Effects of obesity-related anthropometric indices and body composition on erectile dysfunction mediated by coronary artery disease: A Mendelian randomization study.

BACKGROUND: The causal relationship between obesity-related anthropometric indicators/body composition and erectile dysfunction has not been established in previous observational studies. METHOD: We screened single nucleotide polymorphisms significantly associated with exposure from genome-wide association studies as instrumental variables (p < 5.0 × 10-8 ). The summary statistics for erectile dysfunction were collected from a genome-wide association study with a sample size of 223,805. Exposure and outcome populations included are of European ancestry. We used univariate and multivariate Mendelian randomization (i) to investigate the causal relationship between genetically predicted obesity-related anthropometric indicators/body composition and erectile dysfunction and (ii) to examine the mediating role of coronary artery disease. Mendelian randomization analysis was conducted using an inverse variance weighted method. A series of sensitivity analyses validated the results of the Mendelian randomization analysis. Causal estimates are expressed as odds ratios with 95% confidence intervals. RESULTS: Obesity-related anthropometric indicators/body composition were associated with an increased risk of erectile dysfunction in univariate Mendelian randomization analyses. For the 1-SD increase in body mass index, the odds ratio was 1.841 (95% confidence interval: 1.049-1.355, p = 0.006). For the 1-SD increase in waist circumference and hip circumference, the odds ratios were 1.275 (95% confidence interval: 1.101-1.478, p = 0.001) and 1.156 (95% confidence interval: 1.015-1.317, p = 0.009), respectively. The odds ratio for the 1-SD increase in whole body fat mass was 1.221 (95% confidence interval: 1.047-1.388, p = 0.002). For the 1-SD increase in leg fat percentage (left and right), the odds ratios were 1.256 (95% confidence interval: 1.006-1.567, p = 0.044) and 1.285 (95% confidence interval: 1.027-1.608, p = 0.028), respectively. For the 1-SD increase in leg fat mass (left and right), the odds ratios were 1.308 (95% confidence interval: 1.108-1.544, p = 0.001) and 1.290 (95% confidence interval: 1.091-1.524, p = 0.003), respectively. For the 1-SD increase in arm fat mass (left and right), the odds ratios were 1.269 (95% confidence interval: 1.113-1.447, p < 0.001) and 1.254, respectively. Multivariate Mendelian randomization analysis showed that after adjusting for coronary artery disease, some genetic predispositions to obesity-related anthropometric indicators and body composition were still associated with an increased risk of erectile dysfunction. Significant associations were found for waist circumference-erectile dysfunction (odds ratio: 1.218, 95% confidence interval: 1.036-1.432), leg fat percentage (left)-erectile dysfunction (odds ratio: 1.245, 95% confidence interval: 1.035-1.497), leg fat mass (left)-erectile dysfunction (odds ratio: 1.264, 95% confidence interval: 1.051-1.521), arm fat mass (right)-erectile dysfunction (odds ratio: 1.186, 95% confidence interval: 1.024-1.373), and arm fat mass (left)-erectile dysfunction (odds ratio: 1.17, 95% confidence interval: 1.018-1.360). Meanwhile, coronary artery disease mediated the effects of fat on erectile dysfunction, and the proportion of coronary artery disease-mediated cases ranged from 10% to 22%. CONCLUSION: There is a potential causal relationship between obesity-related anthropometric indicators/body composition and erectile dysfunction. Higher waist circumference, leg fat percentage, and arm fat mass may increase the risk of erectile dysfunction, and coronary artery disease partly mediates this overall effect. Understanding the causal relationship between obesity and erectile dysfunction and the mediating role of coronary artery disease may provide more information for erectile dysfunction intervention and prevention strategies.

The association between lipid parameters and erectile dysfunction: a two-sample Mendelian randomization and case-control study.

