Pathogenesis and treatment of diabetes mellitus-related erectile dysfunction: current therapies and potential challenges

Erectile dysfunction(ED)is one of the important complications of diabetes,which is very common in diabetic patients,affecting more than half of male patients,and the incidence of the disease is about 3.5 times that of the normal population.The pathogenesis of diabetic erectile dysfunction(DMED)is complex,involving nerve,vascular,endocrine,muscular and psychological aspects.At present,the therapeutic approaches of DMED include drug therapy,surgery,physical therapy and so on.This article provides a review of current research on the pathogenesis and treatment of DMED.Further elucidation of the pathogenesis of DMED and the development of new therapeutic approaches are of great significance for the prevention and treatment of DMED.

Improvement in erectile dysfunction after insulin-like growth factor-1 gene therapy in diabetic rats

Aim： To determine whether adenoviral gene transfer of insulin like growth factor-1 （IGF-1） to the penis of streptozotocin （STZ）-induced diabetic rats could improve erectile capacity. Methods： The STZ diabetic rats were transfected with AdCMV-βgal or AdCMV-IGF-1. These rats underwent cavernous nerve stimulation to assess erectile function and their responses were compared with those of age-matched control rats 1 to 2 days after transfection. In control and transfected STZ diabetic rats, IGF-1 expression were examined by reverse transcription polymerase chain reaction （RT-PCR）, Western blot and histology. The penis β-galactosidase activity and localization of the STZ diabetic rats were also determined. Results： One to two days after transfection, the β-galactosidase was found in the smooth muscle cells of the diabetic rat penis transfected with AdCMV-βgal. One to 2 days after administration of AdCMV- IGF-1, the cavernosal pressure, as determined by the ratio of maximal intracavernous pressure-to-mean arterial pressure （ICP/MAP） and total intracavernous pressure （ICP）, was increased in response to cavernous nerve stimulation. Transgene expression was confirmed by RT-PCR, Western blot and histology. Conclusion： Gene transfer of IGF-1 significantly increased erectile function in the STZ diabetic rats. These results suggest that in vivo gene transfer of IGF- 1 might be a new therapeutic intervention for the treatment of erectile dysfunction （ED） in the STZ diabetic rats.

Endothelium-specific gene and stem cell-based therapy for erectile dysfunction

Erectile dysfunction （ED） commonly results from endothelial dysfunction of the systemic vasculature. Although phosphodiesterase type 5 （PDE-5） inhibitors are effective at treating most cases of ED, they must be taken routinely and are ineffectual for a meaningful number of men. In recent years gene and stem cell-based therapies targeted at the penile endothelium have been gaining momentum in preclinical studies. These early studies reveal that gene and stem cell-based therapies may be both enduring and efficacious, and may eventually lead to a cure for ED. The following review will highlight our current understanding of endothelial-specific gene and stem cell-based therapies performed to date in a number of experimental animal models.

Combination therapy for erectile dysfunction： an update review

The introduction of oral phosphodiesterase-5 inhibitors （PDE51s） in the late 1990s and early 2000s revolutionized the field of sexual medicine and PDE51s are currently first-line monotherapy for erectile dysfunction （ED）. However, a significant proportion of patients with complex ED will be therapeutic non-responders to PDE51 monotherapy. Combination therapy has recently been adopted for more refractory cases of ED, but a critical evaluation of current combination therapies is lacking. A thorough PubMed and Cochrane Library search was conducted focusing on the effectiveness of combination therapies for ED in therapeutic non-responders to PDE51 therapy. Journal articles spanning the time period between January 1990 and December 2010 were reviewed. Criteria included all pertinent review articles, randomized controlled trials, cohort studies and retrospective analyses. References from retrieved articles were also manually scanned for additional relevant publications. Published combination therapies include PDE51 plus vacuum erectile device （VED）, intraurethral medication, intracavernosal injection （ICI）, androgen supplement, a-blocker or miscellaneous combinations. Based on this review, some of these combination treatments appeared to be quite effective in preliminary testing. Caution must be advised, however, as the majority of combination therapy articles in the last decade have numerous limitations including study biases and small subject size. Regardless of limitations, present combination therapy research provides a solid foundation for future studies in complex ED management.

