Background: Acute ischemic stroke (AIS) is a severe neurological disease with complex pathophysiology, resulting in the disability and death. The goal of this study is to explore the underlying molecular mechanisms of AIS and search for new potential biomarkers and therapeutic targets.Methods: Integrative analysis of mRNA and miRNA profiles downloaded from Gene Expression Omnibus (GEO) was performed. We explored differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMirs) after AIS. Target mRNAs of DEMirs and target miRNAs of DEGs were predicted with target prediction tools, and the intersections between DEGs and target genes were determined. Subsequently, Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses, Gene set enrichment analysis (GSEA), Gene set variation analysis (GSVA), competitive endogenous RNA (ceRNA) (lncRNA-miRNA-mRNA) network, protein–protein interaction (PPI) network, and gene transcription factors (TFs) network analyses were performed to identify hub genes and associated pathways. Furthermore, we obtained AIS samples with evaluation of immune cell infiltration and used CIBERSORT to determine the relationship between the expression of hub genes and infiltrating immune cells. Finally, we used the Genomics of Drug Sensitivity in Cancer (GDSC) database to predict the effect of the identified targets on drug sensitivity.Result: We identified 293 DEGs and 26 DEMirs associated with AIS. DEGs were found to be mainly enriched in inflammation and immune-related signaling pathways through enrichment analysis. The ceRNA network included nine lncRNAs, 13 miRNAs, and 21 mRNAs. We used the criterion AUC >0.8, to screen a 3-gene signature (FBL, RPS3, and RPS15) and the aberrantly expressed miRNAs (hsa-miR-125a-5p, hsa-miR-125b-5p, hsa-miR-148b-3p, and hsa-miR-143-3p) in AIS, which were verified by a method of quantitative PCR (qPCR) in HT22 cells. T cells CD8, B cells naïve, and activated NK cells had statistical increased in number compared with the acute cerebral infarction group. By predicting the IC50 of the patient to the drug, AZD0530, Z.LLNle.CHO and NSC-87877 with significant differences between the groups were screened out. AIS demonstrated heterogeneity in immune infiltrates that correlated with the occurrence and development of diseases.Conclusion: These findings may contribute to a better understanding of the molecular mechanisms of AIS and provide the basis for the development of novel treatment targets in AIS.

This study aimed to determine the relationship between bilirubin levels and carotid atherosclerosis (CAS) in the health screening population. After propensity score matching, this retrospective cohort study included 4360 subjects who underwent health examinations regularly in Hebei General Hospital between January 2010 and December 2019 and had no carotid plaque at baseline. After an average follow-up of 26.76 months, the main endpoint Cox regression analysis of carotid plaques was performed. After adjusting the confounding factors, Cox regression analysis showed that when serum total bilirubin (TBIL) and unconjugated bilirubin (UCB) increased by 1 standard deviation (SD), the risk of carotid plaque decreased by 7.30% (95% confidence interval (CI): 2.80–11.60%) and 15.70% (95% CI: 11.40–19.80%), respectively. When conjugated bilirubin (CB) increased by 1 SD, the risk of carotid plaques increased by 24.3% (95% CI: 19.7–29.0%). TBIL and UCB levels were negatively associated with CAS, and CB levels were positively associated with CAS.