Maturation of Nephrons by Implanting hPSC-derived Kidney Progenitors Under Kidney Capsules of Unilaterally Nephrectomized Mice.

BACKGROUND: Human pluripotent stem cell (hPSC)-derived kidney organoids may contribute to disease modeling and the generation of kidney replacement tissues. However, the realization of such applications requires the induction of hPSCs into functional mature organoids. One of the key questions for this process is whether a specific vascular system exists for nephrogenesis. Our previous study showed that short-term (2 weeks) implantation of hPSC-derived organoids below the kidney capsules of unilaterally nephrectomized and immunodeficient mice resulted in the enlargement of organoids and production of vascular cells, although signs of maturation were lacking. METHODS: Organoids were induced for 15 days in vitro and then grafted below kidney capsules of the same unilaterally nephrectomized immunodeficient mouse model to examine whether medium-term (4 weeks) implantation could improve organoid maturation and vascularization, as evaluated by immunofluorescence and transmission electron microscopy. RESULTS: We demonstrated that after 2-4 weeks of implantation, renal organoids formed host-derived vascularization and matured without any exogenous vascular endothelial growth factor. Glomerular filtration barrier maturation was evidenced by glomerular basement membrane deposition, perforated glomerular endothelial cell development, and apical, basal podocyte polarization. A polarized monolayer epithelium and extensive brush border were also observed for tubular epithelial cells. CONCLUSIONS: Our results indicate that the in vivo microenvironment is important for the maturation of human kidney organoids. Stromal expansion and a reduction of nephron structures were observed following longer-term (12 weeks) implantation, suggesting effects on off-target cells during the induction process. Accordingly, induction efficiency and transplantation models should be improved in the future.

Comprehensive analysis of FRAS1/FREM family as potential biomarkers and therapeutic targets in renal clear cell carcinoma.

Background: FRAS1 (Fraser syndrome protein 1), together with FREM1 (the Fras1-related extracellular matrix proteins 1) and FREM2, belonging to the FRAS1/FREM extracellular matrix protein family, are considered to play essential roles in renal organogenesis and cancer progression. However, their roles in kidney renal clear cell carcinoma (KIRC) remain to be elucidated. Methods: FRAS1/FREM RNA expression analysis was performed using TCGA/GTEx databases, and valided using GEO databases and real-time PCR. Protein expression was peformed using CPTAC databases. Herein, we employed an array of bioinformatics methods and online databases to explore the potential oncogenic roles of FRAS1/FREM in KIRC. Results: We found that FRAS1, FREM1 and FREM2 genes and proteins expression levels were significantly decreased in KIRC tissues than in normal tissues. Decreased FRAS1/FREM expression levels were significantly associated with advanced clinicopathological parameters (pathological stage, grade and tumor metastasis status). Notably, the patients with decreased FRAS1/FREM2 expression showed a high propensity for metastasis and poor prognosis. FRAS1/FREM were correlated with various immune infiltrating cells, especially CD4+ T cells and its corresponding subsets (Th1, Th2, Tfh and Tregs). FRAS1 and FREM2 had association with DNA methylation and their single CpG methylation levels were associated with prognosis. Moreover, FRAS1/FREM might exert antitumor effects by functioning in key oncogenic signalling pathways and metabolic pathways. Drug sensitivity analysis indicated that high FRAS1 and FREM2 expression can be a reliable predictor of targeted therapeutic drug response, highlighting the potential as anticancer drug targets. Conclusion: Together, our results indicated that FRAS1/FREM family members could be potential therapeutic targets and valuable prognostic biomarkers of KIRC.

A case with type â ¡ vesicouterine fistula.

Here, we report a 41-year-old female with type II VUF after hysteromyomectomy.We report the diagnosis of VUF by imaging method, and provide a feasible treatment for this complication after pelvic surgery.

Identification of immune-related genes that predict prognosis and risk of bladder cancer: bioinformatics analysis of TCGA database.

