Erectile Dysfunction in Type-2 Diabetes Mellitus Patients: Predictors of Early Detection and Treatment.

PURPOSE: To identify risk factors and potential predictors of erectile dysfunction (ED) in type-2 diabetes mellitus (T2DM) patients for early detection and treatment. METHODS: A retrospective cohort was used to assess the clinical data of 105 diabetic patients with ED from May 2019 to April 2020 age-matched to 105 diabetic patients without ED. Potential risk factors that could contribute to ED were compared between the groups. Erectile function was evaluated using the International Index of Erectile Function-5 questionnaire. RESULTS: There were higher rates of diabetic peripheral neuropathy (p = 0.036) and retinopathy (p < 0.001), longer duration of diabetes (p < 0.001), lower estimated glomerular filtration rate (p = 0.010) values, and higher uric acid (p < 0.001) and C-reactive protein (p = 0.001) levels in the ED group compared to the non-ED group. Multivariate logistic analysis identified uric acid, diabetic retinopathy, and T2DM course as independent predictors of diabetic ED. Diabetics with retinopathy and T2DM for ≥49 months were 3.028 and 3.860 times more likely to have ED, respectively. Uric acid values ≥392.5 µmol/L were associated with 18.638 times greater risk of having ED, though the values were within normal range. CONCLUSION: In T2DM patients, higher uric acid (≥392.5 µmol/L), longer diabetes duration (≥49 months), and the presence of diabetic retinopathy were important and reliable predictors for diabetic ED. For patients who have high risk factors for developing ED, diligent screening and early treatment are necessary.

Long noncoding RNA linc00346 promotes the malignant phenotypes of bladder cancer.

BACKGROUND: More and more reports have demonstrated that long noncoding RNAs (lncRNAs) play an important role in the development of a variety of carcinomas, including bladder cancer. However, only a small fraction of them have been characterized. Linc00346 have been found to be upregulated in bladder cancer tissues compared to normal tissues in a microarray-based lncRNA profiling study. In this study, we would like to explore the expression pattern and functional role of linc00346 in bladder cancer. METHODS: We determined the expression of linc00346 in a cohort of bladder cancer tissues with matched normal tissues as well as human bladder cancer cell lines. We investigated the biological function of linc00346 with CCK-8 assay, colony formation assay, flow cytometry analysis, transwell assay and tumor xenografts mice model. RESULTS: We found that linc00346 was upregulated in bladder cancer tissues compared to normal tissues. Knockdown of linc00346 inhibited bladder cancer cell proliferation and migration, induced cell cycle arrest and cell apoptosis. CONCLUSION: Our study demonstrates that linc00346 could be a potential oncogene and a therapeutic target in bladder cancer.

Adipose-Derived Stem Cell-Derived Exosomes Ameliorate Erectile Dysfunction in a Rat Model of Type 2 Diabetes.

