Sinularin stabilizes FOXO3 protein to trigger prostate cancer cell intrinsic apoptosis.

Sinularin, a natural product that purified from soft coral, exhibits anti-tumor effects against various human cancers. However, the mechanisms are not well understood. In this study, we demonstrated that Sinularin inhibited the viability of human prostate cancer cells in a dose-dependent manner and displayed significant cytotoxicity only at high concentration against normal prostate epithelial cell RWPE-1. Flow cytometry assay demonstrated that Sinularin induced tumor cell apoptosis. Further investigations revealed that Sinularin exerted anti-tumor activity through intrinsic apoptotic pathway along with up-regulation of pro-apoptotic protein Bax and PUMA, inhibition of anti-apoptotic protein Bcl-2, mitochondrial membrane potential collapses, and release of mitochondrial proteins. Furthermore, we illustrated that Sinularin induced cell apoptosis via up-regulating PUMA through inhibition of FOXO3 degradation by the ubiquitin-proteasome pathway. To explore how Sinularin suppress FOXO3 ubiquitin-proteasome degradation, we tested two important protein kinases AKT and ERK that regulate FOXO3 stabilization. The results revealed that Sinularin stabilized and up-regulated FOXO3 via inhibition of AKT- and ERK1/2-mediated FOXO3 phosphorylation and subsequent ubiquitin-proteasome degradation. Our findings illustrated the potential mechanisms by which Sinularin induced cell apoptosis and Sinularin may be applied as a therapeutic agent for human prostate cancer.

[Analysis of 10 years' data of systematic male reproductive system ultrasonography in diagnosis of azoospermia etiology].

OBJECTIVE: To explore the value of systematic male reproductive system ultrasonography in the diagnosis of azoospermia etiology. METHODS: Retrospective analysis and classification statistics were conducted on the data of azoospermia cases who underwent systematic male reproductive system ultrasound examination at the First Affiliated Hospital of Ningbo University from January 2013 to January 2023. RESULTS: A total of 375 cases were included in the group, of which 303 cases could be diagnosed by ultrasound, including 161 cases of obstructive causes, 110 cases of non obstructive causes, and 32 cases of mixed causes. Obstructive causes mainly include bilateral absence or underdevelopment of the seminal vesicles and vas deferens, non obstructive causes mainly include bilateral simple testicular dysplasia, and the most common combined causes are bilateral absence or underdevelopment of the seminal vesicles and vas deferens combined with bilateral testicular dysplasia. The main causes involved a single organ in 174 cases, with 82 cases, 43 cases, and 4 cases involving 2-4 organs, respectively. In addition, there are multiple accompanying ultrasound manifestations of non primary causes. CONCLUSION: Systematic ultrasound examination can comprehensively evaluate the male reproductive system, effectively diagnose the causes of most azoospermia, and provide valuable imaging evidence for clinical treatment.

[A new procedure of penoplasty for concealed penis reduces postoperative preputial edema].

OBJECTIVE: To investigate the advantage of a new procedure of penoplasty by T-shaped incision and three-point fixation (TSI+TPF) in reducing postoperative preputial edema in the treatment of concealed penis. METHODS: We retrospectively analyzed 244 cases of concealed penis treated in our center between June 2014 and June 2017, 185 by TSI+TPF penoplasty and the other 59 by modified Devine surgery (MDS). We compared the incidence of postoperative preputial edema between the two groups of patients. RESULTS: The incidence rate of preputial edema was obviously lower in the TSI+TPF penoplasty than in the MDS group at 2 (28.1% vs 33.9%) and 4 weeks after surgery (11.4% vs 20.3%), though with no statistically significant difference, and that of moderate to severe edema was significantly lower in the former than in the latter at 4 weeks (1.1% vs 6.8%, P < 0.05). And no long-term residual edema was observed after TSI+TPF penoplasty. CONCLUSIONS: Penoplasty by T-shaped incision and three-point fixation can effectively reduce the incidence of postoperative preputial edema, especially that of moderate to severe edema, in the treatment of concealed penis.

[Penoplasty with T-shaped incision and three-point fixation for concealed penis].

OBJECTIVE: To search for a safe and effective method of penoplasty with low incidence of complications for concealed penis by evaluating penoplasty with T-shaped incision and three-point fixation in comparison with modified Devine's technique. METHODS: We retrospectively analyzed 169 cases of concealed penis treated in our center by penoplasty with T-shaped incision and three-point fixation (group A, n = 110) or modified Devine's surgery (group B, n = 59). We compared the operation time, postoperative complications, and recurrence rate between the two groups of patients. RESULTS: Operations were successfully completed in all the cases, the urinary catheters removed at 3 days and the elastic bandages applied for 2 to 4 weeks. The patients were followed up for 4 to 12 months. The penis was satisfactorily exposed. The operative time was significantly shorter in group A than in B (ï¼»52.8 ± 6.9ï¼½ vs ï¼»61.5 ± 10.6ï¼½ min, P < 0.001), the postoperative complication rate was obviously lower in the former than in the latter (prepuce edema: 17.27% ï¼»19/110ï¼½ vs 33.89% ï¼»20/59ï¼½, P = 0.021; bleeding: 0.90% ï¼»1/110ï¼½ vs 3.38% ï¼»2/59ï¼½, P = 0.552; skin necrosis: 0.90% ï¼»1/110ï¼½ vs 5.08% ï¼»3/59ï¼½, P = 0.123; skin infection: 0.90% ï¼»1/110ï¼½ vs 5.08% ï¼»3/59ï¼½, P = 0.123), and so was the recurrence rate (0.90% ï¼»1/110ï¼½ vs 6.77% ï¼»4/59ï¼½, P = 0.032). CONCLUSIONS: Penoplasty with T-shaped incision and three-point fixation deserves to be popularized clinically for its advantages of minor invasion, clear exposure, reliable penile fixation, low incidence of postoperative complications and recurrence, and satisfactory outcomes.

Chinese Shang Ring Male Circumcision: A Review.

Chinese Shang Ring adult male circumcision (SC) is a safe and effective procedure which is easy to learn and to perform. By a specially designed small device, male circumcision (MC) can be performed in 5 min. Compared with conventional adult MC (CC), SC has shorter operation time, less blood loss, less pain score, higher appearance satisfaction rate, and lower complication rate. SC was first developed in China. As recent studies have demonstrated that MC reduced the risk of acquiring human immunodeficiency virus (HIV) infection via vaginal intercourse in African countries, SC was introduced into Africa to fight HIV. Other sexually transmitted diseases such as human papillomavirus infection may also be prevented by SC. In conclusion, Chinese Shang Ring, a small device, provides an easy, quick, safe, and effective method to perform adult MC.