Objective:EpimediiFolium(EF),a traditional Chinese medicinal material,has the effect of tonifying kidney Yang,strengthening bones and treating rheumatism.However,its clinical applications are limited by its drug-induc...Objective:EpimediiFolium(EF),a traditional Chinese medicinal material,has the effect of tonifying kidney Yang,strengthening bones and treating rheumatism.However,its clinical applications are limited by its drug-induced liver injury(DILI)effects and the underlying mechanisms have not been elucidated.Methods:Active EF compounds were obtained from the TCMSP database and their targets predicted in Targetnet.Next,DILI-targets were obtained from CTD,Genecards and Digsee databases.Protein-protein interactions of EF DILI-targets were determined using STRING and hub targets identified via topological analyses.Then,hub targets were subjected to GO and KEGG pathway enrichment analyses.Finally,HepaRG cells were used for further validation of molecular mechanisms.Results:Fifty seven active compounds and 164 targets that interacted with these active compounds were identified with Sagittatoside A,icariside I,and Icariin being the best active compounds.Enrichment analysis revealed the PI3K/Akt and NF-kB signaling pathways to be markedly enriched.Molecular docking revealed that Sagittatoside A,icariside I and Icariin had good binding activities to RAC1,PTGS2,and NOS3.Validation analysis in HepaRG cells revealed that Epimedium flavonoids upregulated RAC1,PTGS2 and NOS3 levels.Conclusion:Our findings show that EF induces oxidative stress,inflammation,and apoptosis via PI3K/Akt and NF-kB signaling pathways,and provides a basis for more in-depth studies on EF-induced DILI.展开更多
目的:分析生化阴性嗜铬细胞瘤及副神经节瘤(pheochromocytomas and paragangliomas,PPGLs)的电子计算机断层扫描(computed tomography,CT)征象是否有别于生化阳性PPGLs,同时了解生化阳性PPGLs不同表型的CT征象是否存在差异。方法:回顾...目的:分析生化阴性嗜铬细胞瘤及副神经节瘤(pheochromocytomas and paragangliomas,PPGLs)的电子计算机断层扫描(computed tomography,CT)征象是否有别于生化阳性PPGLs,同时了解生化阳性PPGLs不同表型的CT征象是否存在差异。方法:回顾性分析131例PPGLs患者的术前腹部增强CT图像,包括肿瘤位置、大小、形态、囊变坏死、液-液分层、钙化、向心结节状强化、肿瘤内粗大血管、强化包膜、绝对廓清率及相对廓清率。根据生化水平,将患者分为生化阳性组和阴性组,阳性组进一步分为去甲肾上腺素型、肾上腺素型及多巴胺型。比较各组及各表型间的CT征象差异。结果:相较于生化阴性组,阳性组PPGLs更大(Z=-2.064,P=0.039)、囊变坏死(χ2=6.610,P=0.010)及向心结节状强化(χ2=3.909,P=0.048)的比例更高;相较于去甲肾上腺素型,肾上腺素型PPGLs更大(Z=-2.036,P=0.042)、强化包膜比例更高(χ2=7.242,P=0.007)。结论:肿瘤大小、囊变坏死及向心结节状强化的CT征象有助于术前诊断生化阴性PPGLs,肿瘤大小及强化包膜有助于解释去甲肾上腺素型及肾上腺素型PPGLs不同临床表现产生的机制。展开更多
基金National Natural Science Foundation of China(No.51906262)Natural Science Foundation of Hunan Province,China(No.2020JJ5735)Youth Excellent Sci-Tech Talents Training Plan under Hunan Provincial Sci-Tech Talents Sponsorship Program,China(No.2023TJ-N10)。
文摘Objective:EpimediiFolium(EF),a traditional Chinese medicinal material,has the effect of tonifying kidney Yang,strengthening bones and treating rheumatism.However,its clinical applications are limited by its drug-induced liver injury(DILI)effects and the underlying mechanisms have not been elucidated.Methods:Active EF compounds were obtained from the TCMSP database and their targets predicted in Targetnet.Next,DILI-targets were obtained from CTD,Genecards and Digsee databases.Protein-protein interactions of EF DILI-targets were determined using STRING and hub targets identified via topological analyses.Then,hub targets were subjected to GO and KEGG pathway enrichment analyses.Finally,HepaRG cells were used for further validation of molecular mechanisms.Results:Fifty seven active compounds and 164 targets that interacted with these active compounds were identified with Sagittatoside A,icariside I,and Icariin being the best active compounds.Enrichment analysis revealed the PI3K/Akt and NF-kB signaling pathways to be markedly enriched.Molecular docking revealed that Sagittatoside A,icariside I and Icariin had good binding activities to RAC1,PTGS2,and NOS3.Validation analysis in HepaRG cells revealed that Epimedium flavonoids upregulated RAC1,PTGS2 and NOS3 levels.Conclusion:Our findings show that EF induces oxidative stress,inflammation,and apoptosis via PI3K/Akt and NF-kB signaling pathways,and provides a basis for more in-depth studies on EF-induced DILI.
文摘目的:分析生化阴性嗜铬细胞瘤及副神经节瘤(pheochromocytomas and paragangliomas,PPGLs)的电子计算机断层扫描(computed tomography,CT)征象是否有别于生化阳性PPGLs,同时了解生化阳性PPGLs不同表型的CT征象是否存在差异。方法:回顾性分析131例PPGLs患者的术前腹部增强CT图像,包括肿瘤位置、大小、形态、囊变坏死、液-液分层、钙化、向心结节状强化、肿瘤内粗大血管、强化包膜、绝对廓清率及相对廓清率。根据生化水平,将患者分为生化阳性组和阴性组,阳性组进一步分为去甲肾上腺素型、肾上腺素型及多巴胺型。比较各组及各表型间的CT征象差异。结果:相较于生化阴性组,阳性组PPGLs更大(Z=-2.064,P=0.039)、囊变坏死(χ2=6.610,P=0.010)及向心结节状强化(χ2=3.909,P=0.048)的比例更高;相较于去甲肾上腺素型,肾上腺素型PPGLs更大(Z=-2.036,P=0.042)、强化包膜比例更高(χ2=7.242,P=0.007)。结论:肿瘤大小、囊变坏死及向心结节状强化的CT征象有助于术前诊断生化阴性PPGLs,肿瘤大小及强化包膜有助于解释去甲肾上腺素型及肾上腺素型PPGLs不同临床表现产生的机制。
