Corpus Cavernosum Research Articles

MicroRNA-145 Gene Modification Enhances the Retention of Bone Marrow-Derived Mesenchymal Stem Cells within Corpus Cavernosum by Targeting Krüppel-Like Factor 4.

The poor retention and ambiguous differentiation of stem cells (SCs) within corpus cavernosum (CC) limit the cell application in erectile dysfunction (ED). Herein, the effects and mechanism of microRNA-145 (miR-145) gene modification on modulating the traits and fate of bone marrow-derived mesenchymal stem cells (BMSCs) were investigated. The effects of miR-145 on cell apoptosis, proliferation, migration, and differentiation were determined by flow cytometry, cell counting kit-8, transwell assays and myogenic induction. Then, the age-related ED rats were recruited to four groups including phosphate buffer saline, BMSC, vector-BMSC, overexpressed-miR-145-BMSC groups. After cell transplantation, the CC were harvested and prepared to demonstrate the retention and differentiation of BMSCs by immunofluorescent staining. Then, the target of miR-145 was verified by quantitative real-time polymerase chain reaction and immunohistochemical. After that, APTO-253, as an inducer of Krüppel-like factor 4 (KLF4), was introduced for rescue experiments in corpus cavernosum smooth muscle cells (CCSMCs) under the co-culture system. In vitro, miR-145 inhibited the migration and apoptosis of BMSCs and promoted the differentiation of BMSCs into smooth muscle-like cells with stronger contractility. In vivo, the amount of 5-ethynyl-2'-deoxyuridine (EdU)+cells within CC was significantly enhanced and maintained in the miR-145 gene modified BMSC group. The EdU/CD31 co-staning was detected, however, no co-staining of EdU/α-actin was observed. Furthermore, miR-145, which secreted from the gene modified BMSCs, dampened the expression of KLF4. However, the effects of miR-145 on CCSMCs could be rescued by APTO-253. Overall, miR-145 modification prolongs the retention of the transplanted BMSCs within the CC, and this effect might be attributed to the modulation of the miR-145/KLF4 axis. Consequently, our findings offer a promising and innovative strategy to enhance the local stem cell-based treatments.

Novel erectile analyses revealed augmentable penile Lyve-1, the lymphatic marker, expression.

The pathophysiology of penis extends to erectile dysfunction (ED) to conditions including sexually transmitted diseases (STDs) and cancer. To date, there has been little research evaluating vascular drainage from the penis. We aimed to evaluate penile blood flow invivo and analyze its possible relationship with the lymphatic maker. We established an invivo system designed to assess the dynamic blood outflow from the corpus cavernosum (CC) by dye injection. To analyze lymphatic characteristics in the CC, the expression of Lyve-1, the key lymphatic endothelium marker, was examined by the invitro system and lipopolysaccharide (LPS) injection to mimic the inflammatory conditions. A novel cavernography methods enable high-resolution morphological and functional blood drainage analysis. The expression of Lyve-1 was detected along the sinusoids. Furthermore, its prominent expression was also observed after penile LPS injection and in the erectile condition. The current invivo system will potentially contribute to the assessment of penile pathology from a novel viewpoint. In addition, current analyses revealed inducible Lyve-1 expression for LPS injection and the erection state, which requires further analyses on penile lymphatic system.

A novel modified penile disassembly procedure for isolated male epispadias repair: preliminary outcomes.

This study aimed to evaluate the preliminary outcome of a novel modification of a penile disassembly procedure. We retrospectively reviewed the data of 15 patients with isolated male epispadias (IME) who underwent a modified penile disassembly procedure. This modification involved leaving the glans connected while dissecting the urethral plate from the corpus cavernosum. This approach reserves the bundles of the anastomosis at the glans, which can prevent ischemic changes. One of the first two patients experienced glans ischemic changes on the first day after the operation, which ultimately resulted in the loss of half of the hemiglans. Urethral plate shortening was observed in two patients and was addressed with a transverse preputial island flap. Two patients developed a penopubic urethral fistula, which was repaired 6 months postoperatively. Of the 15 patients, 10 (66%) were continent or social continent, while 4 were incontinent and needed bladder neck reconstruction. One patient had not yet reached the age for continence evaluation. Additionally, Two patients had a residual dorsal curvature of approximately 10-15° and were advised to undergo continuous follow-up. The modified penile disassembly procedure is a simple, effective, and safe method for IME repair with an acceptable penile appearance and complication rate.