BACKGROUND: The efficacy of adipose-derived stem cells (ADSCs) in alleviating erectile dysfunction (ED) of diabetic rats has been demonstrated mainly through a paracrine effect. However, exosomes (EXOs), which are important bioactive substance vectors secreted by ADSCs, have never been associated with ED. AIM: To investigate the effect of ADSC-derived EXOs on erectile function in a type 2 diabetic ED rat model. METHODS: EXOs were isolated from the supernatants of cultured ADSCs by ultracentrifugation. We constructed a type 2 diabetic rat model using a high-fat diet and low-dose streptozotocin administered by intraperitoneal injection. In total, 24 diabetic rats were randomly assigned to three groups and were treated with an intracavernous injection of ADSC-derived EXOs, ADSCs, or phosphate buffered saline. Another eight age-matched rats underwent sham operation and composed the normal control group. OUTCOMES: Intracavernous pressure and mean arterial pressure testing and histologic and western blot analyses were performed 4 weeks after the intracavernous injection. RESULTS: ADSC-derived EXOs and ADSCs administered by intracavernous injection led to an increase in the ratio of intracavernous pressure to mean arterial pressure compared with that for phosphate buffered saline treatment. Histologic and western blot analyses demonstrated an increased ratio of smooth muscle to collagen, increased expression of an endothelial marker (CD31), a smooth muscle marker (α-smooth muscle actin), and antiapoptotic protein Bcl-2 and decreased the expression of the apoptotic protein cleaved caspase-3 and apoptosis of endothelial and smooth muscle cells in the corpus cavernosum tissue after EXO or ADSC injection compared with values for the phosphate buffered saline treatment. CLINICAL TRANSLATION: The present results are expected to provide a scientific foundation for clinical application in the near future. STRENGTHS AND LIMITATIONS: Although the results demonstrated that intracavernous injection of ADSC-derived EXOs could ameliorate ED of diabetic rats, the optimum dose and times of injection remain for further study. CONCLUSIONS: ADSC-derived EXOs, similarly to ADSCs, were capable of rescuing corpus cavernosum endothelial and smooth muscle cells by inhibiting apoptosis and thus promoting the recovery of erectile function in type 2 diabetic rats. Chen F, Zhang H, Wang Z, et al. Adipose-Derived Stem Cell-Derived Exosomes Ameliorate Erectile Dysfunction in a Rat Model of Type 2 Diabetes. J Sex Med 2017;14:1084-1094.

Papaverine selectively inhibits human prostate cancer cell (PC-3) growth by inducing mitochondrial mediated apoptosis, cell cycle arrest and downregulation of NF-κB/PI3K/Akt signalling pathway.

PURPOSE: The main objective of the current research work was to investigate the antitumor effects of papaverine in PC-3 human prostate cancer cells along with testing its toxicity in the normal human fibroblast (NHF) cells. METHODS: The cytotoxic effects of papaverine were examined by the MTT cell viability assay. Flow cytometry using annexin V-FITC/PI was used to study the effects on apoptosis, including its quantification. Effects on cell cycle progression were analyzed by flow cytometry while as effects on apoptosis-related proteins, NF-kB and PI3K/Akt pathways were estimated by Western blot assay. RESULTS: The results indicated that papaverine could induce significant, highly selective and dose-dependent cytotoxic effects in PC-3 cells without causing too much toxicity in normal cells. Papaverine also led to induction of early and late apoptosis along with inducing sub-G1 cell cycle arrest in a dose-dependent manner. Papaverine induced a dose-dependent reduction in the expression levels of Blc-2 proteins and a dose-dependent increase in the expression levels of Bax protein. The expression levels of NF-kB were decreased markedly in comparison to the untreated control. Papaverine treatment also led to a dose-dependent downregulation of PI3K and phospho-Akt expression. CONCLUSION: Papaverine showed selective antitumor properties against PC-3 human prostate cancer cells by inducing early and late apoptosis, sub-G1 cell cycle arrest, modulation of apoptosis-related proteins like Bcl-2, Bax, Bid, XIAP and cytochrome C along with downregulation of NFkB, PI3K/Akt signalling pathway.

[Platelet-derived growth factor-BB induces phenotypic transformation of corpus cavernosum smooth muscle cells in SD rats].

OBJECTIVE: To evaluate the effect of the platelet-derived growth factor-BB (PDGF-BB) on the phenotypic transformation of corpus cavernosum smooth muscle cells (CCSMC) in SD rats. METHODS: CCSMCs were primarily cultured in the modified tissue sticking medium and subjected to immunofluorescence assay. The cells were divided into a blank control and four PDGF-BB groups, the latter exposed to 5, 10, 20, and 40 ng/ml of PDGF-BB, respectively, for 24 hours, and the cells in the 20 ng/ml PDGF-BB group treated for 24, 48, and 72 hours. The the relative expressions of α-SMA, SMMHC, calponin, and OPN mRNA were determined by real-time fluorescence quantitative RT-PCR (qRT-PCR). RESULTS: The α-SMA positive rate of the CCSMCs was over 95%. Compared with the blank control group, the expression levels of α-SMA, SMMHC, and calponin mRNA were significantly decreased (P < 0.05) while that of OPN mRNA remarkably increased (P < 0.05) in the PDGF-BB groups. The 20 ng/ml PDGF-BB group also showed significantly downregulated expressions of α-SMA, SMMHC, and calponin mRNA (P < 0.05) and upregulated expression of OPN mRNA (P < 0.05) at 24, 48, and 72 hours. CONCLUSION: PDGF-BB can induce the transformation of the phenotype of CCSMCs in SD rats from the contractile to the synthetic type.

