Inflammation is dominant in the pathogenesis of ischemic stroke (IS). Alpha‐ketoglutarate (AKG), according to previous studies, has demonstrated a variety of pharmacological effects such as antioxidation and inhibitive inflammation activities. However, whether AKG ameliorates cerebral ischemic injury, as well as the underlying molecular events, is still unclear. Therefore, the effect and underlying mechanisms of AKG on ischemic brain injury should be identified. The study established a cerebral ischemia‐reperfusion (I/R) model in mice as well as an oxygen‐glucose deprivation/reperfusion (OGD/R) model in SH‐SY5Y cells, respectively. It was observed that AKG markedly suppressed infarction volume and neuronal injuries and improved the neurological score in vivo. Moreover, AKG reduced the inflammatory response and lowered the expression of proinflammatory cytokines. In vitro, AKG treatment strongly inhibited OGD/R‐induced neuronal injury and the proinflammatory factors. It was also found that the increased SOD and GSH levels, as well as the lower ROS levels, showed that AKG reduced oxidative stress in OGD/R‐treated SY‐SY5Y cells. Mechanistically, AKG largely promoted IL‐10 expression in ischemic brain injury and OGD/R‐induced neuronal injury. Furthermore, IL‐10 silencing neutralized the protective effect of AKG on inflammation. Notably, it was discovered that AKG could upregulate IL‐10 expression by promoting the translocation of c‐Fos from the cytoplasm to the nucleus. The results indicated that AKG demonstrated neuroprotection on cerebral ischemia while inhibiting inflammation through c‐Fos/IL‐10/stat3 pathway.

Background: Cerebrovascular disease has become the leading cause of death in China. The purpose of this article is to analyze China’s contribution to the interventional treatment of cerebrovascular diseases. Methods: Bibliometric analysis was used for evaluating the quantity, quality, research hotspots, and cooperation network of publications regarding interventional treatment of cerebrovascular diseases from China. These articles were searched from the database of Web of Science Core Collection. The authors, publication years, citation times, regions, and source journals of retrieved articles were recorded. Network analysis and visualization were performed on Citespace5.6. Results: From 1991 to 2019, a total of 5052 articles regarding cerebrovascular intervention were contributed by Chinese researchers. The number of publications from China grew fastest annually in the latest 5 years among countries. These publications were cited 61,216 times, with 12.12 average citations per item. The h-index was 82. Affiliated hospitals of Capital Medical University contributed most articles. Cerebral ischemia and intracranial aneurysm were the most popular keywords over the three decades. The timeline view of keywords indicated that cerebral ischemia always was a hot spot. Stent techniques were the main treatment tools and still had a strong developing trend. Neural regeneration and neuroprotection were the hot topics of basic researches related to cerebrovascular intervention. Conclusions: The number of researches grows rapidly in China over the decades, but the quality still needs further improvement. The increasing contributions of Chinese researchers to the global knowledge system of cerebrovascular intervention are promising.

Background. In tumor progression and epigenetic regulation, long non-coding RNA (lncRNA) and necroptosis are crucial regulators. However, in glioma microenvironment, the role of necroptosis-related lncRNAs (NRLs) remains unknown. Method. In this study, the RNA-seq and clinical annotation of glioma patients were analyzed using the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. To investigate prognosis and tumor microenvironment of NRLs in gliomas, we conducted a prediction model based on the training cohort. The accuracy of the model was verified in the verification cohort. Results. A signature composed of 13 NRLs was identified, and all glioma patients were divided into two groups. We found that each group has unique survival outcomes, biological behaviors, and immune infiltrating status. The necroptosis-related lncRNA signature (NRLS) model was found to be an independent risk factor in multivariate Cox analysis. Immunosuppressive microenvironment was positively correlated with the high-risk group. Due to significantly different IC50 between risk groups, NRLS could be used as a guide for chemotherapeutic treatment. Further, the entire cohort was divided into two clusters depending on NRLs. Consensus clustering method and the risk scoring system were basically similar. Survival probability was higher in Cluster 2, while Cluster 1 has stronger immunologic infiltration. Conclusion. The predictive signature could be a prognostic factor independently and serve to detect the role of NRLs in glioma immunotherapy response.

Background: Previous genome-wide association studies (GWAS) have identified several risk genes for stroke; however, it remains unclear how they confer risk for the disease. We conducted an integrative analysis to identify candidate genes for stroke and stroke subtypes by integrating blood-derived multi-omics data with genetic data. Method: We systematically integrated the latest stroke GWAS database (73,652 patients and 1,234,808 controls) with human plasma proteomes (N=7,213) and performed proteome-wide association studies (PWAS), Mendelian randomization (MR), Bayesian colocalization analysis, and transcriptome-wide association study (TWAS) to prioritize genes that associate the risk of stroke and its subtypes with their expression and protein abundance in plasma. Cell-type specificity and functional enrichment analysis using single-cell RNA sequencing (scRNA-seq) and Gene Ontology (GO) databases were then performed to select target genes. A two-step MR analysis was followed to explore the potential mechanisms. Results: We found that the protein abundance of seven genes ( MMP12, F11, SH3BGRL3, ENGASE, SCARA5, SWAP70, and SPATA20 ) in the plasma was associated with stroke and its subtypes, with six genes ( MMP12, F11, SH3BGRL3, SCARA5, SWAP70, and SPATA20 ) causally related with stroke and its subtypes (P < 0.05/proteins identified for PWAS; P < 0.05/8 for MR; posterior probability of hypothesis 4 ≥ 75 % for Bayesian colocalization). The effect of F11, SH3BGRL, SPATA20, and SWAP70 on each subtype was mediated by Factor XI inhibitors (FXI), atrial fibrillation, T2D, and SBP respectively (p<0.05). We also found that SCARA5 and SWAP70 were related to stroke and ischemic stroke at the transcriptome level. Conclusions: Our present proteomic findings have identified new causal genes in the pathogenesis of stroke, which may offer potential future therapeutic targets for stroke prevention.

Patients with systemic lupus erythematosus (SLE) typically have an increased risk of thrombosis, especially at a younger age. The prognosis of those acute ischemic stroke (AIS) patients due to acute intracranial artery occlusion seems to be favorable; however, with few published reports. We report two cases of AIS that were treated with intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) with a prior diagnosis of SLE and were treated with regular oral corticosteroids before the onset. During the 1-year follow-up, these two patients were able to live normally without experiencing another ischemic stroke or changing medication. SLE-associated strokes necessitate urgent attention, with prompt diagnosis and immediate therapeutic measures, including thrombolytic therapy or MT, being crucial for achieving favorable patient outcomes.