BACKGROUND: Bladder cancer (BLCA) is the major tumor of the urinary system, and immune-related genes (IRGs) contribute significantly to its initiation and prognosis. RESULTS: A total of 51 prognostic IRGs significantly associated with overall survival were identified. Functional enrichment analysis revealed that these genes were actively involved in tumor-related functions and pathways. Using multivariate Cox regression analysis, we detected 11 optimal IRGs (ADIPOQ, PPY, NAMPT, TAP1, AHNAK, OLR1, PDGFRA, IL34, MMP9, RAC3, and SH3BP2). We validated the prognostic value of this signature in two validation cohorts: GSE13507 (n = 165) and GSE32894 (n = 224). Furthermore, we performed a western blot and found that the expression of these IRGs matched their mRNA expression in TCGA. Moreover, correlations between risk score and immune-cell infiltration indicated that the prognostic signature reflected infiltration by several types of immune cells. CONCLUSION: We identified and validated an 11-IRG-based risk signature that may be a reliable tool to evaluate the prognosis of BLCA patients and help to devise individualized immunotherapies. METHODS: Bioinformatics analysis was performed using TCGA and ImmPort databases. Cox regression was used to identify prognostic signatures. Two external GEO cohorts and western blotting of samples were performed to validate the IRG signature.

Remdesivir Alleviates Acute Kidney Injury by Inhibiting the Activation of NLRP3 Inflammasome.

Acute kidney injury (AKI) is a frequent clinical complication in critically ill patients, and it rapidly develops into renal failure with high morbidity and mortality. However, other than dialysis, no effective therapeutic interventions can offer reliable treatment to limit renal injury and improve survival. Here, we firstly reported that remdesivir (RDV, GS-5734), a broad-spectrum antiviral nucleotide prodrug, alleviated AKI by specifically inhibiting NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in macrophages. Mechanically, RDV effectively suppressed the activities of nuclear transcription factor (NF)-κB, mitogen-activated protein kinase (MAPK), which further led to the reduction of the inflammasome genes of NLRP3 transcription, limiting the activation of NLRP3 inflammasome in vivo and in vitro. RDV also inhibited other pro-inflammatory genes including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-12, IL-1ß, and interferon-ß (IFN-ß), leading to the reduction of inflammatory factors release. Thus, RDV can ameliorate AKI via modulating macrophage inflammasome activation and inflammatory immune responses and may have a therapeutic potential for patients with AKI in clinical application.

Effect of prostate volume on f/tPSA value: A cross-sectional study.

Previous studies have suggested that there is a positive correlation between prostate-specific antigen (PSA) levels and prostate volume (PV). A better understanding of the possible influence of PV on a ratio of free to total PSA (f/tPSA) may improve the diagnostic value of the prostate disease. The study group consisted of 342 men with lower urinary tract symptoms (LUTS). All patients underwent urinary tract ultrasonography and had tests carried out on PSA, serum glucose, total cholesterol, triglyceride, HDL, LDL and blood pressure. Univariate and multivariate analyses were used to assess the associations between prostate volume and f/tPSA value. We found no obvious relationship between prostate volume and f/tPSA value when PSA >10 ng/ml but did observe a positive correlation when 4 ng/ml < PSA ï¼œ 10 ng/ml (hazard ratio [HR]: 0.0012; 95% confidence interval [CI]: 0.0009-0.0248). With increasing prostate volume, multivariate analysis showed an obvious increase in f/tPSA value (HR: 0.0011; 95% CI: 0.0007-0.0015) (p ≤ .0001). We confirmed that prostate volume could affect the f/tPSA levels in serum. There was an obvious positive correlation between prostate volume and f/tPSA level when PSA levels were between 4 and 10ng/dl. There was no significant correlation between prostate volume and f/tPSA value when PSA >10 ng/ml.

Probucol enhances the therapeutic efficiency of mesenchymal stem cells in the treatment of erectile dysfunction in diabetic rats by prolonging their survival time via Nrf2 pathway.

