■利用网络药理学方法探索塞来昔布治疗异位骨化的有效靶点。
■与异位骨化相关的潜在分子是通过检索GEO和CTD数据库并将其相交获得的。从STITCH数据库获得塞来昔布的潜在结合靶标。使用STRING数据库在塞来昔布的潜在结合靶标和异位骨化的潜在相关分子之间构建了蛋白质-蛋白质相互作用网络。在R软件中使用GO和KEGG富集分析进一步分析蛋白质-蛋白质相互作用网络中的分子,然后对塞来昔布异位骨化目标数据集中的活性分子进行富集分析。基于蛋白质-蛋白质相互作用网络中的“程度”值和富集来选择集线器基因。使用分子对接技术观察到hub基因与塞来昔布的结合亲和力。最后,通过体外实验验证hub基因的有效性,并探讨其在异位骨化进程中的调控作用。此外,塞来昔布的治疗效果,调节中枢基因的表达,在异位骨化的治疗中进行了研究。
■确定了568个与异位骨化相关的潜在分子和76个潜在的塞来昔布结合靶标。交叉后,获得了13个潜在的塞来昔布治疗异位骨化的功能分子。KEGG分析提示了诸如类风湿性关节炎等途径,NF-κB信号通路,癌症的途径,抗叶酸药,癌症中的microRNAs在塞来昔布治疗异位骨化中起作用。对13种潜在功能分子的进一步富集分析鉴定出5种hub基因:IL6、CCND1、PTGS2、IGFBP3、CDH1。分子对接结果表明,塞来昔布在5个hub基因中与CCND1表现出优异的结合亲和力。实验验证发现CCND1在异位骨化进程中高表达,早期促进异位骨化,后期抑制异位骨化,塞来昔布治疗异位骨化取决于CCND1。
■在塞来昔布治疗异位骨化的过程中,免疫和炎症信号通路发挥着重要作用。塞来昔布对异位骨化的治疗作用依赖于hub基因CCND1,在异位骨化进程的不同阶段发挥不同的作用。最终抑制异位骨化的发生。
UNASSIGNED: To explore the effective targets of Celecoxib in the treatment of heterotopic ossification using network pharmacology methods.
UNASSIGNED: Potential molecules related to heterotopic ossification were obtained by retrieving the GEO and CTD databases and intersecting them. Potential binding targets of Celecoxib were acquired from the STITCH database. A protein-protein interaction network was constructed between potential binding targets of Celecoxib and potential related molecules of heterotopic ossification using the STRING database. Molecules in the protein-protein interaction network were further analyzed using GO and KEGG enrichment analysis in R software, followed by enrichment analysis of active molecules in the Celecoxib-heterotopic ossification target dataset. Hub genes were selected based on the \"degree\" value and enrichment within the protein-protein interaction network. The binding affinity of hub genes to Celecoxib was observed using molecular docking techniques. Finally, in vitro experiments were conducted to validate the effectiveness of hub genes and explore their regulatory role in the progression of heterotopic ossification. Additionally, the therapeutic effect of Celecoxib, which modulates the expression of the hub genes, was investigated in the treatment of heterotopic ossification.
UNASSIGNED: 568 potential molecules related to heterotopic ossification and 76 potential binding targets of Celecoxib were identified. After intersection, 13 potential functional molecules in Celecoxib\'s treatment of heterotopic ossification were obtained. KEGG analysis suggested pathways such as Rheumatoid arthritis, NF-kappa B signaling pathway, Pathways in cancer, Antifolate resistance, MicroRNAs in cancer play a role in the treatment of heterotopic ossification by Celecoxib. Further enrichment analysis of the 13 potential functional molecules identified 5 hub genes: IL6, CCND1, PTGS2, IGFBP3, CDH1. Molecular docking results indicated that Celecoxib displayed excellent binding affinity with CCND1 among the 5 hub genes. Experimental validation found that CCND1 is highly expressed in the progression of heterotopic ossification, promoting heterotopic ossification in the early stages and inhibiting it in the later stages, with Celecoxib\'s treatment of heterotopic ossification depending on CCND1.
UNASSIGNED: In the process of treating heterotopic ossification with Celecoxib, immune and inflammatory signaling pathways play a significant role. The therapeutic effect of Celecoxib on heterotopic ossification depends on the hub gene CCND1, which plays different roles at different stages of the progression of heterotopic ossification, ultimately inhibiting the occurrence of heterotopic ossification.