Identifying and validating key genes mediating intracranial aneurysm rupture using weighted correlation network analysis and exploration of personalized treatment.

Background: Intracranial aneurysmal subarachnoid hemorrhage (aSAH) is a dangerous and highly fatal condition if ruptured. Significant advances have been made in the treatment of unruptured intracranial aneurysms (UIAs), but risk assessment methods for early diagnosis of intracranial aneurysm (IA) rupture remain limited. Methods: The datasets of IA GSE13353, GSE15629, and GSE54083 were downloaded through the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in unruptured and ruptured aneurysms were identified by R software using methods such as gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the DEGs, and logistic regression models were used to construct a prediction model to discriminate UIA from healthy samples. We then performed GSEA on the genes in the model, followed by model validation using the GSE54083 dataset. Finally, we used the single-sample (ss)GSEA method to investigate the relationship between the diagnostic model genes and immune cells and immune function. Results: A total of 79 DEGs were obtained in patients with IA rupture compared to unruptured controls. The results of KEGG and GO enrichment analysis showed that neutrophil activation is involved in immune response, neutrophil mediated immunity, and positive regulation of angiogenesis. Interestingly, the results of immunoassays demonstrated that the break in IA may be associated with immune T cells. We used DEGs and WGCNA to determine common genes. The logistic regression model was trained based on 24 intersecting genes, and eventually retained 2 genes, KIAA0226L and UPP1, which we found to be reliable using the validation set, and GSEA revealed that the diagnostic model was associated with the Hippo signaling pathway and vascular smooth muscle contraction, and viral protein interaction with cytokine and cytokine were also associated. Finally explored using the CMap database, Tivozanib could be a potential small molecule drug for the treatment of ruptured intracranial aneurysms (RIAs). Conclusions: We identified new diagnostic genes associated with IA rupture, which may provide a new way of aneurysm diagnosis.

Network pharmacological analysis of active components of Xiaoliu decoction in the treatment of glioblastoma multiforme.

Background: Glioblastoma multiforme (GBM) is the most aggressive primary nervous system brain tumor. There is still a lack of effective methods to control its progression and recurrence in clinical treatment. It is clinically found that Xiaoliu Decoction (XLD) has the effect of treating brain tumors and preventing tumor recurrence. However, its mechanism is still unclear. Methods: Search the Traditional Chinese Medicine System Pharmacology Database (TCSMP) for efficient substances for the treatment of XLD in the treatment of GBM, and target the targeted genes of the effective ingredients to construct a network. At the same time, download GBM-related gene expression data from the TCGA and GTEX databases, screen differential expression bases, and establish a drug target disease network. Through bioinformatics analysis, the target genes and shared genes of the selected Chinese medicines are analyzed. Finally, molecular docking was performed to further clarify the possibility of XLD in multiple GBMs. Results: We screened 894 differentially expressed genes in GBM, 230 XLD active ingredients and 169 predicted targets of its active compounds, of which 19 target genes are related to the differential expression of GBM. Bioinformatics analysis shows that these targets are closely related to cell proliferation, cell cycle regulation, and DNA synthesis. Finally, through molecular docking, it was further confirmed that Tanshinone IIA, the active ingredient of XLD, was tightly bound to key proteins. Conclusion: To sum up, the results of this study suggest that the mechanism of XLD in the treatment of GBM involves multiple targets and signal pathways related to tumorigenesis and development. This study not only provides a new theoretical basis for the treatment of glioblastoma multiforme with traditional Chinese medicine, but also provides a new idea for the research and development of targeted drugs for the treatment of glioblastoma multiforme.

Network pharmacological analysis of active components of Tongqiao Huoxue Decoction in the treatment of intracerebral hemorrhage.

Background: Intracerebral hemorrhage (ICH) is a type of stroke which results in a high disability and mortality rate and has a poor prognosis. Tongqiao Huoxue Decoction (TQHXD) is a classical Chinese prescription. Clinical practice has proven that TQHXD can promote blood circulation and can effectively treat ICH and its sequelae. However, the current mechanism is still unclear. Methods: The chemical components and target genes of TQHXD were collected from the Traditional Chinese medicine (TCM) Systems Pharmacology and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine analysis platforms, and the gene expression data of ICH tissues were downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was performed to obtain differentially co-expressed gene pairs and build a drug-target-disease network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the obtained target genes and shared genes. Finally, molecular docking was carried out to further clarify the utility of TQHXD for the treatment of ICH. Results: A total of 304 differentially expressed genes in ICH, 42 TQHXD active ingredients, and 279 predicted targets of its active compounds were obtained. Bioinformatics analysis showed that they were involved in angiogenesis, the regulation of wound healing, and other biological processes. Furthermore, their participation in fluid shear stress and the atherosclerosis signaling pathway indicated their close association with the pathological processes of ICH. Finally, molecular docking was carried out to further confirm the tightly binding structural sites of the effective components of TQHXD and key proteins. Conclusions: In summary, the results of this study suggest that the mechanism of action of TQHXD in the treatment of ICH involves multiple targets and signaling pathways related to its occurrence and development. This study not only provides a new theoretical basis for the treatment of ICH with traditional Chinese medicine, but also provides new ideas for the research and development of drugs for the treatment of ICH.