Reproductive toxicology (Elmsford, N.Y.) · 2025
Network toxicology and machine learning reveal the impact of acetyl tributyl citrate on erectile dysfunction and identify cathepsin S as a critical regulator.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Liu Zhiyu, Li Yuqi, Wang Juan, Zeng Yang, Wu Qilong, Zhu Xinyao, Zhou Tao, Deng Qingfu
Аннотация
BACKGROUND: Erectile dysfunction (ED), a common male sexual disorder, may be associated with acetyl tributyl citrate (ATBC) exposure. EDCs can interfere with hormonal signaling and physiological homeostasis, but their specific roles and mechanisms in contributing to ED remain inadequately elucidated.
METHODS: Network toxicology and enrichment analyses were utilized to identify potential targets and signaling pathways involved in ATBC-induced ED. A protein-protein interaction (PPI) network was constructed, and key regulatory molecules were identified using EPC, MNC, Betweenness, and Degree algorithms. Single-cell sequencing was conducted to analyze the expression profiles of target genes in penile corpus cavernosum tissue. Five machine learning algorithms were applied to pinpoint core targets and evaluate the association between ATBC and ED. Finally, molecular docking validated the binding characteristics between ATBC and the target proteins.
RESULTS: A total of 71 potential targets were identified, and 11 key genes were determined through PPI network construction and topological analysis. Single-cell sequencing revealed tissue-specific expression patterns of these targets, while machine learning identified cathepsin S (CTSS) as the core target. Molecular docking confirmed a stable binding affinity between ATBC and CTSS. In vitro experiments further demonstrated the impact of ATBC on endothelial cell function and CTSS expression.
CONCLUSIONS: This study systematically elucidates how ATBC regulates CTSS expression, impacting endothelial function and contributing to ED. The findings advance understanding of environmental endocrine disruptors in male sexual dysfunction and highlight novel molecular targets for prevention and intervention.
METHODS: Network toxicology and enrichment analyses were utilized to identify potential targets and signaling pathways involved in ATBC-induced ED. A protein-protein interaction (PPI) network was constructed, and key regulatory molecules were identified using EPC, MNC, Betweenness, and Degree algorithms. Single-cell sequencing was conducted to analyze the expression profiles of target genes in penile corpus cavernosum tissue. Five machine learning algorithms were applied to pinpoint core targets and evaluate the association between ATBC and ED. Finally, molecular docking validated the binding characteristics between ATBC and the target proteins.
RESULTS: A total of 71 potential targets were identified, and 11 key genes were determined through PPI network construction and topological analysis. Single-cell sequencing revealed tissue-specific expression patterns of these targets, while machine learning identified cathepsin S (CTSS) as the core target. Molecular docking confirmed a stable binding affinity between ATBC and CTSS. In vitro experiments further demonstrated the impact of ATBC on endothelial cell function and CTSS expression.
CONCLUSIONS: This study systematically elucidates how ATBC regulates CTSS expression, impacting endothelial function and contributing to ED. The findings advance understanding of environmental endocrine disruptors in male sexual dysfunction and highlight novel molecular targets for prevention and intervention.