Exploring the co-diagnostic genes of gastric cancer and chemotherapy brain damage and the prediction of active ingredients in traditional Chinese medicine based on network pharmacology and bioinformatics

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Abstract

Background Natural products have favorable clinical effects on gastric cancer (GC)-chemotherapy-induced cognitive impairment (CICI), but their specific mechanisms are unknown. Our study used network pharmacology and bioinformatics to explore traditional natural small molecules acting on GC and CICI and their mechanisms of action. Methods GC- and CICI-related target proteins were collected from databases. Protein-protein interaction (PPI) networks were constructed. Core submodules of the networks were screened. Differential genes (DGEs) and module genes were obtained by differential analysis of GSE118916 and weighted network analysis. The core targets were obtained. The effects of the small molecules on the expression of the key targets were investigated by constructing an in vitro cell model. Results 369 “GC and CICI” targets were screened. 1216 differential genes (DGEs) and 2721 modular genes (DGEs) were obtained by differential analysis and weighted network analysis respectively. KEGG enrichment was used to analyze the pathways related to “GC and CICI”. Seven core genes were identified. Finally, two key targets, PTGS2 and VCAM1 were identified through ROC and survival analysis. The molecular docking results showed that Kaempferol binds well to the key targets. In in vitro experiments, the results showed that Kaempferol could down-regulate the levels of PTGS2 and VCAM1. Conclusion The present study suggests that natural products are a promising option for the treatment of GC and CICI, and our demonstration of a specific molecular mechanism of Kaempferol's anti-GC and CICI provides a theoretical basis for a better clinical application of this compound.

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