White matter hyperintensity burden and functional outcomes in acute ischemic stroke patients after mechanical thrombectomy: A systematic review and meta-analysis.

BACKGROUND: The influence of white matter hyperintensity (WMH) on clinical outcomes in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT) remains controversial. We performed a systematic review and meta-analysis to examine whether WMH burden is associated with clinical outcomes in AIS patients after MT. METHODS: PubMed, Embase, and Web of Science were searched from inception to Sep 03, 2023. The registration number for PROSPERO is CRD42022340568. Studies reporting an association between the burden of WMH in AIS patients and clinical outcomes after MT were included in the meta-analysis. A random-effects model was used for meta-analysis. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Additionally, the presence of imprecise-study effects was evaluated using Egger's test and funnel plot. RESULTS: Fifteen studies with 3,456 patients were enrolled in this meta-analysis. Among AIS patients who underwent MT, moderate/severe WMH had higher odds of 90-day unfavorable functional outcomes (odds ratio [OR] 2.72, 95% confidence interval [CI] 2.14-3.44; I2 = 0.0%; 95% CI 0.0%-42.7%), 90-day mortality (OR 1.94, 95% CI 1.45-2.60; I2 = 19.5%; 95% CI 0.0%-65.2%) and futile recanalization (OR 2.99, 95% CI 1.42-6.28; I2 = 69.7%; 95% CI 0.0%-91.0%) compared with none/mild WMH. However, the two groups had no significant difference in successful recanalization, symptomatic hemorrhagic transformation, and hemorrhagic transformation. A subset analysis of patients from 3 articles showed that WMH volume was not significantly associated with these outcomes. A notable limitation is that this meta-analysis lacks direct adjustment for imbalances in important baseline covariates. CONCLUSIONS: Patients with moderate/severe WMH on baseline imaging are associated with substantially increased odds of 90-day unfavorable outcomes, futile recanalization, and 90-day mortality after MT. This association suggests that moderate/severe WMH may contribute to the prediction of clinical outcomes in AIS patients after MT.

SMARCC2 combined with c­Myc inhibits the migration and invasion of glioma cells via modulation of the Wnt/ß­catenin signaling pathway.

Glioma is the most common type of central nervous system tumor. SWItch/sucrose non­fermentable (SWI/SNF) is a tumor suppressor that serves an important role in epithelial­mesenchymal transition (EMT). The present study aimed to identify key molecules involved in the EMT process. SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily c member 2 (SMARCC2) is mutated in and its expression is low in multiple types of cancer. SMARCC2 is the core subunit of the chromatin­remodeling complex, SWI/SNF. Relative mRNA SMARCC2 expression levels in human glioma tissue were analyzed via reverse transcription­quantitative PCR, whereas the protein expression levels were determined via immunohistochemistry staining. SMARCC2 expression was knocked down in glioma cells using small interfering RNA (si) and overexpressed by infection with adenovirus vectors carrying SMARCC2 cDNA. Wound healing and Transwell assays were performed to assess cell migration and invasion, respectively. Subsequently, immunofluorescence and western blotting were performed to analyze the expression levels of the oncogene c­Myc, which is associated with SMARCC2. SMARCC2 combines with C­MYC to downregulate its expression. Consistent with the results of the bioinformatics analysis, which revealed that the upregulated expression levels of SMARCC2 were associated with a more favorable prognosis in patients with glioma, the mRNA and protein expression levels of SMARCC2 were significantly upregulated in low­grade glioma tissues compared with high­grade glioma tissues. The results of the wound healing assay demonstrated that cell migration was significantly increased in the siSMARCC2­1/3 groups compared with the negative control (NC) group. By contrast, the migratory ability of cells was significantly reduced following transduction with adenovirus overexpressing SMARCC2, which upregulated the expression of SMARCC2, compared with the lentiviral vector­non­specific control (LVS­NC) group. The Transwell assay results further showed that SMARCC2 overexpression significantly inhibited the migratory and invasive abilities of U87MG and LN229 cells compared with the LVS­NC group. Co­immunoprecipitation assays were subsequently conducted to validate the binding of SMARCC2 and c­Myc; the results demonstrated that the expression of c­Myc was downregulated in adenovirus­transfected cells compared with LVS­NC­transfected cells. The results of the western blotting experiments demonstrated that the expression levels of N­cadherin, vimentin, snail family transcriptional repressor 1 and ß­catenin were notably downregulated, whereas the expression levels of T­cadherin were markedly upregulated in cell lines stably overexpressing SMARCC2 compared with the LVS­NC group. In conclusion, the results of the present study suggested that SMARCC2 may inhibit Wnt/ß­catenin signaling by regulating c­Myc expression in glioma. SMARCC2 regulates the EMT status of the glioblastoma cell line by mediating the expression of the oncogene C­MYC to inhibit its migration and invasion ability. Thus, SMARCC2 may function as a tumor suppressor or oncogene by regulating associated oncogenes or tumor suppressor genes.