Single-cell RNA sequencing reveals critical modulators of extracellular matrix of penile cavernous cells in erectile dysfunction.

Erectile dysfunction (ED) is a common and difficult to treat disease, and has a high incidence rate worldwide. As a marker of vascular disease, ED usually occurs in cardiovascular disease, 2-5 years prior to cardiovascular disease events. The extracellular matrix (ECM) network plays a crucial role in maintaining cardiac homeostasis, not only by providing structural support, but also by promoting force transmission, and by transducing key signals to intracardiac cells. However, the relationship between ECM and ED remains unclear. To help fill this gap, we profiled single-cell RNA-seq (scRNA-seq) to obtain transcriptome maps of 82,554 cavernous single cells from ED and non-ED samples. Cellular composition of cavernous tissues was explored by uniform manifold approximation and projection. Pseudo-time cell trajectory combined with gene enrichment analysis were performed to unveil the molecular pathways of cell fate determination. The relationship between cavernous cells and the ECM, and the changes in related genes were elucidated. The CellChat identified ligand-receptor pairs (e.g., PTN-SDC2, PTN-NCL, and MDK-SDC2) among the major cell types in the cavernous tissue microenvironment. Differential analysis revealed that the cell type-specific transcriptomic changes in ED are related to ECM and extracellular structure organization, external encapsulating structure organization, and regulation of vasculature development. Trajectory analysis predicted the underlying target genes to modulate ECM (e.g., COL3A1, MDK, MMP2, and POSTN). Together, this study highlights potential cell-cell interactions and the main regulatory factors of ECM, and reveals that genes may represent potential marker features of ED progression.

[Transperitoneal versus extraperitoneal laparoscopic radical prostatectomy for localized prostate cancer: a meta analysis].

OBJECTIVE: To evaluate the effects and safety of transperitoneal laparoscopic radical prostatectomy (TLRP) and extraperitoneal laparoscopic radical prostatectomy (ELRP) in the treatment of localized prostate cancer. METHODS: We searched the Cochrane Library, Medline, Chinese Journal Full-text Database, Wanfang and CBM for clinical controlled trials addressing TLRP and ELRP in the treatment of localized prostate cancer. Two independent reviewers extracted comparable data from eligible studies and performed meta-analysis with the Statal 2.0 software on the relevant indexes of operation time, intraoperative blood loss, postoperative catheterization, postoperative intestinal function recovery, and postoperative hospital stay. RESULTS: Nine clinical controlled trials with 942 cases were included in this analysis, 492 treated by TLRP and the other 450 by ELRP. Meta-analysis showed no statistically significant differences between the TLRP and ELRP groups in operation time (SMD = 0.60, 95% CI: -0.06,1.26), intraoperative blood loss (SMD = 0.01, 95% CI: -0.35, 0.36) , postoperative catheterization time (SMD = 0.10, 95% CI: -0.21, 0.40) and postoperative hospital stay (SMD = 0.45, 95% CI: -0.01, 0.91), except in the time of postoperative intestinal function recovery, which was significantly shorter in the ELRP than in the TLRP group (SMD = 1.18, 95% CI: 0.26, 2.10). CONCLUSION: For the treatment of localized prostate cancer, ELRP is similar to TLRP with respect to operation time, intraoperative blood loss, postoperative catheterization and postoperative hospital stay, but superior to the latter in postoperative intestinal function recovery.

Myocardin Reverses Hypoxia-Inducible Factor-1α Mediated Phenotypic Modulation of Corpus Cavernosum Smooth Muscle Cells in Hypoxia Induced by Cobalt Chloride.

