Biochemical and biophysical research communications · 2026
Cyclo(Ser-Tyr) L/D spatial isomerism exerts opposing effects on benign prostatic hyperplasia.
СтатьяНазвание 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.
Xun Liu, Rulan Tan, Tianyan Wang, Wenting Geng, Caiyun Shao, Qiqi Song
Аннотация
OBJECTIVE: To investigate the role of two isomers Cyclo (L-Ser-L-Tyr) and Cyclo (D-Ser-L-Tyr) in benign prostatic hyperplasia. Additionally, it seeks to elucidate their mechanisms of action through both in vitro and in vivo experiments.
METHODS: Benign prostatic hyperplasia (BPH) was induced using testosterone propionate. The pharmacological effects of Cyclo (L-Ser-L-Tyr) and Cyclo (D-Ser-L-Tyr) were evaluated. Efficacy and safety were assessed by measuring prostate weight, calculating the prostate index, and conducting histopathological and biochemical analyses. Mechanistic studies incorporated transcriptomics, immunohistochemistry, CCK-8 assays, siRNAs transfection, Western blotting, molecular docking, and molecular dynamics simulations.
RESULTS: Cyclo (L-Ser-L-Tyr) reduced prostate index, attenuated prostatic epithelial hyperplasia and interstitial fibrosis, lowered TNF-α and IL-1β levels, and suppressed inflammation. In contrast, finasteride fails to alleviate prostate fibrosis, while Cyclo (D-Ser-L-Tyr) showed no therapeutic effect and significantly increased serum ALT and AST, indicating potential hepatotoxicity. Transcriptomic analysis showed that Cyclo (L-Ser-L-Tyr) reversed elevated expression of BPH-associated genes and affected pathways including cancer, apoptosis, p53, and MAPK signaling. In prostate tissues and cells, Cyclo (L-Ser-L-Tyr) reduced protein levels of AR and BCL-2. In BPH-1 cells, AR knockout markedly decreased BCL-2 expression. Molecular dynamics simulations showed that Cyclo (L-Ser-L-Tyr) forms a stable complex with AR.
CONCLUSION: Cyclo (L-Ser-L-Tyr) ameliorates BPH by modulating the AR/BCL-2 axis and inflammatory mediators, whereas Cyclo (D-Ser-L-Tyr) is ineffective and may be hepatotoxic. These results support the clinical potential of Cyclo (L-Ser-L-Tyr).
METHODS: Benign prostatic hyperplasia (BPH) was induced using testosterone propionate. The pharmacological effects of Cyclo (L-Ser-L-Tyr) and Cyclo (D-Ser-L-Tyr) were evaluated. Efficacy and safety were assessed by measuring prostate weight, calculating the prostate index, and conducting histopathological and biochemical analyses. Mechanistic studies incorporated transcriptomics, immunohistochemistry, CCK-8 assays, siRNAs transfection, Western blotting, molecular docking, and molecular dynamics simulations.
RESULTS: Cyclo (L-Ser-L-Tyr) reduced prostate index, attenuated prostatic epithelial hyperplasia and interstitial fibrosis, lowered TNF-α and IL-1β levels, and suppressed inflammation. In contrast, finasteride fails to alleviate prostate fibrosis, while Cyclo (D-Ser-L-Tyr) showed no therapeutic effect and significantly increased serum ALT and AST, indicating potential hepatotoxicity. Transcriptomic analysis showed that Cyclo (L-Ser-L-Tyr) reversed elevated expression of BPH-associated genes and affected pathways including cancer, apoptosis, p53, and MAPK signaling. In prostate tissues and cells, Cyclo (L-Ser-L-Tyr) reduced protein levels of AR and BCL-2. In BPH-1 cells, AR knockout markedly decreased BCL-2 expression. Molecular dynamics simulations showed that Cyclo (L-Ser-L-Tyr) forms a stable complex with AR.
CONCLUSION: Cyclo (L-Ser-L-Tyr) ameliorates BPH by modulating the AR/BCL-2 axis and inflammatory mediators, whereas Cyclo (D-Ser-L-Tyr) is ineffective and may be hepatotoxic. These results support the clinical potential of Cyclo (L-Ser-L-Tyr).