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1.
Neurourol Urodyn ; 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38634519

ABSTRACT

BACKGROUND: The relationship between waist circumference and nocturia has not been previously studied. This study investigated the association between waist circumference and the occurrence of nocturia in adults. METHODS: We analyzed data from the National Health and Nutrition Examination Survey covering 2005-2020, encompassing 6287 adults aged ≥20. Nocturia was defined as the need to urinate two or more times during the night. First, we compared baseline characteristics between the nocturia and non-nocturia groups. Subsequently, we used multivariate logistic regression analysis to investigate the relationship between waist circumference and nocturia prevalence. We also employed restricted cubic spline analysis to study the potential nonlinear correlation between waist circumference and the prevalence of nocturia. Recognizing the baseline data's heterogeneity based on nocturia prevalence, we conducted subgroup analyses according to age, sex, body mass index (BMI), and ethnicity. RESULTS: Our findings indicated that females, individuals aged ≥50, citizens, Non-Hispanic Black, those with lower education levels (high school or less), higher BMIs, lower family income-to-poverty ratios, higher waist circumference, hypertension, and diabetes were more likely to experience nocturia. Compared with individuals in the lowest waist circumference quartile (Q1), those in the higher quartiles (Q4) exhibited an increased risk of nocturia in Model 1 (Q4, OR:2.00, 95% CI:1.64, 2.45, p < 0.0001). These results remained consistent after adjusting for covariates in models 2 and 3. A restricted cubic spline analysis suggested a linear association between waist circumference and nocturia (P for nonlinearity = 0.066). Subgroup analyses based on age, sex, BMI, and ethnicity revealed no significant differences in the interaction tests between waist circumference and nocturia (P for interaction = 0.437, 0.331, 0.121, and 0.889, respectively), indicating that these baseline characteristics did not influence the association. CONCLUSIONS: Our findings indicated an association between increased waist circumference and a higher prevalence of nocturia. Knowledge of this association reinforces the importance of lifestyle modifications in maintaining a healthy waist circumference and informs public health strategies to address other potential risk factors for nocturia.

2.
Front Pharmacol ; 15: 1376535, 2024.
Article in English | MEDLINE | ID: mdl-38562462

ABSTRACT

Background: Mirabegron, the first ß-3 adrenergic receptor agonist, received approval from the Food and Drug Administration (FDA) in 2012 for the treatment of overactive bladder (OAB). This pharmacovigilance study investigated the safety profile of mirabegron treatment using the US FDA Adverse Event Reporting System (FAERS) database. Methods: This study employed disproportionality analyses, including the reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) algorithm, to quantify signals of adverse events associated with mirabegron. Results: From the first quarter of 2012 to the third quarter of 2023, a comprehensive total of 14,356,234 adverse event (AE) reports were submitted to the FDA Adverse Event Reporting System database. Within this dataset, encompassing 18,763 reports specifically associated with mirabegron, healthcare professionals notably contributed 2,902 of these reports. A total of 80 preferred terms (PTs) of interest were identified using both the ROR and information component algorithms. The most common AEs included blood pressure increased, urinary retention, atrial fibrillation, dry mouth, and tachycardia, which were consistent with the product instructions. Unexpected significant AEs, such as arrhythmia, palpitations, dementia, transient ischemic attack, Parkinson's disease, anti-neutrophil cytoplasmic antibody positive vasculitis, lip swelling, and swollen tongue, were also identified. The study findings indicated that the majority of onset time occurred within 30 days (n = 358, 55.68%). However, AEs were still possible after 1 year of mirabegron treatment. Conclusion: This study provided valuable evidence for the real-world safety of mirabegron, helping clinical professionals enhance their understanding of mirabegron's safety in clinical practice. It also contributed valuable evidence for further safety studies on mirabegron.