PURPOSE: We aimed to investigate the mechanism of phenotypic transformation of corporal cavernosum smooth muscle cells (CCSMCs) under hypoxic conditions in vitro. MATERIALS AND METHODS: In this study, a hypoxia model was established using cobalt chloride (CoCl2). CCSMCs were treated with different concentrations of CoCl2 for varying time periods, and cell viability was assessed. Hypoxia-inducible factor-1α (HIF-1α), myocardin (Myocd) and phenotypic markers were detected in the CCSMCs. We also transfected the CCSMCs with si-HIF-1α and Ad-Myocd and evaluated the effects on phenotypic modulation of CCSMCs and the relationship between HIF-1α and Myocd was evaluated. RESULTS: CoCl2 inhibited the viability of CCSMCs in a dose- and time-dependent manner, and treatment with 300 µM CoCl2 for 48 hours were the optimal conditions for establishing the hypoxia model. The results showed increased expression levels of HIF-1α and osteopontin and decreased Myocd, alpha-smooth muscle actin, and calponin levels in CCSMCs under hypoxia. HIF-1α knockdown reversed hypoxia-induced phenotypic transformation with elevated Myocd expression. Overexpression of Myocd also reversed the effect of hypoxia on the phenotypic switch, but did not affect HIF-1α expression. CONCLUSIONS: Our findings showed that HIF-1α was involved in the effect of hypoxia induced by CoCl2 on CCSMC phenotypic modulation, and Myocd overexpression could inhibit this process. Thus, Myocd might be a potential therapeutic target for erectile dysfunction under hypoxia or HIF-1α activation.

N-acetylcysteine ameliorates erectile dysfunction in rats with hyperlipidemia by inhibiting oxidative stress and corpus cavernosum smooth muscle cells phenotypic modulation.

Hyperlipidemia is a major risk factor for erectile dysfunction (ED). Oxidative stress and phenotypic modulation of corpus cavernosum smooth muscle cells (CCSMCs) are the key pathological factors of ED. N-acetylcysteine (NAC) can inhibit oxidative stress; however, whether NAC can alleviate pathological variations in the corpus cavernosum and promote erectile function recovery in hyperlipidemic rats remains unclear. A hyperlipidemia model was established using 27 eight-week-old male Sprague-Dawley (SD) rats fed a high-fat and high-cholesterol diet (hyperlipidemic rats, HR). In addition, 9 male SD rats were fed a normal diet to serve as controls (NC). HR rats were divided into three groups: HR, HR+normal saline (NS), and HR+NAC (n = 9 for each group; NS or NAC intraperitoneal injections were administered daily for 16 weeks). Subsequently, the lipid profiles, erectile function, oxidative stress, phenotypic modulation markers of CCSMCs, and tissue histology were analyzed. The experimental results revealed that erectile function was significantly impaired in the HR and HR + NS groups, but enhanced in the HR + NAC group. Abnormal lipid levels, over-activated oxidative stress, and multi-organ lesions observed in the HR and HR + NS groups were improved in the HR + NAC group. Moreover, the HR group showed significant phenotypic modulation of CCSMCs, which was also inhibited by NAC treatment. This report focuses on the therapeutic effect of NAC in restoring erectile function using a hyperlipidemic rat model by preventing CCSMC phenotypic modulation and attenuating oxidative stress.

Clinical and Biological Significance of DNA Methylation-Driven Differentially Expressed Genes in Biochemical Recurrence After Radical Prostatectomy.