Tipik muayene bulguları olmadan üretral yaralanmanın eşlik ettiği penil fraktür: Nadir bir olgu sunumu

Penile fractures typically present unilaterally, although bilateral occurrences account for 2–10% of cases. Urethral injury concomitant with penile fracture is exceedingly rare and constitutes a urologic emergency. Emergency surgery is widely accepted as the standard approach. In the presented case, a 25-year-old male patient presented to the emergency department approximately two hours after experiencing blunt trauma to the penis during sexual intercourse, accompanied by a sudden crackling sound. Physical examination did not reveal classic signs of penile fracture such as eggplant deformity, butterfly sign, or penile deviation; however, urethrorrhagia was evident. Ultrasonography revealed a defect in the tunica albuginea at the distal portion of both cavernous bodies. Retrograde urethrography demonstrated filling of the corpus cavernosum from the urethra with an opaque substance. Surgical exploration identified rupture along two fracture lines on the dorsal aspect of the urethra. Primary anastomosis of the urethra was performed over a Foley catheter, and defects in both corpus cavernosum were sutured. This case underscores the variability in presentation of penile fractures and emphasizes the necessity of considering urethral injury in cases of penile fracture with associated symptoms. Keywords: penile erection, urethra, trauma

Immunohistochemical analysis of E-cadherin and Caspase-3 expression in equine penile squamous cell carcinoma

Neoplasms are an important cause of morbidity and mortality in horses, with squamous cell carcinoma (SCC), also called squamous cell carcinoma, being the most common genital malignant tumor in the species and the most common neoplasm in horses in the State of São Paulo. Neoplasms frequently infiltrate the corpus cavernosum and can cause metastases in regional lymph nodes, generally having a guarded to poor prognosis due to local invasion and recurrence. Given the importance of the disease, the objective was to verify whether there is a difference in the expression pattern of immunomarkers of apoptosis and cell adhesion, according to the degree of cellular differentiation of the neoplasms. Twenty equine penile SCC samples from the Animal Pathology Service of the Veterinary Hospital of the Faculty of Veterinary Medicine and Animal Science of the University of São Paulo were histologically analyzed and classified according to their degree of differentiation. In addition, they were also subjected to the immunohistochemistry technique, with the immunomarkers Caspase-3 and E-cadherin. Data were analyzed using Kendall’s correlation and the Mann-Whitney test. It was found that there is a positive correlation between the expression of immunomarkers and that there is no statistically significant difference in the expression of immunomarkers according to the degree of differentiation.

Argonaute 2 restored erectile function and corpus cavernosum mitochondrial function by reducing apoptosis in a mouse model of cavernous nerve injury.

To determine whether the overexpression of the Argonaute RNA-induced silencing complex catalytic component 2 (Ago2) improves erectile function in mice after cavernous nerve injury (CNI). Lentiviruses containing Ago2 open reading frame (ORF) mouse clone (Ago2 O/E) were used to overexpress Ago2, and lentiviruses ORF negative control particles (NC) were used as a negative control. Three days before preparing the CNI model, we injected lentiviruses into the penises of 8-week-old male C57BL/6 mice. Animals were then divided into four groups: the sham operation control group and the CNI+phosphate-buffered saline, CNI+NC, and CNI+Ago2 O/E groups. One week later, erectile function was assessed by electrically stimulating cavernous nerves bilaterally and obtaining intracavernous pressure parameters. Penile tissue was also collected for molecular mechanism studies. Ago2 overexpression improved erectile function in mice after CNI-induced erectile dysfunction (ED). Immunofluorescence staining and Western blot analysis showed that under Ago2 overexpressing conditions, the contents of endothelial cells, pericytes, and neuronal cells increased in the penile tissues of CNI mice, and this was attributed to reduced apoptosis and ROS production. In addition, we also found that Ago2 overexpression could restore penile mitochondrial function, thereby improving erectile function in CNI-induced ED mice. Our findings demonstrate that Ago2 overexpression can reduce penile cell apoptosis, restore penile mitochondrial function, and improve erectile function in CNI-induced ED mice.