BACKGROUND: Intracavernous injection of mesenchymal stem cells (MSCs) is a promising method for diabetic mellitus-induced erectile dysfunction (DMED), but short survival time of MSCs in cavernous is a fatal defect for therapy. This study investigated therapeutic efficiency and potential mechanism of probucol combined with MSCs. METHODS: In vivo study, a total of forty-eight 10-week-old male Sprague-Dawley (SD) rats were used. Twelve rats received intraperitoneal injection of PBS as the sham group; the rest received intraperitoneal injection of 60 mg/kg streptozotocin to establish DM models. DM rats were randomly divided into three groups: received intracavernosal (IC) injection of either PBS (DM group), MSCs (M group), or administrated probucol after intracavernosal injection of MSCs (P + M group). Erectile function was assessed by electrical stimulation of the cavernous nerves with real-time intracavernous pressure measurement. After euthanasia, penile tissue was investigated for histologic examination and Western blotting. In in vitro experiment, H2O2 was used to create oxidative stress environment to detect changes in cell viability. CCK8 was used to measure cell viability of MSCs treated with or without probucol. Intracellular ROS changes were detected by flow cytometry. Autophagy and apoptosis were detected by Western blotting and confocal microscopy. RESULTS: Recovery of erectile function was observed in the P + M group. The combination therapy decreased fibrosis and increased endothelial function compared with MSC therapy alone. Western blotting results confirmed the increased expression of Nrf2 and HO-1 in cavernous body. H2O2 induced high oxidative stress and reduced cell viability in vitro, which was gradually reversed with increased concentration of probucol. H2O2 reduced Nrf2 expression, which was reversed by probucol's intervention. Furthermore, the expression of Bax, Caspase3, and Cleaved-Caspase3 decreased, and the expression of Bcl-2 increased in a dose-dependent manner because of probucol's intervention. In addition, Beclin1 and LC3II both increased in a dose-dependent manner. Meanwhile, the expression of P62 decreased. In the study of autophagy flux, we found probucol did not block it. CONCLUSION: Probucol enhanced therapeutic efficiency of MSCs in DMED by prolonging their survival time, which mediated through improving the transplanted microenvironment of MSCs, increasing self-antioxidant ability of MSCs, strengthening protective autophagy, and inhibiting apoptosis of MSCs via Nrf2 pathway. Schematic model showing combined probucol and MSCs to improve DMED. Probucol increases self-antioxidant ability of MSCs, strengthening protective autophagy and inhibiting apoptosis via Nrf2/HO-1 and Nrf2/autophagy pathways.

Relationship between penile erection and the ratio of estradiol to testosterone: A retrospective study.

Previous studies have found that the ratio of estradiol to testosterone (E2/T ratio) has a negative effect on sexual function, but the relationship between the E2/T ratio and erection of the penis is not clarified. We conducted a retrospective study of 183 patients with erectile dysfunction and 52 healthy men to investigate the relationship between penis base erection and tip erection. All participants underwent nocturnal penile tumescence tests and medical history checks and had relevant biochemical and endocrine indicators measured. The ratio of estradiol to testosterone was calculated. The relationship between E2/T ratio and erectile time of penile tip and penile base was determined by univariate analysis, multivariate analysis and stratification analysis. After adjusting for mixed factors, the results showed that the E2/T ratio had a more significant negative effect on the base of the penis compared with the tip of the penis (Hazard ratio: -4.34 95% CI: -6.52, -2.16 p = .0001). Moreover, when the effective erection time was ≥10 min, the negative effect of E2/T on penile root erection was more obvious (HR ratio: -4.46 95% CI: -6.50, -2.43 p < .0001). In summary, our study demonstrated a negative relationship between E2/T ratio and penile erection, particularly at the root of the penis.

GABPA is a master regulator of luminal identity and restrains aggressive diseases in bladder cancer.

TERT promoter mutations occur in the majority of glioblastoma, bladder cancer (BC), and other malignancies while the ETS family transcription factors GABPA and its partner GABPB1 activate the mutant TERT promoter and telomerase in these tumors. GABPA depletion or the disruption of the GABPA/GABPB1 complex by knocking down GABPB1 was shown to inhibit telomerase, thereby eliminating the tumorigenic potential of glioblastoma cells. GABPA/B1 is thus suggested as a cancer therapeutic target. However, it is unclear about its role in BC. Here we unexpectedly observed that GABPA ablation inhibited TERT expression, but robustly increased proliferation, stem, and invasive phenotypes and cisplatin resistance in BC cells, while its overexpression exhibited opposite effects, and inhibited in vivo metastasizing in a xenograft transplant model. Mechanistically, GABPA directly activates the transcription of FoxA1 and GATA3, key transcription factors driving luminal differentiation of urothelial cells. Consistently, TCGA/GEO dataset analyses show that GABPA expression is correlated positively with luminal while negatively with basal signatures. Luminal tumors express higher GABPA than do basal ones. Lower GABPA expression is associated with the GABPA gene methylation or deletion (especially in basal subtype of BC tumors), and predicted significantly shorter patient survival based on TCGA and our cohort of BC patient analyses. Taken together, GABPA dictates luminal identity of BC cells and inhibits aggressive diseases in BC by promoting cellular differentiation despite its stimulatory effect on telomerase/TERT activation. Given these biological functions and its frequent methylation and/or deletion, GABPA serves as a tumor suppressor rather than oncogenic factor in BC. The GABPA effect on oncogenesis is context-dependent and its targeting for telomerase inhibition in BC may promote disease metastasizing.

