Objective:Pelvic organ prolapse(POP)is a common condition in postmenopausal women,with an increasing prevalence due to aging.Some women experience POP recurrence after surgical treatment,significantly affecting their ...Objective:Pelvic organ prolapse(POP)is a common condition in postmenopausal women,with an increasing prevalence due to aging.Some women experience POP recurrence after surgical treatment,significantly affecting their physical and mental health.The uterosacral ligament is a critical pelvic support structure.This study aims to investigate the molecular pathological changes in the uterosacral ligament of postmenopausal women with recurrent POP using transcriptomic analysis.Methods:Transcriptomic data of uterosacral ligament tissues were obtained from the public dataset GSE28660,which includes samples from 4 postmenopausal women with recurrent POP,4 with primary POP,and 4 without POP.Differentially expressed genes(DEGs)were identified between recurrent POP and both primary and non-POP groups.Further analysis included intersection analysis of DEGs,gene ontology enrichment,protein protein interaction(PPI)network construction,gene set enrichment analysis(GSEA),single-sample GSEA,and xCell immune cell infiltration analysis to explore molecular pathological changes in recurrent POP.Additionally,histological and molecular differences in the uterosacral ligament were compared between simulated vaginal delivery(SVD)rat models with and without ovariectomy.Results:Compared with primary POP and non-POP groups,recurrent POP exhibited activation of adipogenesis and inflammation-related pathways,while pathways related to muscle proliferation and contraction were downregulated in the uterosacral ligament.Nine key DEGs(ADIPOQ,FABP4,IL-6,LIPE,LPL,PCK1,PLIN1,PPARG,and CD36)were identified,with most enriched in the peroxisome proliferator-activated receptor(PPAR)signaling pathway.These genes were significantly correlated with lipid accumulation,monocyte infiltration,and neutrophil infiltration in the uterosacral ligament.Urodynamic testing revealed that the bladder leak point pressure was significantly higher in ovariectomized SVD rats,both of which had higher values than the sham group.Masson staining showed pronounced adipogenesis in the uterosacral ligament of ovariectomized SVD rats,along with reduced collagen and muscle fibers compared to the sham and non ovariectomized SVD groups.Furthermore,real-time RT-PCR confirmed significantly elevated expression of key DEGs,including ADIPOQ,IL-6,PCK1,and PLIN1,in the uterosacral ligaments of ovariectomized SVD rats.Conclusion:Adipogenesis and inflammation in the uterosacral ligament may contribute to its reduced supportive function,potentially leading to recurrence POP in postmenopausal women.展开更多
目的:探讨p53凋亡刺激蛋白2(apoptosis stimulating proteins of p53 2,ASPP2)、ASPP家族抑制成员(inhibitory member of the ASPP family,iASPP)在宫颈癌发生中的意义及其与p53的关系。方法:采用免疫组织化学法检测ASPP2,iASPP,p53在5...目的:探讨p53凋亡刺激蛋白2(apoptosis stimulating proteins of p53 2,ASPP2)、ASPP家族抑制成员(inhibitory member of the ASPP family,iASPP)在宫颈癌发生中的意义及其与p53的关系。方法:采用免疫组织化学法检测ASPP2,iASPP,p53在51例早期宫颈癌、53例子宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)Ⅱ-Ⅲ期、48例CIN I期及45例正常宫颈组织中的表达,分析ASPP2,iASPP与p53的相互关系。结果:p53阴性时,ASPP2在宫颈癌组、CIN Ⅱ-Ⅲ组、CIN I组、正常宫颈组中的阳性表达率逐渐升高,且CIN Ⅱ-Ⅲ组、宫颈癌组与正常宫颈组比较差异有统计学意义(P<0.05),余各组两两比较差异无统计学意义(P>0.05);iASPP在宫颈癌组、CIN Ⅱ-Ⅲ组、CIN Ⅰ组、正常宫颈组中的阳性表达率逐渐降低,且宫颈癌组与正常宫颈组比较,差异有统计学意义(P<0.05),余各组两两比较差异无统计学意义(P>0.05)。p53阳性时,ASPP2和iASPP在各组中的表达差异均无统计学意义(P>0.05)。结论:ASPP2和iASPP可能通过调节野生型p53诱导细胞凋亡的能力参与早期宫颈癌的发生,ASPP2和iASPP可能成为治疗宫颈癌潜在的分子靶点。展开更多