Stem cell therapy and diabetic erectile dysfunction:A critical review

Erectile dysfunction(ED)has been identified as one of the most frequent chronic complications of diabetes mellitus(DM).The prevalence of ED is estimated to be about 67.4%in all DM cases worldwide.The pathophysiological process leading to ED involves endothelial,neurological,hormonal,and psychological factors.In DM,endothelial and neurological factors play a crucial role.Damages in the blood vessels and erectile tissue due to insulin resistance are the hallmark of ED in DM.The current treatments for ED include phosphodiesterase-5 inhibitors and penile prosthesis surgery.However,these treatments are limited in terms of just relieving the symptoms,but not resolving the cause of the problem.The use of stem cells for treating ED is currently being studied mostly in experimental animals.The stem cells used are derived from adipose tissue,bone,or human urine.Most of the studies observed an improvement in erectile quality in the experimental animals as well as an improvement in erectile tissue.However,research on stem cell therapy for ED in humans remains to be limited.Nevertheless,significant findings from studies using animal models indicate a potential use of stem cells in the treatment of ED.

Gene therapy and erectile dysfunction： the current status

Current available treatment options for erectile dysfunction （ED） are effective but not without failure and/or side effects. Although the development of phosphodiesterase type 5 （PDE5） inhibitors （i.e. sildenafil, tadalafil and vardenafil） has revolutionized the treatment of ED, these oral medications require on-demand access and are not as effective in treating ED related to diabetic, post-prostatectomy and severe veno-occlusive disease states. Improvement in the treatment of ED is dependent on understanding the regulation of human corporal smooth muscle tone and on the identification of relevant molecular targets. Future ED therapies might consider the application of molecular technologies such as gene therapy. As a potential therapeutic tool, gene therapy might provide an effective and specific means for altering intracavernous pressure ＂on demand＂ without affecting resting penile function. However, the safety of gene therapy remains a major hurdle to overcome before being accepted as a mainstream treatment for ED. Gene therapy aims to cure the underlying conditions in ED, including fibrosis. Furthermore, gene therapy might help prolong the efficacy of the PDE5 inhibitors by improving penile nitric oxide bioactivity. It is feasible to apply gene therapy to the penis because of its location and accessibility, low penile circulatory flow in the flaccid state and the presence of endothelial lined （lacunar） spaces. This review provides a brief insight of the current role of gene therapy in the management of ED.

Stem cell therapy for erectile dysfunction

Erectile dysfunction(ED)is an important health problem that has commonly been clinically treated using phosphodiesterase type 5 inhibitors(PDE5Is).However,PDE5Is are less effective when the structure of the cavernous body has been severely injured,and thus regeneration is required.Stem cell therapy has been investigated as a possible means for regenerating the injured cavernous body.Stem cells are classified into embryonic stem cells and adult stem cells(ASCs),and the intracavernous injection of ASCs has been explored as a therapy in animal ED models.Bone marrowderived mesenchymal stem cells and adipose tissuederived stem cells are major sources of ASCs used for the treatment of ED,and accumulated evidence now suggests that ASCs are useful in the restoration of erectile function and the regeneration of the cavernous body.However,the mechanisms by which ASCs recover erectile function remain controversial.Some studies indicated that ASCs were differentiated into the vascular endothelial cells,vascular smooth muscle cells,and nerve cells that originally resided in the cavernous body,whereas other studies have suggested that ASCs improved erectile function via the secretion of anti-apoptotic and/or proangiogenic cytokines ratherthan differentiation into other cell types.In this paper,we reviewed the characteristics of stem cells used for the treatment of ED,and the possible mechanisms by which these cells exert their effects.We also discussed the problems to be solved before implementation in the clinical setting.

Common approach to managing lower urinary tract symptoms and erectile dysfunction

