Aims/IntroductionAn elevated level of plasma homocysteine has long been suspected as a metabolic risk factor for the development of atherosclerotic vascular diseases in diabetes. Berberine (BBR) has several preventive effects on cardiovascular diseases. The effects of BBR on atherosclerotic plaque stability increased by homocysteine thiolactone (HTL) remain unknown.Materials and MethodsThe model of atherosclerotic vulnerable plaque was induced by placing a collar around the carotid artery in Apoe −/− mice. Endothelium‐dependent relaxation was assayed by organ chamber.ResultsHomocysteine thiolactone (50 mg/kg/day, 8 weeks) reduced the atherosclerotic plaque stability in the carotid artery of Apoe −/− mice, which was reversed by BBR administration (1.0 g/kg/day). In vivo and ex vivo experiments showed that HTL dramatically reduced acetylcholine‐induced endothelium‐dependent relaxation and superoxide dismutase activity, and increased malondialdehyde content, which were inhibited by BBR. Importantly, all effects induced by BBR were abolished by GW9662, an antagonist of peroxisome proliferator‐activated receptor‐γ. Incubation of cultured endothelial cells with HTL significantly reduced cell viabilities and enhanced production of reactive oxygen species. Pretreatment of cells with BBR dose‐dependently reversed HTL‐induced detrimental effects, which were GW9662‐reversible.ConclusionsBerberine increases atherosclerotic plaque stability in hyperhomocysteinemia mice, which is related to the activation of peroxisome proliferator‐activated receptor‐γ and subsequent suppression of oxidative stress in endothelial cells.

Background Breast cancer is a heterogeneous disease. Compared with other subtypes of breast cancer, triple-negative breast cancer (TNBC) is easy to metastasize and has a short survival time, less choice of treatment options. Here, we aimed to identify the potential biomarkers to TNBC diagnosis and prognosis. Material/Methods Three independent data sets (GSE45827, GSE38959, GSE65194) were downloaded from the Gene Expression Omnibus (GEO). The R software packages were used to integrate the gene profiles and identify differentially expressed genes (DEGs). A variety of bioinformatics tools were used to explore the hub genes, including the DAVID database, STRING database and Cytoscape software. Reverse transcription quantitative PCR (RT-qPCR) was used to verify the hub genes in 14 pairs of TNBC paired tissues. Results In this study, we screened out 161 DEGs between 222 non-TNBC and 126 TNBC samples, of which 105 genes were up-regulated and 56 were down-regulated. These DEGs were enriched for 27 GO terms and two pathways. GO analysis enriched mainly in “cell division”, “chromosome, centromeric region” and “microtubule motor activity”. KEGG pathway analysis enriched mostly in “Cell cycle” and “Oocyte meiosis”. PPI network was constructed and then 10 top hub genes were screened. According to the analysis results of the Kaplan-Meier survival curve, the expression levels of only NUF2, FAM83D and CENPH were associated with the recurrence-free survival in TNBC samples (P < 0.05). RT-qPCR confirmed that the expression levels of NUF2 and FAM83D in TNBC tissues were indeed up-regulated significantly. Conclusions The comprehensive analysis showed that NUF2 and FAM83D could be used as potential biomarkers for diagnosis and prognosis of TNBC.

No abstract

No abstract