PURPOSE: Lipid parameters have been shown to have significant predictive value for cardiovascular disease, but few studies have evaluated their correlation with erectile dysfunction (ED) in young men. METHODS: The case-control study encompassed 186 young ED patients (ages 20-40) and 186 healthy controls. Lipid parameters, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), TC/HDL ratio, TG/HDL ratio, and LDL-C/HDL-C ratio, were assessed in all participants. The International Index of Erectile Function (IIEF-5) scores were collected for all participants to evaluate erectile status. Multivariate logistic regression analysis was utilized to appraise the association of lipid-related parameters with ED. Single-nucleotide polymorphisms (SNPs) significantly correlated with lipid parameters (TC, TG, LDL-C, HDL-C) were selected from genome-wide association studies (GWAS) as instrumental variables (IV) (P < 5.0 × 10-8). Summary data for ED was gathered from a GWAS with a sample size of (n = 17,353 cases/28,210 controls). The inverse variance weighted (IVW) method was employed as the primary mendelian randomization (MR) analysis method to assess causal effects. Causal estimates were represented as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Results from the case-control study revealed that, when compared with the control group, levels of LDL-C, TG, UA, LDL-C/HDL-C, TG/HDL-C, and TC/HDL-C in the ED group were significantly elevated (P < 0.01), while HDL-C was significantly decreased (P < 0.01) in the ED group. Multivariate logistic regression analysis indicated LDL-C/HDL-C as a risk factor for both the incidence and severity of ED (P < 0.001). Two-sample MR analysis demonstrated no significant causal correlation between lipid parameters-LDL-C (OR, 0.98, 95% CI, 0.88-1.08, P = 0.616), HDL-C (OR, 1.07, 95% CI: 0.96-1.19, P = 0.249), TC (OR, 1.07, 95% CI, 0.96-1.18, P = 0.208), TG (OR, 0.98, 95% CI, 0.80-1.13, P = 0.579) -and an increased risk of ED (all P > 0.05). CONCLUSIONS: The case-control analysis ascertained a significant association between LDL-C, HDL-C, LDL-C/HDL-C, and ED and its severity. However, results from the MR study do not support a causal role of lipid parameters in ED.

Global research trends on maternal separation paradigms as an early life stress model: A bibliometric analysis.

Background: Maternal separation (MS) is an early life stress model that is often studied to determine how early life stress affects brain development and psychopathological adaptation. As society has developed, public health problems have become increasingly prominent, and this research area has attracted significant attention. However, to date, there has been no systematic bibliometric study on MS. The aim of this study was to analyze the trends and frontiers in MS using bibliometrics and provide a scientific reference to researchers in the field. Methods: Utilizing VOSviewer, CiteSpace, and Microsoft Excel, examined data obtained from the WoSCC, which encompasses the years 2002-2021. Results: In this bibliometric study, we analyzed 6209 articles related to MS authored by 24,174 researchers across 121 countries and regions and published in 2219 journals. The United States had the most publications (2,232, 35.95%) and both the United States and the United Kingdom had the highest h-index. Institutions in the United States and France had the most published articles and citations. Keyword clustering analysis revealed associations between MS and adverse early life experiences, the hypothalamic-pituitary-adrenal (HPA) axis, stress, gene expression, and depression. Conclusions: This bibliometric analysis highlights the current research focus on the long-term effects of MS on emotional cognition, the HPA axis, epigenetic changes, and their links to gut microbiome imbalances. Future research may expand on these findings to investigate the underlying mechanisms and broader health and societal implications of MS. These results provide a comprehensive overview of the current research landscape in MS and offer valuable insights for researchers to guide future investigations in this field.

Current status and prospects of diabetes mellitus induced erectile dysfunction: A bibliometric and visualization study.

