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1.
Int Immunopharmacol ; 134: 112217, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38718658

ABSTRACT

The imbalance between T helper cell 17 (Th17)and regulatory T cells (Treg) cells leading to inflammation has an important role in the pathogenesis of ulcerative colitis (UC). Mammalian target of rapamycin (mTOR) can regulate the differentiation of T cells, but the specific pathway leading mTOR to regulate Th17/Treg cells in UC remains unclear. Our aim with this study was to investigate the effects of mTOR overexpression and silencing on the hypoxia inducible factor-1α (HIF-1α) - Th17/Treg signaling pathway. To mimic a human study, we established a colon cancer epithelial cell line (HT-29) co-culture system with human CD4+ T cells, and we treated the cells with TNF-α. We observed the effects of mTOR on the HIF-Th17/Treg signaling pathway to determine whether mTOR is involved in the regulatory mechanism. Under the stimulation of TNF-α, the levels of HIF-1α in CD4+T cells were increased in the HT-29 co-culture with CD4+ T cells, promoting glycolysis, increasing the Th17 proportion, decreasing the Treg proportion, increasing the pro-inflammatory factors levels, and decreasing the anti-inflammatory factors levels. Moreover, after mTOR silencing, the HIF-1α level and cell glycolysis levels decreased, Th17 cell differentiation decreased, the pro-inflammatory factor levels decreased, and the anti-inflammatory factor levels increased. In contrast, mTOR overexpression lead to the opposite results.mTOR promotes inflammation by regulating the HIF signaling pathway during UC, and silencing mTOR may alleviate inflammation. An mTOR inhibitor is a potential therapeutic target for UC treatment.


Subject(s)
Coculture Techniques , Colitis, Ulcerative , Hypoxia-Inducible Factor 1, alpha Subunit , Signal Transduction , T-Lymphocytes, Regulatory , TOR Serine-Threonine Kinases , Th17 Cells , Humans , Colitis, Ulcerative/immunology , Colitis, Ulcerative/metabolism , Colitis, Ulcerative/pathology , TOR Serine-Threonine Kinases/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Th17 Cells/immunology , HT29 Cells , T-Lymphocytes, Regulatory/immunology , Tumor Necrosis Factor-alpha/metabolism , Inflammation/metabolism , Inflammation/immunology , Glycolysis
2.
Article in English | MEDLINE | ID: mdl-30949220

ABSTRACT

The objective of the meta-analysis was to evaluate the efficacy and safety of Traditional Chinese Medicine (TCM) in the treatment of Crohn's disease (CD). Pubmed, Embase, Medline, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature, Wanfang Database, and Cochrane Central Register of Controlled Trials were searched (through October 2018). The quality of randomized clinical trials meeting the inclusion criteria was assessed and the data were extracted according to the Cochrane Review Handbook v5.0 by two evaluators. A meta-analysis was performed using the software Stata 12.0. Twelve randomized controlled trials (RCTs) were selected. The studies were of low methodological quality. The meta-analysis indicated that treatment with TCM and Western Medicine (WM) was significantly superior compared to treatment with WM alone with regard to total effective rate, remission maintenance rate, reduction of C-reactive protein (CRP), reduction of erythrocyte sedimentation rate (ESR), clinical score reduction, and reduction of adverse events. Mucosal healing was improved in both the TCM-WM and WM groups; however, there were no significant differences between the two groups. There was a certain publication bias in the studies with regard to efficiency, adverse reactions, mucosal healing, and recurrence rate; however, there was no obvious publication bias with regard to other indicators. TCM, as an adjuvant therapy with WM, shows advantages in inducing remission in CD. The current evidence suggests that TCM-WM treatment might be more efficient in terms of total effective rate, remission maintenance rate, CRP reduction, ESR reduction, clinical score reduction, and reduction of adverse events than treatment with WM alone. Because of the low quality of the included RCTs, high quality confirmatory evidence is needed to assess the clinical value of TCM in the treatment of CD.

3.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 31(11): 1528-32, 2015 Nov.
Article in Chinese | MEDLINE | ID: mdl-26522363

ABSTRACT

OBJECTIVE: To evaluate the changes of blood coagulation in patients with active ulcerative colitis. METHODS: We searched the PubMed, Medline, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), Wanfang Database for the Chinese or English literatures published until January 2015. The data that met the inclusion criteria were screened and evaluated. After evaluation, the eligible ones were subjected to Newcastle-Ottawa Scale (NOS) and meta analysis using the Stata12.0 software. RESULTS: A total of 28 case-control studies were recruited for the meta analysis. The analysis results showed that the levels of platelet (PLT), fibrinogen (FIB) and D-dimer significantly increased in active ulcerative colitis group compared with normal control group. The levels of mean platelet volume (MPV) and prothrombin time (PT) significantly decreased in active ulcerative colitis group compared with normal control group. Sensitivity analysis showed that the evaluation result was stable. Egger and Begg tests suggested no evidence of substantial publication bias except for the literatures about D-dimer. CONCLUSION: Abnormal blood coagulation indexes of active ulcerative colitis patients indicate there may be high coagulation state in ulcerative colitis.


Subject(s)
Blood Coagulation , Colitis, Ulcerative/blood , Fibrinogen/analysis , Humans , Mean Platelet Volume , Partial Thromboplastin Time , Platelet Count
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