探索糖尿病微血管疾病中的毒理网络
Siyuan Song1,2,3, Liji Huang1,2,3, Xiqiao Zhou1,2,3
1Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
International journal of surgery (London, England)
|April 11, 2025
概括
内分泌干扰化学物质 (EDC) 与糖尿病微血管并发症有关. 这项研究确定了糖尿病病,视网膜病变和神经病变中的关键分子标和途径,为疾病机制提供了洞察力.
科学领域:
- 内分泌学和毒理学.
- 分子生物学和生物信息学
- 糖尿病学 糖尿病学
背景情况:
- 糖尿病微血管并发症,包括脏病,视网膜病变和神经病变,对健康构成重大挑战.
- 内分泌干扰化学物质 (EDC) 是干扰荷尔蒙系统的环境剂,并且越来越多地与代谢疾病有关.
研究的目的:
- 研究EDCs对糖尿病微血管疾病的发展有所贡献的分子机制.
- 确定EDCs在糖尿病病,视网膜病变和感官多神经病变中影响的特定毒性标和途径.
主要方法:
- 利用数据库 (PubChem,ChEMBL) 来评估EDC毒性,并使用SwissTargetPrediction和相似性组合方法确定了潜在的目标.
- 来自CTD,GeneCards和OMIM的糖尿病微血管疾病的综合基因标,以找到重叠的EDC和与疾病有关的标.
- 构建了蛋白质-蛋白质相互作用网络 (STRING) 来识别枢纽基因,进行了功能丰富分析 (Metascape),并进行了分子对接 (发现工作室,CDOCKER).
- 通过免疫组织化学,单细胞分析,亚细胞定位和公共数据集的基因表达分析验证了关键目标.
主要成果:
- 分别确定了843,474和623个糖尿病病,视网膜病变和感官多神经病变的潜在毒性标.
- 凯格路径分析揭示了糖尿病病 (癌症,亡,信号传导),视网膜病变 (MAPK,ERBB) 和神经病变 (化学因子,亡,ERBB) 中的EDC相关路径.
- 在疾病中确定的关键枢纽标包括EGFR,ALB,MYC,ESR1和BCL2,通过分子对接证实EDC与这些标之间有很强的结合.
结论:
- 这项研究提供了一个全面的理论框架,以了解EDCs对糖尿病微血管疾病的有毒目标和机制.
- 已确定的枢纽基因和通路为未来的治疗干预提供了潜在的目标,旨在缓解EDC诱导的糖尿病并发症.
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