The Effects of a Red-Light Controllable Nitric Oxide Donor, NORD-1, on Erectile Dysfunction in Rats with Streptozotocin Induced Diabetes Mellitus.

Patients with diabetes mellitus (DM) often exhibit refractory erectile dysfunction (ED). Red-light-controllable nitric oxide donor (NORD-1) and red-light irradiation have successfully enhanced erectile function in intact rats. In this study, we investigated whether the combination of NORD-1 and red-light irradiation effectively treated ED in streptozotocin (STZ)-treated rats with DM. Seven-week-old male Sprague-Dawley rats were used in this study. Rats in the DM and sham groups received intravenous STZ (50 mg/kg) and saline, respectively. One week after treatment, the blood glucose level of rats in the DM group was >250 mg/dL. Five weeks after the treatment, we performed a functional study by measuring intracavernous pressure (ICP) under cavernous nerve stimulation before and after NORD-1 treatment with and without light irradiation. Additionally, we performed an isometric tension study using the corpus cavernosum of rats treated with NORD-1 or the control compound, SiR650. The ICP/mean arterial pressure (MAP) ratio was significantly lower in the DM group than in the sham group before and after NORD-1 treatment without light irradiation (both p<0.05). After NORD-1 treatment with light irradiation, the ICP/MAP ratio in the sham and DM groups was significantly enhanced than before and after NORD-1 treatment without light irradiation (all p<0.05). The ICP/MAP ratio in the DM group after NORD-1 with light irradiation was similar to that in the sham group under normal conditions before NORD-1 treatment. Moreover, the systemic blood pressure was not affected by NORD-1 or light irradiation. In the tension study, the corpus cavernosum of rats treated with SiR650 was not changed by red light in the sham or DM groups. However, the rats treated with NORD-1 were strongly relaxed by red light in both groups. NORD-1 and red-light irradiation could improve ED in the presence of DM without lowering blood pressure.

Priapism in a Young Adult With Sickle Cell Disease.

This article presents a case study focusing on priapism in a patient with sickle cell disease, with repeated emergency department (ED) visits and hospitalizations. The patient was successfully identified and treated by the ED nurse practitioner (NP) with aspiration of the corpus cavernosum. Priapism is a persistent penile erection that continues for an extended time. There is some argument about what that length of time is, but generally, the consensus is more than 4 hr beyond sexual stimulation or unrelated to sexual stimulation or sexual interest (Bivalacqua et al., 2022). Priapism is a fairly common but underrecognized complication of sickle cell disease. It represents a urological emergency in which timely diagnosis and appropriate treatment are vital to preserving penile tissue and sexual function. The diagnosis is made clinically with a comprehensive history, physical examination, and appropriate laboratory test values. Initial management can be conservative with hydration and analgesics or, if necessary, more invasive with needle aspiration to promote detumescence. Permanent tissue damage or erectile dysfunction can result if priapism is unrecognized, untreated, or not treated immediately. The NP plays an integral role in treating and preventing permanent damage. Patient education should focus on instructions for preventing priapism and managing episodes at home.

Inhibition of the RIP3/MLKL/TRPM7 necroptotic pathway ameliorates diabetes mellitus-induced erectile dysfunction by reducing cell death, fibrosis, and inflammation.