Paris polyphylla ethanol extract induces G2/M arrest and suppresses migration and invasion in bladder cancer.

BACKGROUND: Paris polyphylla is a traditional Chinese medicinal herb with multiple antitumor activities, but the role of P. polyphylla in bladder cancer (BC) is under investigation. This study aims to examine the antitumor activities of P. polyphylla ethanol extract (PPE) on BC cells and elucidate the underlying mechanisms. METHODS: Viable cells were counted using the trypan blue exclusion assay. The cell cycle was analyzed using flow cytometry, and scratch wound-healing and transwell assays were used to evaluate cell migration and invasion abilities, respectively. The protein expression levels were determined by western blotting. A xenograft model was used to assess the in vivo inhibitory effect of PPE on BC tumor growth. RESULTS: Our results showed that PPE inhibited the growth of BC cells in vivo and in vitro. Mechanistically, PPE regulated the levels of cell cycle-associated proteins, with PPE-induced G2/M phase arrest occurring through cyclin-dependent kinase inhibitor 1 (CDKN1A) accumulation and cyclin B1 (CCNB1)/cyclin-dependent kinase 1 (CDK1) inhibition. BC tumor growth was also inhibited by PPE treatment. Moreover, the migration and invasion abilities of J82 cells were suppressed through modulating epithelial-mesenchymal transition (EMT) regulatory factors with upregulation of cadherin-1 (CDH1) and downregulation of cadherin-2 (CDH2), snail family transcriptional repressor 2 (SNAI2), and twist family bHLH transcription factor 1 (TWIST1). CONCLUSIONS: PPE inhibited cell growth, induced G2/M arrest, and suppressed the migration and invasion of J82 cells. BC tumor growth in vivo was also inhibited by PPE. Our results lay the foundation for further studies on the antitumor mechanisms of PPE.

Polyphyllin I induces cell cycle arrest in prostate cancer cells via the upregulation of IL6 and P21 expression.

BACKGROUND: Polyphyllin I has been reported to possess anticancer properties in various cancer types, including prostate cancer. However, little is known about the potential of Polyphyllin I in induction of prostate cancer cell cycle arrest and its underlying mechanisms. METHODS: The anti-proliferation activity of Polyphyllin I was tested using cell counting kit-8 assay. The cell cycle arrest effects of Polyphyllin I were confirmed by flow cytometry. Western blot was used to test the effect of Polyphyllin I on cell cycle-related protein expression. Reverse transcription-polymerase chain reaction was used to test the expression of genes regulating P21 expression. RESULTS: Polyphyllin I induced prostate cancer cell cycle arrest in G0/G1 phase in concentration-dependent manner. Polyphyllin I induced cell cycle arrest by upregulating the expression of P21. Further studies showed that the upregulation of p21 expression induced by Polyphyllin I via the upregulation of IL6 expression. CONCLUSION: Polyphyllin I could induce cell cycle arrest in G0/G1 phase in prostate cancer cells by upregulating the expression of P21 and IL6.

GCN5 inhibition prevents IL-6-induced prostate cancer metastases through PI3K/PTEN/Akt signaling by inactivating Egr-1.

General control non-derepressible 5 (GCN5) is ectopically expressed in different types of human cancer and association with the carcinogenesis, development, and poor prognosis of cancers. The present study was aimed to investigate the potential role and related mechanisms of GCN5 in IL-6-treated prostate cancer (PCa) cell. The results showed that an elevated GCN5 expression was stimulated by IL-6. Knockdown of GCN5 significantly inhibited IL-6-driven proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Moreover, early growth response-1 (Egr-1) expression was elevated by IL-6 treatment and GCN5 siRNA down-regulated the expression of Egr-1. Furthermore, overexpression of Egr-1 attenuated the effects of GCN5 silence on cell proliferation, migration, invasion, and EMT in PCa. Besides, knockdown of GCN5 resulted in the down-regulation of p-Akt and up-regulation of PTEN, which was partly impeded by Egr-1 overexpression. The effects of GCN5 overexpression on cell proliferation and invasion were suppressed by LY294002, In conclusion, these data demonstrated the negative effect of up-regulated GCN5 in IL-6-induced metastasis and EMT in PCa cells through PI3K/PTEN/Akt signaling pathway down-regulating Egr-1 expression.

