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综合分析揭示了模拟腹股沟疝模型中的六个基因特征和相关药物。

Comprehensive analysis reveals a six-gene signature and associated drugs in mimic inguinal hernia model.

机构信息

Department of Oncology and Vascular Interventional Radiology, Zhongshan Hospital, Xiamen University, Xiamen, China.

School of Medicine, Xiamen University, Xiamen, China.

出版信息

Hernia. 2020 Dec;24(6):1211-1219. doi: 10.1007/s10029-020-02213-7. Epub 2020 May 18.

Abstract

PURPOSE

Inguinal hernia often occurs in elderly men, and more than one in five men will undergo inguinal hernia repair during their lifetime. Nevertheless, the underlying molecular mechanisms of the pathogenesis behind hernia formation is still unclear. The aims in this study are finding out the potential gene markers and available drugs.

METHODS

Firstly, we re-analyzed the GSE92748 datasets, including four high and four low expressions of humanized aromatase transgenic mice, which refers to mimic humanized hernia, to identify differentially expressed genes (DEGs) in AromH group compared with AromL group by the criteria: fold change ≥ 1.4 and adjust P value < 0.05. Secondly, the gene ontology and signaling pathway enrichment analyses of these DEGs were performed through online databases. In addition to the protein and protein interaction networks among these DEGs were constructed and the significant gene modules were chosen for further gene-drug interaction analysis. Lastly, the existing drugs target to these module genes were screen to explore the therapeutic effect for treatment of hernia.

RESULTS

We have identified 64 DEGs, which were associated with muscle system process, actomyosin structure organization etc. Moreover, the significant module genes in PPI networks were Cmya1, Casq2, Cmya5, Ttn, Csrp3 and Actc1, and one existing drug, DEXAMETHASONE, have targeted to Actc1 gene.

CONCLUSIONS

In the paper, we identified 6 potential genes and one existing drug for inguinal hernia, which might be used as targets and drugs for the study of inguinal hernia.

摘要

目的

腹股沟疝常发生于老年男性,超过五分之一的男性在其一生中将接受腹股沟疝修补术。然而,疝形成的发病机制背后的潜在分子机制仍不清楚。本研究的目的是寻找潜在的基因标志物和可用的药物。

方法

首先,我们重新分析了 GSE92748 数据集,包括四个高表达和四个低表达的人源化芳香酶转基因小鼠,这些小鼠模拟了人类的疝,通过以下标准来鉴定 AromH 组与 AromL 组之间差异表达的基因(DEGs):倍数变化≥1.4,调整后的 P 值<0.05。其次,通过在线数据库对这些 DEGs 进行基因本体论和信号通路富集分析。此外,构建了这些 DEGs 之间的蛋白质和蛋白质相互作用网络,并选择了显著的基因模块进行进一步的基因-药物相互作用分析。最后,筛选这些模块基因的现有药物靶标,以探索治疗疝的治疗效果。

结果

我们确定了 64 个 DEGs,这些基因与肌肉系统过程、肌球蛋白结构组织等有关。此外,PPI 网络中的显著模块基因有 Cmya1、Casq2、Cmya5、Ttn、Csrp3 和 Actc1,一种现有药物,DEXAMETHASONE,已靶向 Actc1 基因。

结论

在本文中,我们确定了 6 个潜在基因和 1 种现有药物用于腹股沟疝,它们可能作为腹股沟疝研究的靶点和药物。

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