Diabetes mellitus-induced erectile dysfunction (DMED) is a common complication in patients with diabetes mellitus. Necroptosis is regarded as a form of cell death that is intimately associated with the inflammatory response, which is not only initiated by inflammatory factors such as TNF-α, but also triggers the inflammatory cascade through the rupture of the dying cell. There is no definitive study on the role of necroptosis in the pathological process of DMED. In light of the pathological features of high inflammation levels in DMED patients, we assessed whether the necroptosis plays an important role in the course of DMED. Our study revealed that penile tissues of DMED rats showed high levels of key necroptosis factors such as receptor-interacting protein kinase 3 (RIP3), mixed-lineage kinase domain-like protein (MLKL), and transient receptor potential melatonin 7 (TRPM7). Furthermore, the inhibition of necroptosis with a receptor-interacting protein kinase 3 (RIP3) inhibitor or Yimusake (a common herbal remedy for ED) effectively rescued damage to corpus cavernosum smooth muscle cells (CCSMC) under high glucose conditions. Our findings suggest that inhibition of the RIP3/MLKL/TRPM7 necroptotic pathway could effectively ameliorate CCSMCs fibrosis and death induced by high glucose and inhibited the inflammatory response.

The Role of Autophagy in Erectile Dysfunction.

Autophagy is a conservative lysosome-dependent material catabolic pathway, and exists in all eukaryotic cells. Autophagy controls cell quality and survival by eliminating intracellular dysfunction substances, and plays an important role in various pathophysiology processes. Erectile dysfunction (ED) is a common male disease. It is resulted from a variety of causes and pathologies, such as diabetes, hypertension, hyperlipidemia, aging, spinal cord injury, or cavernous nerve injury caused by radical prostatectomy, and others. In the past decade, autophagy has begun to be investigated in ED. Subsequently, an increasing number of studies have revealed the regulation of autophagy contributes to the recovery of ED, and which is mainly involved in improving endothelial function, smooth muscle cell apoptosis, penile fibrosis, and corpus cavernosum nerve injury. Therefore, in this review, we aim to summarize the possible role of autophagy in ED from a cellular perspective, and we look forward to providing a new idea for the pathogenesis investigation and clinical treatment of ED in the future.

6-Nitrodopamine is an endogenous mediator of the rabbit corpus cavernosum relaxation.

6-Nitrodopamine (6-ND) is a novel endogenous catecholamine that has a potent relaxant action on vascular smooth muscle in vitro. To evaluate the basal release of 6-ND and noradrenaline from rabbit-isolated corpus cavernosum (RbCC) and its relaxing action on this tissue. Rabbit corpus cavernosa were dissected and suspended in a 5-mL organ bath containing oxygenated Krebs-Henseleit's solution. 6-ND and noradrenaline release was quantified by liquid chromatography coupled to tandem mass spectrometry. The relaxant activity of 6-ND was assessed in RbCC strips pre-contracted with endothelin-1 (10nM). Rabbit corpus cavernosum presented basal release of both 6-ND (2.9±0.8ng/mL, n=12) and noradrenaline (1.7±1.3ng/mL, n=12). The 6-ND release was reduced by pre-treatment with Nω-nitro-l-arginine methyl ester (l-NAME) (100 µM), whereas that of noradrenaline was unaffected. Tetrodotoxin (TTX, 1 µM) abolished the noradrenaline release but had no effect on 6-ND release, indicating a non-neurogenic origin for 6-ND. 6-ND and the selective dopamine D2-agonist L-741,626 caused concentration-dependent RbCC relaxations (pEC50 of 11±0.15 and 11.15±0.28, respectively). Pre-treatment with either l-NAME or the soluble guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-on (ODQ) (100 µM) caused a rightward shift of the concentration-response curve to 6-ND, without affecting the L-741,626 responses. In TTX (100nM)-pre-treated preparations, neither l-NAME nor ODQ shifted the 6-ND concentration-response curve. Dopamine, noradrenaline, and adrenaline caused concentration-dependent RbCC contractions. Pre-incubation with 6-ND concentration-dependently inhibited the dopamine-induced contractions, without affecting those induced by either noradrenaline or adrenaline. 6-Nitrodopamine is the most potent endogenous relaxant agent in RbCC ever described and represents a novel mechanism by which NO causes corpus cavernosum smooth muscle relaxation. The finding that 6-ND acts as a truly selective dopamine D2-receptor antagonist indicates that the balance of dopamine and 6-ND release/synthesis may be the main mechanism that modulates corpus cavernosum smooth muscle tonus in vivo.

