Strokes usually results in long-term disability and death, and they occur worldwide. Recently, increased research on both on the physiopathological mechanisms and the transcriptome during stroke progression, have highlighted the relationship between stroke progression and immunity, with a special focus on inflammation. Here, we applied proteome analysis to a middle carotid artery occlusion (MCAO) mouse model at 0 h, 6 h, 12 h and 24 h, in which proteome profiling was performed with 23 samples, and 41 differentially expressed proteins (DEPs) were identified. Bioinformatics studies on our data revealed the importance of the immune response and particularly identified the inflammatory response, cytokine- cytokine receptor interactions, the innate immune response and reactive oxygen species (ROS) during stroke progression. In addition, we compared our data with multiple gene expression omnibus (GEO) datasets with and without a time series, in which similar pathways were identified, and three proteins, C3, Apoa4 and S100a9, were highlighted as markers or drug targets for stroke; these three proteins were significantly upregulated in the MCAO model, both in our proteomic data and in the GEO database.

Abstact: Background: DRAGON was a phase 3, randomised, double-blind, placebo-controlled study which evaluated the efficacy and safety of erenumab in patients with chronic migraine (CM) from Asia not adequately represented in the global pivotal CM study. Methods: DRAGON study was conducted across 9 Asian countries or regions including mainland China, India, the Republic of Korea, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam. Patients (N = 557) with CM (aged 18–65 years) were randomised (1:1) to receive once-monthly subcutaneous erenumab 70 mg or matching placebo for 12 weeks. The primary endpoint was the change in monthly migraine days (MMD) from baseline to the last 4 weeks of the 12-week double-blind treatment phase (DBTP). Secondary endpoints included achievement of ≥ 50% reduction in MMD, change in monthly acute headache medication days, modified migraine disability assessment (mMIDAS), and safety. Study was powered for the primary endpoint of change from baseline in MMD. Results: At baseline, the mean (SD) age was 41.7 (± 10.9) years, and 81.5% (n = 454) patients were women. The mean migraine duration was 18.0 (± 11.6) years, and the mean MMD was 19.2 (± 5.4). 97.8% (n = 545) randomised patients completed the DBTP. Overall, demographics and baseline characteristics were balanced between the erenumab and placebo groups except for a slightly higher proportion of women in the placebo group. At Week 12, the adjusted mean change from baseline in MMD was − 8.2 days for erenumab and − 6.6 days for placebo, with a statistically significant difference for erenumab versus placebo (adjusted mean difference vs placebo: − 1.57 [95%CI: − 2.83, − 0.30]; P = 0.015). A greater proportion of patients treated with erenumab achieved ≥ 50% reduction in MMD versus placebo (47.0% vs 36.7%, P = 0.014). At Week 12, greater reductions in monthly acute headache medication days (− 5.34 vs − 4.66) and mMIDAS scores (− 14.67 vs − 12.93) were observed in patients treated with erenumab versus placebo. Safety and tolerability profile of erenumab was comparable to placebo, except the incidence of constipation (8.6% for erenumab vs 3.2% for placebo). Conclusion: DRAGON study demonstrated the efficacy and safety of erenumab 70 mg in patients with CM from Asia. No new safety signals were observed during the DBTP compared with the previous trials. Trial registration: NCT03867201

Ligustrazine is a traditional Chinese herbal medicine that has long been used to treat cerebral ischemic disorders. However, the molecular mechanisms of ligustrazine in cerebral ischemia/reperfusion (I/R) damage have not been clear elucidated. The aim of this study was to examine the neuroprotective mechanisms of ligustrazine in cerebral I/R. 9 C57BL/6 mice were randomly divided to three groups: Sham group (n = 3), Middle cerebral artery occlusion (MCAO) group (n = 3), and MCAO + Ligustrazine group (n = 3). The neurological deficit score was evaluated, the cerebral infarct volume was measured by triphenylterazolium chloride (TTC) staining. Differentially expressed (DE) messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) were analyzed using the R package DEseq2 based on P-value < 0.05 and Log2 |fold change (FC)| ≥ 2 in sham group vs MCAO group and MCAO group vs ligustrazine group by high-throughput sequencing. Function enrichment analysis, the protein-protein interaction (PPI) of neurogenesis related genes were performed. The neurogenesis related competitive endogenous RNA (ceRNA) network was constructed. The expression of circ_0008146 was considerably higher in the MCAO group than the Sham group, and ligustrazine treatment markedly decreased the expression of circ_0008146 in MCAO. Next, the circ_0008146 ceRNA network was established, including circ_0008146-miR-709-Cx3cr1 ceRNA network. Besides, real time quantitative polymerase chain reaction (RT-qPCR) assay identified that miR-709 expression was considerably lower and Cx3cr1 expression was higher in the MCAO group than Sham group, and ligustrazine treatment markedly increased the miR-709 expression and reduced Cx3cr1 expression in MCAO. Further, silencing of circ_0008146 inhibited the concentration of Interleukin 6 (IL-6), Tumor Necrosis Factor alpha (TNF-α) and reduced neuron cell death and up-regulated miR-709 expression and down-regulated Cx3cr1 expression in Lipopolysaccharide (LPS) induced BV-2 cells. Dual-Luciferase reporter gene assay verified that circ_0008146 targeted miR-709. Ligustrazine targets circ_0008146/miR-709/Cx3cr1 axis to inhibit cell apoptosis and inflammation after cerebral ischemia/reperfusion injury.