Terpenoids with vasorelaxant effects from the Chinese liverwort Scapania carinthiaca.

Four new diterpenoids scapanacins A-D (1-4) including one kaurane and three clerodane derivatives, along with eleven known compounds (9-15), were isolated from the Chinese liverwort Scapania carinthiaca J.B. Jack ex Lindb. Their structures were determined based on extensive spectroscopic analyses, and electronic circular dichroism (ECD) calculations. Vasorelaxant activity assays of the clerodane-type diterpenoids 2, and 4-8 revealed that they relaxed 3rd-order rat mesenteric arterioles pre-contracted with norepinephrine (NE). Further assays with scapanacin D (4) confirmed that the vasodilatation was mediated through inhibition of Ca2+ influx via voltage-dependent Ca2+ channels (VDCs), and this Ca2+ channel blocking effect was also confirmed by inhibiting the extracellular Ca2+ influx in MOVAS cells. Besides, very little decrease of the relaxant activity caused by 4 on endothelium-denuded mesenteric arterioles with NE also suggested the vasodilatation was mainly produced by inhibiting Ca2+-induced contraction of smooth muscle. In addition, cytotoxicity testing showed that compounds 1 and 9 with α,ß-unsaturated ketone exhibited inhibitory activities against a small panel of human cancer cell lines.

Paris Polyphylla-Derived Saponins Inhibit Growth of Bladder Cancer Cells by Inducing Mutant P53 Degradation While Up-Regulating CDKN1A Expression.

OBJECTIVES: Paris polyphylla var. yunnanensis (PPVY), a Chinese herb, has long been used for cancer treatment, and its steroidal saponins are suggested to exert an anti-tumor activity, however, the underlying mechanism is incompletely understood and their effect on bladder cancer (BC) remains unknown. The present study is thus designed to address these issues. MATERIAL AND METHODS: Total steroidal saponins were extracted with ethanol from PPVY and used to treat BC cells (HT1197 and J82 carrying mutant p53). Gene expression was determined using qPCR and immunoblotting and cell cycle analyzed using flow cytometry. DNA damage response activation was assessed using immunofluorescence staining. RESULTS: PPVY saponins treatment led to dose-dependent declines in the number of both HT1197 and J82 cells with IC50 approximately 1.2 µg/ml, which was coupled with strong growth arrest at G2/M phase and the activation of DNA damage response pathway. Moreover, the clonogenic potential of these cells was severely impaired even in the presence of low concentrations of PPVY saponins. Mechanistically, PPVY saponins induced the degradation of mutant p53 while stimulated CDKN1A gene transcription. Phosphorylated AKT was diminished in PPVY saponin-treated cells, but its specific inhibitor LY294002 exhibited significantly weaker efficacy in inducing CDKN1A expression than did PPVY saponins. CONCLUSION: PPVY saponins activate DNA damage response pathway, degrade mutant p53 and stimulate CDKN1A expression, thereby inhibiting BC cell growth. Given their poor absorption via oral administration, PPVY saponins may be applicable for intravesical instillations in BC treatment.

Anti-Cancer Effects of Paris Polyphylla Ethanol Extract by Inducing Cancer Cell Apoptosis and Cycle Arrest in Prostate Cancer Cells.