3.
Neurourol Urodyn ; 43(3): 628-637, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38379416

ABSTRACT

AIMS: This study aimed to examine the correlation between television (TV) and/or video viewing time and the occurrence of nocturia in adults. METHODS: An analysis of data from the National Health and Nutrition Examination Survey for 2011-2016 was conducted, involving 13 294 adults aged 20 and older. The main outcome was specified as nocturia, which refers to the requirement of urinating two or more times during the night. Initially, baseline characteristics were contrasted between individuals with and without nocturia. The effects of TV and/or video viewing time on nocturia were further explored using multivariable logistic regression models. To acknowledge the variation in baseline data regarding the prevalence of nocturia, subgroup analyses were performed. RESULTS: Adjusted multivariate analysis revealed that individuals in the group with the longest TV and/or video viewing time had a significantly 48% higher risk of experiencing nocturia compared to those with the shortest TV and/or video viewing time. The results of subgroup analyses revealed no significant differences in the interaction tests between TV and/or video viewing time and nocturia. CONCLUSIONS: Our research showed that individuals who spent 5 or more hours a day watching TV and/or videos were significantly more likely to develop nocturia.


Subject(s)
Nocturia , Adult , Humans , Nutrition Surveys , Nocturia/epidemiology , Television , Time Factors
4.
Andrology ; 11(7): 1368-1376, 2023 10.
Article in English | MEDLINE | ID: mdl-36891666

ABSTRACT

BACKGROUND: The association between cardiovascular diseases (CVD), including ischemic stroke (IS), heart failure (HF), myocardial infarction (MI), and coronary heart disease (CHD), and erectile dysfunction (ED) remains unclear from observational studies. OBJECTIVES: We explored the potential bidirectional association between CVD and ED by Mendelian randomization (MR). METHODS: Data from genome-wide association studies for CVD in individuals with European ancestry were obtained from several databases, with 1,711,875-977,323 participants, while that for ED included 223,805 participants. We conducted univariate MR (UVMR), inverse variance-weighting (IVW), weighted median, MR-Egger, and multivariate MR (MVMR) analyses to explore the bidirectional causal effects between CVD and ED. RESULTS: UVMR indicated that IS (odds ratios [OR] = 1.34, 95% confidence interval [CI]: 1.08-1.21, P = 0.007), HF (OR = 1.36, 95% CI 1.07-1.74, P = 0.013), and CHD (OR = 1.15, 95% CI 1.09-1.18, P = 0.022) were associated with ED. By MVMR, IS estimates remained significant after accounting for combining single nucleotide polymorphisms from CVDs (OR = 1.42, 95%CI: 1.13-1.79, P = 0.002). Moreover, the effect of a genetic susceptibility to IS on ED was not mediated by type 2 diabetes or triglycerides; that of HF was not mediated by type 2 diabetes, and that of CHD was not mediated by body mass index. Bidirectional analyses showed that genetic susceptibility to ED did not confer any increased CVD risk. CONCLUSIONS: Our results, based on MR, indicated that genetic susceptibility to IS, HF, and CHD was causally associated with ED. These findings can inform prevention and intervention strategies for ED in IS, HF, and CHD patients.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Erectile Dysfunction , Male , Humans , Cardiovascular Diseases/complications , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/genetics , Mendelian Randomization Analysis , Erectile Dysfunction/complications , Erectile Dysfunction/epidemiology , Erectile Dysfunction/genetics , Genetic Predisposition to Disease , Genome-Wide Association Study
5.
Chin J Integr Med ; 29(9): 791-800, 2023 Sep.
Article in English | MEDLINE | ID: mdl-35679003

