With the wide application of non-steroidal anti-inflammatory drugs (NSAIDs), their gastrointestinal side effects are an urgent health burden. There are currently sound preventive measures for upper gastrointestinal injury, however, there is a lack of effective defense against lower gastrointestinal damage. According to a large number of previous animal experiments, a variety of NSAIDs have been demonstrated to induce small intestinal mucosal injury in vivo. This article reviews the descriptive data on the administration dose, administration method, mucosal injury site, and morphological characteristics of inflammatory sites of various NSAIDs. The cells, cytokines, receptors and ligands, pathways, enzyme inhibition, bacteria, enterohepatic circulation, oxidative stress, and other potential pathogenic factors involved in NSAID-associated enteropathy are also reviewed. We point out the limitations of drug modeling at this stage and are also pleased to discover the application prospects of chemically modified NSAIDs, dietary therapy, and many natural products against intestinal mucosal injury.
Intestinal metabolites are attracting increasing interest, especially more and more studies have found they are closely related to diseases. Microbial fermentation of indigestible dietary fibers in the gut produces short chain fatty acids (SCFAs) as the main product. SCFAs can exert influences on the integrity of the intestinal epithelial and mucosal barrier, immune reactions, and the diversity of microbiota in humans. Thus, alteration in SCFAs may affect inflammatory bowel disease (IBD). In IBD, SCFAs are involved in the main pathogenic process and play an important role in the development of intestinal inflammation. Although many studies have proved that pretreatment with SCFAs can effectively ameliorate inflammation in the gut, the mechanisms are not fully understood. In this review, we describe the relationship between SCFAs and IBD from the aspects of defense barrier, immune effects, and microbial alterations. We also summarize the effects of SCFAs on comorbidities in IBD via the gut-brain, gut-liver, and gut-lung axis, and we give an overview of the prospects of their clinical application. A better understanding of the relevance of SCFAs in IBD may reveal novel targets for future study
The main reason for poor prognosis in hepatocellular carcinoma (HCC) patients is high metastasis and recurrence. Cancer progression depends on a tumor-supportive microenvironment. Therefore, illustrating the mechanisms of tumor immunity in underlying HCC metastasis is essential. Here, we report a novel role of solute carrier family 7 member 2 (SLC7A2), a member of the solute carrier family, in HCC metastasis. The reduction of SLC7A2 was an independent and significant risk factor for the survival of HCC patients. Upregulation of SLC7A2 decreased HCC invasion and metastasis, whereas downregulation of SLC7A2 promoted HCC invasion and metastasis. We further found that deficient SLC7A2 medicated the upregulation of CXCL1 through PI3K/Akt/NF-kκB pathway to recruit myeloid-derived suppressor cells (MDSCs), exerting tumor immunosuppressive effect. Moreover, we found that G9a-mediated di-methylation of H3K9 (H3K9me2) silenced the expression of SLC7A2 to suppress HCC metastasis and immune escape. In conclusion, G9a-mediated silencing of SLC7A2 exerts unexpected functions in cancer metastasis by fostering a tumor-supportive microenvironment through CXCL1 secretion and MDSCs recruitment. Thus, SLC7A2 may provide new mechanistic insight into the cancer-promoting property of MDSCs.
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