Lysophosphatidylcholine‐induced cytotoxicity and protection by heparin in mouse brain bEND.3 endothelial cells

A pathological feature in atherosclerosis is the dysfunction and death of vascular endothelial cells (EC). Oxidized low‐density lipoprotein (LDL), known to accumulate in the atherosclerotic arterial walls, impairs endothelium‐dependent relaxation and causes EC apoptosis. A major bioactive ingredient of the oxidized LDL is lysophosphatidylcholine (LPC), which at higher concentrations causes apoptosis and necrosis in various EC. There is hitherto no report on LPC‐induced cytotoxicity in brain EC. In this work, we found that LPC caused cytosolic Ca²⁺ overload, mitochondrial membrane potential decrease, p38 activation, caspase 3 activation and eventually apoptotic death in mouse cerebral bEND.3 EC. In contrast to reported reactive oxygen species (ROS) generation by LPC in other EC, LPC did not trigger ROS formation in bEND.3 cells. Pharmacological inhibition of p38 alleviated LPC‐inflicted cell death. We examined whether heparin could be cytoprotective: although it could not suppress LPC‐triggered Ca²⁺ signal, p38 activation and mitochondrial membrane potential drop, it did suppress LPC‐induced caspase 3 activation and alleviate LPC‐inflicted cytotoxicity. Our data suggest LPC apoptotic death mechanisms in bEND.3 might involve mitochondrial membrane potential decrease and p38 activation. Heparin is protective against LPC cytotoxicity and might intervene steps between mitochondrial membrane potential drop/p38 activation and caspase 3 activation.     

基于代谢组学探讨艾灸关元穴对老年大鼠肾能量代谢的影响＊

目的 通过UHPLC-Q-TOF-MS代谢组学探讨艾灸关元穴对老年大鼠肾代谢物的影响，进而为艾灸关元穴的作用机制提供参考。方法 将8月龄SD雄性大鼠设为成年对照组（8只），21月龄SD雄性大鼠随机分为老年对照组（8只）、老年金匮肾气丸组（7只）、老年艾灸组（8只）。老年金匮肾气丸组每日按体重给药，老年艾灸组每日艾灸关元穴15 min，均每周5天。实验持续13周后检测大鼠肾组织线粒体呼吸耗氧速率、琥珀酸脱氢酶（SDH）活性以及血清肾功能指标，观察肾脏病理变化，结合UHPLC-Q-TOF-MS技术对大鼠的肾组织进行代谢轮廓分析，筛选代谢差异物并进行鉴定。结果 与老年对照组比较，老年艾灸组大鼠肾线粒体的呼吸耗氧速率和SDH酶的活力显著提高（P<0.01）。代谢组学结果显示，肾组织中筛选出13个共同差异化合物，分别是丁酸十二烷基酯、亚油酰胺、5-甲基四氢叶酸、PC（16∶0/22∶5（7Z，10Z，13Z，16Z，19Z））、6，8-二羟基嘌呤、1，2，3-丙烷三羧酸、3-（4-甲氧基苯基）-2-氧代丙酸、吲哚-3-乙酰甘氨酸、亚麻油酸、9，10-环氧十八烷酸、二十二碳五烯酸（22n-6）、牛磺胆酸、LysoPS （18∶0/0∶0）。结论 艾灸关元穴可通过调控老年大鼠的牛磺酸和亚牛磺酸代谢、α-亚麻酸代谢、亚油酸代谢、甘油磷脂代谢来调节肾的能量代谢。     

Identification of key genes and pathways in discoid lupus skin via bioinformatics analysis

Discoid lupus erythematosus (DLE) is the most common skin manifestation of lupus; however, the molecular mechanisms underlying DLE remain unknown. Therefore, we aimed to identify key differentially expressed genes (DEGs) in discoid lupus skin and investigate their potential pathways.To identify candidate genes involved in the occurrence and development of the disease, we downloaded the microarray datasets {"type":"entrez-geo","attrs":{"text":"GSE52471","term_id":"52471"}}GSE52471 and {"type":"entrez-geo","attrs":{"text":"GSE72535","term_id":"72535"}}GSE72535 from the Gene Expression Database (GEO). DEGs between discoid lupus skin and normal controls were selected using the GEO2R tool and Venn diagram software (http://bioinformatics.psb.ugent.be/webtools/Venn/). The Database for Annotation, Visualization, and Integrated Discovery (DAVID), Enrichr, and Cytoscape ClueGo were used to analyze the Kyoto Encyclopedia of Gene and Genome pathways and gene ontology. Protein-protein interactions (PPIs) of these DEGs were further assessed using the Search Tool for the Retrieval Interacting Genes version 10.0.Seventy three DEGs were co-expressed in both datasets. DEGs were predominantly upregulated in receptor signaling pathways of the immune response. In the PPI network, 69 upregulated genes were selected. Furthermore, 4 genes (CXCL10, ISG15, IFIH1, and IRF7) were found to be significantly upregulated in the RIG-I-like receptor signaling pathway, from analysis of Enrichr and Cytoscape ClueGo.The results of this study may provide new insights into the potential molecular mechanisms of DLE. However, further experimentation is required to confirm these findings.