ABSTRACT

OBJECTIVE: To verify the effect of Buyang Huanwu Decoction (BHD) in ameliorating erectile dysfunction (ED) after radical prostatectomy (RP). METHODS: The composition of BHD was verified by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) analysis. Bilateral cavernous nerve crush injury (BCNI) in rats was used to mimic the neurovascular injury occurring after RP. By the envelope method, forty rats were randomly divided into 4 groups as follows: sham (cavernous nerves exposed only), model (BCNI), low-dosage BHD [LBHD, 12.8 g/(kg·d)], and high-dosage BHD [HBHD, 51.2 g/(kg·d)] groups, 10 rats in each group, feeding for 3 weeks respectively. Erectile function was evaluated by measuring intracavernosal pressure (ICP). Changes in the histopathology of corpus cavernosum (CC) were examined by hematoxylin-eosin staining. Meanwhile, the fibrosis of CC was measured by Masson's trichrome staining and Western blot was used to detect the expressions of collagen I, transforming growth factor beta 1 (TGF- ß 1) and α-smooth muscle actin (α-SMA). Apoptosis index was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) and Western blot for determining the expressions of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax). The oxidative stress in the CC were assessed by the superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species (ROS) levels. The proteins expression of c-Jun N-terminal kinase (JNK) and c-Jun were detected by Western blot. In addition, the expression of α-SMA and p-c-Jun in the CC was observed by double immunofluorescence staining. RESULTS: The UPLC-QTOF-MS/MS analysis showed that BHD contained calycosin-7-O- ß -D-glucoside, ononin, calycosin and formononetin. Compared with the model group, LBHD and HBHD treatment improved the ICP and the circumference, area, and weight of CC (P<0.05 or P<0.01). Furthermore, LBHD and HBHD treatments increased CC smooth muscle content and decreased apoptosis index (P<0.05 or P<0.01). LBHD and HBHD also elevated SOD and expression level of α -SMA and Bcl-2, and reduced MDA and ROS levels, as well as expression of TGF- ß 1, collagen I, Bax, p-c-JNK, p-JNK in the CC compared with the model group (P<0.05 or P<0.01). The double immunofluorescence staining showed that the fluorescence degree of p-c-Jun in both LBHD and HBHD treatment groups was significantly reduced, whereas the α -SMA expression increased (P<0.05 or P<0.01). CONCLUSIONS: BHD can improve ED of rats with BCNI, which is related to inhibiting fibrosis, apoptosis, and oxidative stress of CC. The ROS/JNK/c-Jun signaling pathway may play an important role in the process.


Subject(s)
Erectile Dysfunction , Tandem Mass Spectrometry , Male , Humans , Rats , Animals , Reactive Oxygen Species , bcl-2-Associated X Protein , Rats, Sprague-Dawley , Erectile Dysfunction/drug therapy , Collagen , Fibrosis , Disease Models, Animal
6.
Andrologia ; 54(1): e14264, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34608665

ABSTRACT

Intracavernosal pressure measurement is the gold standard for evaluating erectile function in experimental animals, but it has the shortcoming of being invasive. This study aimed to explore the application of laser speckle perfusion imaging in evaluating erectile function in rats. Sixty Sprague Dawley rats were randomly divided into the sham operation and model groups (n = 30 each). A rat model of neuroinjury erectile dysfunction was established by surgically damaging the bilateral cavernous nerves in the model group. Simulated surgery was performed in the sham operation group; the nerves were not damaged. Erectile function was evaluated by comparing the changes in intracavernosal pressure and blood flow fluctuations when the cavernous nerve was stimulated using the same voltage parameters. Intracavernosal pressure in the model group was significantly lower than that in the other group when using 2.5 V. No significant difference was found in cavernous blood flow fluctuation between the two groups when using 0.5 V. Cavernous blood flow fluctuation in the model group after 2.5 V, 5 V and 7.5 V stimulations was significantly lower than that in the sham operation group. Evaluating erectile function in rats is feasible by measuring the cavernous blood flow using laser speckle perfusion imaging.


Subject(s)
Erectile Dysfunction , Animals , Disease Models, Animal , Humans , Lasers , Male , Penile Erection , Penis/diagnostic imaging , Perfusion Imaging , Rats , Rats, Sprague-Dawley
8.
Article in English | MEDLINE | ID: mdl-34457027

