Exploring the causal association between serum metabolites and erectile dysfunction: a bidirectional Mendelian randomisation study.

Erectile dysfunction is a common sexual disorder in men. Some studies have found a strong association between some serum metabolites and erectile dysfunction. To investigate this association further, we used bidirectional Mendelian randomisation to investigate causality and possible biological mechanisms.Firstly, this study screened the statistics of genome-wide association studies of serum metabolites and erectile dysfunction to obtain instrumental variables. Inverse variance weighting was used as the primary method for causal effect analysis of instrumental variables in forward or reverse Mendelian randomisation, and the results obtained by MR-Egger regression and the weighted median method were used as references. Subsequently, the metabolites causally associated with erectile dysfunction were subjected to replication analyses and meta-analyses, and the results of the meta-analyses were analysed by pathway analyses to find influential pathways. In this process, Mendelian randomisation results need to be assessed for stability and reliability using sensitivity analysis.It was found that a total of six serum metabolites were causally associated with erectile dysfunction in a forward Mendelian randomisation study. 1,3,7-trimethyluraten (0.85 (0.73-0.99), P = 0.0368), ergothioneine (0.65 (0.45-0.94), P = 0.0226) and gamma-glutamylglutamate (0.63 (0.46-0.88), P = 0.0059) were protective against the development of erectile dysfunction, whereas 2-hydroxyhippurate (1.10 (1.02-1.19), P = 0.0152), N2,N2-dimethylguanosine (1.57 (1.02-2.40), P = 0.0395) and octanoylcarnitine (1.38 (1.06-1.82), P = 0.0183) were able to induce the development of erectile dysfunction. In addition, metabolic pathway analysis showed that 1,3,7-trimethylurate was able to influence the development of erectile dysfunction via the caffeine metabolism pathway (P = 0.0454). On the other hand, reverse Mendelian randomisation analysis showed that erectile dysfunction reduced serum homocitrulline levels (0.99 (0.97-1.00), P = 0.0360). Sensitivity analyses, including heterogeneity tests and pleiotropy tests, confirmed the reliability of the results.In conclusion, this study demonstrated a bidirectional causal relationship between serum metabolites and erectile dysfunction using bidirectional Mendelian randomisation analysis and replication meta-analysis. On this basis, this study provides a new direction of thinking and strong evidence for the therapeutic application and adjunctive diagnosis of serum metabolites in erectile dysfunction, and provides a certain reference value for subsequent related studies.

miR-26 suppresses renal cell cancer via down-regulating coronin-3.

Coronin-3 (coronin-1C), a homotrimer F-actin-binding protein, has been reported to be important for metastasis in several types of cancers such as lung cancer, gastric cancer, and breast cancer. Here, we present an investigation of the expression and function of coronin-3 in renal cell cancer for the first time. We also confirmed that miR-26 directly targets coronin-3 and down-regulates its expression by western blot assay and dual-luciferase reporter system. The results of MTT and colony formation assay showed that miR-26 suppressed cell proliferation. Wound healing and transwell assay revealed that miR-26 inhibited migration and invasion of renal cancer cell. Moreover, overexpression of coronin-3 could reverse the miR-26-induced inhibition in cell growth and metastasis. Thus, our study suggests that coronin-3 should serve as a potential therapeutic target in renal cell cancer and provide a candidate for miRNA therapy.

[Effects of melatonin on oxidative stress and apoptosis-related gene signaling pathways following testicular torsion in rats].

OBJECTIVE: To investigate the effects of melatonin on the oxidative stress and signaling pathways of apoptosis-related genes following testicular torsion/detorsion in male rats. METHODS: Twenty-four healthy male Sprague-Dawley rats were randomly divided into a control, a torsion and a melatonin group of equal number. The torsion model was made in the animals of the latter two groups by 720° torsion of the left testis for 2 hours. The rats of the torsion and melatonin groups received intraperitoneal injection of isotonic saline and melatonin (17 mg/kg) respectively at 15 minutes prior to detorsion. At 24 hours after modeling, testis tissues were collected from the rats for detection of the apoptosis of the germ cells by flow cytometry (FCM), analysis of the expressions of Fas, Fas ligand (FasL) and Bax mRNA by quantitative real-time PCR (qRT-PCR), measurement of the cytochrome C content released from the mitochondrion by Western blot, and determination of the total antioxidant capacity (T-AOC) and the levels of myeloperoxidase (MPO) and malodialdehyde (MDA) by spectrophotometry. RESULTS: Compared with the torsion group, the rats treated with melatonin showed significantly increased normal testicular cells (ï¼»77.81 ± 6.52ï¼½% vs ï¼»88.61 ± 7.93ï¼½%, P < 0.05), decreased early apoptotic germ cells (ï¼»16.74 ± 3.16ï¼½% vs ï¼»6.97 ± 1.65ï¼½%, P < 0.05), down-regulated expressions of Fas (ï¼»4.52 ± 0.29ï¼½ vs ï¼»2.66 ± 0.37ï¼½, P < 0.01), FasL (ï¼»2.82 ± 0.30ï¼½ vs ï¼»1.73 ± 0.18ï¼½, P < 0.01) and Bax mRNA (ï¼»2.39 ± 0.18ï¼½ vs ï¼»1.50 ± 0.14ï¼½, P < 0.01), reduced levels of cytochrome C (ï¼»1.40 ± 0.38ï¼½ vs ï¼»0.67 ± 0.30ï¼½, P < 0.01), MPO (ï¼»0.52 ± 0.15ï¼½ vs ï¼»0.19 ± 0.10ï¼½ U/g prot, P < 0.01) and MDA ï¼»6.37 ± 1.73ï¼½ vs ï¼»3.98 ± 0.90ï¼½ nmol/mg prot, P < 0.01) and elevated T-AOC (ï¼»0.76 ± 0.25ï¼½ vs ï¼»1.55 ± 0.32ï¼½ U/mg prot, P < 0.01). CONCLUSIONS: Melatonin has a significant protective effect on spermatogenesis after testicular torsion by regulating the expressions of apoptosis-related genes and increasing T-AOC in the testis tissue.