ABSTRACT
Ischemic stroke is one of the leading causes of death worldwide. In the post-stroke stage, cardiac dysfunction is common and is known as the brain-heart interaction. Diabetes mellitus worsens the post-stroke outcome. Stroke-induced systemic inflammation is the major causative factor for the sequential complications, but the mechanism underlying the brain-heart interaction in diabetes has not been clarified. The NLRP3 (NLR pyrin domain-containing 3) inflammasome, an important component of the inflammation after stroke, is mainly activated in M1-polarized macrophages. In this study, we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 diabetes. Meanwhile, M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic stroke. Importantly, the NLRP3 inflammasome inhibitor CY-09 restored cardiac function, indicating that the M1-polarized macrophage-NLRP3 inflammasome activation is a pathway underlying the brain-heart interaction after diabetic stroke.
ABSTRACT
Ischemic stroke is one of the leading causes of death worldwide. In the post-stroke stage, cardiac dysfunction is common and is known as the brain-heart interaction. Diabetes mellitus worsens the post-stroke outcome. Stroke-induced systemic inflammation is the major causative factor for the sequential complications, but the mechanism underlying the brain-heart interaction in diabetes has not been clarified. The NLRP3 (NLR pyrin domain-containing 3) inflammasome, an important component of the inflammation after stroke, is mainly activated in M1-polarized macrophages. In this study, we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 diabetes. Meanwhile, M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic stroke. Importantly, the NLRP3 inflammasome inhibitor CY-09 restored cardiac function, indicating that the M1-polarized macrophage-NLRP3 inflammasome activation is a pathway underlying the brain-heart interaction after diabetic stroke.
ABSTRACT
Purpose Analysis of correlation between FOXM1 gene expression levels and clinicopathological features and prognosis of patients with esophageal squamous cancer (ESC). The effect of down-regulation of FOXM1 expression on the proliferation of human ESC cell line KYSE-30 was also inves-tigated. Methods Quantitative real-time PCR (qRT-PCR) and immunohistochemistry ( IHC) methods were used to detect the expression of FOXM1 in ESC tissues and non-cancer tissues in mRNA and protein level. The expression of FOXM1 was down-regulated by RNA interference (RNAi) technique, and the pro-liferation activity of KYSE-30 cells was detected by CCK-8 as-say. Results Compared with the corresponding non-cancer tis-sues, the expression of FOXM1 was significant higher in ESC tis-sues(P＜0. 01). Meanwhile, the expression levels of FOXM1 in poorly differentiated esophageal carcinoma was higher than that in well-differentiated ESC group ( P ＜0. 01 ). The expression of FOXM1 was significantly correlated with poor tumor differentia-tion (P＜0. 001), lymphatic metastasis (P=0. 000), advanced stage (P=0. 004) of ESC patients after surgical resection. High FOXM1 expression was related to shorter overall survival ( OS) (P＜0. 001). After down-regulating FOXM1 expression in KYSE-30 cells, cell proliferation rate was inhibited (P＜0. 01). Conclusion FOXM1 expression is up-regulated in ESC and is closely related to the degree of differentiation, lymph node me-tastasis, clinical stage and prognosis of ESC. FOXM1 may be participated in regulating the proliferation of human esophageal carcinoma cell line KYSE-30.