ABSTRACT

BACKGROUND: Polycystic ovary syndrome (PCOS) causes low fertility in females. Coptis chinensis (C. chinensis) is used to clear heat and dampness, purify fire, and detoxify in traditional Chinese medicine (TCM). Although C. chinensis has demonstrated efficacy against PCOS in clinical practice, there are no available data regarding the bioactive components of C. chinensis, their targets, and molecular mechanisms underlying their effects. METHODS AND RESULTS: Network pharmacology was used to analyze the bioactive components of C. chinensis, their targets, and signaling pathways underlying their effects. The TCM systems pharmacology database and analysis platform (TCMSP) was used to screen 14 effective active ingredients and 218 targets of C. chinensis. The GeneCards, OMIM, and PharmGkb databases were used to screen 3517 disease targets for PCOS, and 102 common targets of drugs and diseases were screened using R Cytoscape that was utilized to build a drug-active ingredient-disease target interaction network, and the STRING platform was utilized to construct a common target protein-protein interaction network, including 102 nodes and 221 edges. Key targets of C. chinensis for the treatment of PCOS included JUN, MAPK, IL6, CXCL8, FOS, and IL1B. A total of 123 gene ontology (GO) terms and 129 pathways were acquired by GO and KEGG enrichment analyses. The AGEs/RAGE, TNF, IL-17, MAPK, and HIF-1 signaling pathways were closely related to PCOS and may be the core pathways involved in PCOS. Schrodinger software was used to evaluate the interaction between active components and their targets and explore binding modes. Furthermore, based on the prediction of network pharmacology study, a mouse model of PCOS was established to evaluate the curative role and underlying mechanisms of C. chinensis. The results showed that C. chinensis treatment reversed histopathological damage of the ovary and also ameliorated the mRNA and protein expression levels of the predicted hub targets (MAPK1, CXCL8, IL-6, and IL-1ß). These results indicated that WZYZP has a protective effect on spermatogenesis disorder, suggesting that it could be an alternative choice for male infertility therapy. CONCLUSIONS: This preliminary study verified the basic pharmacological effects and mechanisms of C. chinensis, a TCM, in the treatment of PCOS. These results indicate that the therapeutic effects of C. chinensis on PCOS may be achieved by regulating the expression of inflammatory factors. This study provides new insights for the systematic exploration of the mechanism of traditional Chinese medicine.

9.
Andrologia ; 53(6): e14044, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33709426

ABSTRACT

We explored the efficacy and mechanisms of salidroside treatment for erectile dysfunction induced by bilateral cavernous nerve injury (BCNI). Forty male rats were divided into four groups as follows: sham (cavernous nerves exposed only) (S); BCNI (M); BCNI + rapamycin (M + rapamycin); and BCNI + salidroside (M + salidroside). Erectile function in the rats was measured by intracavernosal pressure. Penile tissue was harvested for transmission electron microscopy, immunohistochemistry, immunofluorescence, Masson's trichrome staining, haematoxylin-eosin staining, TdT-mediated dUTP Nick End Labeling and western blotting. The M group exhibited a decrease in erectile responses and increased apoptosis and fibrosis compared to these in the S group. Meanwhile, nerve content and the penile atrophy index were also decreased in the M group. Treatment with salidroside and rapamycin for 3 weeks partially restored erectile function and significantly attenuated corporal apoptosis, fibrosis, nerve content and penile atrophy in the M group. Moreover, the autophagy level was further enhanced in the M + salidroside group, which was the same as that in the positive observation group (M + rapamycin). Salidroside treatment not only improved erectile function in rats with BCNI, but also inhibited apoptosis and fibrosis and ameliorated the loss of nerve content and endothelial and corpus cavernosum smooth muscle cells by promoting protective autophagy.


Subject(s)
Erectile Dysfunction , Animals , Autophagy , Disease Models, Animal , Erectile Dysfunction/drug therapy , Glucosides , Humans , Male , Penile Erection , Penis , Phenols , Rats , Rats, Sprague-Dawley
10.
Biomed Pharmacother ; 130: 110405, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32679461

ABSTRACT

Neurogenic erectile dysfunction (NED) is an inevitable postoperative disease of cavernous nerve injury which will lead to various pathophysiological changes in the corpus cavernosum and dorsal penile nerve caused by radical prostatectomy (RP). Although serval years of clinical application of HJIG I granules (HJIG), an innovative formulation, has demonstrated its reliable clinical efficacy against NED, the mechanism of HJIG remains unclear. This study aimed to assess the neuroprotective effect of HJIG, to repair damaged nerves in a rat model of bilateral cavernous nerve injury (BCNI) in vivo and their effects on neurites of major pelvic ganglia (MPG) regeneration and Schwann cells (SCs) proliferation in vitro. Rats were divided into five groups randomly: normal control (NC), BCNI-induced ED model (M), M + low-dose HJIG (HL), M + medium-dose HJIG (HM), and M + high-dose HJIG (HH). All groups were treated with normal saline or the relevant drug for 28 consecutive days after a standard NED animal model. Our data revealed that administration of HJIG improved NED that was detected by intracavernous pressure (ICP) in a dose-dependent manner. The haematoxylin-eosin (HE) and Immunofluorescence (IF) staining demonstrated that HJIG ameliorate the shape of penis and induced the protein synthesis of GAP43, NF200, S100, and nNOS. NF200 and S100 level were also detected by western blotting. Moreover, HJIG (0.78 mg/mL) markedly increased SCs viability and promoted neurites regeneration of MPG. These findings provide new insights into the NED therapy by HJIG.


