ABSTRACT
OBJECTIVE: Network pharmacology is a bioinformatics-based research strategy for identifying the mechanisms of drugs and promoting drug development. This study used network pharmacology to investigate the mechanism of the Loulu-Cremastrae Pseudobulbus drug pair treating breast cancer (BC). MATERIALS AND METHODS: The ingredients and potential targets of the drug pair were searched with Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCSMP). National Center for Biotechnology Information (NCBI) and gene cards were used to search the targets of BC. Networks of "drugs-components-targets" and protein-protein interaction were constructed through Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out through common targets. Using AutoDock tool, molecular docking was performed to verify the binding between key targets and compounds. RESULTS: Finally, we selected 6 active compounds from the drug pair. A total of 61 targets were associated with the drug pair, and 15,295 targets were related to BC. 55 common targets were obtained after the intersection. The key targets included Transcription factor Jun (JUN), Heat shock protein HSP 90-alpha (HSP90AA1), and Caspase-3(CASP3). 327 terms were obtained by GO analysis. 78 pathways (p < 0.05) were identified through KEGG analysis. Molecular docking indicated that important compounds combined well with key targets. CONCLUSIONS: Various active compounds, including beta-sitosterol, 2-methoxy-9,10-dihydrophenanthrene-4,5-diol, and stigmasterol, can regulate multiple signaling pathways related to BC, such as the estrogen and prolactin signaling pathways, playing therapeutic roles in BC.
Subject(s)
Neoplasms , Network Pharmacology , Molecular Docking Simulation , Estrogens , Computational Biology , Databases, FactualABSTRACT
Neurosyphilis (NS) is a neurological disorder caused by Treponema pallidum subspecies pallidum (T. pallidum), but how T. pallidum attach to and cross the blood-brain barrier (BBB) and how BBB response to this bacteria remain unclear. To explore how the human brain microvascular endothelial cells (HBMECs) response to T. pallidum, the Agilent SurePrint G3 Human Gene Expression 8×60K microarray was used. The results revealed that 249 genes were differentially expressed in HBMECs infected with T. pallidum. In particular, genes encoding proteins involved in bacterial adhesion, endothelial cell activation and immune response were regulated by T. pallidum. Furthermore, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to determine the biological functions of differentially expressed genes. In summary, T. pallidum changes the gene expression profile in HBMECs, and differentially expressed genes are associated with widespread biological and pathophysiological functions. Above all, this is the first paper reporting the effects of T. pallidum on HBMECs. These data develop a new platform for further molecular experiments on the pathogenesis of NS.
