Genetically predicted insomnia causally increases the risk of erectile dysfunction

Sleep has attracted extensive attention due to its significance in health.However,its association with erectile dysfunction(ED)is insufficiently investigated.To investigate the potential causal links between sleep traits(insomnia,sleep duration,and chronotype)and ED,this study was performed.The single-nucleotide polymorphisms(SNPs)associated with insomnia,sleep duration,and chronotype were retrieved from previous genome-wide association studies(GWAS).A conventional two-sample Mendelian randomization(MR)was used to estimate the causal links between sleep traits and ED.The summary statistics of ED were from individuals of European ancestry(6175 cases vs 217630 controls).As shown by the random effect inverse-variance-weighting(IVW)estimator,genetically predicted insomnia was causally associated with a 1.15-fold risk of ED(95%confidence interval:1.07-1.23,P<0.001).Sleep duration and morningness were not causally associated with ED,as indicated by the IVW(all P>0.05).These findings were consistent with the results of sensitivity analyses.Based on genetic data,this study provides causal evidence that genetically predicted insomnia increases the risk of ED,whereas sleep duration and chronotype do not.

Optimal pressure in penile rehabilitation with a vacuum erection device: evidenee based on a rat model

Vacuum erecti on device(VED),used to treat radical prostatectomy(RP)-associated erectile dysfunction,has attracted con siderable attention.However,the optimal negative pressure remains to be determined.This investigation explored the optimal pressure for VED therapy in penile rehabilitation.Thirty-six 9-week-old male rats were randomly divided into six groups:control groups(sham group,bilateral cavernous nerve crush[BCNC]group)and VED therapy groups(-200 mmHg group,-300 mmHg group,-400 mmHg group,-500 mmHg group).BCNC group and VED therapy groups underwent BCNC surgery.Intracavernosal pressure(ICP)/mean arterial pressure(MAP)ratio was calculated to assess erectile function.Mass on's trichrome(MT)staining,terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assay,immunohistochemistry,and real-time polymerase chain reaction(RT-PCR)were performed to explore cellular and molecular changes of the penis.Compared to the BCNC group,ICP/MAP ratios in all VED treatment groups were improved significantly(all P<0.05),but there were no statistically significant differences among VED therapy groups.With increased pressure,complications gradually emerged and increased in frequency.Expression of molecular indicators,such as endothelial nitric oxide synthase(eNOS)and alpha-smooth muscle actin(a?SMA),increased after VED therapy,and hypoxia-inducible factor la(HIF-la)and transforming growth factor beta(TGF-p)decreased.In addition,VED therapy improved the outcomes of MT and TUNEL assay.This investigation demonstrated a pressure of-200 mmHg in a rat model is optimal for VED therapy for penile rehabilitation after RP.No further benefits were observed with increased pressure,despite an increase in complications.

Vacuum therapy ameliorates erectile dysfunction in bilateral cavernous nerve crush rats by inhibiting apoptosis and activating autophagy

Postprostatectomy erectile dysfunction(pPED)remains a current problem despite improvements in surgical techniques.Vacuum therapy is clinically confirmed as a type of pPED rehabilitation.However,its underlying mechanisms are incompletely understood.Recently,autophagy and apoptosis were extensively studied in erectile dysfunction resulting from diabetes,senescence,and androgen deprivation but not in the context of pPED and vacuum therapy.Therefore,this study was designed to investigate the roles of autophagy and apoptosis in pPED and vacuum therapy.Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups:the control group,bilateral cavernous nerve crush(BCNC)group,and BCNC+vacuum group.After 4 weeks of treatment,intracavernosal pressure was used to evaluate erectile function.Real-time quantitative polymerase chain reaction,western blot,and immunohistochemistry were used to measure the molecular expression.TdT-mediated dUTP nick-end labeling staining was used to assess apoptosis.Transmission electron microscopy was used to observe autophagosomes.After treatment,compared with those of the BCNC group,erectile function and cavernosal hypoxia had statistically significantly improved(P<0.05).Apoptosis and the relative protein expression of B-cell lymphoma-2-associated X and cleaved Caspase3 were decreased(P<0.05).Autophagy-related molecules such as phosphorylated unc-51-like autophagy-activating kinase 1(Ser757)and p62 were decreased.Beclinl,microtubule-associated protein 1 light chain 3 A/B,and autophagosomes were increased(P<0.05).Besides,the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathway,as a negative regulator of autophagy to some degree,was inhibited.This study revealed that vacuum therapy ameliorated pPED in BCNC rats by inhibiting apoptosis and activating autophagy.

