Objective:The novel coronavirus(severe acute respiratory syndrome coronavirus 2)has been spreading worldwide since December 2019,posing a serious danger to human health and socioeconomic development.A large number of ...Objective:The novel coronavirus(severe acute respiratory syndrome coronavirus 2)has been spreading worldwide since December 2019,posing a serious danger to human health and socioeconomic development.A large number of clinical trials have revealed that coronavirus disease 2019(COVID-19)results in multi-organ damage including the urogenital system.This study aimed to explore the potential mechanisms of genitourinary damage associated with COVID-19 infection through bioinformatics and molecular simulation analysis.Methods:We used multiple publicly available databases to explore the expression patterns of angiotensin-converting enzyme 2(ACE2),transmembrane serine protease 2(TMPRSS2),and CD147 in major organs in the healthy and disease-specific populations,particularly the genitourinary organs.Single-cell RNA sequencing was used to analyze the cell-specific expression patterns of ACE2,TMPRSS2,CD147,cytokine receptors,and cytokine interacting proteins in genitourinary organs,such as the bladder,kidney,prostate,and testis.Additionally,gene set enrichmentanalysis was used to investigate the relationship between testosterone levels and COVID-19 vulnerability in patients with prostate cancer.Results:The results revealed that ACE2,TMPRSS2,and CD147 were highly expressed in normal urogenital organs.Then,they were also highly expressed in multiple tumors and chronic kidney diseases.Additionally,ACE2,TMPRSS2,and CD147 were significantly expressed in a range of cells in urogenital organs according to single-cell RNA sequencing.Cytokine receptors and cytokine interacting proteins,especially CCL2,JUN,and TIMP1,were commonly highly expressed in urogenital organs.Finally,gene set enrichment analysis results showed that high testosterone levels in prostate cancer patients were significantly related to the JAK-STAT signaling pathway and the Toll-like receptor signaling pathway which were associated with COVID-19.Conclusion:Our study provides new insights into the potential mechanisms of severe acute respiratory syndrome coronavirus 2 damage to urogenital organs from multiple perspectives,which may draw the attention of urologists to COVID-19 and contribute to the development of targeted drugs.展开更多
Biochemical or clinical changes of hyperandrogenism are important elements of polycystic ovary syndrome （PCOS）. There is currently no consensus on the definition and diagnostic criteria of hyperandrogenism in PCOS. ...Biochemical or clinical changes of hyperandrogenism are important elements of polycystic ovary syndrome （PCOS）. There is currently no consensus on the definition and diagnostic criteria of hyperandrogenism in PCOS. The aim of this study was to investigate the complex symptoms of hyperandrogenic disorders and the correlations between metabolism and hyperandrogenism in patients with PCOS from an outpatient reproductive medicine clinic in China. We conducted a case control study of 125 PCOS patients and 130 controls to evaluate differences in body mass index （BMI）, total testosterone （TT）, modified Ferriman-Gallwey hirsutism score, sex hormone binding globulin （SHBG）, homeostasis model assessment-estimated insulin resistance （HOMA-IR） and free androgen index （FAI） between PCOS patients and controls and subgroups of PCOS. The prevalence of acne and hirsutism did not differ significantly between the hyperandrogenic and non-hyperandrogenic subgroup. Patients with signs of hyper- androgenism had significantly higher BMI （P 〈 0.05）, but differences in TT, SHBG, FAI and waist/hip ratio were insignificant. The odds ratio of overweight was calculated for all PCOS patients. Our results suggest that PCOS patients with high BMI tend to have functional disorders of androgen excess; therefore, BMI may be a strong pre-dictor of hyperandrogenism in PCOS.展开更多
Spermatogenesis is a complex, unique process that takes place in the testis. It consists of a set of events including mitotic （from spermatogonia to primary spermatocytes） and meiotic divisions （from primary sperma...Spermatogenesis is a complex, unique process that takes place in the testis. It consists of a set of events including mitotic （from spermatogonia to primary spermatocytes） and meiotic divisions （from primary spermatocytes to early round spermatids）, and spermiogenesis, a differentiation step from early round spermatids to testicular spermatozoa Although spermatogenesis is known as a well autocrine- and paracrine-regulated process, some proteins involved in its regulation remain to be determined. Related to this, the recent study conducted by Dai et al. have shed light on the relevant function of SET protein, a protein phosphatase 2A （PP2A） inhibitor, also known as I2PP2A, or TAF-Ib. This protein, identified for the first time in 1992, has been described to be involved in multiple cell functions, such as control of cell cycle and apoptosis, gene transcription, epigenetic regulation, and nucleosome assembly. Apart from these functions, it is worth noting that SET has been to be involved in the regulation found in theca cells, where appears of androgen biosynthesis, and in mature oocytes, where plays a key role in the segregation of sister chromatids during the second meiotic division SET protein inhibits PP2A by enhancing lyase activity of P450c17, a substrate for PP2A when it is Serand Thr-phosphorylated. PP2A function in reproductive physiology is not restricted to gamete production （i.e. spermatogenesis and oogenesis）, but this protein is also involved in human sperm capacitation.展开更多