Background: Biochemical recurrence (BCR) after radical prostatectomy indicates poor prognosis in patients with prostate cancer (PCA). DNA methylation (DNAm) is a critical factor in tumorigenesis and has attracted attention as a biomarker for the diagnosis, treatment, and prognosis of PCA. However, the predictive value of DNAm-derived differentially expressed genes (DMGs) in PCA with BCR remains elusive. Methods: We filtered the methylated genes and the differentially expressed genes (DGEs) for more than 1,000 clinical samples from the TCGA cohort using the chAMP and DESeq2 packages of R language, respectively. Next, we integrated the DNAm beta value and gene expression data with the Mithymix package of R language to obtain the DMGs. Then, 1,000 times Cox LASSO regression with 10-fold cross validation was performed to screen signature DMGs and establish a predictive classifier. Univariate and multivariate cox regressive analyses were used to identify the prognostic factors to build a predictive model, and its performance was measured by receiver operating characteristic, calibration curves, and Harrell's concordance index (C-index). Additionally, a GEO dataset was used to validate the prognostic classifier. Results: One hundred DMGs were mined using the chAMP and Methymix packages of R language. Of these, seven DMGs (CCK, CD38, CYP27A1, EID3, HABP2, LRRC4, and LY6G6D) were identified to build the prognostic classifier (Classifier) through LASSO analysis. Moreover, univariate and multivariate Cox regression analysis determined that the Classifier and pathological T stage (pathological_T) were independent predictors of BCR (hazard ratio (HR 2.2), (95% CI 1.4-3.5), p < 0.0012, and (HR 1.8), (95% CI 1.0-3.2), p < 0.046). A nomogram based on the Classifier was constructed, with high prediction accuracy for BCR-free survival in TCGA and GEO datasets. GSEA enrichment analysis showed that the DMGs were mainly enriched in the metabolism pathways. Conclusion: We identified and validated the nomogram of BCR-free survival for PCA patients, which has the potential to guide treatment decisions for patients at differing risks of BCR. Our study deepens the understanding of DMGs in the pathogenesis of PCA.

NLRP3 downregulation enhances engraftment and functionality of adipose-derived stem cells to alleviate erectile dysfunction in diabetic rats.

Background: The transplantation of adipose-derived stem cells (ASCs) is a most promising treatment for diabetic erectile dysfunction (DMED). However, the effect of high glucose on the post-transplantation survival of stem cells limits the efficacy of ASCs transplantation. Prolonging the survival time of ASCs in vivo after transplantation is a key issue in the utilization of ASCs for DMED. Herein, we aimed to investigate the therapeutic effect of ASCs by downregulating NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) as well as its mechanism of action in DMED. Methods: ASCs were obtained by isolating subcutaneous fat from SD rats and were identified using lipogenic and osteogenic differentiation assays, as well as flow cytometric analysis. The shNLRP3 lentivirus with the best downregulating effect was screened, and shNLRP3 lentivirus (LV-shNLRP3) was transfected into ASCs (ASCsshNLRP3) to detect apoptosis and the reactive oxygen species (ROS) levels in each group under high glucose conditions. In DMED rats, ASCsLV-shNLRP3, ASCsLV-control, or phosphate buffered saline (PBS) were administrated via intra-cavernous injection, and normal rats served as normal controls. One week post-injection, animal imaging was performed to track the ASCs. Four weeks post-injection, erectile function was evaluated by measuring the intra-cavernosal pressure and mean arterial pressure. Corpus cavernosum pyroptosis and endothelial function were examined by western blotting and immunofluorescence. Results: NLRP3-mediated pyroptosis might be a pathogenic mechanism of ED and DMED. ASCs were isolated successfully. Thereafter, the LV-shNLRP3 with the highest transfection efficiency was selected and used to modify ASCs successfully. LV-shNLRP3 could protect ASCs paracrine function under hyperglycemia through anti-apoptosis and anti-ROS deposition mechanisms. Furthermore, ASCsLV-shNLRP3 showed an advantage in the suppression of pyroptosis compared to ASCsLV-control. The ASCsLV-shNLRP3 group had improved cavernous endothelial function and smooth muscle injury, thus reversing erectile function, and was superior to the ASCsLV-control group. Conclusions: NLRP3 Inflammasome-mediated pyroptosis might be involved in DMED formation. Intra-cavernous injection of ASCsLV-shNLRP3 could suppress cavernosal pyroptosis, contributing to improved erectile function in DMED rats.

[Calcitonin gene-related peptide induces phenotypic transformation of corpus cavernosum smooth muscle cells in diabetic rats with erectile dysfunction].

