonic weight index were evaluated. Histomorphological changes in the mouse colon were observed through hematoxylin-eosin staining. Levels of Th/mTh and Tfh/mTfh cell subsets in the spleen were detected through flow cytometry. Western blotting was performed to detect SOCS-1, SOCS-3, STAT3, p-STAT3, JAK1, p-JAK1, and NF-κB p65 protein expression levels in colon tissues. RESULTS: Cur effectively mitigates DSS-induced colitis, facilitates the restoration of mouse weight and colonic length, and diminishes the colonic weight and colonic weight index. Simultaneously, it hinders ulcer development and inflammatory cell infiltration in the colonic mucous membrane. While the percentage of Th1, mTh1, Th7, mTh7, Th17, mTh17, Tfh1, mTfh1, Tfh7, mTfh7, Tfh17, and mTfh17 cells decreased after Cur treatment of the mice for 7 d, and the frequency of mTh10, Th10, mTfh10, and Tfh10 cells in the mouse spleen increased. Further studies revealed that Cur administration prominently decreased the SOCS-1, SOCS-3, STAT3, p-STAT3, JAK1, p-JAK1, and NF-κB p65 protein expression levels in the colon tissue. CONCLUSION: Cur regulated the mTh/mTfh cell homeostasis to reduce DSS-induced colonic pathological damage, potentially by suppressing the JAK1/STAT3/SOCS signaling pathway.