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基于生物信息学与分子对接分析整合的小儿支气管肺发育不良诊断标志物及药物的鉴定与验证

Identification and validation of diagnostic markers and drugs for pediatric bronchopulmonary dysplasia based on integrating bioinformatics and molecular docking analysis.

作者信息

Guo Rui, Zheng Qirui, Zhang Liang

机构信息

Neonatology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.

Department of Ultrasound, The People's Hospital of China Medical University, The People's Hospital of Liaoning Province, Shenyang, Liaoning Province, China.

出版信息

PLoS One. 2025 May 7;20(5):e0323006. doi: 10.1371/journal.pone.0323006. eCollection 2025.

Abstract

BACKGROUND

BPD is a prevalent chronic lung disease in infancy with lifelong impacts. Its early diagnosis and treatment are hindered by complex pathophysiology and limited mechanistic understanding. This study seeks to establish a foundation for early diagnosis and targeted therapy by identifying diagnostic markers and exploring drug-gene associations.

METHODS

Gene expression data were retrieved from the GEO database. Functional enrichment analyses were conducted on the differentially expressed genes (DEGs). DEGs were used to construct a PPI network. Three algorithms were applied to identify diagnostic markers. Immune cell infiltration was analyzed using the CIBERSORT tool, assessing relationships between immune cells and diagnostic markers. Molecular docking was performed to evaluate interactions between predict candidate drugs and diagnostic markers.

RESULTS

Six hub genes were identified as diagnostic markers. Diagnostic markers showed significant correlations with specific immune cells. Resveratrol and progesterone were found to stably bind to all six diagnostic markers in molecular docking analyses, suggesting therapeutic potential.

CONCLUSION

In conclusion, our results show that IL7R, CXCL10, DEFA4, PRTN3, NCAPG and CCNB1 are BPD diagnostic indicators, and revealing immunological features associated with BPD. The molecular interactions of resveratrol and progesterone with the aforementioned key targets suggest their potential as therapeutic drugs for treating BPD.

摘要

背景

支气管肺发育不良(BPD)是一种在婴儿期常见的慢性肺部疾病,具有终身影响。其复杂的病理生理学和有限的机制理解阻碍了早期诊断和治疗。本研究旨在通过识别诊断标志物和探索药物-基因关联,为早期诊断和靶向治疗奠定基础。

方法

从基因表达综合数据库(GEO数据库)检索基因表达数据。对差异表达基因(DEGs)进行功能富集分析。利用DEGs构建蛋白质-蛋白质相互作用(PPI)网络。应用三种算法识别诊断标志物。使用CIBERSORT工具分析免疫细胞浸润情况,评估免疫细胞与诊断标志物之间的关系。进行分子对接以评估预测的候选药物与诊断标志物之间的相互作用。

结果

鉴定出六个中心基因作为诊断标志物。诊断标志物与特定免疫细胞显示出显著相关性。在分子对接分析中发现白藜芦醇和孕酮与所有六个诊断标志物稳定结合,表明具有治疗潜力。

结论

总之,我们的结果表明白细胞介素7受体(IL7R)、CXC趋化因子配体10(CXCL10)、防御素A4(DEFA4)、蛋白酶3(PRTN3)、核仁磷酸蛋白(NCAPG)和细胞周期蛋白B1(CCNB1)是BPD的诊断指标,并揭示了与BPD相关的免疫学特征。白藜芦醇和孕酮与上述关键靶点的分子相互作用表明它们作为治疗BPD的治疗药物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/519e/12057968/61f48898126e/pone.0323006.g001.jpg

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