Background: The prevalence of diabetes mellitus-induced erectile dysfunction (DMED) has recently increased, which has prompted numerous DMED studies. Here, we conduct a bibliometric analysis of relevant literature in the field of DMED and to discuss the research hotspots and future development directions. Methods: The Web of Science Core Collection database was searched for literature on DMED, and literature characterization including the number of articles, journals, countries/regions, institutions, authors, keywords, and other information was performed using VOS viewer and CiteSpace software. In addition, Pajek software was used for visual map adjustment, and GraphPad Prism was used to generate line graphs. Results: A total of 804 articles concerning DMED were included in this study. The Journal of Sexual Medicine issued the most documents(92 articles). The United States and China were in the leading position in the field of DMED research, and cross-institutional collaboration on DMED research worldwide needs to be further strengthened. Ryu JK were the authors with the highest number of documents issued (22 articles) while Bivalacqua TJ was the author with the most co-citated(249 co-citated). The keywords analysis shows that the main research hotspots in the field of DMED were mechanism discussions and disease treatment and management. Conclusions: Global research on DMED is expected to increase further. The investigation of the mechanism of DMED and the exploration of new therapeutic means and targets are the focus of future research.

[Short-term impact of COVID-19 on semen parameters: A retrospective study].

OBJECTIVE: To observe the changes in semen parameters after COVID-19 infection and clarify its impact on male fertility. METHODS: We collected semen samples from 82 male patients infected with COVID-19 in the past 2 months (the infection group) and 14 normal healthy men (the control group), obtained their semen parameters and compared them between the two groups before and after COVID-19 infection. RESULTS: There were no statistically significant differences in the baseline semen parameters between the infection and control groups (P > 0.05), nor in the semen volume within the infection group before and after infection (P > 0.05). Compared with the normal controls, the patients showed significantly decreased sperm concentration, total sperm count, percentage of progressively motile sperm, sperm motility and percentage of morphologically normal sperm after COVID-19 infection (P < 0.05), which were reduced even more significantly in those with than in those without fever during infection (P < 0.05). No statistically significant difference was observed in the semen quality of the patients with normal body temperature before and after COVID-19 infection (P > 0.05). Spearman correlation analysis showed no significant correlation between semen parameters and the severity of fever during infection (P > 0.05). CONCLUSION: COVID-19 infection decreases the semen quality of the patient, and fever during infection is a significant influencing factor. The severity of fever, however, is not related to the reduction of semen quality.

Bibliometrics and visualisation analysis of literature on varicocele: From 2002 to 2021.

Varicocele is a common disease in men, with a global incidence of approximately 25%. A comprehensive and systematic analysis of the knowledge map on it will help in assessing frontier research and identify knowledge gaps. In total, 4103 articles published from 2002 to 2021 in 1066 journals were included. They represent the current research status worldwide, potential hotspots and future research directions. In the past decades, the number of publications and citations of varicocele-related studies have increased steadily. Academic institutions in the United States played a leading role in varicocele research. The country, institution, journal and author with the most publications were the United States (779), Cleveland Clinic Foundation (132), Andrologia (246) and Agarwal A (106), respectively. The most frequently used keywords were Varicocele (1620), Male Infertility (944), Varicocelectomy (288), Testis (245), Sperm (166), Oxidative Stress (144), Azoospermia (119), Semen Analysis (118), Laparoscopy (116) and Adolescent (97). Currently, the main focus of current varicocele research is its surgical treatment method and effect on sperm quality. The frontier research hotspot is the specific mechanism of varicocele-induced decrease in sperm quality.

Bibliometrics and Visual Analysis of Adult-onset Still Disease (1976-2020).

Background: Adult-onset Still Disease (AoSD) is a rare disorder without standardized diagnostic criteria. People are paying more and more attention to its research. At present, no published studies have assessed the AoSD field using bibliometric tools. This study aimed to analyze research hotspots and frontiers through bibliometrics to provide a scientific and accurate reference for new and existing researchers. Methods: Data were obtained from the Web of Science core database and analyzed by CiteSpace, VOSviewer, and Microsoft Excel. Results: Involving 86 countries and regions, a total of 11,121 authors published 2,199 articles in 676 journals. These studies were published from 1976 to 2020. The United States published the most related articles (397). The United States, France, Italy, and Germany were the top four countries with a high H-index. Authors and institutions with high number of published articles and high citations are mainly located in France and Italy. High-frequency keywords include classification, criteria, diagnosis, and therapy method. Keyword clustering covers the connection between AoSD and rheumatoid arthritis, disease diagnosis, classification, and risk factors. Conclusions: The research on AoSD focuses on the diagnosis and differential diagnosis of the disease. Targeted therapy will become a research hotspot in the future, and relevant clinical research needs to appropriately expand the sample size and improve the credibility of the conclusions. The data reported in this study can serve as a useful resource for researchers studying AoSD.

