Ischemic stroke caused by a thrombus clog and ischemia is one of the most lethal and disabling cerebrovascular diseases. A sequentially targeted delivery system is highly desired to deliver thrombolytics and neuroprotectant to the site of the thrombus and ischemic penumbra, respectively, to pursue a maximized combinational effect. Inspired by the vital roles that platelets play in thrombus formation, herein, we develop a bioengineered "nanoplatelet" (tP-NP-rtPA/ZL006e) for sequentially site-specific delivery of recombinant tissue plasminogen activator (rtPA) and neuroprotectant (ZL006e) for ischemic stroke treatment. The tP-NP-rtPA/ZL006e consists of a ZL006e-loaded dextran derivative polymeric nanoparticle core and platelet membrane shell conjugated with thrombin-cleavable Tat-peptide-coupled rtPA. Mediated by the cloak of the platelet membrane, tP-NP-rtPA/ZL006e targets the thrombus site and rtPA is triggered to release by the upregulated thrombin. Subsequently, the in situ exposed Tat peptide enhanced penetration of the "nanoplatelet" across the blood−brain barrier into ischemic brain for ZL006e site-specific delivery. From the in vitro and in vivo evaluation, tP-NP-rtPA/ZL006e is demonstrated to significantly enhance the anti-ischemic stroke efficacy in the rat model with middle cerebral artery occlusion, showing a 63 and 72% decrease in ischemic area and reactive oxygen species level compared to that with free drug combination, respectively.

Background: The use of antiplatelet agents in ischemic moyamoya disease (MMD) is controversial. This study aimed to investigate the effectiveness and safety of antiplatelet therapy compared with conservative treatment and surgical revascularization in ischemic MMD patients.Methods: Ischemic MMD patients were retrospectively enrolled from eight clinical sites from January 2013 to December 2018. Follow-up was performed through clinical visits and/or telephone interviews from first discharge to December 2019. The primary outcome was the episodes of further ischemic attacks, and the secondary outcome was the individual functional status. Risk factors for future stroke were identified by the LASSO-Cox regression model. Propensity score matching was applied to assemble a cohort of patients with similar baseline characteristics using the TriMatch package.Results: Among 217 eligible patients, 159 patients were included in the analyses after a 1:1:1 propensity score matching. At a mean follow-up of 33 months, 12 patients (7.5%) developed further incident cerebral ischemic events (surgical:antiplatelet:conservative = 1:3:8; p = 0.030), 26 patients (16.4%) developed a poor functional status (surgical:antiplatelet:conservative = 7:12:7; p = 0.317), and 3 patients (1.8%) died of cerebral hemorrhage (surgical:antiplatelet:conservative = 1:2:0; p = 0.361). The survival curve showed that the risk of further cerebral ischemic attacks was lowest with surgical revascularization, while antiplatelet therapy was statistically significant for preventing recurrent risks compared with conservative treatment (χ2 = 8.987; p = 0.011). No significant difference was found in the functional status and bleeding events. The LASSO-Cox regression model revealed that a family history of MMD (HR = 6.93; 95% CI: 1.28–37.52; p = 0.025), a past history of stroke or transient ischemic attack (HR = 4.35; 95% CI: 1.09–17.33; p = 0.037), and treatment (HR = 0.05; 95% CI: 0.01–0.32; p = 0.001) were significantly related to the risk of recurrent strokes.Conclusions: Antiplatelet agents were effective and safe in preventing further cerebral ischemic attacks in adult patients with ischemic MMD. They may be a replacement therapy for patients with surgical contraindications and for patients prior to revascularization.

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To analyze the effects of extracellular matrix metalloproteinase inducer (CD147) on glioma proliferation, apoptosis, invasion, and angiogenesis. Tissue samples were obtained from 101 glioma cases while normal brain tissues were obtained from 30 brain injury cases. Immunohistochemical assay was performed to detect the expressions of CD147, CD34, and VEGF in tissue samples. QRT-PCR was performed to detect the relative expression of CD147 mRNA in human glioma cell lines. CD147 siRNA was transfected into glioma cell line U251. Cell proliferation, apoptosis, invasion, and angiogenesis were tested by MTT, flow cytometry, Transwell assay, and vasculogenic mimicry assay, respectively. Expressions of relative proteins were analyzed with western blot. CD147 was positively expressed with the percentage of 0, 37.5, 44.8, 67.9, and 85.7 % in normal tissues and glioma tissues with WHO grades I-IV, respectively, and the scores of MVDand VEGF were associated with the expression of CD147. CD147 was significantly upregulated in the human glioma cell lines (P < 0.05). Downregulated the expression of CD147 suppressed cell proliferation, blocked cell cycle, induced apoptosis, inhibited cell invasion and angiogenesis in glioma cells in vitro. The expression of CD147 was significantly associated with WHO tumor grade and angiogenesis; silencing of CD147 contributed to inhibition of glioma proliferation, invasion, and angiogenesis. Our study provided firm evidence that CD 147 is a potential glioma target for anti-angiogenic therapies.

Atherosclerosis (AS) is one of the most common chronic inflammatory diseases and a major cause of morbidity and mortality. However, the underlying molecular mechanisms of the progression of AS are still largely unknown. Increasing evidence has demonstrated that long noncoding RNAs (lncRNAs) play important roles in a variety of biological processes and the physiological and pathological progression of human diseases. In this study, we aimed to explore the role and underlying molecular mechanism of lncRNA MEG3 in Raw264.7 cells treated with oxidized low-density lipoprotein (ox-LDL). First, we found that ox-LDL inhibited the cell viability and proliferation, increased TNFa and IL1b secretion and induced the apoptosis of Raw264.7 cells. Second, we demonstrated that ox-LDL upregulated MEG3 expression and that knockdown of MEG3 inhibited the action of ox-LDL in Raw264.7 cells. Third, we showed that MEG3 sponged miR-204 in Raw264.7 cells treated with ox-LDL. Fourth, we demonstrated that miR-204 regulated the expression of cyclin-dependent kinase inhibitor 2A (CDKN2A) in Raw264.7 cells treated with ox-LDL. Finally, we revealed that MEG3 exerted its function via the regulation of the MEG3/miR-204/CDKN2A regulatory axis in Raw264.7 cells treated with ox-LDL. In summary, our study identified the role of the MEG3/miR-204/CDKN2A pathway in Raw264.7 cells treated with ox-LDL, revealed a novel regulatory pathway in AS and indicated potential novel characteristic biomarkers and therapeutic targets for AS.