ABSTRACT
Intestinal inflammation is a common disease which can further lead to inflammatory bowel disease and even intestinal cancer. The increasing focus has come to the role of short-chain fatty acid (SCFA) in various bowel diseases. Hence, this study was designed to explore the specific role of SCFA in intestinal inflammation. In vivo and in vitro models of intestinal inflammation were constructed by lipopolysaccharide (LPS) injection in mice and LPS treatment on intestinal epithelial cells. A possible regulatory mechanism involving SCFA, CCAAT enhancer-binding protein beta (CEBPB), microRNA-145 (miR-145), and dual-specificity phosphatase 6 (DUSP6) in intestinal inflammation was verified by ChIP assay and dual-luciferase reporter gene assay. To evaluate the effects of SCFA on LPS-treated intestinal epithelial cells, the expression of relevant genes and inflammatory factors (IL-6, TNF-α, and IL-1ß) were determined. Last, the role of SCFA in vivo was explored through the scoring of disease activity index (DAI) and observation of colonic histology of LPS-treated mice. SCFA decreased the CEBPB expression in mouse colon tissues and small intestine epithelial cells induced by LPS. Furthermore, CEBPB could bind to the miR-145 promoter to inhibit its expression, thereby promoting the expression of DUSP6. In addition, SCFA improved the DAI, colonic histology, and the expression of serum inflammatory factors in LPS-treated mice and cells, noting that SCFA alleviated intestinal inflammation in vitro and in vivo. To sum up, SCFA inhibited DUSP6 by upregulating miR-145 through CEBPB repression and thus prevented the development of intestinal inflammation.
Subject(s)
CCAAT-Enhancer-Binding Protein-beta/metabolism , Colitis/metabolism , Colon/metabolism , Dual Specificity Phosphatase 6/metabolism , Fatty Acids, Volatile/metabolism , Intestinal Mucosa/metabolism , MicroRNAs/metabolism , Animals , CCAAT-Enhancer-Binding Protein-beta/immunology , Colitis/immunology , Colitis/pathology , Colon/immunology , Colon/pathology , Dual Specificity Phosphatase 6/immunology , Epithelial Cells/immunology , Epithelial Cells/metabolism , Epithelial Cells/pathology , Fatty Acids, Volatile/immunology , Intestinal Mucosa/immunology , Intestinal Mucosa/pathology , Lipopolysaccharides/immunology , Male , Mice , Mice, Inbred C57BL , MicroRNAs/immunologyABSTRACT
Anesthetic drug wastage has increasingly become the main resource of operating room sewage, which poses a great risk to the safety of humans and other organisms. Propofol is the most widely used anesthetic drug in the world, and also occupies the largest proportion of the total anesthetic wastage in the operating room. In this work, a 2D Cu2O anchored carbon catalyst (Cu2O@NC) was prepared by the assembly-pyrolysis process and successfully applied to peroxymonosulfate (PMS) activation. We took propofol as a typical example and investigated the removal activity through heterostructure-enhanced advanced oxidation processes (AOPs). Through the degradation process, propofol can be removed from 20 ppm to ultralow levels within 5 min using the PMS/Cu2O@NC system. The degradation pathway of propofol was deduced through quantum chemical calculation and LC/GC-MS results. The final products were verified as CO2 and H2O. Moreover, sulfate radicals (SO4Ë-) proved to be the dominant reactive oxidation species by radical scavenger experiments and ESR results. In addition, it has great universality for various pharmaceuticals such as tetracycline (TC), amoxicillin (AMX), cephalexin (CPX), and norfloxacin (NFX). Our work provided the possibility to treat operation room sewage in a rapid, high-efficiency, and feasible way.