A rat study model of depression-driven chronic prostatitis by modulating the PI3K/Akt/mTOR network.

Depression and chronic prostatitis (CP) are two common diseases that affect the human population worldwide. Clinically, it has been demonstrated that andrological patients often simultaneously suffer from depression and CP. Prior investigations have established that depression acts as an independent risk factor for CP. Herein, we explored the correlation between depression and CP using bioinformatics tools and through animal experiments. The potential targets and signalling pathways involved in depression and CP were predicted using bioinformatics tool, while depression in the rat model was established through chronic restraint stress. The expression of the related proteins and mRNA was assessed by Western blotting and real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Relative to those in the control rats, the protein contents of PI3K, p-Akt, and p-mTOR were lower in the model rats (p < 0.05). Similarly, the transcript levels of PI3K, Akt, and mTOR was also relatively lower in the model rats (p < 0.05). And PI3K/Akt agonists reduced inflammation in rat prostate tissue, accompanied by significant increases in the transcript and protein expression levels of PI3K, Akt, and mTOR. Thus, we proposed that depression model rats may induce CP as a result of mediation by the negative regulation of the PI3K/Akt/mTOR signalling network.

Explore the Effect of Asthma Regulating HIF-1 Pathway on Sperm Quality Based on Rat Model.

This study is to verify the effect of asthma on sperm quality and explore its potential underlying mechanism. We randomly categorized the Sprague-Dawley (SD) rats into control (Group C) and asthma model (Group M) groups. Rats in the asthma model group were induced allergic asthma by intraperitoneal injection of ovalbumin solution. We evaluated the sperm motility and sperm concentration. The expression of the Interleukin-6 (IL6), phosphorylation-signal transducer and activator of transcription 3 (p-Stat3), and hypoxia-inducible factor-1α (HIF-1α) proteins and mRNAs in the testicular tissue was detected by western blotting and RT-qPCR. Compared with group C, sperm concentration and sperm motility in group M rats were significantly decreased (P < 0.05). Meanwhile, compared with group C, the expression levels of IL6, Stat3, and HIF-1α proteins and mRNAs in group M rats were significantly increased (P < 0.05). Asthma can regulate the HIF-1 signaling pathway, promoting the expression of IL6, Stat3, and HIF-1α protein and mRNAs, so as to promote sperm apoptosis and ultimately causing male infertility.

Zuogui Wan improves spermatogenesis of GC1-spg cells through modulating AR-related pathways.

Zuogui Wan (ZGW) is a common prescription medication used in traditional Chinese medicine (TCM) to significantly improve the sperm quality and treat male infertility. This study evaluated the repair effect of ZGW and Levocarnitine (LEV) on GC1-spg cell injury induced by Glucosides of Tripterygium WilforDII Hook (GTW). The results showed that the ultrastructure and apoptosis rate of GC1- spg cells in LEV and ZGW group were considerably better than GTW. The transcriptional and translational level of CYP1A1, CYP17A1, androgen receptor (AR), SRD5A2 and proliferating cell nuclear antigen (PCNA) in GC-1spg cells of the LEV group were considerably elevated than GTW group (p < 0.05 or 0.01). Furthermore, the transcriptional and translational levels of CYP19A1, CYP17A1, AR, SRD5A2 and PCNA in GC-1spg cells in ZGW group were found to be considerably elevated than the LEV group (p < 0.05 or 0.01). The findings indicate that ZGW and LEV could increase the expression of PCNA, CYP17A1, CYP19A1, SRD5A2 and AR at transcriptional and translational levels, inhibit GC-1spg cell apoptosis and promoting cell proliferation, and the effect of ZGW was found to be significantly better than that of LEV.