Treatment Options for Erectile Dysfunction in Diabetics

Erectile dysfunction (ED) is defined as the persistent inability to achieve or maintain a penile erection suitable for sexual intercourse. This condition is common with diabetic males. This article comprehensively reviews various treatment options for Erectile Dysfunction (ED) in diabetic men, with a specific focus on the potential of Low-Intensity Extracorporeal Shockwave Therapy (LI-ESWT). Persistent hyperglycemia may decrease nitric oxide (NO) generation, the cycloguanosine monophosphate (cGMP) pathway, reactive free radical levels, the RhoA/Rho kinase pathway, and nerve function, all of which may be contributing factors to ED in diabetic patients. Elevated AGE expression in diabetes individuals' corpus cavernosum may result in structural alterations to the tissue, including thicker arterial walls, decreased flexibility, endothelial dysfunction, and atherosclerosis. Chronic hyperglycemia can produce nerve injury that affects both autonomic and other sensory patterns. The following are existing treatment options for ED; oral phosphodiesterase type 5 (PDE5) inhibitor, intracavernosal injection therapy, Intraurethral PGE1 suppository (IUS), Vacuum Erection Device (VED) and penile prosthesis or penile implant. Low-Intensity Extracorporeal Shockwave therapy (LI-ESWT), the treatment options for ED is a non-invasive procedure that focuses on address the root causes of ED. The mechanism underlying the efficacy of shock wave treatment is vasodilation and angiogenesis leading to improved blood flow to the penis by upregulating vascular endothelial growth factor (VEGF), nitric oxide synthase (NOS) and proliferating cell nuclear antigen. The review unveiled the success potential of (LI-ESWT) in treating diabetic impotence.

Dual Strategy with Adipose-Derived Stem Cells and l-arginine Recovered Cavernosal Functions in a Rat Model of Radical Prostatectomy.

As standard therapy for prostate cancer, radical prostatectomy causes cavernous nerve (CN) injury and increases fibrosis and hypoxia-induced penile structural alterations. This study aimed to determine the potential beneficial effects of adipose-derived stem cells (ADSCs) and l-arginine alone or in combination on the penile erection in a rat model of erectile dysfunction caused by bilateral cavernous nerve transection (CNT). Male rats (n = 35) were randomized into five groups: Sham-operated; CNT (4-weeks); CNT plus ADSCs (1 × 106 cells by intracavernosal injection); CNT plus l-arginine (4 weeks, 10 mg/kg/day, oral); and ADSCs combined with l-arginine in CNT. In vivo erectile responses and in vitro relaxant responses were measured. Western blot and immunohistochemistry analyses were used to determine the expression and localization of endothelial nitric oxide synthase, neuronal nitric oxide synthase, transforming growth factor-beta 1, hypoxia-inducible factor-1 alpha (HIF-1α), and apoptosis markers (Bax and Bcl-2). The ratio of smooth muscle to collagen and nerve regeneration were calculated using Masson's trichrome and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining. The combined treatment restored diminished erectile responses, endothelium-dependent acetylcholine, and electrical field stimulation-induced relaxation of the corpus cavernosum in rats with CNT, whereas either monotherapy produced only partial improvements. All treatment regimens restored increases in the protein expression of HIF-1 and Bax in rats with CNT. The decrease in smooth muscle mass and NADPH-diaphorase-positive nerve fibers was partially ameliorated by monotherapy, whereas combined therapy led to recovery. These findings indicate that combined treatment with ADSCs and l-arginine may restore erectile function in rats with CNT by inhibiting hypoxia-induced neurotoxicity and preserving endothelium function and smooth muscle content.

