The aim of this study is to determine the expression levels and clinical significance of circulating microRNAs (miRNAs), let-7e and miR-338 at different stages following ischemic stroke (IS). Seventy-two patients with IS at the acute stage were enrolled and monitored at different stages, and 51 healthy volunteers were served as the normal controls. Expression of let-7e and miR-338 in serum and cerebral spinal fluid (CSF) samples was analyzed by real-time quantitative PCR. The relationship between expression levels of let-7e and miR-338, National Institutes of Health Stroke Scale (NIHSS) scores, and the levels of serum CRP was analyzed, respectively. Compared to healthy controls, serum let-7e expression levels were significantly increased, while serum miR-338 expression levels were slightly increased in IS patients. Expression levels of Let-7e in serum varied at different stages in IS patients with the lowest expression in the recover stage and highest expression in the acute stage. However, serum miR-338 expression in IS patients was not significantly different in any stage. Compared to healthy controls and nonacute stages of IS groups, let-7e expression in CSF was markedly upregulated in IS patients at the acute stage. Different from that of let-7e, miR-338 expression in CSF was upregulated in IS patients only at the subacute stage but not in the acute stage. Meanwhile, let-7e, which was not significantly correlated with NIHSS scores (r = 0.29, P > 0.05), was positively correlated with the serum CRP levels (r = 0.67, P = 0.033). There is no significant correlation between the miR-338 expression levels and NIHSS scores or serum CRP levels. Moreover, let-7e, but not miR-338, had a high consistency in expression when tested both in CSF and serum samples. Finally, serum let-7e showed a specificity up to 73.4 % and a sensitivity of 82.8 % in IS patients at the acute stage, whereas serum miR-338 in IS patients showed a specificity up to 53.2 % and a sensitivity of 71.9 % in the acute stage. Expression levels of let-7e in serum may serve as a useful noninvasive circulating biomarker for the acute stage of ischemic stroke.

ObjectiveAtherosclerosis (AS), characterized by cholesterol overloaded-macrophages accumulation and plaque formation in blood vessels, is the major cause of cardiovascular disease. Transactive response DNA-binding protein∼43 kDa (TDP43) has recently been identified as an independent driver of neurodegenerative diseases through triggering inflammatory response. This study investigated whether TDP43 is involved in AS development, especially in macrophages-mediated-foam cell formation and inflammatory responses.MethodsTransactive response DNA-binding protein∼43 kDa expressions in oxidized low-density lipoprotein (oxLDL)-treated macrophages and peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD) were detected by real time-polymerase chain reaction (RT-PCR), Western blot, and immunofluorescence. Gene gain or loss of function was used to investigate the effects of TDP43 on macrophages-mediated lipid untake and inflammation with ELISA, protein immunoprecipitation, RT-PCR, Western blot, and immunofluorescence. Macrophage TDP43 specific knockout mice with ApoE–/– background were fed with western diet for 12 weeks to establish AS model, and used to explore the role of TDP43 on AS progression.ResultsTransactive response DNA-binding protein∼43 kDa expression increases in oxLDL-treated macrophages and PBMCs from patients with CAD. Furthermore, we find that TDP43 promotes activation of NF-κB to increase inflammatory factor expression in macrophages through triggering mitochondrial DNA release to activate cGAS-STING signaling. Moreover, TDP43 strengthens lipid uptake of macrophages through regulating β-catenin and PPAR-γ complex to promote scavenger receptor gene CD36 transcription. Finally, using macrophage TDP43 specific knockout mice with ApoE–/– background fed with western diet for 12 weeks to establish AS model, we find that specific knockout of TDP43 in macrophages obviously alleviates western diet-induced AS progression in mice.ConclusionsTransactive response DNA-binding protein∼43 kDa exacerbates atherosclerosis progression by promoting inflammation and lipid uptake of macrophages, suggesting TDP43 as a potential target for developing atherosclerotic drug.

Our results suggested that high-dose atorvastatin application before PCI triggered early EPC circulation. Furthermore, postoperative inflammatory cytokine sICAM-1 as well as hCRP serum levels were reduced, while postinterventional myocardial injury marker TnI elevations were inversely correlated with statin reloadings.

Background. Visfatin is an adipocytokine that has been demonstrated to be involved in cardiovascular diseases. This study aims at determining the role of visfatin in sepsis-induced cardiac injury and identify its possible mechanisms. Methods. Dynamic changes in visfatin expression in mice with lipopolysaccharide- (LPS-) induced septicemia were measured. Additionally, mice were pretreated with visfatin and further administered LPS to observe the effects of visfatin on cardiac injury. Finally, septic mice were also pretreated with JSH-23 to investigate whether visfatin regulates cardiac injury via the NF-κB p65 pathway. Results. Visfatin expression levels in both the heart and serum were increased in LPS-treated mice and peaked at 6 hours, and visfatin was derived from cardiac macrophages. In septic mice, pretreatment with visfatin reduced the survival rate, worsened cardiac dysfunction, and increased the expression of cardiac injury markers, including creatine kinase myocardial bound (CK-MB) and lactate dehydrogenase (LDH). Treatment with visfatin also increased the infiltration of CD3+ cells and F4/80+ cells, amplified the cardiac inflammatory response, and elevated myocardial cell apoptosis. Treatment with JSH-23 reversed the effects of visfatin in septic mice. Conclusions. This study showed that visfatin amplifies the cardiac inflammatory response and aggravates cardiac injury through the p65 signaling pathway. Visfatin may be a clinical target for preventing cardiac injury in sepsis.