OBJECTIVE: To evaluate the potential anti-prostate cancer effects of Paris polyphylla ethanol extract (PPEE) and its underlying mechanisms. MATERIALS AND METHODS: The anti-proliferation activity of PPEE was tested on PC3 and DU145 cells using Cell Counting Kit-8 assay. The pro-apoptotic and cell cycle arrest effects of PPEE were confirmed by flow cytometry. Apoptosis of prostate cancer cells was induced by PPEE through endogenous and exogenous pathways. A mouse xenograft model was used to examine its anti-prostate cancer effects in vivo. RESULTS: We found that the IC50 of PPEE on PC3 cells was 3.98 µg/ml and the IC50 of PPEE on DU145 cells was 8 µg/ml. PPEE induced prostate cancer cell apoptosis in a concentration dependent manner, through endogenous and exogenous pathways. PPEE induced PC3 cell cycle arrest in G0/G1 and G2/M phases, while in DU145cell it induced cell arrest in the G0/G1 phase. PPEE inhibited the growth of prostate cancer cells in vivo. CONCLUSION: PPEE could inhibit prostate cancer growth in vitro and in vivo, induce apoptosis of prostate cancer cells, and cause cell cycle arrest, which laid the foundation for further research on the anti-tumor mechanism of PPEE.

Recellularization of well-preserved decellularized kidney scaffold using adipose tissue-derived stem cells.

To establish a recellularization kidney model by using adipose tissue-derived stem cells (ADSCs) as seeding cells and to investigate the growth and differentiation of ADSCs in decellularized kidney scaffolds. ADSCs were isolated using a modified method and then identified using flow cytometry analysis. Osteogenesis and adipogenesis differentiation were performed. Rat kidneys were decellularized using 0.5% sodium dodecyl sulfate. Immunofluorescence, immunohistochemistry, and scanning electron microscope were conducted to examine the scaffold microstructure. The decellularized kidney scaffold was seeded with ADSCs antegrade through the artery or retrograde through the ureter and cultured for 5-10 days. Hematoxylin and eosin staining, immunofluorescence, and immunohistochemistry were applied to assess growth and differentiation of seeding cells within the scaffold. ADSCs populated within the glomerular, vascular, and tubular area of kidney scaffolds. Cells differentiated toward endothelial or tubular cells. Stromal cell-derived factor 1 promoted cell attachment in the scaffold. These findings suggest that ADSCs can be used as an additional new source of seeding cells within decellularized kidney scaffold. This combination may offer an alternative to donor kidney transplant. In this way, autologous ADSCs can be utilized as seeding cells in cell-scaffold kidney regeneration for further clinical transplantation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 805-814, 2018.

Construction of engineered corpus cavernosum with primary mesenchymal stem cells in vitro.

Various methods have been used to reconstruct the penis. The objective of this study was to investigate the feasibility of constructing engineered corpus cavernosum with primary mesenchymal stem cells (MSCs) in a rabbit model in vitro. Acellular corporal matrices (ACMs) were obtained from adult rabbit penile tissues through an established decellularization procedure. MSCs were separated, purified, and then seeded on ACMs to construct engineered corpus cavernosum. The seeded ACMs were subsequently cultured in an incubator for 14 days. Histological analyses showed that MSCs seeded on the ACMs had proliferated and were well distributed. Detection of CD31, vWF, smooth muscle actin (SMA), and myosin protein as well as vWF and myosin mRNA revealed that the MSCs had differentiated into endothelial cells and smooth muscle cells. In addition, cell morphology of the engineered corpus cavernosum was directly observed by transmission electron microscopy. This study demonstrated that engineered corpus cavernosum could be successfully constructed using primary MSCs in vitro. This technology represents another step towards developing engineered corpus cavernosum in vitro.

The application of laparoscopic Doppler ultrasound during laparoscopic varicocelectomy in infertile men.

The aim of this study is to evaluate the benefits of laparoscopic Doppler ultrasound (LDU) application during laparoscopic varicocelectomy (LV), and to compare the surgical outcomes and complications between LDU-assisted LV (LDU-LV) and conventional LV for infertile patients with varicoceles; 147 infertile patients were randomly divided into two groups. Operative and postoperative parameters, semen parameters, and the pregnancy rate were compared. There were no differences in baseline demographics. The operative time was significantly longer in LDU-LV group than LV group. The incidence of postoperative hydrocele was 1.4% (1/72) in LDU-LV group versus 10.7% (8/75) in LV group, which showed a significant difference (P < 0.05). However, other surgical outcomes, such as postoperative hospital stay, postoperative recurrence, and testicular atrophy, were similar between the two groups. Sperm concentration and sperm motility were significantly increased in both groups at 3, 6, and 12 months after surgery (P < 0.01), and they were higher in LDU-LV than LV group in 12 months after surgery (34.21 ± 6.36 vs 29.99 ± 6.04 for concentration, P < 0.05; 40.72 ± 8.12 vs 37.31 ± 6.12 for motility, P < 0.05). Sperm morphology was comparable between the two groups. The pregnancy rate showed no significant difference (44.4% of the LDU-LV vs 37.3% of the LV, P > 0.05). In conclusion, compared with LV, LDU-LV could safely and effectively ligate all spermatic veins and preserve spermatic arteries without leading to high varicocele recurrence and postoperative hydrocele. Given the benefits that sperm counts as well as sperm motility favoring LDU-LV, we recommend that LDU should be routinely used as an effective tool to improve outcomes and safety of laparoscopic varicocelectomy.