基金supported by the Key Research and Development Program of Hunan Province(2023SK2038)the Natural Science Foundation of Hunan Province(2024JJ8121),China。
文摘Objective:Pelvic organ prolapse(POP)is a common condition in postmenopausal women,with an increasing prevalence due to aging.Some women experience POP recurrence after surgical treatment,significantly affecting their physical and mental health.The uterosacral ligament is a critical pelvic support structure.This study aims to investigate the molecular pathological changes in the uterosacral ligament of postmenopausal women with recurrent POP using transcriptomic analysis.Methods:Transcriptomic data of uterosacral ligament tissues were obtained from the public dataset GSE28660,which includes samples from 4 postmenopausal women with recurrent POP,4 with primary POP,and 4 without POP.Differentially expressed genes(DEGs)were identified between recurrent POP and both primary and non-POP groups.Further analysis included intersection analysis of DEGs,gene ontology enrichment,protein protein interaction(PPI)network construction,gene set enrichment analysis(GSEA),single-sample GSEA,and xCell immune cell infiltration analysis to explore molecular pathological changes in recurrent POP.Additionally,histological and molecular differences in the uterosacral ligament were compared between simulated vaginal delivery(SVD)rat models with and without ovariectomy.Results:Compared with primary POP and non-POP groups,recurrent POP exhibited activation of adipogenesis and inflammation-related pathways,while pathways related to muscle proliferation and contraction were downregulated in the uterosacral ligament.Nine key DEGs(ADIPOQ,FABP4,IL-6,LIPE,LPL,PCK1,PLIN1,PPARG,and CD36)were identified,with most enriched in the peroxisome proliferator-activated receptor(PPAR)signaling pathway.These genes were significantly correlated with lipid accumulation,monocyte infiltration,and neutrophil infiltration in the uterosacral ligament.Urodynamic testing revealed that the bladder leak point pressure was significantly higher in ovariectomized SVD rats,both of which had higher values than the sham group.Masson staining showed pronounced adipogenesis in the uterosacral ligament of ovariectomized SVD rats,along with reduced collagen and muscle fibers compared to the sham and non ovariectomized SVD groups.Furthermore,real-time RT-PCR confirmed significantly elevated expression of key DEGs,including ADIPOQ,IL-6,PCK1,and PLIN1,in the uterosacral ligaments of ovariectomized SVD rats.Conclusion:Adipogenesis and inflammation in the uterosacral ligament may contribute to its reduced supportive function,potentially leading to recurrence POP in postmenopausal women.
文摘目的:探讨p53凋亡刺激蛋白2(apoptosis stimulating proteins of p53 2,ASPP2)、ASPP家族抑制成员(inhibitory member of the ASPP family,iASPP)在宫颈癌发生中的意义及其与p53的关系。方法:采用免疫组织化学法检测ASPP2,iASPP,p53在51例早期宫颈癌、53例子宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)Ⅱ-Ⅲ期、48例CIN I期及45例正常宫颈组织中的表达,分析ASPP2,iASPP与p53的相互关系。结果:p53阴性时,ASPP2在宫颈癌组、CIN Ⅱ-Ⅲ组、CIN I组、正常宫颈组中的阳性表达率逐渐升高,且CIN Ⅱ-Ⅲ组、宫颈癌组与正常宫颈组比较差异有统计学意义(P<0.05),余各组两两比较差异无统计学意义(P>0.05);iASPP在宫颈癌组、CIN Ⅱ-Ⅲ组、CIN Ⅰ组、正常宫颈组中的阳性表达率逐渐降低,且宫颈癌组与正常宫颈组比较,差异有统计学意义(P<0.05),余各组两两比较差异无统计学意义(P>0.05)。p53阳性时,ASPP2和iASPP在各组中的表达差异均无统计学意义(P>0.05)。结论:ASPP2和iASPP可能通过调节野生型p53诱导细胞凋亡的能力参与早期宫颈癌的发生,ASPP2和iASPP可能成为治疗宫颈癌潜在的分子靶点。
