Ferroptosis plays a critical role in ischemic stroke, and anti-ferroptosis strategies were regarded as potentially effective measures. Based on ferroptosis-related mechanisms, this study aims to design and prepare anti-ferroptosis exosomes from adipose-derived mesenchymal stem cells (ADSC-Exo) for treating ischemic brain injury via intranasal (IN) administration. According to the bioinformatic analysis, CHAC1 was a key gene in the progress of ferroptosis in ischemic stroke. miR-760-3p can inhibit the expression of CHAC1 and may be abundant in ADSC-Exo. Therefore, ADSC-Exo were successfully isolated and the immunofluorescence showed that they can be efficiently delivered to the brain via IN administration. Additionally, IN administration of ADSC-Exo can effectively improve the neurobehavior function of mice after I/R, and improve the ferroptosis-related outcomes. As the immunofluorescence showed the co-localization of NeuN with CHAC1 obviously, we further evaluated the systematic effect of ADSC-Exo in an oxygen–glucose deprivation (OGD) mouse neuroblastoma cell line N2a model. The results showed that miR-760-3p in ADSC‐Exo contributed to their function in inhibiting ferroptosis by targeting CHAC1 in neurons. Collectively, the present study successfully designed and prepared anti-CHAC1 ADSC-Exo and suggested a promising exosome-based strategy for anti-ferroptosis therapy in cerebral ischemia/reperfusion injury. Graphical abstract

BackgroundHuman enterovirus 71 (EV71) causes severe hand, foot and mouse disease, accompanied by neurological complications. During the interaction between EV71 and the host, the virus subverts host cell machinery for its own replication. However, the roles of microRNAs (miRNAs) in this process remain obscure.ResultsIn this study, we found that the miRNA hsa-let-7c-5p was significantly upregulated in EV71-infected rhabdomyosarcoma cells. The overexpression of hsa-let-7c-5p promoted replication of the virus, and the hsa-let-7c-5p inhibitor suppressed viral replication. Furthermore, hsa-let-7c-5p targeted mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) and inhibited its expression. Interestingly, downregulation of MAP4K4 expression led to an increase in EV71 replication. In addition, MAP4K4 knockdown or transfection with the hsa-let-7c-5p mimic led to activation of the c-Jun NH2-terminal kinase (JNK) signaling pathway, whereas the hsa-let-7c-5p inhibitor inhibited activation of this pathway. Moreover, EV71 infection promoted JNK pathway activation to facilitate viral replication.ConclusionsOur data suggested that hsa-let-7c-5p facilitated EV71 replication by inhibiting MAP4K4 expression, which might be related to subversion of the JNK pathway by the virus. These results may shed light on a novel mechanism underlying the defense of EV71 against cellular responses. In addition, these findings may facilitate the development of new antiviral strategies for use in future therapies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13578-017-0135-9) contains supplementary material, which is available to authorized users.

IntroductionA crucial aspect of stroke progression is the inflammatory response. As novel inflammatory and prognostic markers, the systemic immune inflammation index (SII) and the systemic inflammation response index (SIRI) have recently been studied. The objective of our study was to evaluate the prognostic value of SII and SIRI in mild acute ischemic stroke (AIS) patients following intravenous thrombolysis (IVT).MethodsOur study screened the clinical data of patients with mild AIS admitted to the Minhang Hospital of Fudan University for retrospective analysis. The SIRI and SII were examined by the emergency laboratory before IVT. Functional outcome was evaluated 3 months after the onset of stroke using the modified Rankin Scale (mRS). mRS ≥ 2 was defined as an unfavorable outcome. The relationship between SIRI and SII and the 3-month prognosis was determined using both univariate and multivariate analysis. Receiver operating characteristic curve was performed to evaluate the predictive value of SIRI for AIS prognosis.ResultsA total of 240 patients were included in this study. Both SIRI and SII were higher in the unfavorable outcome group than in the favorable outcome group [1.28 (0.70–1.88) vs. 0.79 (0.51–1.08), P < 0.001 and 531.93 (377.55–797.12) vs. 397.23 (263.32–577.65), P < 0.001]. Multivariate logistic regression analyses showed that SIRI was significantly associated with 3-month unfavorable outcome of mild AIS patients [odds ratio (OR) = 2.938, 95% confidence interval (CI) = 1.805–4.782, P < 0.001], conversely, SII had no prognostic value. When SIRI combined with the established clinical factors, the area under the curve (AUC) showed a significant improvement (0.773 vs. 0.683, P for comparison = 0.0017).ConclusionsHigher SIRI could be valuable in predicting poor clinical outcomes for patients with mild AIS following IVT.