OBJECTIVE: To explore the effect of the calcitonin gene related peptide (CGRP) on the phenotypic transformation of corpus cavernosum smooth muscle cells (CCSM) in diabetic rats with erectile dysfunction (ED). METHODS: Models of diabetes and diabetic ED were established in male Sprague-Dawley rats by administration of streptozotocin, and CCSMs were primarily cultured and subjected to immunocytochemical assay. The cells were divided into a diabetic ED and a normal control group, and exposed to 0, 10, 60 and 100 nmol/L of CGRP for 24 hours. Then the relative expressions of calponin 1 (Cnn1) and osteopontin (OPN) mRNA were determined by real-time fluorescence quantitative RT-PCR (qRT-PCR). RESULTS: The rate of SMalpha-actin positive cells in the CCSMs was (95.94 +/- 0.03) %. The expression of Cnn1 mRNA was significantly lower while that of OPN mRNA remarkably higher in the diabetic ED rats (4.41 +/- 0.29 and 5.28 +/- 0.32) than in the normal controls (10.35 +/- 0.62 and 1.32 +/- 0.24) (P < 0.01). Exposure to 100 nmol/L of CGRP significantly upregulated the expression of Cnn1 mRNA and downregulated that of OPN mRNA as compared with the unexposed rats (6.9 +/- 0.22 vs 4.41 +/- 0.29 and 3.26 +/- 0.31 vs 5.28 +/- 0.32, P < 0.01). CONCLUSION: CGRP can transform the phenotype of CCSMs in diabetic ED rats from contractile to synthetic type.

Effects of "metabolic memory" on erectile function in diabetic men: A retrospective case-control study.

OBJECTIVE: This study was performed to explore the effects of metabolic memory on diabetic erectile dysfunction (ED), especially the severity and response to treatment. METHODS: Through medical records and follow-up by telephone, 67 patients meeting the criteria with a clinical diagnosis of ED and a diabetic history of more than 5 years were enrolled for erectile function analysis. They were divided into a glycemic control group, a glycemic non-control group and a metabolic memory group according to glycemic levels and treatments for diabetes in the past 5 years, and they were treated with phosphodiesterase type 5 (PDE5) inhibitors for 4 weeks. Erectile function and efficacy were assessed by the International Index for Erectile Function (IIEF), the Erection Hardness Score (EHS), and the Sexual Encounter Profile (SEP). RESULTS: The patients in the glycemic control group performed better in erectile function than those in the other groups. The patients in the glycemic control group received a significantly greater score on both the EHS and the five domains of the IIEF than did the patients in the glycemic non-control group and the metabolic memory group (all P < .001). There were also statistically significant differences favoring the glycemic control group (P < .05) in SEP2 and SEP3 success rates. However, there were no significant differences between the metabolic memory group and the glycemic non-control group in these erectile function assessments (P > .05). Significant negative correlations were seen between HbA1c levels at the time of consultation and the scores on the IIEF-EF and the EHS (Pearson r-values of -0.338 with P = .005 and -0.273 with P = .025, respectively). HbA1c levels at the first diagnosis of diabetes mellitus (DM) were also significantly negatively correlated with scores on the IIEF-EF and the EHS with greater Pearson correlation coefficients (Pearson r-values of -0.478 with P < .001 and -0.392 with P = .001, respectively). Significant improvements on each of the erectile function assessments were observed among diabetic patients with ED, but no significant difference in efficacy was observed between each group. CONCLUSIONS: The phenomenon of metabolic memory did have a significant influence on ED in men with diabetes, associated with the severity of ED but not the response to medical treatment. Early hyperglycemia exposure would have long-term disadvantageous effects on erectile function in diabetic patients with ED, which would be sustained even after the patients achieve better glycemic control. PATIENTS SUMMARY: In this report, we looked at the erectile functions of 67 patients with a clinical diagnosis of ED and a diabetic history of more than 5 years. We found that early hyperglycemia exposure would have long-term disadvantageous effects on erectile function in diabetic patients with ED, which would be sustained even after the patients achieve better glycemic control. We further found that the effects were associated with the severity of ED but not the response to medical treatment in men with diabetes.

