Hu Tairan, Fang Zhaohui
Anhui University of Traditional Chinese Medicine, Hefei, China.
Department of Cardioiogy, First Hospital Affiliated to Anhui University of Traditional Chinese Medicine, Branch of National Clinical Research Center for Chinese Medicine Cardiology, Institution of Cardiovascular Disease, Anhui Academy of Chinese Medicine Sciences, Hefei, China.
Front Genet. 2025 Apr 14;16:1554622. doi: 10.3389/fgene.2025.1554622. eCollection 2025.
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that poses a significant global health burden due to its profound effects on systemic physiological homeostasis. Without timely intervention, the disease can progress insidiously, leading to multisystem complications such as cardiovascular, renal, and neuropathic pathologies. Consequently, pharmacological intervention becomes crucial in managing the condition. Leeches have been traditionally used in Chinese medicine for their potential to inhibit the progression of T2DM and its associated complications; however, the specific mechanisms underlying their action and target pathways remain poorly understood. The objective of this study was to predict potential therapeutic targets of leeches in the treatment of T2DM.
We collected active components and targets associated with leeches from four online databases, while disease-related targets were sourced from the GeneCards and OMIM databases. Following this, we performed Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Gene expression data were obtained from the GSE184050 dataset. Important immune cell types were identified through immunoinfiltration analysis in conjunction with single sample enrichment analysis (ssGSEA). Additionally, weighted co-expression network analysis (WGCNA) was utilized to identify significantly associated genes. Finally, we employed LASSO regression, SVM-RFE, XGBoost, and random forest algorithms to further predict potential targets, followed by validation through molecular docking.
Leeches may influence cellular immunity by modulating immune receptor activity, particularly through the activation of RGS10, CAPS2, and OPA1, thereby impacting the pathology of Type 2 Diabetes Mellitus (T2DM).
However, it is important to note that our results lack experimental validation; therefore, further research is warranted to substantiate these findings.
2型糖尿病（T2DM）是一种慢性代谢紊乱疾病，因其对全身生理稳态有深远影响，给全球健康带来重大负担。若不及时干预，该疾病会悄然进展，导致心血管、肾脏和神经病变等多系统并发症。因此，药物干预对于控制病情至关重要。水蛭在传统中医中一直被用于抑制T2DM进展及其相关并发症；然而，其作用的具体机制和靶标途径仍知之甚少。本研究的目的是预测水蛭治疗T2DM的潜在治疗靶点。
我们从四个在线数据库收集了与水蛭相关的活性成分和靶点，而疾病相关靶点则来自GeneCards和OMIM数据库。随后，我们进行了基因本体（GO）分析和京都基因与基因组百科全书（KEGG）富集分析。基因表达数据从GSE184050数据集中获取。通过免疫浸润分析结合单样本富集分析（ssGSEA）确定重要的免疫细胞类型。此外，利用加权共表达网络分析（WGCNA）来识别显著相关基因。最后，我们采用LASSO回归、支持向量机递归特征消除（SVM - RFE）、极端梯度提升（XGBoost）和随机森林算法进一步预测潜在靶点，随后通过分子对接进行验证。
水蛭可能通过调节免疫受体活性来影响细胞免疫，特别是通过激活RGS10、CAPS2和OPA1，从而影响2型糖尿病（T2DM）的病理过程。
然而，需要注意的是，我们的结果缺乏实验验证；因此，有必要进行进一步研究以证实这些发现。