文摘Objective:The novel coronavirus(severe acute respiratory syndrome coronavirus 2)has been spreading worldwide since December 2019,posing a serious danger to human health and socioeconomic development.A large number of clinical trials have revealed that coronavirus disease 2019(COVID-19)results in multi-organ damage including the urogenital system.This study aimed to explore the potential mechanisms of genitourinary damage associated with COVID-19 infection through bioinformatics and molecular simulation analysis.Methods:We used multiple publicly available databases to explore the expression patterns of angiotensin-converting enzyme 2(ACE2),transmembrane serine protease 2(TMPRSS2),and CD147 in major organs in the healthy and disease-specific populations,particularly the genitourinary organs.Single-cell RNA sequencing was used to analyze the cell-specific expression patterns of ACE2,TMPRSS2,CD147,cytokine receptors,and cytokine interacting proteins in genitourinary organs,such as the bladder,kidney,prostate,and testis.Additionally,gene set enrichmentanalysis was used to investigate the relationship between testosterone levels and COVID-19 vulnerability in patients with prostate cancer.Results:The results revealed that ACE2,TMPRSS2,and CD147 were highly expressed in normal urogenital organs.Then,they were also highly expressed in multiple tumors and chronic kidney diseases.Additionally,ACE2,TMPRSS2,and CD147 were significantly expressed in a range of cells in urogenital organs according to single-cell RNA sequencing.Cytokine receptors and cytokine interacting proteins,especially CCL2,JUN,and TIMP1,were commonly highly expressed in urogenital organs.Finally,gene set enrichment analysis results showed that high testosterone levels in prostate cancer patients were significantly related to the JAK-STAT signaling pathway and the Toll-like receptor signaling pathway which were associated with COVID-19.Conclusion:Our study provides new insights into the potential mechanisms of severe acute respiratory syndrome coronavirus 2 damage to urogenital organs from multiple perspectives,which may draw the attention of urologists to COVID-19 and contribute to the development of targeted drugs.
基金supported by grants from the Major State Basic Research Development Program of China(973 Program:No.2012CB944902 and No.2012CB944703)the National Natural Science Foundation of China(No.30801236)the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘Biochemical or clinical changes of hyperandrogenism are important elements of polycystic ovary syndrome （PCOS）. There is currently no consensus on the definition and diagnostic criteria of hyperandrogenism in PCOS. The aim of this study was to investigate the complex symptoms of hyperandrogenic disorders and the correlations between metabolism and hyperandrogenism in patients with PCOS from an outpatient reproductive medicine clinic in China. We conducted a case control study of 125 PCOS patients and 130 controls to evaluate differences in body mass index （BMI）, total testosterone （TT）, modified Ferriman-Gallwey hirsutism score, sex hormone binding globulin （SHBG）, homeostasis model assessment-estimated insulin resistance （HOMA-IR） and free androgen index （FAI） between PCOS patients and controls and subgroups of PCOS. The prevalence of acne and hirsutism did not differ significantly between the hyperandrogenic and non-hyperandrogenic subgroup. Patients with signs of hyper- androgenism had significantly higher BMI （P 〈 0.05）, but differences in TT, SHBG, FAI and waist/hip ratio were insignificant. The odds ratio of overweight was calculated for all PCOS patients. Our results suggest that PCOS patients with high BMI tend to have functional disorders of androgen excess; therefore, BMI may be a strong pre-dictor of hyperandrogenism in PCOS.
文摘Spermatogenesis is a complex, unique process that takes place in the testis. It consists of a set of events including mitotic （from spermatogonia to primary spermatocytes） and meiotic divisions （from primary spermatocytes to early round spermatids）, and spermiogenesis, a differentiation step from early round spermatids to testicular spermatozoa Although spermatogenesis is known as a well autocrine- and paracrine-regulated process, some proteins involved in its regulation remain to be determined. Related to this, the recent study conducted by Dai et al. have shed light on the relevant function of SET protein, a protein phosphatase 2A （PP2A） inhibitor, also known as I2PP2A, or TAF-Ib. This protein, identified for the first time in 1992, has been described to be involved in multiple cell functions, such as control of cell cycle and apoptosis, gene transcription, epigenetic regulation, and nucleosome assembly. Apart from these functions, it is worth noting that SET has been to be involved in the regulation found in theca cells, where appears of androgen biosynthesis, and in mature oocytes, where plays a key role in the segregation of sister chromatids during the second meiotic division SET protein inhibits PP2A by enhancing lyase activity of P450c17, a substrate for PP2A when it is Serand Thr-phosphorylated. PP2A function in reproductive physiology is not restricted to gamete production （i.e. spermatogenesis and oogenesis）, but this protein is also involved in human sperm capacitation.
