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purpose of this paper was to study the effect of Lactobacillus fermentum ZS09 (L. fermentum ZS09) on the EMT pathway in mouse with azoxymethane/dextran sulfate sodium salt (AOM/DSS) induced colon cancer and the potential underlying mechanism. Materials and Methods: In this study, a mouse colon cancer model was established through intraperitoneal injection of 10 mg/kg azoxymethane (AOM) and three cycles of 2.5% dextran sulfate sodium salt (DSS) in the drinking water. H&E staining, enzyme-linked immunosorbent assay (ELISA), real-time fluorescent quantitative PCR (RT-qPCR) and Western blotting (WB) were used to study the antitumour mechanisms of L. fermentum ZS09 through the EMT pathway. Results: The results of this study showed that compared with the model group, the high-dose L. fermentum ZS09 intervention group exhibited decreased serum levels of MMP-9, TNF-α, IL-6R, Ang-2 and VEGFR-2 and increased contents of DKK1 (P< 0.05). The expression of Wnt/β-catenin signalling pathway-related genes (Dv1, GSK-3β, β-catenin, c-myc, cyclinD1, Vim, and MMP-9) was significantly reduced, and the gene expression levels of APC, CDH1, and Axin were increased. The levels of related proteins (β-catenin, N-cadherin, and VEGF) were downregulated, and the levels of p-β-catenin and E-cadherin were upregulated. Conclusion: The results indicate that L. fermentum ZS09 could inhibit EMT and angiogenesis pathways by inhibiting the Wnt/β-catenin signalling pathway, which could inhibit tumour metastasis. [ABSTRACT FROM AUTHOR]

The pathogenesis and course of inflammatory bowel diseases are related to both immune system disorders and dysfunction of colon permeability. Moreover, co-existing diseases in patients with Crohn's disease and ulcerative colitis are identified. Currently, there are some therapeutic strategies that affect the function of cytokine/s causing inflammation in the intestinal wall. However, additional approaches which target other components of inflammatory bowel diseases pathogenesis are still needed. Accumulating evidence suggests that proteases and protease-activated receptors seem to be responsible for colitis progression. Experimental and observational studies showed alteration of protease-activated receptors expression in the colon of patients with Crohn's disease and ulcerative colitis. Furthermore, it was suggested that the expression of protease-activated receptors correlated with inflammatory bowel diseases activity. Moreover, regulation of protease-activated receptors seems to be responsible for the modulation of colitis and clinical manifestation of inflammatory bowel diseases. In this review, we present the current state of knowledge about the contribution of protease-activated receptors to Crohn's disease and ulcerative colitis and its implications for diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Purpose: Jintiange capsule (JTG), an approved drug developed as a substitute for tiger bone (TB), has been clinically applied for osteoporosis therapy since 2003. The drug is composed of bionic TB powder, in which peptides and proteins are primarily enriched from other bone extracts. However, as a precious material of traditional Chinese medicine (TCM), TB has been mainly understood and used in TCM to relieve osteoporosis, rheumatoid arthritis and bone injury. Inspired by those, the purpose of this study was to investigate whether JTG also had an effect on relieving rheumatoid arthritis in collagen-induced arthritic (CIA) rats and explore potential mechanism from the perspective of serum metabolic profile changes. Methods: JTG was analyzed using Nano LC-MS/MS and orally administered in CIA rats for 6 weeks. After administration, intervention effects of JTG on synovial inflammation, bone micro-architecture and bone metabolism were studied, and the impact of JTG on serum metabolic profiles in CIA rats was investigated by metabolomics. Results: Nine bioactive peptides were identified in JTG. In animal treatments, JTG alleviated paw swelling (P < 0.01), arthritic severity (P < 0.01) and synovial tissue proliferation, as well as inflammatory cell infiltration of ankle joint, decreased bone loss, improved microstructure of bone in CIA rats by regulating bone absorption and formation, specifically increasing bone mineral density (BMD) (P < 0.05), bone volume fraction (BVF) (P < 0.05), trabecular number (Tb.N) (P < 0.05) and decreasing trabecular separation (Tb.Sp) (P < 0.05). Besides, serum IL-6 was down-regulated remarkably in CIA rats (P < 0.05). Furthermore, metabolomics analysis revealed that 32 metabolites were regulated significantly (P < 0.05) by comparison between CIA model and JTG in 360 mg/kg dose. The pathway analysis implied that JTG was involved in regulation of biosynthesis of phenylalanine. Conclusion: JTG alleviates rheumatoid arthritis and reverses changes in serum metabolic profile in CIA rats. [ABSTRACT FROM AUTHOR]