Suppression of LASP-1 attenuates the carcinogenesis of prostatic cancer cell lines: Key role of the NF-κB pathway.

Prostate cancer (PCa) is one of the most frequently diagnosed cancers among males worldwide and causes a considerable number of deaths each year. One of the newly explored targets for the development of therapies against PCa is LIM and SH3 protein 1 (LASP-1). In the present study, the function of LASP-1 in the oncogenesis and metastasis of PCa was investigated using a series of in vitro experiments. Moreover, the mechanism through which LASP-1 exerted its effect on the carcinogenesis of PCa was also explored. The expression levels of LASP-1 in clinical PCa specimens were determined both at the mRNA and protein levels. Afterwards, the activity of LASP-1 in human PCa cell lines PC3 and DU145 was inhibited using a short hairpin RNA (shRNA) interfering method. The effects of LASP-1 knockdown on the cell growth, apoptosis, cell cycle distribution, migration and invasion were assessed. It was demonstrated that the expression of LASP-1 was significantly higher in the clinical PCa tissues than the level in the corresponding para-carcinoma tissues. Following the knockdown of the LASP-1 gene in human PCa cell lines, the viability, migration and invasion of the cancer cells were decreased. It was also demonstrated that the change in the cell viability and motile ability were associated with an induction of cell apoptosis and G1 phase cell cycle arrest. Based on the results of the detection of the expression of NF-κB-related factors, it was indicated that LASP-1 may affect the carcinogenesis of PCa through a NF-κB inhibition-dependent manner. Although the detailed explanation of the mechanism of LASP-1 in the carcinogenesis of PCa requires further elucidation, the present study highlights the potential of LASP-1 as a promising therapeutic target to ameliorate the oncogenesis and metastasis of PCa.

Relationship among diet habit and lower urinary tract symptoms and sexual function in outpatient-based males with LUTS/BPH: a multiregional and cross-sectional study in China.

OBJECTIVES: This study assessed the effect of diet habits on lower urinary tract symptoms (LUTS) and sexual function in Chinese men with LUTS/benign prostatic hypertrophy (LUTS/BPH). SETTING: Multicentre study conducted between July 2013 and December 2013 in 11 hospitals in 3 geographic regions in China. PARTICIPANTS: Overall, participants with LUTS/BPH accounted for 61.4% (2584/4208) of the respondents, whose data were processed in the following statistical analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: LUTS and sexual function were assessed based on the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function 5 (IIEF-5) score. Prostate volume (PV) was determined by ultrasound. RESULTS: A total of 4208 participants met the inclusion criteria. The average age of the whole participants was 65.8±7.7 years. Overall, participants with LUTS/BPH accounted for 61.4% (2584/4208) of the respondents, whose data were processed in the following statistical analysis. Generally, prostate enlargement was greatest in south China. LUTS and male sexual dysfunction (MSD) were most severe in northwest China. Based on multivariable analysis, PV enlarged as the age (p<0.001), body mass index (BMI; p<0.001) and vegetable intake (p<0.001) increased. Age (p<0.001) and BMI (p<0.05) independently increased the IPSS. A higher level of education (p<0.001) and more frequent meat, fish and egg intake (p<0.05) decreased the IPSS. Age (p<0.001), BMI (p<0.001), low education level (p<0.05), vegetable intake (p=0.001), and milk and dairy product intake (p=0.001) decreased the IIEF-5 score. CONCLUSIONS: In addition to factors including age, obesity and level of education, dietary habits and geographic difference might also play an important role in the variation of PV, LUTS and MSD for Chinese men with LUTS/BPH.