Subject(s)
Drugs, Chinese Herbal/administration & dosage , Erectile Dysfunction/drug therapy , Neuroprotective Agents/administration & dosage , Peripheral Nerve Injuries/drug therapy , Animals , Cells, Cultured/drug effects , Disease Models, Animal , Erectile Dysfunction/complications , Male , Neurites/drug effects , Penis/drug effects , Peripheral Nerve Injuries/complications , Rats, Sprague-Dawley
11.
Urol Int ; 104(7-8): 594-603, 2020.
Article in English | MEDLINE | ID: mdl-32615556

ABSTRACT

INTRODUCTION: Connexin 43 (Cx43) is the major component of gap junction in corpus cavernosum smooth muscle, which allows rapid intercellular communication. Cx43 coordinates corpus cavernosum smooth muscle cells and ensures erectile function. The role of hypoxia in Cx43 dysfunction resulting in erectile dysfunction has not been well studied, and salidroside has shown cell protective effects under hypoxia. OBJECTIVE: We aimed to investigate the protective role of salidroside and the underlying mechanisms in hypoxia-induced dysfunction of Cx43. METHODS: Corpus cavernosum smooth muscle cells prepared from young male Sprague-Dawley rats were pretreated with or without salidroside and exposed to hypoxic condition for 48 h. The cell viability, expression of hypoxia-inducible factor-1α (HIF-1α) and Cx43, and Ca2+ signals were investigated. RESULTS: Pretreatment with salidroside attenuated loss of hypoxia-induced cell viability markedly and could downregulate the HIF-1α protein expression under hypoxia. Moreover, the expression of Cx43 was significantly increased by hypoxia but was decreased with salidroside pretreatment. The salidroside pretreated group exhibited enhanced release of intracellular Ca2+ in corpus cavernosum smooth muscle cells compared with the hypoxia group after stimulation. CONCLUSION: Salidroside has a protective effect against hypoxia-induced damage to corpus cavernosum smooth muscle cells.


Subject(s)
Cell Hypoxia , Connexin 43/biosynthesis , Connexin 43/drug effects , Glucosides/pharmacology , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/metabolism , Penis/cytology , Phenols/pharmacology , Animals , Male , Rats , Rats, Sprague-Dawley
12.
Article in English | MEDLINE | ID: mdl-31636680

ABSTRACT

HongJing I (HJI), a traditional Chinese herbal formula, has been confirmed to be effective for the clinical treatment of erectile dysfunction (ED). However, the mechanism of action of HJI remains unclear. Here, we aimed to investigate the effect and underlying mechanisms of HJI against ED in a rat model of bilateral cavernous nerve injury (BCNI). Rats were divided into five groups: normal control (NC), BCNI-induced ED model (M), M + low-dose HJI (HL), M + medium-dose HJI (HM), and M + high-dose HJI (HH). All groups were treated with normal saline or the relevant drug for 28 consecutive days after inducing BCNI-ED. At the end of the treatment period, the intracavernous pressure (ICP) was recorded, and histological examination was conducted using Masson's trichrome staining. Immunofluorescence staining and western blotting were applied to detect the changes in fibrosis protein and Ras homolog A (RhoA), Rho-associated protein kinase 1 (ROCK1), and ROCK2 expression. We found that HJI effectively improved the ICP in the treatment groups. In addition, RhoA, ROCK1, and ROCK2 expression levels were increased upon BCNI-ED induction, and HJI successfully inhibited cavernosum fibrosis and the activation of RhoA/ROCK2 signaling. Overall, these results suggest that the effects of HJI in attenuating ED may be caused, at least in part, by the suppression of RhoA/ROCK2 signaling and alleviation of fibrosis. However, the precise mechanism surrounding this requires further investigation in future studies.

