Upregulation of miR150-5p in generalized myasthenia gravis patients is associated with decreased serum levels of IL-17 and increased serum levels of IL-10.

BACKGROUND: MiR150-5p has been reported to be involved in generalized myasthenia gravis, in which different cytokines play critical roles. The regulatory network of cytokines in generalized myasthenia gravis has not been fully elucidated. Our study aimed to investigate the interactions between miR150-5p and different cytokines in generalized myasthenia gravis. MATERIALS AND METHOD: Serum levels of miR150-5p and different cytokines including IL-2, IL-17, IL-10, IL-19, IL-20 and IL-35 were detected by qRT-PCR and ELISA, respectively. ROC curve analysis was performed to evaluate the diagnostic value of miR150-5p for generalized myasthenia gravis. Correlation between serum levels of miR150-5p and different cytokines were analyzed by Pearson correlation coefficient. RESULTS: Compared with healthy controls, decreased serum levels of IL-2 and IL-17 and increased serum levels of miR150-5p, IL-10, IL-19, IL-20 and IL-35 were observed in patients with generalized myasthenia gravis. Serum levels of miR150-5p were positively correlated with IL-10 and negatively correlated with IL-17. After treatments, serum levels of miR150-5p and IL-10 decreased, while serum levels of IL-2 and IL-17 increased. CONCLUSION: Upregulation of miR150-5p is involved in generalized myasthenia gravis patients and is associated with decreased serum levels of IL-17 as well as increased serum levels of IL-10.

Association of lower leukocyte count before thrombolysis with early neurological improvement in acute ischemic stroke patients.

Early neurological improvement (ENI) after thrombolysis in acute ischemic stroke is associated with a favorable long-term outcome. With the goal to evaluate ENI, we aimed to investigate whether ENI bears a relationship with routine blood tests before thrombolysis. A total of 240 patients with confirmed early ischemic stroke and intravenous recombinant tissue plasminogen activator (rtPA) treatment were enrolled from two teaching hospitals, between June 2010 and March 2016. The primary endpoint was ENI that was defined as a decrease of National Institutes of Health Stroke Scale (NIHSS) scores ≥4 points or complete recovery in 24 h after thrombolysis. Patients underwent NIHSS score evaluation and head CT scan before and after 24 h of IV rtPA treatment. Blood samples for routine blood tests were drawn at admission before IV rtPA administration. Multivariate regression analysis was used to explore the relationship between test results and ENI. Of the results of routine blood tests, leukocyte count before thrombolysis was found to associated independently with ENI (adjusted odds ratio[adjOR] = 0.894, P = 0.025, 95% CI = 0.810-0.986). Onset-to-treatment time (OTT; adjOR = 0.993, P = 0.003, 95% CI = 0.988-0.997) and negative CT sign (adjOR = 3.975, P < 0.001, 95% CI = 1.916-8.246) both were associated with ENI. The change of NIHSS score after 24 h of thrombolysis correlated with the leukocyte and neutrophil count, and neutrophil-to-lymphocyte ratio. A model that combined leukocyte count, positive CT sign, and OTT was generated to predict non-ENI (AUC = 0.717). Therefore, we determined that the leukocyte count was independently associated with ENI. Predicting non-ENI aid in selecting patients for mechanical thrombectomy after thrombolysis.

Plasma let-7i and miR-15a expression are associated with the effect of recombinant tissue plasminogen activator treatment in acute ischemic stroke patients.

Circulating microRNAs (miRNAs) have been reported as diagnosis biomarkers and predictors in acute ischemic stroke (AIS). However, how the expression of circulating miRNAs changes after recombinant tissue plasminogen activator (rt-PA) treatment in AIS patients is still unknown. OBJECTIVE: To determine the expression of circulating miRNAs in AIS patients receiving rt-PA treatment and those not receiving it. METHODS: Blood samples were collected 24h after onset from 40 AIS patients receiving rt-PA treatment and 46 AIS patients (admission at 8-24h of onset) not receiving rt-PA treatment. Thirty-nine age- and sex-matched healthy volunteers were used as the control group. We used miRNA microarrays to detect plasma miRNA expression and real-time PCR to verify miRNA expression. RESULTS: Compared to the non-rt-PA treatment group, the rt-PA treatment group showed 16 differentially expressed miRNAs. The change in the expression of let-7i and miR-15a was confirmed by real-time PCR. Compared to the heathy controls, the non-rt-PA group showed decreased let-7i expression and the rt-PA group showed a 4-fold increased let-7i expression. The let-7i expression was also found to correlate with the National Institute of Health stroke scale (NIHSS) score (rho=0.297, P=0.005). On the contrary, miR-15a expression decreased by 0.5-fold in the rt-PA group compared to that in the non-rt-PA group. CONCLUSION: The circulating miRNAs let-7i and miR-15a showed differential expression between AIS patients receiving thrombolysis treatment (rt-PA group) and those not receiving it (non-rt-PA group). Compared to the non-rt-PA group, the rt-PA group showed upregulation of let-7i and downregulation of miR-15a.

Let-7i attenuates human brain microvascular endothelial cell damage in oxygen glucose deprivation model by decreasing toll-like receptor 4 expression.

The let-7 family of microRNAs (miRNAs) plays an important role on endothelial cell function. However, there have been few studies on their role under ischemic conditions. In this study, we demonstrate that let-7i, belonging to the let-7 family, rescues human brain microvascular endothelial cells (HBMECs) in an oxygen-glucose deprivation (OGD) model. Our data show that the expression of let-7 family miRNAs was downregulated after OGD. Overexpression of let-7i significantly alleviated cell death and improved survival of OGD-treated HBMECs. Let-7i also protected permeability in an in vitro blood brain barrier (BBB) model. Further, let-7i downregulated the expression of toll-like receptor 4 (TLR4), an inflammation trigger. Moreover, overexpression of let-7i decreased matrix metallopeptidase 9 (MMP9) and inducible nitric oxide synthase (iNOS) expression under OGD. Upon silencing TLR4 expression in HBMECs, the anti-inflammatory effect of let-7i was abolished. Our research suggests that let-7i promotes OGD-induced inflammation via downregulating TLR4 expression.