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Background MicroRNAs (miRNAs) are implicated in the progression of ischemic stroke (IS) and bone marrow-derived mesenchymal stem cells (BMSCs)-derived exosomes play a role in IS therapy. Herein we hypothesized that the BMSCs-derived exosomes containing overexpressed miR-138-5p could protect the astrocytes following IS involved with lipocalin 2 (LCN2). Methods The differentially expressed gene related to IS was initially identified by bioinformatics analysis. miR-138-5p was predicted to regulate LCN2. The expression of miR-138-5p and LCN2 was altered in the oxygen-glucose deprivation (OGD)-induced astrocytes. Furthermore, the cell behaviors and inflammatory responses were evaluated both in astrocytes alone and astrocytes co-cultured with exosomes derived from BMSCs overexpressing miR-138-5p to explore the involvement of miR-138-5p and LCN2 in IS. Besides, middle cerebral artery occlusion (MCAO) mouse model was established to explore the effect of BMSCs-derived exosomal miR-138-5p in IS in vivo. Results LCN2 was highly expressed in IS. Besides, LCN2 was a target gene of miR-138-5p. BMSCs-derived exosomes could be endocytosed by astrocytes via co-culture. Overexpression of miR-138-5p promoted the proliferation and inhibited apoptosis of astrocytes injured by OGD, accompanied by the reduced expression of inflammatory factors, which was achieved by down-regulating LCN2. More importantly, BMSCs delivered miR-138-5p to the astrocytes via exosomes and BMSCs-derived exosomal miR-138-5p alleviated neuron injury in IS mice. Conclusion BMSCs-derived exosomal miR-138-5p reduces neurological impairment by promoting proliferation and inhibiting inflammatory responses of astrocytes following IS by targeting LCN2, which may provide a novel target for IS treatment.

Background and Purpose: The benefit of endovascular treatment (EVT) for large vessel occlusion in clinical practice in developing countries like China needs to be confirmed. The aim of the study was to determine whether the benefit of EVT for acute ischemic stroke in randomized trials could be generalized to clinical practice in Chinese population. Methods: We conducted a prospective registry of EVT at 111 centers in China. Patients with acute ischemic stroke caused by imaging-confirmed intracranial large vessel occlusion and receiving EVT were included. The primary outcome was functional independence at 90 days defined as a modified Rankin Scale score of 0 to 2. Outcomes of specific subgroups in the anterior circulation were reported and logistic regression was performed to predict the primary outcome. Results: Among the 1793 enrolled patients, 1396 (77.9%) had anterior circulation large vessel occlusion (median age, 66 [56–73] years) and 397 (22.1%) had posterior circulation large vessel occlusion (median age, 64 [55–72] years). Functional independence at 90 days was reached in 45% and 44% in anterior and posterior circulation groups, respectively. For anterior circulation population, underlying intracranial atherosclerotic disease was identified in 29% of patients, with higher functional independence at 90 days (52% versus 44%; P =0.0122) than patients without intracranial atherosclerotic disease. In the anterior circulation population, after adjusting for baseline characteristics, procedure details, and early outcomes, the independent predictors for functional independence at 90 days were age <66 years (odds ratio [OR], 1.733 [95% CI, 1.213–2.476]), time from onset to puncture >6 hours (OR, 1.536 [95% CI, 1.065–2.216]), local anesthesia (OR, 2.194 [95% CI, 1.325–3.633]), final modified Thrombolysis in Cerebral Infarction 2b/3 (OR, 2.052 [95% CI, 1.085–3.878]), puncture-to-reperfusion time ≤1.5 hours (OR, 1.628 [95% CI, 1.098–2.413]), and National Institutes of Health Stroke Scale score 24 hours after the procedure <11 (OR, 9.126 [95% CI, 6.222–13.385]). Conclusions: Despite distinct characteristics in the Chinese population, favorable outcome of EVT can be achieved in clinical practice in China. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03370939.

Alzheimer's disease (AD) is a common worldwide progressive neurodegenerative disease. The dysregulation of miRNA is crucial in neurodegenerative diseases and neuron apoptosis during AD and is closely associated with the MAPK pathway. By bioinformatic website, we found that there was target inhibiting relationship between microRNA (miR)-132 and MAPK1. Therefore, the current study speculated that miR-132 could improve the cognitive function of rats with AD by inhibiting MAPK1 expression. To verify our hypothesis, 10 normal rats and 60 rats with AD were selected and divided into model, Ad-miR-132 negative control (NC), Ad-miR-132, Ad-small interfering (si)MAPK1 NC, Ad-siMAPK1 and Ad-miR-132 + Ad-MAPK1 groups. Rats were evaluated for learning by performing morris water maze tests and pathological changes of the hippocampus were assessed via HE staining. Additionally, hippocampus cell apoptosis was determined using a TUNEL assay and levels of acetylcholinesterase (AChE), reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were evaluated in sera via ELISA. The mRNA and protein expression of miR-132, iNOS, MAPK1 and phosphorylated (p)-MAPK1 was determined in hippocampus tissues via reverse transcription-quantitative PCR and western blotting, respectively. Compared with normal mice, rats with AD had significantly decreased learning abilities, increased cell apoptosis rates, increased levels of AChE, iNOS, ROS, MDA, MAPK1 and p-MAPK1 and decreased levels of SOD, GSH-Px and miR-132. Upregulation of miR-132 group improved the above indictors and silencing MAKP1 worsened the condition of rats. miR-132 upregulation therefore reversed the negative effects caused by MAPK1 silencing in rats with AD. In conclusion, miR-132 inhibited hippocampal iNOS expression and oxidative stress by inhibiting MAPK1expression to improve the cognitive function of rats with AD.