Mechanism by which Huoxue Tongluo Qiwei Decoction improves the erectile function of rats with diabetic erectile dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Huoxue Tongluo Qiwei Decoction is a classical herbal formula, which can improve the symptoms of erectile dysfunction (ED) patients and has a good therapeutic effect on patients with diabetic erectile dysfunction (DIED). The main function of Huoxue Tongluo Qiwei Decoction is to stimulate the blood circulation and dredge collaterals, remove blood stasis, and calm wind. RATIONALE: To further explore the mechanism of Huoxue Tongluo Qiwei Decoction in the treatment of DIED, related animal experiments were designed. MATERIALS AND METHODS: The chemical constituents of Huoxue Tongluo Qiwei Decoction were identified with the help of high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). A rat model was induced by streptozotocin (STZ) and screened by apomorphine (APO). Serum sE-selectin, lysyl oxidase-1 (LOX-1), malondialdehyde (MDA) and other markers of vascular endothelial injury and related indicators of oxidative stress were studied through enzyme-linked immunosorbent assay (ELISA). The endothelial cells and ultrastructure of the corpus cavernosum were examined by electron microscopy and HE staining. The expression of protein and mRNA was detected by western blotting (WB) and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The results of the study revealed that the sE-selectin, LOX-1, intercellular adhesion molecule-1 (sICAM-1), endothelial microparticles (EMPs), P-selectin (CD62P), and MDA levels in the serum of group M rats were considerably higher than rats of group K, while the superoxide dismutase (SOD) level showed a significant decrease. In addition, the PKC pathway was activated, and the expression of related proteins and mRNA was increased. After 8 weeks of intervention with Huoxue Tongluo Qiwei Decoction and LY333531, serum level of sE-selectin, LOX-1, sICAM-1, EMPs, CD62P and MDA in L, D and G groups were remarkably lower than group M while SOD level increased significantly, protein kinase C (PKC) pathway was inhibited with the improved erectile function of rats. CONCLUSION: Huoxue Tongluo Qiwei Decoction can inhibit the expression of protein and mRNA of the PKCß signaling pathway related molecules in DIED rats to cure the injury of vascular endothelial, enhance antioxidant capacity, and prevent the activation of platelet, thus improving erectile function in rats with DIED.

The mechanism analysis using PI3K/AKT pathway for the effects of levocarnitine in the treatment of spermatogenic dysfunction.

LEV improves the percentage of forward-motion spermatozoon and total sperm motility in patients with oligozoospermia or asthenospermia in clinical settings. However, the mechanism of action of levocarnitine (LEV) in the treatment of spermatogenic dysfunction was unclear. Based on in vitro and in vivo experiments, we used Glucosides of Tripterygium wilfordii Hook F (GTW) to construct a cell model (using spermatogenic GC-1 spg cells) and an animal model (using rats) of spermatogenic dysfunction. LEV and LY294002 (a PI3K pathway inhibitor) were then administered. By assessing apoptosis and sperm quality and motility, the underlying mechanism was explored. We found that GTW induced spermatogenic dysfunction, and LEV ameliorated the GTW-induced spermatogenic dysfunction. LEV inhibited GC-1 spg cell apoptosis and improved the sperm count and percentages of PR (forward motion) + NP (non-forward motion) (p < .01). Besides, the morphology of testicular tissue in the GTW + LEV and LY + LEV groups was superior to that in the GTW group. We can to the conclusion that LEV may operate via the PI3K/AKT signalling pathway, with increases in PI3K, p-AKT, and BCL-2 protein and mRNA expression, so that the percentages of GC-1 spg cells apoptosis decrease, and the sperm count and motility improve.

Network Pharmacology Analysis of the Effects of Achyranthis Bidentatae Radix Plus Semen Vaccariae on Migraine-induced Erectile Dysfunction.