A bibliometric analysis of international publication trends in premature ejaculation research (2008-2018).

The incidence of premature ejaculation (PE) has been on the rise over the years. Thus, significant research efforts have been directed toward understanding the pathogenesis and hence treatment of PE. Here, we performed a comprehensive analysis of the worldwide trends in research outputs in the field of PE. This study investigated the universal findings of previous PE studies and the trending issues surrounding the condition. We employed the Web of Science Core Collection for data collection. The Excel (2016) and CiteSpace IV were used for information analysis. The information was categorized using journal names, institutions, research frontiers, citation reports, regions/countries, and authors. A sum of 886 publications concerning PE between 2008 and 2018 were identified as of July 6, 2019. The highest number of publications was identified in the Journal of Sexual Medicine published. The United States of America (USA) had the highest number of publications and H-index value. The highest co-citations were from Waldinger MD. The most common keyword was 'drug treatment'. A steady pattern was observed for PE publications done between the period of 2008-2018. Thus, the USA is at the forefront of research on PE research. The interesting advanced research frontiers were drug treatment, circumcision, and sertraline.

Screening and identification of NOTCH1, CDKN2A, and NOS3 as differentially expressed autophagy-related genes in erectile dysfunction.

BACKGROUND: Loss of function of key autophagy genes are associated with a variety of diseases. However specific role of autophagy-related genes in erectile dysfunction ED remains unclear. This study explores the autophagy-related differentially expressed genes (ARGs) profiles and related molecular mechanisms in Corpus Cavernosum endothelial dysfunction, which is a leading cause of ED. METHODS: The Gene Expression Omnibus (GEO) database was used to identify the key genes and pathways. Differentially expressed genes (DEGs) were mined using the limma package in R language. Next, ARGs were obtained by matching DEGs and autophagy-related genes from GeneCard using Venn diagrams. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of ARGs were described using clusterProfiler and org.Hs.eg.db in R. Moreover, hub ARGs were screened out through protein-protein interaction (PPI), gene-microRNAs, and gene-transcription factors (TFs) networks then visualized using Cytoscape. Of note, the rat model of diabetic ED was established to validate some hub ARGs with qRT-PCR and Western blots. RESULTS: Twenty ARGs were identified from four ED samples and eight non-ED samples. GO analysis revealed that molecular functions (MF) of upregulated ARGs were mainly enriched in nuclear receptor activity. Also, MF of downregulated ARGs were mainly enriched in oxidoreductase activity, acting on NAD(P)H and heme proteins as acceptors. Moreover, six hub ARGs were identified by setting high degrees in the network. Additionally, hsa-mir-24-3p and hsa-mir-335-5p might play a central role in several ARGs regulation, and the transcription factors-hub genes network was centered with 13 ARGs. The experimental results further showed that the expression of Notch1, NOS3, and CDKN2A in the diabetic ED group was downregulated compared to the control. CONCLUSIONS: Our study deepens the autophagy-related mechanistic understanding of endothelial dysfunction of ED. NOTCH1, CDKN2A, and NOS3 are involved in the regulation of endothelial dysfunction and may be potential therapeutic targets for ED by modulating autophagy.

Screening and identification of critical biomarkers in erectile dysfunction: evidence from bioinformatic analysis.

PURPOSE: Erectile dysfunction (ED) is one of the most common male-disease globally. Despite efforts to explain its pathogenesis, the molecular mechanisms of ED are still not well understood. METHODS: The microarray dataset GSE10804 was downloaded from the Gene Expression Omnibus (GEO) to find candidate genes in ED progression. After differentially expressed genes (DEGs) were identified, functional enrichment analysis was performed. In addition, a protein-protein interaction network (PPI) was established and module analysis was performed through the STRING and Cytoscape. RESULTS AND CONCLUSIONS: A total of 618 DEGs were identified in all, containing 430 downregulated genes and 188 upregulated genes. The enriched functions and pathways of the DEGs include transcription from RNA polymerase II promoter, cell adhesion, calcium ion binding, receptor binding, Akt signaling pathway, receptor interaction, protein digestion, and absorption. We picked out twenty-five hub genes, with biological process (BP) analyses revealing that the genes were principally associated with cellular responses to amino acid stimuli, extracellular matrix structural constituent, collagen trimer, protein digestion and absorption, ECM-receptor interaction and PI3K-Akt signaling pathway. To sum up, DEGs and hub genes distinguished in this study not only help us understand the molecular mechanisms behind the carcinogenesis and progression of ED, but also play a part in the diagnosis and treatment of ED by providing candidate targets.

