Background Ulcerative colitis (UC) is an intestinal disease which was characterized by intestinal inflammation, mucosal injury and fibrosis. In this paper, the effect of Huanglian Jiedu Decoction (HJD), a well-known traditional Chinese medicine with significant anti-inflammatory effect, on dextran sulphate sodium (DSS)-induced UC in mice and inhibition of JAK2/STAT3 pathway were investigated. Methods BALB/c mice were randomly divided into 6 groups: HJD group (high, medium and low dose), USAN group, UC group, and control group. UC in mice were induced through free access to 3% DSS solution. After being treated with HJD for 8 days, all animals were sacrifice. Pathological examination of colonic specimen was performed by H&E staining. Cytokines (TNF-α, IL-6, and IL-1β) in colon were assayed by ELISA and immunofluorescence, MPO in colon and ATT in serum were detected by ELISA. Moreover, mice in HJD group and UC group were treated with AG490 to inhibit the expression of JAK2 protein, then the expression of JAK2 and STAT3 protein in colon was determined by western blotting and immunofluorescence staining. Furthermore, KI67 in colon was examined by immunohistochemistry, and apoptosis was detected by TUNEL staining, and collagen deposition was assayed by Masson staining after JAK2/STAT3 pathway in UC mice was inhibited by HJD. Results After mice being treated with HJD, the symptoms (weight loss and haematochezia) of UC were alleviated, and the contents of inflammatory cytokines (TNF-α, IL-6 and IL-1β) and MPO in colon were significantly decreased. The expression of JAK2 and STAT3 protein was reduced after administration with HJD. After JAK2/STAT3 pathway being inhibited with HJD, the cell apoptosis, collagen deposition and immunoreactivity of macrophage in colon were significantly reduced, but the expression of Ki67 was markedly enhanced in both UC group and HJD group compare with control group. Conclusions HJD treatment can alleviate intestinal mucosal damage and has the protective effect on UC by downregulating JAK2 and STAT3 expression to reduce inflammation via JAK2/STAT3 pathway.

No abstract

Background: Colon cancer is one of the most common cancer worldwide and has a poor prognosis. Through the analysis of transcriptome and clinical data of colon cancer, immune gene-set signature was identified by single sample enrichment analysis (ssGSEA) scoring to predict patient survival and discover new therapeutic targets. Objective: To study the role of immune gene-set signature in colon cancer. Methods: First, RNASeq and clinical follow-up information were downloaded from The Cancer Genome Atlas (TCGA). Immune gene-related gene sets were collected from ImmPort database. Genes and immunological pathways related to prognosis were screened in the training set and integrated for feature selection using random forest. Immune gene-related prognosis model was verified in the entire TCGA test set and GEO validation set and compared with immune cells scores and matrix score. Results: 1650 prognostic genes and 13 immunological pathways were identified. These genes and pathways are closely related to the development of tumors. 13-immune gene-set signature was established, which is an independent prognostic factor for patients with colon cancer. Risk stratification of samples could be carried out in the training set, test set and external validation set. The AUC of five-year survival in the training set and validation set is greater than 0.6. Immunosuppression occurs in high-risk samples. Compared with published models, Riskscore has better prediction effect. Conclusion: This study constructed 13-immune gene-set signature as a new prognostic marker to predict the survival of patients with colon cancer, and provided new diagnostic/prognostic biomarkers and therapeutic targets for colon cancer.