13.
Sex Med ; 7(4): 433-440, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31540881

ABSTRACT

INTRODUCTION: Cavernosal nerve (CN) injury is commonly caused by radical prostatectomy surgery, and it might directly lead to erectile dysfunction (ED). Currently, the role of mitogen-activated protein kinase (MAPK) family proteins in phenotypic transformation of corpus cavernosum smooth muscle cell (CCSMC) after CNs injury is poorly understood. AIM: To investigate the role of p38 MAPK in hypoxia-induced phenotypic transformation of CCSMCs after CN injury. METHODS: In total, 20 Sprague-Dawley rats (male and 8 weeks of age) were randomly divided into 2 groups, including a sham group and CNCI group. In the sham group, rats were sham-operated by identifying 2 CNs without causing direct damage to the CNs. In the CNCI group, rats were subjected to bilateral CN crush injury. CCSMCs were isolated from the normal corpus cavernosum tissues of the Sprague-Dawley rat and then cultured in 21% or 1% O2 concentration context for 48 hours. MAIN OUTCOME MEASURES: Intracavernous pressure/mean arterial pressure were analyzed to measure erectile response. The impact of hypoxia on penile pathology, as well as the expression of extracellular signal-regulated kinases, the c-Jun NH2-terminal kinase, and p38 MAPK, were analyzed. RESULTS: Compared with the sham group, the intracavernous pressure/mean arterial pressure rate and α-smooth muscle actin expression of CNCI group were decreased significantly (P = .0001; P = .016, respectively), but vimentin expression was significantly increased (P = .023). Phosphorylated p38 level in CNCI group was decreased significantly (P = .017; sham: 0.17 ± 0.005; CNCI: 0.14 ± 0.02). The CCSMCs in the normoxia group were long fusiform, whereas the morphology of CCSMCs in the hypoxia group became hypertrophic. After hypoxia for 48 hours, the expression of α-smooth muscle actin and phosphorylated p38 MAPK was decreased significantly (P = .01; P = .024, normoxia: 0.66 ± 0.18, hypoxia: 0.26 ± 0.08, respectively), and the expression of hypoxia-inducible factor-1α and collagen I was increased significantly in hypoxia group (P = .04; P = .012, respectively). CONCLUSIONS: Hypoxia induced the phenotypic transformation of CCSMCs after CNCI might be associated with the downregulation of phosphorylated p38 MAPK. Chen S, Huang X, Kong X, et al. Hypoxia-Induced Phenotypic Transformation of Corpus Cavernosum Smooth Muscle Cells After Cavernous Nerve Crush Injury by Down-Regulating p38 Mitogen-Activated Protein Kinase Expression. Sex Med 2019;7:433-440.

14.
Andrologia ; 51(3): e13200, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30467872

ABSTRACT

We explored whether platelet-derived growth factor (PDGF)-BB regulates corpus cavernosum smooth muscle cell gap junctions and can ameliorate erectile dysfunction and how it modulates connexin43 (CX43) after bilateral cavernous neurectomy. Primary cultured rat corpus cavernosum smooth muscle cells were treated with PDGF-BB with or without a PDGFR inhibitor, Akt siRNA or the depletion or promotion of ß-catenin. PDGF-BB improved CCSMCs gap junction coupling and increased CX43 and PDGFRß expression; inhibition of PDGFR activity down-regulated CX43 and decreased Akt and nuclear ß-catenin. Knockdown or promotion of ß-catenin down-regulated and up-regulated CX43 expression respectively. Moreover, ß-catenin activation induced CX43 nuclear accumulation, which impeded CX43 down-regulation induced by PDGFR inhibition, suggesting that CX43 expression is positively correlated with nuclear ß-catenin expression. Furthermore, CX43 promoter luciferase and chromatin immunoprecipitation assays indicated that ß-catenin regulates CX43 transcription by directly interacting with its promoter. Male rats underwent bilateral cavernous neurectomy. After 12 weeks, they were injected with PDGF-BB, CX43 and PDGFRß expression was significantly lower than in the control group, which was reversed by PDGF-BB injection. These results suggested that PDGF-BB contributed to the improvement of gap junction intracellular communication among corpus cavernosum smooth muscle cells, increased CX43 through PDGFRß/Akt/nuclear ß-catenin signalling, and ameliorated cavernous nerve injury-induced erectile dysfunction.