Correction to: Trends in erectile dysfunction research from 2008 to 2018: a bibliometric analysis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Trends in erectile dysfunction research from 2008 to 2018: a bibliometric analysis.

Insufficient penile erection to facilitate vaginal penetration is a medical condition referred to as erectile dysfunction (ED). By the year 2025, the number of ED cases across the world is expected to reach 322 million. There are numerous publications and studies in the field of ED over the past decades. Our aim is to comprehensively analyze the global scientific outputs of ED research and show the trends and hotspots in ED research. Data of publications were downloaded from the Web of Science Core Collection. We used CiteSpace IV and Excel 2016 to analyze literature information, including journals, countries/regions, institutes, authors, citation reports, and research frontiers. Until October 26, 2018, a total of 8880 papers in ED research were identified as published between 2008 and 2018. Journal of Sexual Medicine published the most articles. The United States contributed the most publications and occupied leading positions in H-index value and the number of ESI top papers. Maggi M owned the highest co-citations. The keyword "Oxidative stress" ranked first in the research front-line. The amount of articles published in ED research has been stable from 2008 to 2018. The United States showed enormous progress in ED research, and is still the dominant country. Oxidative stress, vardenafil, and late-onset hypogonadism were the latest research frontiers and should be paid more attention.

Corrigendum to "Sodium Tanshinone IIA Sulfonate Attenuates Erectile Dysfunction in Rats with Hyperlipidemia".

[This corrects the article DOI: 10.1155/2020/7286958.].

Sodium Tanshinone IIA Sulfonate Attenuates Erectile Dysfunction in Rats with Hyperlipidemia.

Hyperlipidemia is considered one of the most important risk factors for erectile dysfunction (ED). To determine the effect of sodium tanshinone IIA sulfonate (STS) as an antioxidant agent on ED in high-fat diet- (HFD-) induced hyperlipidemia in rats and to investigate if STS administration could improve erectile function via hydrogen sulfide (H2S) production by inhibition of oxidative stress. Hyperlipidemia was induced in Sprague-Dawley rats by feeding HFD for 16 weeks. The rats were randomly divided into 3 groups: control, HFD, and HFD treated with STS (10 mg/kg/day for 12 weeks, intraperitoneal injection). Erectile function including intracavernosal pressure (ICP), H2S production, and antioxidant capacity was assessed. In addition, cavernosal smooth muscle cells (CSMC) isolated from SD rats were pretreated with STS in vitro and exposed to H2O2. Expressions of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), activity of antioxidant enzymes, and H2S-generating enzymes within CSMC were examined. ICP was significantly decreased in HFD rats compared with control. In addition, decreased H2S production and expression of cystathionine É£-lyase (CSE) and cystathionine ß-synthase (CBS) associated with increased oxidative stress were observed in the penile tissue of HFD rats. However, all these changes were reversed by 16 weeks after STS administration. STS also increased antioxidant defense as evidenced by increased expression of Nrf2/HO-1 in the penile tissue of HFD rats. In CSMC, pretreatment with STS attenuated the decreased expression of CSE and CBS and H2S production by H2O2. STS exerted similar protective antioxidative effect as shown in the in vivo hyperlipidemia model. The present study demonstrated the redox effect of STS treatment on ED via increased H2S production in HFD-induced hyperlipidemia rat model by increased antioxidant capacity via activation of the Nrf2/HO-1 pathway, which provides STS potential clinical application in the treatment of hyperlipidemia-related ED.