Effect of prepubertal caffeine consumption and recovery on adult erectile tissue functions in Wistar rats

The study examines the impact of caffeine consumption during prepubertal development and recovery on the contractile function of the adult corpus cavernosum in Wistar rats. Prepubertal male rats consumed distilled water (vehicle) and caffeine (5 mg/kg). A third group consumed caffeine and was allowed a period of recovery. Cavernosa tissues were excised at adulthood, and their contractile functions in the presence of Ca2+, K+, indomethacin, glibenclamide, methyl blue, L-NAME, and sodium nitroprusside were assessed. K+-induced increase in contraction in the caffeine-treated group was similar to that in the recovery group. Ca2+ ions, however, increased contraction significantly in the caffeine group compared to the recovery group. Acetylcholine-mediated relaxation (%) was significantly higher in the recovery compared to the caffeine treated after incubation with indomethacin and methyl blue. Acetylcholine-mediated relaxation, however, was higher in caffeine as compared to the recovery group after incubation with glibenclamide and L-NAME. Relaxation in the presence of sodium nitroprusside was significantly reduced in recovery than in the caffeine-treated group. Prepubertal caffeine intake had an erectogenic effect on the cavernous tissues in the presence of glibenclamide, nifedipine, and L-NAME. Inhibitors of prostacyclin (indomethacin) and cGMP (methyl blue) militate caffeine-induced relaxation. Effects were reversed after recovery.

Biodegradable nano black phosphorus based SDF1-α delivery system ameliorates Erectile Dysfunction in a cavernous nerve injury rat model by recruiting endogenous stem/progenitor cells

Stem cell (SC) therapy has been shown high prospects in erectile dysfunction (ED) treatment. Without ethical issues and risks of immune rejection and tumorigenesis of exogenous SC therapy, endogenous stem/progenitor cells (S/PCs) have a better potential for ED management, and their homing and redistribution are controlled by SDF1-α/CXCR4 axis. Considering black phosphorus nanosheet (BPNS) has emerged as an efficient and safe drug vehicle due to its large surface area, biodegradability, and the ability to retain and slowly release its loaded drugs, BPNS is utilized to load SDF1-α, a chemokine for S/PCs, to construct the BP@SDF1-α complex to efficiently recruit stem cells (SCs) by injury-site injection and thus ameliorate ED within the bilateral cavernous nerve injury (BCNI) rat models. We find that BP@SDF1-α can efficiently recruit exogenous SCs and endogenous S/PCs to corpus cavernosum and main pelvic ganglion (MPG) by local administration. Of note, ascribing to endogenous S/PCs recruitment, it also successfully alleviates ED in BCNI rat models by enhancing the protein expression levels of α-SMA, CD31, and nNOs, and eliciting less collagen deposition in the penis after its combined injection at corpus cavernosum and MPG. Thus, this study provides a new insight into the treatment of ED with endogenous S/PCs.Biodegradable Nano Black Phosphorus based SDF1-α delivery system ameliorates Erectile Dysfunction in a cavernous nerve Injury Rat Model by recruiting endogenous Stem/Progenitor cells

Differential Myosin 5a splice variants in innervation of pelvic organs.