BACKGROUND AND AIM: Achyranthis Bidentatae Radix plus Semen Vaccariae are traditional Chinese medicines, which have been widely applied in the treatment of migraine and Erectile Dysfunction (ED) for many years. This study verified the effect of Achyranthis Bidentatae Radix plus Semen Vaccariae in improving migraine-induced ED and explored its potential mechanism. METHODS: Key targets and signaling pathways of Achyranthis Bidentatae Radix plus Semen Vaccariae in migraine-induced erectile dysfunction treatment were predicted by network pharmacology. A rat model of migraine was established by nitroglycerin injection. Apomorphine was injected into rats to screen the migraine-induced erectile dysfunction model, Achyranthis Bidentatae Radix-Semen Vaccariae granule suspension administered, and erectile function evaluated. Hematoxylin and eosin staining was used to compare the histological structure of the penile tissue, while RT-qPCR and Western blotting were used to determine mRNA and protein levels, respectively. RESULTS: Screening allowed us to identify common targets for migraine and ED; the signaling pathway exhibiting the greatest change was the Myosin light chain kinase- Calcium (MLCK-CaM) signal pathway. From Western blotting and RT-qPCR, we found that the levels of MLCK mRNA and protein in rats from Group B rats were significantly higher (P <0.05) than those in Groups A and C. Furthermore, the mRNA and protein levels of CaM were significantly higher in Group B (P <0.05) than in Groups A and C. CONCLUSION: Data indicate that the regulatory effects of Achyranthis Bidentatae Radix plus Semen Vaccariae on migraine-induced ED in a rat model are mediated by the MLCK-CaM signaling pathway.

Explore the effects of pulmonary fibrosis on sperm quality and the role of the PI3K/Akt pathway based on rat model.

Researches were reported that respiratory diseases can lead to male infertility; however, it is unclear whether there is a relationship between pulmonary fibrosis (PF) and male infertility. This study examined the influence of PF on sperm quality and its mechanisms. The key signalling pathway of male infertility caused by PF was predicted based on bioinformatics research. After modelling, we evaluated semen quality. Real-time quantitative polymerase chain reaction and Western blotting were used to measure the protein and mRNA expression levels of phosphatidylinositol 3-kinase (PI3K), phosphorylation-protein kinase B (p-Akt) and B-cell lymphoma 2 (Bcl2) in rat testicular cells. Compared with group A (48.77 ± 4.67; 59.77 ± 4.79), the sperm concentration and total sperm viability of group B (8.44 ± 1.71; 15.39 ± 3.48) showed a downward trend (p < 0.05). Western blotting showed that the protein expressions of PI3K, p-Akt and Bcl2 in the testes of group B (0.30 ± 0.06; 0.27 ± 0.05; 0.15 ± 0.03) was significantly lower than those of group A (0.71 ± 0.07; 0.72 ± 0.06; 0.50 ± 0.06) (p < 0.05). The hypoxic environment induced by PF can inhibit the expression of PI3K, p-Akt and Bcl2 protein and eventually cause dysfunctional spermatogenesis.

Xuefu Zhuyu decoction improves asthma-induced asthenozoospermia based on network pharmacology and in vivo experiment.

This study aimed to verify that Xuefu Zhuyu decoction (XFZYD) can improve asthenozoospermia caused by asthma, and explore its potential mechanism. Ovalbumin solution is used to induce asthma rat models. Sperm concentration and motility are used to evaluate semen quality. Immunohistochemistry (IHC), Western blotting and real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) are used to detect proteins and mRNA related to rat testis tissue. Haematoxylin and eosin (H&E) staining was used to observe changes in testicular tissues. Through network pharmacology, eriodictyol, 18-ß-glycyrrhetinic acid, naringenin, chrysin and Hispidulin were prominent active ingredients of XFZYD. We found that XFZYD regulates the expression levels of albumin (ALB), vascular endothelial growth factor A (VEGFA), interleukin 6 (IL-6) protein and mRNA, thereby improving the histopathological morphology of the testis, increasing the concentration and motility of spermatozoa. We suggest that future research can increase the detection of hormones and oxidative stress and other related indicators, so as to conduct more in-depth exploration.

