Autoimmune myocarditis is the limited or diffuse inflammation of the myocardium due to dysfunctional cellular and humoral immunity mechanisms. We constructed mouse models of experimental autoimmune myocarditis (EAM) using peptide MyHC-α614-629. On the day after secondary immunization, the mice were intraperitoneally injected with Rho kinase (ROCK) inhibitor Y-27632. On day 21, the cardiac tissues were harvested and weighed. The hearts of EAM mice were significantly enlarged and whitened. Furthermore, body weight (BW) slowly increased during the treatment period, the heart weight (HW) and the ratio of HW/eventual BW were increased, and inflammatory infiltration and fibrosis were aggravated in the myocardial tissue. Y-27632 treatment improved the aforementioned phenotypic and pathological features of EAM mice. Mechanistic analysis revealed a significant increase in Notch1, Hes1, Jag2, Dil1, Toll-like receptor (Tlr) 2, and interleukin (IL)-1β expression in the myocardial tissue of EAM mice. Notably, IL-1β expression was correlated with that of Notch1 and Tlr2. Following Y-27632 treatment, the expression of key target genes of the Notch signaling pathway (Notch1, Hes1, Dil1, and Jag2) and Tlr2 were obviously decreased. Y-27632 treatment also decreased the number of monocytes in the spleen of EAM mice. Thus, ROCK inhibitor Y-27632 exerted a protective effect in EAM mice by downregulating IL-1β expression. This study aimed to provide a reference point for the future treatment of myocarditis in clinical settings.

Autoimmune myocarditis is a limited or diffuse inflammation of the myocardium brought on by dysfunction in the normal function of cellular and humoral immunity of the body. Mouse models of experimental autoimmune myocarditis (EAM) were constructed using peptide MyHC-α614–629. After secondary immunization, the mice were given intraperitoneal injection of the Rho kinase (ROCK) inhibitor Y-27632 the next day, and the heart tissues of the EAM mice were isolated and weighed on day 21. As a result, the hearts of EAM mice were significantly enlarged and whitened; the body weight (BW) of mice in the EAM group increased slowly, and the heart weight (HW) and the ratio of HW/eventual body weight (e-BW) were raised; the inflammatory infiltration and fibrosis of the myocardial tissue were aggravated. But Y-27632 treatment improved the above-mentioned phenotypic or pathological features of EAM mice. Besides, the monocytes in the spleen of EAM mice mounted up, which showed a decline in number after Y-27632 treatment. Mechanistic analysis revealed a significant increase in the expression of Notch1, Hes1, Jag2, Dil1, Tlr2 and Il-1β in the myocardial tissue of the EAM mice. Notably, the expression of IL-1β was consistent with that of Notch1 and Tlr2. After Y-27632 treatment, the expression of key target genes (Notch1, Hes1, Dil1 and Jag2) of the NOTCH signaling pathway and Tlr2 expression were obviously decreased. The ROCK inhibitor Y-27632 exerts a protective effect in EAM mice by down-regulating Il-1β expression. This study aims to provide a reference value for the future treatment of myocarditis in clinical settings.

目的 探究CUL4B在肿瘤患者来源的结直肠癌肿瘤类器官中调控miRNAs.方法 利用干扰CUL4B的和其对照的PDOs样本,进行miRNA-seq,对差异miRNAs的靶基因进行KEGG和GO等分析.利用TargetScan和miRDB 2个数据库分别预测可能受CUL4B调控的并且评分≥85分的miRNAs,结合miRNA-seq差异miRNAs进行韦恩分析.结果 miRNA-seq结果显示共有41个差异miRNAs.TargetScan和miRDB两个数据库和测序数据韦恩分析发现miR495-3p、miR381-3p和miR148b-5p 3个共同交集的miRNAs.KEGG结果显示代谢通路富集的基因个数最多,溶酶体富集基因Q值最小.GO分析结果显示单有机体过程、蛋白质结合和细胞质富集基因最多.流式细胞仪检测发现干扰CUL4B的表达并不影响PDOs的细胞周期.结论 CUL4B可能是通过代谢通路和溶酶体2个信号通路调控miR495-3p、miR381-3p和miR148b-5p.

半个世纪前一项经典的实验证明了脊椎动物细胞的巨大自组织能力. 即使在完全解离的条件下,细胞也可以重新聚集并重建器官的原始结构. 近年来,这一神奇的特征被用于从组织或干细胞中重建部分器官甚至完整的器官.