The present paper serves as a review of the associations between lower urinary tract symptoms （LUTS） and erectile dysfunction （ED）, with a focus on common and combined pathways for treatment. LUTS and ED are common conditions seen in general urologic practice. Research has started to establish epidemiologic and pathophysiologic links between the two conditions and a strong association confirmed across multiple studies. Men seeking care for one condition should always be interviewed for complaints of the other condition. Proposed common pathways include α-1 adrenergic receptor imbalance, Rho-kinase overactivity, endothelial cell dysfunction and atherosclerosis-induced ischemia. Medical therapy has replaced surgery as the first-line treatment for LUTS in most patients, with the incorporation of α-adrenergic receptor antagonists （α-ARAs） and 5-α-reductase inhibitors （5-ARIs） into everyday practice. Treatment with α-ARAs contributes to some improvement in ED, whereas use of 5-ARIs results in worsened sexual function in some patients. Phosphodiesterase-5 （PDE-5） inhibitors have revolutionized the treatment of ED with a simple oral regimen, and new insights demonstrate a benefit of combined use of PDE-5 inhibitors and α-ARAs. The mechanisms of action of these medications support these observed benefits, and they are being studied in the basic science and clinical settings. In addition, novel mechanisms for therapy have been proposed based on clinical and research observations. The minimally invasive and surgical treatments for LUTS are known to have adverse effects on ejaculatory function, while their effects on erectile function are still debated. Much remains to be investigated, but it is clear that the associations between LUTS and ED lay the foundation for future therapies and possible preventative strategies.

New oral agents for erectile dysfunction: what is changing in our practice?

Erectile dysfunction (ED) is a highly prevalent disorder affecting an estimated 152 million men worldwide and isassociated with a variety of behavioral risk factors, such as cigarette smoking and excessive alcohol consumption, aswell as numerous age - related medical conditions, notably type-2 diabetes mellitus and cardiovascular disease. A ratio-nal step - wise approach which includes comprehensive medical and sexual history, a focused physical examination andessential laboratory tests such as fasting glucose, lipid profile and testosterone assay is to be preferred. Current diagnos-tic work - up does not recommend any of the specialized tests which were previously considered mandatory-i. e. penilepharmacotesting, Duplex ultrasound and nocturnal penile tumescence. Hormonal replacement therapy is appropriate onlyin the hypogonadal male with ED. Prior to direct intervention, the physician should consider altering modifiable riskfactors or causes, although frequently insufficient to reverse ED completely. When indicated, oral therapy with newmolecules (phosphodiesterase inhibitors or apomorphine) is the first - line treatment for the majority of patients becauseof potential benefits and lack of invasiveness. (Asian J Androl 2001 Sep; 3: 175-179 )

Management of erectile dysfunction in hypertension:Tips and tricks

Arterial hypertension is a major risk factor for cardiovascular disease and affects approximately one third of the adult population worldwide. The vascular origin of erectile dysfunction is now widely accepted in the vast majority of cases. Erectile dysfunction is frequently encountered in patients with arterial hypertension and greatly affects their quality of life of hypertensive patients and their sexual partners. Therefore, the management of erectile dysfunction in hypertensive patients is of paramount importance. Unfortunately, erectile dysfunction remains under-reported, under-recognized, and under-treated in hypertensive patients, mainly due to the lack of familiarity with this clinical entity by treating physicians. This review aims to discuss the more frequent problems in the management of hypertensive patients with erectile dysfunction and propose ways to overcome these problems in everyday clinical practice.

Treatment of Vasculogenic Erectile Dysfunction with Piezowave2 Device. Application of Low Intensity Shockwaves Using Novel Linear Shockwave Tissue Coverage (LSTC-ED®) Technique. A Prospective, Multicentric, Placebo-Controlled Study

Low intensity shockwave (LiSW) treatment is known to improve revascularization. The method has been evaluated and is used to treat vasculogenic erectile dysfunction (ED). The present study aimed to demonstrate the efficacy of a linear focused piezoelectric shockwave device (Richard Wolf/ELvationPiezowave2) to treat patients with vasculogenic ED using a novel linear shockwave tissue coverage LSTC-ED® technique. A total of 75 patients were treated using the Piezowave2 device and the LSTC-ED® technique. Patients’ erectile function was evaluated using the modified IIEF-5 (International Index of Erectile Function) scale at the beginning of treatment and at 1 month post treatment;patients were additionally questioned using our own Treatment Satisfaction Questionnaire (TSQ). The study also included a group of 50 patients treated by placebo;the outcomes of both groups were compared. The average IIEF-5 score of patients in the treatment group increased from 14.4 at baseline to 18.6 at 1 month post treatment. According to the IIEF-5 scale, treatment was successful in 81.33% of patients (61/75). According to the Treatment Satisfaction Questionnaire (answers 1 to 3 of the TSQ), treatment was successful in 77.3% of patients (58/75). In the placebo group of 50 patients only 5 patients showed an improvement based on IIEF score, and 8 reported an improvement based on their answers to the TSQ. No significant adverse effects were observed during treatment or in the follow-up period. The Piezowave2 device and the LSTC-ED® technique proved to be suitable and effective to treat erectile dysfunction.