Exploration of the effect of pulmonary fibrosis on erectile function in rats: A study based on bioinformatics and experimental research.

First, the bioinformatics database was used to predict the potential targets and signaling pathways of pulmonary fibrosis (PF) leading to erectile dysfunction (ED), and bleomycin sulfate was used to create a PF rat model. Then, enzyme-linked immunosorbent assay (ELISA), Western blotting, Real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to detect the expression of sex hormones and related proteins and mRNA, and Hematoxylin and eosin (H&E) staining was used to compare the pathological changes of penile tissue. The results showed that, compared with group A, cyclic guanosine phosphate (cGMP) content in group B decreased, protein kinase CGMP-dependent 1(PKG1) and nitric oxide synthase 3 (eNOS) protein and mRNA expression were down-regulated, and phosphodiesterase 5A (PDE5A) protein and mRNA expression was up-regulated (p < .05); the penile tissue of rats in group B had pathological damage. And there was no change in sex hormone-related indicators in the two groups (p > .05). Therefore, PF inhibits erectile function by inhibiting the cGMP-PKG pathway and reducing the expression of eNOS and PKG1 protein and mRNA. And by up-regulating the expression of PDE5A to impair erectile function.

Potential mechanism of Achyranthis bidentatae radix plus semen vaccariae granules in the treatment of diabetes mellitus-induced erectile dysfunction in rats utilizing combined experimental model and network pharmacology.

CONTEXT: Achyranthes bidentata Blume (Amaranthaceae) (ABR) and semen vaccariae (SV) are used commonly in the clinical treatment of erectile dysfunction in males with diabetes mellitus (DMED) to strengthen the kidney and promote blood circulation, and often achieve good curative effects. OBJECTIVE: Explore mechanistic details of ABR + SV treatment against DMED. MATERIALS AND METHODS: Prediction of key targets by network pharmacology. A rat model of DM was established by streptozotocin injection (55 mg/kg). Apomorphine (100 µg/kg) was injected into rats to screen the DMED model. Group C (n = 6) and group M (n = 6) were gavaged with deionized water; group T (n = 6) was given Achyranthis bidentatae radix-semen vaccariae granule suspension (2.5 g/kg). It lasted 8 weeks. Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) were used to measure the expression of tissue-related proteins and mRNA. RESULTS: The predicted key targets are albumin (ALB), caspase-3 (CASP3), vascular endothelial growth factor A (VEGFA), angiotensin-converting enzyme (ACE), and endothelial nitric oxide synthase (eNOS). Compared with the M group (0.52 ± 0.04; 0.50 ± 0.03; 0.49 ± 0.02; 0.23 ± 0.03), CASP3, VEGFA, and ACE protein expression reduced in the T group (0.39 ± 0.06; 0.34 ± 0.03; 0.39 ± 0.03), and eNOS protein expression increased (0.34 ± 0.03). CONCLUSION: ABR + SV can improve erectile function in DMED rats. This study provides a potential mechanism for the treatment of DMED with ABR + SV and can benefit from more patients.

A Bioinformatic Investigation of the Mechanism Underlying Migraine-Induced Erectile Dysfunction.

BACKGROUND: Over recent years, an increasing body of literature has focused on the relationship between erectile dysfunction (ED) and migraine. However, the specific mechanism is unclear. MATERIALS AND METHODS: We used a bioinformatic database to predict the targets and pathways associated with migraine and ED. Twenty male SD rats were randomly divided into a blank group (Group A, n = 10) and a migraine model group (Group B, n = 10). The rats in Group A were subcutaneously injected with normal saline (2 ml/kg) into the back of the neck. Rats in Group B were subcutaneously injected with nitroglycerin 10 mg/kg (5 mg/ml) into the back of the neck in order to create an animal model of migraine. Next, we carried out the measurement of erectile function. We used hematoxylin and eosin (HE) to compare the tissue structure of the cavernous body of the penis. Western blotting was used to determine the expression levels of PI3K, p-AKT, and p-mTOR in the protein; Reverse Transcription-Polymerase Chain Reaction (RT-qPCR) was used to determine the expression levels of PI3K, AKT, and mTOR in the messenger ribonucleic acid (mRNA). RESULTS: There are 117 intersection targets of migraine and ED, involving 188 cell biological processes (BP), 21 cellular components (CC), 31 molecular functions (MF), and 65 signaling pathways. HE staining results show that there were no significant differences between Group A and Group B with regard to any of the parameters. Compared with Group A, the levels of the PI3K, p-AKT, and p-mTOR proteins and PI3K, AKT, and mTOR mRNAs in Group B decreased (P < 0.01). CONCLUSIONS: The decline of erectile function in a rat model of migraine was associated with the PI3K/Akt/mTOR signaling pathway.

