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2023 4

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CPAL 1

心肌梗死 1

核因子κB 1

炎症 1

细胞焦亡 1

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A new perspective in pyroptosis: lifting the veil on GSDMA activation

《医学前沿（英文）》 2023年第17卷第3期页码 581-583 doi: 10.1007/s11684-022-0971-9

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Hyperosmolarity promotes macrophage pyroptosis by driving the glycolytic reprogramming of corneal epithelial

《医学前沿（英文）》 2023年第17卷第4期页码 781-795 doi: 10.1007/s11684-023-0986-x

摘要： Tear film hyperosmolarity plays a core role in the development of dry eye disease (DED) by mediating the disruption of ocular surface homeostasis and triggering inflammation in ocular surface epithelium. In this study, the mechanisms involving the hyperosmolar microenvironment, glycolysis mediating metabolic reprogramming, and pyroptosis were explored clinically, in vitro, and in vivo. Data from DED clinical samples indicated that the expression of glycolysis and pyroptosis-related genes, including PKM2 and GSDMD, was significantly upregulated and that the secretion of IL-1β significantly increased. In vitro, the indirect coculture of macrophages derived from THP-1 and human corneal epithelial cells (HCECs) was used to discuss the interaction among cells. The hyperosmolar environment was found to greatly induce HCECs’ metabolic reprogramming, which may be the primary cause of the subsequent inflammation in macrophages upon the activation of the related gene and protein expression. 2-Deoxy-d-glucose (2-DG) could inhibit the glycolysis of HCECs and subsequently suppress the pyroptosis of macrophages. In vivo, 2-DG showed potential efficacy in relieving DED activity and could significantly reduce the overexpression of genes and proteins related to glycolysis and pyroptosis. In summary, our findings suggested that hyperosmolar-induced glycolytic reprogramming played an active role in promoting DED inflammation by mediating pyroptosis.

关键词： dry eye disease glycolytic reprogramming pyroptosis inflammation 2-DG

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作为一种新的心肌细胞代谢改变和焦亡调节剂，CPAL可调节小鼠心肌梗死损伤 Article

李佳敏, 薛宏儒, 徐宁, 龚丽玲, 李鸣, 李思佳, 黄迪, 张庆伟, 李鹏宇, 李青穗, 于航, 刘伊宁, 薛亚东, 陈海鑫, 刘佳丽, 张万玉, 刘明彬, 常思雨, 郎宪治, 赵星淼, 杜伟杰, 蔡本志, 王宁, 杨宝峰

《工程（英文）》 2023年第20卷第1期页码 49-62 doi: 10.1016/j.eng.2022.08.012

摘要：

心肌梗死（myocardial infarction, MI）是一种严重的缺血性心脏病疾病，常伴有心肌代谢紊乱和心肌细胞死亡。越来越多的证据表明，长链非编码RNA（lncRNA）参与癌症及心血管疾病（cardiovascular diseases, CVD）等多种疾病的病理过程，并逐渐成为这些疾病的一种新的生物标志物。本研究旨在探究lncRNA在调节心肌梗死后心肌重构中的作用及机制。研究发现三磷酸腺苷（ATP）在急性心肌梗死边缘区心肌组织中含量减少，糖脂代谢相关基因如分化抗原簇36（CD36）、己糖激酶1（HK1）和葡萄糖转运蛋白4（GLUT4）的表达水平也明显异常，并伴有心肌细胞焦亡的发生。随后发现一种此前未知的保守的lncRNA，即AK009126（心肌细胞焦亡相关lncRNA, CPAL）。实时荧光定量PCR结果显示，CPAL在心肌梗死小鼠的心脏梗死边缘区组织中显著上调。此外，腺相关病毒9（AAV9）通过其短发夹RNA（shRNA）介导的内源性CPAL沉默，可以部分消除缺血小鼠的心肌代谢紊乱，并抑制心肌细胞焦亡。研究结果显示CPAL具有直接结合核因子kappa B（NFκB）的能力，并作为NFκB的激活剂诱导心肌细胞NFκB磷酸化，活化后的NFκB在转录水平促进含半胱氨酸的天冬氨酸蛋白水解酶1（caspase-1）的转录，进而促进其翻译。同时，CPAL增加了心肌细胞中白细胞介素（interleukin, IL）-18 和IL-1β的释放。总的来说，本研究揭示了lncRNA CPAL可能是心肌梗死后诱导心脏代谢异常和心肌细胞焦亡的一种新调节因子，并提示CPAL可能成为治疗心肌细胞缺血损伤的新靶点。

关键词：心肌梗死细胞焦亡 CPAL 核因子κB 炎症