N-acetylcysteine maintains penile length and erectile function in bilateral cavernous nerve crush rat model by reducing penile fibrosis

Penile length shortening and erectile dysfunction are common complications after radical prostatectomy.Various methods have been used to maintain erectile function,but less attention has been paid to preserving penis length.N-acetylcysteine(NAC)has the effect of antioxidation and antifibrotic,which may be beneficial to improve those postoperative complications.This study investigated the effect of NAC on maintaining the penile length and the erectile function after bilateral cavernous nerve crush(BCNC)and its underlying mechanism.Twenty-four male rats were randomly divided into three groups:control group,BCNC group,and BCNC+NAC group.NAC or equal volume of saline was daily administrated by intragastric gavage for 4 weeks.The initial and end penile lengths were measured.Intracavernosal pressure/mean arterial pressure(ICP/MAP)ratio was calculated to assess erectile function.Hematoxylin-eosin staining,Masson's trichrome staining,immunohistochemistry,and Western blot were performed to explore cellular and molecular changes of the penis.Compared to the BCNC group,the penile length,ICP/MAP ratio and smooth muscle/collagen ratio in the BCNC+NAC group were improved significantly(all P<0.05),and the expressions of endothelial nitric oxide synthase,α-smooth muscle actin,glutathione,and glutathione peroxidase 1 were significantly increased after NAC treated(all P<0.05),along with the decreased expressions of hypoxia-inducible factor-1α,transforming growth factor-β1,collagen I,collagen III,collagen IV,malonaldehyde,and lysine oxidase(all P<0.05).This study demonstrated that NAC could maintain penile length and partly improve erectile function.Possible mechanism is directly and/or indirectly related to antihypoxic and antifibrosis.

Anti-lysyl oxidase combined with a vacuum device induces penile lengthening by remodeling the tunica albuginea

This study aimed to explore whether and how anti-lysyl oxidase(anti-LOX)combined with a vacuum device(VD)could promote penile lengthening and to evaluate the effect on erectile function.This study was performed on four groups of adult rats:control,anti-LOX,VD(negative pressure value of-300 mmHg),and anti-LOX+VD.Penile length was measured by a modified VD method and verified on exposed length data.Intracavernous pressure(ICP)and maximum ICP/mean arterial pressure(MAP)ratio were recorded to assess erectile function.For corpus cavernosum,LOX activity and concentrations of pyridinoline,desmosine,hydroxyproline,and elastin were analyzed;transmission electron microscope and Hart’s elastin staining were performed to monitor microstructural changes.Anti-LOX and VD significantly lengthened the penis by 10.8%(3.75 mm)and 8.2%(2.48 mm)compared with the control group,respectively,while anti-LOX+VD achieved the longest penile size(40.58±0.40 mm)which was 17.4%longer than the control group(34.58±0.54 mm).After 1-week washout,no penile retraction was observed.Meanwhile,exposed penile length data confirmed that the penis in the anti-LOX+VD group was also significantly longer.Anti-LOX inhibited LOX activity to reduce pyridinoline level,which led the penile tunica albuginea remodeling.However,it had no effect on hydroxyproline,desmosine,and elastin levels.Moreover,anti-LOX had no impact on erectile function,which was determined by ICP and ICP/MAP ratio.These results suggest that anti-LOX elongates the penis by reducing pyridinoline,which induces tunica albuginea remodeling.This lengthening effect was more obvious when combined with a VD.All procedures had no impact on erectile function.