Introduction: Myosin proteins interact with filamentous actin and translate the chemical energy generated by ATP hydrolysis into a wide variety of mechanical functions in all cell types. The classic function of conventional myosins is mediation of muscle contraction, but myosins also participate in processes as diverse as exocytosis/endocytosis, membrane remodeling, and cytokinesis. Myosin 5a (Myo5a) is an unconventional motor protein well-suited to the processive transport of diverse molecular cargo within cells and interactions with multiprotein membrane complexes that facilitate exocytosis. Myo5a includes a region consisting of six small alternative exons which can undergo differential splicing. Neurons and skin melanocytes express characteristic splice variants of Myo5a, which are specialized for transport processes unique to those cell types. But less is known about the expression of Myo5a splice variants in other tissues, their cargos and interactive partners, and their regulation. Methods: In visceral organs, neurotransmission-induced contraction or relaxation of smooth muscle is mediated by Myo5a. Axons within urogenital organs and distal colon of rodents arise from cell bodies located in the major pelvic ganglion (MPG). However, in contrast to urogenital organs, the distal colon also contains soma of the enteric nervous system. Therefore, the rodent pelvic organs provide an opportunity to compare the expression of Myo5a splice variants, not only in different tissues innervated by the pelvic nerves, but also in different subcellular compartments of those nerves. This study examines the expression and distribution of Myo5a splice variants in the MPG, compared to the bladder, corpus cavernosum of the penis (CCP) and distal colon using immunohistochemistry and mRNA analyses. Results/discussion: We report detection of characteristic Myo5a variants in these tissues, with bladder and CCP displaying a similar variant pattern but one which differed from that of distal colon. In all three organs, Myo5a variants were distinct compared to the MPG, implying segregation of one variant within nerve soma and its exclusion from axons. The expression of distinct Myo5a variant arrays is likely to be adaptive, and to underlie specific functions fulfilled by Myo5a in those particular locations.

Penile cavernous sinusoids are Prox1-positive hybrid vessels.

Endothelial cells (ECs) of blood and lymphatic vessels have distinct identity markers that define their specialized functions. Recently, hybrid vasculatures with both blood and lymphatic vessel-specific features have been discovered in multiple tissues. Here, we identify the penile cavernous sinusoidal vessels (pc-Ss) as a new hybrid vascular bed expressing key lymphatic EC identity genes Prox1, Vegfr3,and Lyve1. Using single-cell transcriptome data of human corpus cavernosum tissue, we found heterogeneity within pc-S endothelia and observed distinct transcriptional alterations related to inflammatory processes in hybrid ECs in erectile dysfunction associated with diabetes. Molecular, ultrastructural, and functional studies further established hybrid identity of pc-Ss in mouse, and revealed their morphological adaptations and ability to perform lymphatic-like function in draining high-molecular-weight tracers. Interestingly, we found that inhibition of the key lymphangiogenic growth factor VEGF-C did not block the development of pc-Ss in mice, distinguishing them from other lymphatic and hybrid vessels analyzed so far. Our findings provide a detailed molecular characterization of hybrid pc-Ss and pave the way for the identification of molecular targets for therapies in conditions of dysregulated penile vasculature, including erectile dysfunction.

Exploring potential genes and mechanisms linking erectile dysfunction and depression.

The clinical correlation between erectile dysfunction (ED) and depression has been revealed in cumulative studies. However, the evidence of shared mechanisms between them was insufficient. This study aimed to explore common transcriptomic alterations associated with ED and depression. The gene sets associated with ED and depression were collected from the Gene Expression Omnibus (GEO) database. Comparative analysis was conducted to obtain common genes. Using R software and other appropriate tools, we conducted a range of analyses, including function enrichment, interactive network creation, gene cluster analysis, and transcriptional and post-transcriptional signature profiling. Candidate hub crosslinks between ED and depression were selected after external validation and molecular experiments. Furthermore, subpopulation location and disease association of hub genes were explored. A total of 85 common genes were identified between ED and depression. These genes strongly correlate with cell adhesion, redox homeostasis, reactive oxygen species metabolic process, and neuronal cell body. An interactive network consisting of 80 proteins and 216 interactions was thereby developed. Analysis of the proteomic signature of common genes highlighted eight major shared genes: CLDN5, COL7A1, LDHA, MAP2K2, RETSAT, SEMA3A, TAGLN, and TBC1D1. These genes were involved in blood vessel morphogenesis and muscle cell activity. A subsequent transcription factor (TF)-miRNA network showed 47 TFs and 88 miRNAs relevant to shared genes. Finally, CLDN5 and TBC1D1 were well-validated and identified as the hub crosslinks between ED and depression. These genes had specific subpopulation locations in the corpus cavernosum and brain tissue, respectively. Our study is the first to investigate common transcriptomic alterations and the shared biological roles of ED and depression. The findings of this study provide insights into the referential molecular mechanisms underlying the co-existence between depression and ED.

