Hustedhollis7514

Background Intestinal barrier contributes as an important role in maintaining intestinal homeostasis. Oxidative stress can cause critical damages in intestinal integrity of animals. Objectives This study was conducted to investigate the alleviated effect of taurine against small intestine (duodenum, jejunum, ileum) injury induced by oxidative stress. Methods The piglet model of diquat-induced oxidative stress was employed. In addition, analysis of intestinal morphology, reverse transcription PCR (RT-PCR), and Western blot were used in this study. Results Compared with the control group (CON), diquat-induced oxidative stress triggers immune response; the content of immunoglobulin M (IgM) and immunoglobulin G (IgG) was significantly changed, but 0.60% taurine supplementation could restore the level of serum immunoglobulin. Oxidative stress induces serious damage in intestinal morphology structure and tight junction barrier. Compared with the CON, the villus height of intestine was significantly decreased, the crypt depth and villus height/crypt depth (V/C) were also decreased, and 0.60% taurine supplementation could restore impaired morphology and even improve crypt depth and V/C of the jejunum and ileum. Compared with the CON, oxidative stress markedly increased the messenger RNA (mRNA) expression level of claudin-1 and occludin in the duodenum, and the value of occludin was significantly decreased in the jejunum of the diquat group (DIQ). Relative to the DIQ, 0.60% taurine supplementation increased the mRNA expression level of claudin-1, occludin, and ZO-1 in the ileum. Compared with the CON, the expression of claudin-1 protein was significantly upregulated, and occludin and ZO-1 protein were both downregulated in the small intestine of DIQ. Conclusion Taurine exerts protective effects by regulating immune response and restores the intestinal tight junction barrier when piglets suffer from oxidative stress.The cyclooxygenase-2 (COX-2) enzyme is frequently overexpressed in epithelial malignancies including those of the breast, prostate, lung, kidney, ovary, and liver and elevated expression is associated with worse outcomes. COX-2 catalyzes the metabolism of arachidonic acid to prostaglandins. The COX-2 product prostaglandin E2 (PGE2) binds to four G-protein-coupled EP receptors designated EP1-EP4. EP4 is commonly upregulated in cancer and supports cell proliferation, migration, invasion, and metastasis through activation of multiple signaling pathways including ERK, cAMP/PKA, PI3K/AKT, and NF-κB. EP4 antagonists inhibit metastasis in preclinical models. Cancer stem cells, that underlie therapy resistance and disease relapse, are driven by the expression of EP4. Resistance to several chemotherapies is reversed in the presence of EP4 antagonists. FRAX486 clinical trial In addition to tumor cell-autonomous roles of EP4, many EP4-positive host cells play a role in tumor behavior. Endothelial cell-EP4 supports tumor angiogenesis and lymphangiogenesis. Natural Killer (NK) cells are critical to the mechanism by which systemically administered EP4 antagonists inhibit metastasis. PGE2 acts on EP4 expressed on the NK cell to inhibit tumor target cell killing, cytokine production, and chemotactic activity. Myeloid-derived suppressor cells (MDSCs), that inhibit the development of cytotoxic T cells, are induced by PGE2 acting on myeloid-expressed EP2 and EP4 receptors. Inhibition of MDSC-EP4 leads to maturation of effector T cells and suppresses the induction of T regulatory cells. A number of EP4 antagonists have proven useful in dissecting these mechanisms. There is growing evidence that EP4 antagonism, particularly in combination with either chemotherapy, endocrine therapy, or immune-based therapies, should be investigated further as a promising novel approach to cancer therapy. Several EP4 antagonists have now progressed to early phase clinical trials and we eagerly await the results of those studies.The traditional Chinese medicine Shen-ling-bai-zhu-san (SLBZS) is described in "Tai Ping Hui Min He Ji Ju Fang." SLBZS has been shown to be effective against many gastrointestinal diseases. The present study aimed to investigate the effect of SLBZS on experimental colitis in mice and to define the potential mechanisms. Our data suggest that compared to the model group, SLBZS treatment increases mouse body weight and colon length, decreases the DAI score, and improves colonic injury. SLBZS reduces the production of cytokines (IL-1β, IL-18, and TNF-α) in colon tissue and mouse colonic mucosal epithelial (MCME) cells. Mechanistically, SLBZS inhibits inflammation by inhibiting the MAPK and NF-κB signaling pathways. Further mechanistic analyses showed that SLBZS attenuates the expression levels of pyroptosis-related genes, including NLRP3, ASC, and GSDMD-N in the colons of mice. In addition, SLBZS restores the levels of the colon tight junction proteins ZO-1 and occludin, suggesting that it protects colonic barrier integrity and ameliorates the progression of colitis. In this paper, we demonstrate that SLBZS attenuates DSS-induced ulcerative colitis injury in mice via the MAPK/NF-κB and pyroptosis signaling pathway. These results indicate that SLBZS is a potential drug for the treatment of UC.Although increasing reports from the literature on herbal-related hepatotoxicity, the identification of susceptibility-related factors and biomarkers remains challenging due to idiosyncratic drug-induced liver injury (IDILI). As a well-known Chinese medicine prescription, Xianling Gubao Capsule (XLGB) has attracted great attention due to reports of potential liver toxicity. But the mechanism behind it is difficult to determine. In this paper, we found that XLGB-induced liver injury belongs to IDILI through the analysis of clinical liver injury cases. In toxicological experiment assessment, co-exposure to XLGB and non-toxic dose of lipopolysaccharide (LPS) could cause evident liver injury as manifested by significantly increased plasma alanine aminotransferase activity and obvious liver histological damage. However, it failed to induce observable liver injury in normal rats, suggesting that mild immune stress may be a susceptibility factor for XLGB-induced idiosyncratic liver injury. Furthermore, plasma cytokines were determined and 15 cytokines (such as IL-1β, IFN-γ, and MIP-2α etc) were acquired by receiver operating characteristic (ROC) curves analysis.