Impact of low-intensity extracorporeal shockwave therapy on vascular parameters and sexual function in patients with arteriogenic erectile dysfunction

Previous published studies have shown an improvement of penile hemodynamic parameters after low-intensity extracorporeal shockwave therapy(Li-ESWT).However,the clinical significance of these findings remains unclear,and definitive selection criteria for Li-ESWT based on preexisting comorbidities have yet to be established.This was an observational study of 113 patients with ED,evaluated between January 2019 and December 2021 in Andrology Unit at the Department of Urology and Renal Transplantation,University of Foggia(Foggia,Italy).Penile dynamic Doppler was performed to evaluate vascular parameters and 5-item version of the International Index of Erectile Dysfunction(IIEF-5)questionnaire was administered to assess the severity of ED.This was repeated 1 month after treatment.Patients with a peak systolic velocity(PSV)<30 cm s−1 were considered eligible for Li-ESWT.Our protocol consisted of 8 weekly sessions with 1500 strokes distributed in 5 different locations along the penis.After treatment,a significant mean(±standard deviation[s.d.])PSV increase of 5.0(±3.4)cm s−1 was recorded and 52/113(46.0%)patients reached a PSV>30 cm s−1 at posttherapeutic penile dynamic Doppler.A clinically significant IIEF-5 score improvement was observed in 7 patients,21 patients,and 2 patients with mild-to-moderate,moderate,and severe pretreatment ED,respectively.No different outcomes were assessed based on smoking habits,previous pelvic surgery,or use of oral phosphodiesterase-5 inhibitor(PDE5i).On the other side,only 1(6.7%)in 15 patients with diabetes mellitus showed an IIEF-5 score improvement after Li-ESWT.Shockwave treatment determined a significant increase in PSV and correlated IIEF-5 improvement in ED patients.This advantage seemed particularly evident for moderate ED and was not affected by smoking habits,previous pelvic surgery,and use of PDE5i.Conversely,diabetic patients did not benefit from the treatment.

Value of phosphodiesterase 5 inhibitors as a combination therapy for treating erectile dysfunction:A literature review

Erectile dysfunction(ED)is increasing in prevalence,with estimates that 50%of men between 40 and 70 years of age suffer from the disease.Due to a wide array of available medical interventions,significant focus has been put on combination therapies that can treat ED refractory to first-line treatments such as phosphodiesterase 5 inhibitors(PDE5is).However,reviews evaluating monotherapy noninferiority and patient satisfaction of monotherapy versus combination therapy are lacking.A thorough PubMed search was performed to evaluate combination therapy in ED treatment.Articles published between January 2008 and June 2023 were reviewed,including randomized control trials,retrospective analyses,and cohort studies.Combination therapies included PDE5i plus another PDE5i,testosterone supplementation,α-blockers,vacuum erectile devices,intracavernosal injections,and low-intensity shockwave therapy.Based on this review,PDE5i monotherapy is not inferior to combination therapy and has increased satisfaction,convenience,and ease of use for patients with ED.Limitations of current literature on combination therapy include small sample size,limited data on patient satisfaction,possible biases,and limited follow-up time.Further studies will need larger randomized control trials with follow-up times greater than 1 year.

A review of regenerative therapies as penile rehabilitation in men following primary prostate cancer treatment:Evidence for erectile restoration and cavernous nerve regeneration

Objective:The following article explores our evolving understandings of the role of regenerative technology as an effective penile rehabilitation tool in men with erectile dysfunction(ED)in the setting of prostate cancer(PCa)treatment and PCa survivorship.Methods:This narrative clinical review paper summarizes what is currently known about various modalities of regenerative therapy in restoring spontaneous erectile function(EF)in men following PCa treatment with an emphasis on penile rehabilitation strategies.Results:Conventional medical therapy often does not reverse underlying endothelial dysfunction or promote neuro-vasculogenesis to preserve penile health in men with ED.Over the past decade,there has been considerable interest in the role of regenerative therapy to restore endothelial dysfunction and ED without future dependency on medical therapy.Regenerative therapy can be classified into cellular-based(immunomodulators,stem cells,and platelet-rich plasma),biomaterials(nerve graft transfer),and device-related technology(low-intensity shockwave).Although published literature shows early promise in the role of regenerative technology for ED,there is a paucity of high-quality clinical trials in the setting of penile rehabilitation and PCa survivorship to support their use as standard care and be adopted in clinical guidelines.

