Synthetic Guaiacol Derivatives as Promising Myeloperoxidase Inhibitors Targeting Atherosclerotic Cardiovascular Disease.

Myeloperoxidase (MPO) is known to cause oxidative stress and inflammation leading to cardiovascular disease (CVD) complications. MPO-mediated oxidation of lipoproteins leads to dysfunctional entities altering the landscape of lipoprotein functionality. The specificity of guaiacol derivatives toward preventing MPO-mediated oxidation to limit MPO's harmful effects is unknown. Diligent in silico studies were accomplished for a portfolio of compounds with guaiacol as a building block. The compounds' activity toward MPO inhibition was also validated. The role of these chemical entities in controlling MPO-mediated oxidation of lipoproteins (LDL and HDL) was shown to agree with our approach of developing powerful MPO inhibitors. The mechanism of MPO inhibition was demonstrated to be reversible in nature. This study reveals that there is great potential for guaiacol derivatives as therapeutics for CVD by modulating lipid profiles, reducing atherosclerotic plaque burden, and subsequently optimizing cardiovascular functions.

Function of peritoneal mesothelial cells on the microenvironment by administration of endometrial cells / 中国病理生理杂志

AIM:To determine the function of peritoneal mesothelial cells on the inflammatory microenvironment by administration of endometrial cells,and further define the pathogenesis of endometriosis.METHODS:Homogenous mouse endometrial epithelial and stromal cells were injected into the peritoneal cavities of Swiss Webster mice.After 4,24,and 72 h,a number of endpoints evaluated:protein concentrations of cytokine MCP-1,IL-1 ?,IL-6 in peritoneal lavage and gene expressions of MCP-1,IL-1 ?,IL-6 in peritoneal mesothelial cells and macrophages.RESULTS:The intraperitoneal administration of endometrial cells increased the protein expressions of cytokines in the peritoneal lavage of the recipient mice,which increased at 4-hour points and subsequently decreased with time.Gene expressions of cytokines in peritoneal mesothelial cells paralleled with the protein quantities in peritoneal lavage.The peak time of gene expression of cytokines in peritoneal macrophages was at the 24-hour point.The endometrial epithelial cells stimulated stronger inflammatory responses in the peritoneal cavity than the endometrial stromal cells.CONCLUSION:The recipient mice have a non-specific inflammatory response to the presence of endometrial cells in the peritoneal cavity.Mesothelial cells may be the targets of early inflammatory stress initiated in the presence of endometrial cells.