Subject(s)
Becaplermin/pharmacology , Connexin 43/metabolism , Gap Junctions/metabolism , Muscle, Smooth, Vascular/drug effects , Myocytes, Smooth Muscle/drug effects , Penis/blood supply , Animals , Cells, Cultured , Male , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Penis/drug effects , Penis/metabolism , Phosphorylation , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , RNA, Small Interfering , Rats , Signal Transduction/drug effects , beta Catenin/genetics , beta Catenin/metabolism
15.
Zhonghua Nan Ke Xue ; 25(8): 690-695, 2019 Aug.
Article in Chinese | MEDLINE | ID: mdl-32227710

ABSTRACT

OBJECTIVE: To explore the regulatory effect of salidroside on H2O2-induced decrease in the expression of the connexin43 (Cx43) protein in corpus cavernosum smooth muscle cells (CCSMC). METHODS: Rat CCSMCs were isolated, primarily cultured in vitro and identified by immunocytochemical assay. The optimum concentration of H2O2 for intervention was determined by detecting its effect on the viability of the CCSMCs and used in the treatment of the CCSMCs for different lengths of time, and meanwhile salidroside was applied at 16 µg/ml (low dose) or 64 µg/ml (high dose) for intervention. Finally, the expressions of the Cx43 protein in the CCSMCs of different groups of rats were determined by Western blot. RESULTS: The CCSMCs grew normally, with a positive rate of over 90%. At 1, 2 and 4 hours of treatment with H2O2 at the optimum concentration of 200 µmol/L, the expression of Cx43 in the CCSMCs was significantly decreased as compared with that in the blank control group (P < 0.01), even more significantly at 4 hours than at 1 and 2 (P < 0.01). Intervention with high-dose salidroside, however, markedly inhibited the down-regulation of the Cx43 expression (P < 0.05), which showed no statistically significant difference from that in the normal control group (P = 0.322 2). CONCLUSIONS: Salidroside can suppress H2O2-induced decrease in the expression of the Cx43 protein in rat CCSMCs.


Subject(s)
Connexin 43/metabolism , Glucosides/pharmacology , Myocytes, Smooth Muscle/drug effects , Penis/cytology , Phenols/pharmacology , Animals , Cells, Cultured , Down-Regulation , Gene Expression Regulation , Hydrogen Peroxide , Male , Myocytes, Smooth Muscle/metabolism , Rats
16.
Zhonghua Nan Ke Xue ; 25(9): 833-837, 2019 Sep.
Article in Chinese | MEDLINE | ID: mdl-32233212

ABSTRACT

Sonic hedgehog (Shh) is an important regulator of penile erectile function in adult males, and abnormal Shh signals may be involved in the mechanisms of ED. Current studies on the relationship of the Shh signaling pathway with ED are mainly concentrated on neurogenic ED caused by bilateral cavernous nerve injury, diabetes-induced endocrinological ED, and senile ED. This review focuses on the changes of the Shh signaling pathway in different types of ED and clarifies the mechanisms of the Shh signaling pathway regulating ED, hoping to give some inspiration to further related studies.


Subject(s)
Erectile Dysfunction , Hedgehog Proteins/physiology , Penis/physiopathology , Signal Transduction , Humans , Male
17.
Zhonghua Nan Ke Xue ; 24(10): 927-932, 2018 Oct.
Article in Chinese | MEDLINE | ID: mdl-32212450

ABSTRACT

Erectile dysfunction (ED) is closely related with the phenotypic modulation of corporal cavernosum smooth muscle cells (CCSMC), a transitional tendency of CCSMCs switching from the contractile phenotype to the synthetic or proliferative phenotype. The molecular markers of contractile CCSMCs include α-SMA, SMMHC, Calponin, Smoothelin, and Desmin, while those of synthetic or proliferative CCSMCs involve Vimentin, Osteopontin, and Collagen I. Current studies show that phenotypic transformation of CCSMCs is related to the pathophysiological processes of different types of ED, such as bilateral cavernous nerve injury-induced ED, diabetes mellitus-associated ED, arterial ED, hypertension-associated ED, and so on. In addition, such external factors as hypoxia, platelet-derived growth factor, and tobacco combustion gas may directly affect rats or CCSMCs and consequently lead to phenotypic conversion of CCSMCs. This article presents a systematic review of the studies on the correlation of phenotypic transition of CCSMCs with ED.


Subject(s)
Erectile Dysfunction , Myocytes, Smooth Muscle , Animals , Humans , Male , Muscle Contraction , Penis , Phenotype , Rats , Rats, Sprague-Dawley
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