Penile rehabilitation with a vacuum erectile device in an animal model is related to an antihypoxic mechanism： blood gas evidence

Our previous study showed that vacuum erectile device （VED） therapy has improved erectile function in rats with bilateral cavernous nerve crush （BCNC） injuries. This study was designed to explore the mechanism of VED in penile rehabilitation by analyzing cavernous oxygen saturation （SO2） and to examine the effect of VED therapy on preventing penile shrinkage after BCNC. Thirty adult Sprague- Dawley rats were randomly assigned into three groups： group 1, sham surgery; group 2, BCNC; and group 3, BCNC＋VED. Penile length and diameter were measured on a weekly basis. After 4 weeks of therapy, the penile blood was extracted by three methods for blood gas analysis （BGA）： method 1, cavernous blood was aspirated at the flaccid state; method 2, cavernous blood was aspirated at the traction state; and method 3, cavernous blood was aspirated immediately after applying VED. SO2 values were tested by the blood gas analyzer. The results showed that VED therapy is effective in preventing penile shrinkage induced by BCNC （Penile shortening： BCNC group 1.9±1.1 mm; VED group 0.3±1.0 mm; P〈0.01. Penile diameter reduction： BCNC group 0.28±0.14 mm; VED group 0.04±0.14 mm; P〈0.01）. The mean SO2±s.d. values were increased by VED application （88.25%±4.94%） compared to the flaccid （76.53%±4.16%） or traction groups （78.93%±2.56%） （P〈0.05）. The calculated blood constructs in the corpus cavernosum right after VED application were 62% arterial and 38% venous blood. These findings suggest that VED therapy can effectively preserve penile size in rats with BCNC injury. The beneficial effect of VED therapy is related to antihypoxia by increasing cavernous blood SO2.

The Use of Natural Products for the Treatment of Female Sexual Dysfunction: A Systematic Review of Randomized Clinical Trials

Female sexual dysfunction (FSD) affects 40% of the world’s females, most of which are disorders linked to desire or interest/excitement. Whilst all types of therapy that attempt to improve female sexual desire have long been established, the results are contradictory. Objective: To analyze all available evidence to validate the effectiveness of natural therapies in the treatment of FSD. Method: The study was registered at http://www.prospero.org (CRD42019127700). We searched the Institute for Scientific Information Web of Knowledge, MEDLINE, Pubmed, Scopus and Cochrane databases for all articles published in peer- reviewed journals in April 2019 (in any language). The PICOS standard is women with FSD;(intervention) of any type of Natural therapy;(outcome) primary outcome: frequency of changes, severity, and average mean scores on sexual symptoms measured with a validated instrument, secondary outcome: quality of life;(study design) and randomized clinical trial (RCT). Results: The literature search strategy identified 95 articles, 81 of which were excluded at the different search stages. Finally, we systematically reviewed 15 RCTs, 11 of which referred to primary FSD, and four of which analyzed women with drug-induced FSD (DFSD). Most of them analyzed hypoactive sexual desire disorder. Although differences related to placebo were found in most people, the majority of the studies are considered to be of poor quality and low external effectiveness. Conclusion: Although the quality of the evidence is not high, most natural product interventions appear to improve FSD, particularly hypoactive sexual desire disorders including those categorized as primary and drug-induced.

