RESUMO
Background: The purpose of this study was to investigate the mechanism of action of muscone on breast cancer using network pharmacology and molecular docking techniques. Methods: Targets of muscone acid action were collected using the PubChem and SwissTargetPrediction databases. Relevant target sets of breast cancer were collected using the GeneCards database, and the intersection of the drug-disease targets was used as the potential target of muscone action in breast cancer. The STRING database was used to construct a target protein-protein interaction (PPI) network, and the data were imported into Cytoscape 3.7.1 for topological network analysis to obtain the core target genes of muscone in breast cancer. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID database. The correlation of core gene expression with breast cancer survival was analyzed using the online Kaplan-Meier plotter tool. Molecular docking of core target genes to muscone was performed using AutoDock Vina. Results: A total of 18 common targets of muscone and breast cancer were obtained through target intersection. The PPI map and topology analysis revealed that androgen receptor (AR), progesterone receptor (PGR), matrix metalloproteinase 9 (MMP9), prostaglandin-endoperoxide synthase 2 (PTGS2), heat shock protein 90 alpha family class A member 1 (HSP90AA1), mitogen-activated protein kinase 14 (MAPK14), and cytochrome P450 family 19 subfamily A member 1 (CYP19A1) might be the key targets of muscone acting on breast cancer. The GO enrichment analysis identified 60 terms, while the KEGG pathway enrichment analysis identified 7 signaling pathways, including steroid hormone biosynthesis, ovarian steroidogenesis, cancer pathways, and the tumor necrosis factor (TNF) signaling pathway. The results of survival stage analysis showed that the binding activity between muskone and key targets was better than other targets. The molecular docking results showed that muscone had the highest docking affinity for the key target CYP19A1 gene at -7.0 kJ/moL. Conclusions: Muscone might exert anti-breast cancer effects through cancer pathways, ovarian steroidogenesis, and TNF signaling pathways and has the potential to be developed as a clinical agent.
RESUMO
BACKGROUND: The three- and four-part fractures of the proximal humerus are often combined with rotator cuff injury, and shoulder joint replacement is often selected clinically. The concept of "shoulder preservation" can greatly restore the function of the shoulder joint through internal fixation of the proximal humerus fracture and rotator cuff suture. This study investigated the clinical effect of the concept of "shoulder preservation" in the treatment of three- and four-part fractures of the proximal humerus. METHODS: We conducted a retrospective analysis of 66 patients with proximal humeral fractures (PHFs) who were treated at the Affiliated Hospital of Qinghai University between 2016 and 2019. The patients were divided into 3 groups according to the Neer fracture classification system, and the fracture healing time of the 3 groups was compared. A visual analog scale (VAS) was used to evaluate the pain, and the Neer score was used to evaluate shoulder joint function. RESULTS: The operations were successfully completed and the 3 groups of patients were compared in pairs. All incisions healed by first intention after operation, and no early complications occurred. The average follow-up time was 18 months. All fractures had healed. The VAS score of the 3 groups of patients was 1.5±0.5 at 1 month after operation and 1.0±0.5 at the final follow-up, which was significantly improved compared with preoperative scores, although the difference was not statistically significant (P>0.05). The Neer scores of the first group of patients at 1, 3, and 9 months postsurgery were higher than those of the second and third groups, and the difference was statistically significant (P<0.05). There was no significant difference among the 3 groups in Neer score 12 months after the operation (P>0.05). CONCLUSIONS: Proximal humeral internal locking osteosynthesis system (PHILOS) fixation + rotator cuff suture is a reliable treatment method involving a simple operation, firm fixation, and good postoperative recovery. It can restore shoulder joint function to the greatest extent, but it also has some shortcomings, including slow recovery time.