Circadian disturbance induces erectile dysfunction by impairing endothelial function.

In order to explore the impact of circadian disturbance on erectile function, we randomly divided 24 adult male rats into groups of control (light on at 8:00 a.m. and off at 8:00 p.m.), dark/dark (DD; constant dark), light/light (LL; constant light), and shift dark/light (DL; light off at 8:00 a.m. and on at 8:00 p.m.). Four weeks later, erectile function was measured and corpora cavernosa were harvested for analysis. The maximum intracavernous pressure (mICP) and mICP/mean arterial pressure (MAP) ratio in the DD, LL, and DL groups were significantly lower than that in the control group. The LL and DL groups showed significantly attenuated endothelial nitric oxide synthase (eNOS), while DD, LL, and DL showed reduced neuronal nitric oxide synthase (nNOS) at both mRNA and protein levels. The production of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) was inhibited by altered light/dark cycles to varying degrees. Circadian disturbance impaired endothelial function and contributed to erectile dysfunction. For the core circadian elements, mRNA expression of circadian locomotor output cycles kaput ( Clock ) and brain/muscle aryl-hydrocarbon receptor nuclear translocator-like protein 1 ( Bmal1 ) was elevated in the DL group, but their protein expression was not significantly changed. DD, LL, and DL increased period 1 ( Per1 ) and Per3 levels, while LL and DL increased PER1 levels. No significant difference was found for Per2 levels, and PER2 and PER3 concentrations were not significantly changed. Moreover, LL and DL significantly increased cryptochrome-1 (CRY1) and CRY2 at both mRNA and protein levels. The altered light/dark rat model showed that circadian disturbance contributed to erectile dysfunction probably by impairing endothelial function. Meanwhile, the core circadian elements were detected in the corpora cavernosa, but these were disrupted. However, which circadian element regulates erectile function and how it works need further analysis.

Penile fracture: a case series of 18 patients

Introduction: Penile fractures are a rare urological emergency. It is defined as ‘rupture of the tunica albuginea of one or both corpora cavernosa. The corpus spongiosum and the urethra may also be involved in this process.’ The tunica albuginea is stiff and significantly thinner during erection than in the flaccid state, which is when injury generally happens. Method: This case series was completed between January 2018 and January 2023 at the Department of General Surgery. Eighteen patients suspected of having penile fractures participated in were included this study. All patients were thoroughly evaluated upon hospital admission to identify the diagnosis, length of time since the accident, the site of the fracture, the extent of the penile hematoma, occurrence of blood at the external meatus, presence of urine retention, and intraoperative outcomes. Results: The patients were between the ages of 24 and 70, with a mean age of 37. The duration before the presentation ranged from 7 h to 1 month (the median was 22 h). Sexual intercourse was the cause in 12 (66%) cases, rolling in the bed in three cases (16%), and blunt trauma in three cases (kicking and the edge of the bed) (16%). Pain and swelling were present in all of the patients. In 15 patients (or 83%), there was evidence of penile deviation. At presentation, 15 (72%) patients reported experiencing rapid detumescence, discomfort, and penile swelling after hearing a cracking (popping) sound. None of these individuals experienced urine retention or urethral hemorrhage, and all were emptied on their own following the episode. Physical examination showed penile ecchymosis, swelling, and substantial discomfort when the penile shaft was examined. All but three patients had an evident penile deformity. Surgery was performed under spinal anesthesia in 14 (77.7%) patients. Four patients with a delayed presentation (more than 1 week) were managed conservatively. Conclusion: As a true urologic emergency, penile fractures should be treated immediately to reduce pain and swelling and ensure better functional and esthetic outcomes. Despite taking more time, a subcoronal circumcising degloving incision is the ideal method because it is exploratory and esthetically pleasing.