In vitro and in vivo investigation of the therapeutic mechanism of Lycium Chinense and Cuscutae Semen on oligoasthenozoospermia.

Through network pharmacology research, we found that CYP19, CYP17, AR and SRD5A2 were potential targets for lycium chinense-cuscutae semen (LC-CS) treatment of oligoasthenozoospermia. Using in vitro and in vivo experiments, tripterygium glycosides were used to induce spermatogenic dysfunction models in GC-1spg cells and SD male rats, respectively, and LC-CS was used to intervene in a spermatogenic dysfunction model. In vitro, LC-CS could repair the ultrastructure of GC-1spg cells damaged by tripterygium glycosides (TG). Compared with TG group, LC-CS could upregulate protein and mRNA expression of CYP19, CYP17, AR and SRD5A2. In vivo, compared with TG, the body mass, testicular mass and epididymal weights of rats in TG + LC-CS increased. Progressive motility + nonprogressive motility spermatozoon (PR + NP) of TG + LC-CS were upregulate than TG. The levels of FSH, LH and testosterone in TG + LC-CS were upregulate than TG. LC-CS can repair the ultrastructure of spermatogonia damaged by TG (the above results are statistically significant, p <.05). Results of H&E staining and TEM showed that the morphology and ultrastructure of testicular tissue in TG + LC-CS were better than that in TG. Compared with TG, LC-CS could upregulate the expression of CYP19, CYP17, AR and SRD5A2 proteins and mRNA.

Prevalence and associated factors of erectile dysfunction, psychological disorders, and sexual performance in primary vs. secondary infertility men.

BACKGROUND: Many infertile couples might experience erectile dysfunction (ED) and significant changes in the quality of sexual life and psychological state though information is limited in secondary infertile men in China. To determine whether primary or secondary infertility is associated with ED, psychological disorders, and sexual performance. METHODS: This was a cross-sectional survey conducted at the Dongzhimen Hospital of Beijing University of Chinese Medicine (06/2019-01/2020). The participants completed a questionnaire including general information, sexual life, simplified International Index of Erectile Function (IIEF-5), Patient Health Questionnaire-9 (PHQ-9), and 7-item Generalized Anxiety Disorder Scale (GAD-7). Multivariable logistic regression was used to identify the factors associated with ED, depression, and anxiety. RESULTS: ED was more frequent in secondary vs. primary infertility (46.5 % vs. 26.7 %, P < 0.001). Compared with men with primary infertility, those with secondary infertility showed lower IIEF-5 scores (P < 0.001), higher occurrence of TOIF (P = 0.001), had a higher awareness of partner's ovulation when having ED (P = 0.001), lower GAD-7 scores (P = 0.016), lower libido (P = 0.005), fewer intercourses per month (P = 0.001) and a lower sexual satisfaction score (P = 0.027). In the multivariate analysis, primary infertility was found to be an independent risk factor of anxiety (OR: 1.812, 95 %CI: 1.015-3.236). Some overlap is observed in factors associated with ED, psychological disorders, and sexual performance between primary and secondary infertility, but some factors are distinct. CONCLUSIONS: The prevalence of ED in secondary infertility men was higher than that of primary infertility men, and the quality of sexual life was decreased. Primary infertility is an independent risk factor of anxiety.