Background and Purpose— Ischemic stroke is one of the leading causes of morbidity and mortality worldwide and a major cause of long-term disability. Recently, long noncoding RNAs have been revealed, which are tightly associated with several human diseases. However, the functions of long noncoding RNAs in ischemic stroke still remain largely unknown. In the current study, for the first time, we investigated the role of long noncoding RNA Nespas in ischemic stroke. Methods— We used in vivo models of middle cerebral artery occlusion and in vitro models of oxygen-glucose deprivation to illustrate the effect of long noncoding RNA Nespas on ischemic stroke. Results— We found expression of Nespas was significantly increased in ischemic cerebral tissues and oxygen-glucose deprivation–treated BV2 cells in a time-dependent manner. Silencing of Nespas aggravated middle cerebral artery occlusion operation–induced IR injury and cell death. In addition, proinflammatory cytokine production and NF-κB (nuclear factor-κB) signaling activation were inhibited by Nespas overexpression. TAK1 (transforming growth factor-β–activated kinase 1) was found to directly interact with Nespas, and TAK1 activation was significantly suppressed by Nespas. At last, we found Nespas-inhibited TRIM8 (tripartite motif 8)-induced K63-linked polyubiquitination of TAK1. Conclusions— We showed that Nespas played anti-inflammatory and antiapoptotic roles in cultured microglial cells after oxygen-glucose deprivation stimulation and in mice after ischemic stroke by inhibiting TRIM8-related K63-linked polyubiquitination of TAK1.

Background and Aim The aim of this study is to evaluate the association of the regulatory T cells (Treg)/T‐helper (Th) 17 cells and transforming growth factor‐β1 (TGF‐β1)/interleukin‐17 (IL‐17) ratios with the survival and disease progression in patients with hepatitis B virus (HBV)‐associated liver cirrhosis (LC). Methods The frequencies of Treg and Th17 cells were analyzed in 28 patients with HBV‐LC, 70 patients with chronic hepatitis B (CHB) and 20 normal controls (NC) by flow cytometry. The levels of cytokines related to Treg/Th17 differentiation, including IL‐10, TGF‐β1, IL‐17, and IL‐23, were measured by ELISA. Results Compared with NC, Treg cells were significantly increased in CHB patients and slightly increased in HBV‐LC patients, whereas Th17 cells were markedly increased both in patients with CHB and HBV‐LC. HBV‐LC patients, especially the nonsurvival ones, manifested a profound decrease in the Treg/Th17 ratio, which was negatively correlated with Child‐Pugh and model of end‐stage liver disease scores. Serum IL‐10, TGF‐β1, IL‐17, and IL‐23 levels were all significantly higher in HBV‐LC patients than in NC. In addition, the TGF‐β1/IL‐17 ratio was also markedly increased in patients with HBV‐LC, especially in nonsurvival and decompensated liver cirrhosis patients, and positively correlated with total bilirubin, Child‐Pugh, and model of end‐stage liver disease scores. Conclusions The decreased Treg/Th17 ratio and increased TGF‐β1/IL‐17 ratio may be associated with the survival and disease progression in HBV‐LC patients, and both of the two ratios can be used independently to predict the prognosis and disease progression of HBV‐LC patients.

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The proinflammatory cytokines transforming growth factor beta 1 (TGF-β1) and interleukin (IL)-31 have been implicated in tissue injury. However, whether TGF-β1/IL-31 are stimulated and elevated in response to liver injury that leads to fibrogenesis in hepatitis B virus-related liver cirrhosis (HBV-LC) remains unclear. To investigate the association between TGF-β1/IL-31 and stages of chronic HBV infection, serum TGF-β1, IL-9, IL-10,IL-17, IL-22, IL-23, IL-31, IL-33, and IL-35 were determined among patients with chronic hepatitis B (CHB; n=19), HBV-LC (n=20), and a normal control population (NC; n=18). Disease severity in patients with HBV-LC was assessed using model for end-stage liver disease (MELD) scores. Serum TGF-β1 and IL-31 levels were strongly positively linked in all subjects, and both correlated positively with IL-22, IL-33, and IL-17. TGF-β1 and IL-31 levels in the blood were both significantly higher in CHB and HBV-LC patients than in NC subjects. Elevated serum TGF-β1 and IL-31 levels were positively associated with albumin, alpha-fetoprotein, creatinine, white blood cell count, and platelet levels. Serum TGF-β1 and IL-31 were markedly higher in HBV-LC patients who did not have esophageal varices, and IL-31 had the highest sensitivity and specificity (90.9% and 66.7%, respectively) for indicating the absence of this complication. In summary, TGF-β1 and IL-31 were linked to progression from CHB to LC, and correlated well with the severity of HBV-LC. These findings suggest possible roles of the TGF-β1/IL-31 pathway in the pathogenesis of liver fibrosis during chronic HBV infection.