针药并用治疗气阴两虚兼瘀型糖尿病性勃起功能障碍的疗效观察及对血管内皮功能及相关生长因子的影响

目的 观察针刺联合益气养阴活血方治疗气阴两虚兼瘀型糖尿病性勃起功能障碍的临床疗效及对血管内皮功能及相关生长因子的影响。方法 将90例气阴两虚兼瘀型糖尿病性勃起功能障碍患者随机分为治疗组和对照组,每组45例。对照组予糖尿病基础治疗及他达拉非片口服治疗,治疗组在对照组基础上采用针刺联合益气养阴活血方。比较两组国际勃起功能指数-5(international index of erectile function-5, IIEF-5)评分和中医证候积分变化,比较两组血清内皮素-1(endothelin-1, ET-1)、血管紧张素-Ⅱ(angiotensin Ⅱ, Ang-Ⅱ)、一氧化氮(nitric oxide, NO)和血管活性肠肽(vasoactive intestinal peptide, VIP)含量变化,比较两组血清内皮生长因子(vascular endothelial growth factor, VEGF)、转化生长因子-β(transforming growth factor-β, TGF-β)、成纤维细胞生长因子-21(fibroblast growth factor 21, FGF-21)和胰岛素样生长因子-1(insulin-like growth factor 1, IGF-1)含量变化,并比较两组临床疗效。结果 治疗后,两组IIEF-5评分高于治疗前(P<0.05),对照组勃起无力、腰膝酸软、阴部刺痛及中医证候积分总分低于治疗前(P<0.05),治疗组中医证候各项积分及总分低于治疗前(P<0.05);且治疗组IIEF-5评分高于对照组(P<0.05),治疗组中医证候各项积分及总分低于对照组(P<0.05)。治疗后,两组血清ET-1和AngⅡ低于治疗前,NO和VIP高于治疗前(P<0.05);且治疗组血清ET-1和AngⅡ低于对照组,NO和VIP高于对照组(P<0.05)。治疗后,两组血清VEGF和IGF-1高于治疗前,TGF-β和FGF-21低于治疗前(P<0.05);且治疗组血清VEGF和IGF-1高于对照组,TGF-β和FGF-21低于对照组(P<0.05)。治疗组总有效率为90.7%,高于对照组的73.8%(P<0.05)。结论 在西药治疗的基础上,针刺联合益气养阴活血方能够改善气阴两虚兼瘀型糖尿病性勃起功能障碍患者临床症状,提高治疗效果,可能与改善血管内皮功能、调节相关生长因子有关。

Efficacy and safety of low-intensity shockwave therapy plus tadalafil 5 mg once daily in men with type 2 diabetes mellitus and erectile dysfunction:a matched-pair comparison study

Low-intensity extracorporeal shockwave therapy(LiESWT)represents a promising treatment for patients with erectile dysfunction(ED).We investigated the efficacy of LiESWT combined with tadalafil 5 mg once daily in men with type 2 diabetes mellitus(T2DM)and ED and compared LiESWT protocols administering different number of shockwaves.We performed a retrospective matched-pair comparison using data from a prospectively maintained database.Seventy-eight patients who received tadalafil 5 mg once dai7ly for 12 weeks+LiESWT performed with an electrohydraulic source for 3 weeks(Group A)were matched 1:1 to patients who received tadalafil 5 mg once daily alone for 12 weeks(Group B).A subgroup analysis was performed according to the number of shockwaves delivered during each session(1500,1800,and 2400 in subgroup A1,A2,and A3,respectively).The mean International Index of Erectile Function-5(IIEF-5)score variations with respect to baseline recorded at 4,12,and 24 weeks after the end of the treatment were investigated as treatment outcomes.The mean IIEF-5 scores significantly improved in all groups and subgroups at 4-week follow-up without intergroup differences.At 12-and 24-week follow-up,the mean IIEF-5 improvement was significantly higher among patients in the A3 subgroup(+5.0±2.1[P<0.001]and+4.7±2.3[P<0.001],respectively).The combined approach with tadalafil 5 mg once daily and LiESWT with a protocol involving 2400 shockwaves provides significant advantages in terms of IIEF-5 improvement and durability compared to tadalafil 5 mg once daily alone in patients with T2DM and ED.

Stem cell-based therapy for erectile dysfunction

Objective To review the effect of stem cells in erectile dysfunction as well as their application to the therapy of erectile dysfunction. Data sources The data used in the present article were mainly from PubMed with relevant English articles published from 1974 to 2011. The search terms were ＂stem cells＂ and ＂erectile dysfunction＂. Study selection Articles regarding the role of stem cells in erectile dysfunction and their application to the therapy of erectile dysfunction were selected. Results Stem cells hold great promise for regenerative medicine because of their ability to self-renew and to differentiate into various cell types. Meanwhile, in preclinical experiments, therapeutic gene-modified stem cells have been approved to offer a novel strategy for cell therapy and gene therapy of erectile dysfunction. Conclusion The transplantation of stem cells has the potential to provide cell types capable of restoring normal function after injury or degradation inerectile dysfunction. However, a series of problems, such as the safety of stem cells transplantation, their application in cell therapy and gene therapy of erectile dysfunction need further investigation.

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.