Association between prostate cancer and susceptibility, hospitalization, and severity of COVID-19: Based on a Mendelian randomization study.

Several observational studies indicated a close association between prostate cancer and COVID-19. Nevertheless, whether there was a causal effect between them remained obscure. In this study, we aimed to detect the potential association between genetically determined prostate cancer and the risk of COVID-19. A bidirectional Mendelian randomization (MR) study was conducted to investigate the causal links between prostate cancer and COVID-19. Inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode were used to estimate the causality. PIVW < 0.05 was considered statistically significant. The top single nucleotide polymorphisms associated with prostate cancer cases (n = 79,148) and COVID-19 cases (n = 54,071) were extracted from the summary genome-wide association study data obtained from a publicly available database. Cochran Q test was utilized to calculate the degree of heterogeneity. Additionally, we validated our findings in another replication cohort. In the forward MR study, the IVW method suggested no evidence for the causal effect of prostate cancer on COVID-19 susceptibility (OR = 1.00, 95%CI: 0.98-1.02, P = .978), COVID-19 hospitalization (OR = 1.05, 95%CI: 0.99-1.09, P = .054), and COVID-19 severity (OR = 1.03, 95%CI: 0.95-1.11, P = .453). Reverse MR analysis also showed no causal effect of COVID-19 diverse phenotypes on prostate cancer. Furthermore, the result of the East Asian cohort study was consistent with the European cohort. Sensitivity analysis showed no evidence of pleiotropy and heterogeneity. We did not discover genetic evidence to substantiate causal links between prostate cancer and COVID-19. Large-scale randomized controlled trials were required to enhance a more profound comprehension of this relationship in the future.

Genetic liability to human serum metabolites is causally linked to telomere length: insights from genome-wide Mendelian randomization and metabolic pathways analysis.

Background: Telomere has been recognized as a biomarker of accelerating aging, and telomere length (TL) shortening is closely related to diverse chronic illnesses. Human serum metabolites have demonstrated close correlations with TL maintenance or shortening in observational studies. Nevertheless, little is known about the underlying pathological mechanisms, and Mendelian randomization (MR) analysis of serum metabolites may provide a more comprehensive understanding of the potential biological process. Methods: We employed a two-sample MR analysis method to assess the causal links between 486 serum metabolites and TL. We applied the inverse-variance weighted (IVW) approach as our primary analysis, and to assure the stability and robustness of our results, additional analysis methods including the weighted median, MR-Egger, and weighted mode were conducted. MR-Egger intercept test was utilized to detect the pleiotropy. Cochran's Q test was implemented to quantify the extent of heterogeneity. Furthermore, the pathway analysis was conducted to identify potential metabolic pathways. Results: We identified 11 known blood metabolites associated with TL. Among these metabolites, four were lipid (taurocholate, dodecanedioate, 5,8-tetradecadienoate, and 15-methylpalmitate), one amino acid (levulinate (4-oxovaleate)), one carbohydrate (lactate), one nucleotide (pseudouridine), one energy (phosphate), and three xenobiotics (2-hydroxyacetaminophen sulfate, paraxanthine, and ergothioneine). The known protective metabolites included levulinate (4-oxovaleate), dodecanedioate, 5,8-tetradecadienoate, lactate, phosphate, paraxanthine, and ergothioneine. Multiple metabolic pathways have been identified as being implicated in the maintenance of telomere length. Conclusion: Our MR analysis provided suggestive evidence supporting the causal relationships between 11 identified blood metabolites and TL, necessitating further exploration to clarify the mechanisms by which these serum metabolites and metabolic pathways may affect the progression of telomeres.

Genetic liability to inflammatory bowel disease is causally associated with increased risk of erectile dysfunction: Evidence from a bidirectional Mendelian randomization study.

Background: Several observational cohort studies suggested a close correlation between inflammatory bowel disease and erectile dysfunction. Nevertheless, whether there was a causal effect between them remained debatable. In this study, we aimed to detect the underlying causal links between genetically predicted inflammatory bowel disease and the risk of erectile dysfunction. Methods: A bidirectional Mendelian randomization (MR) study was performed to assess the causal link between inflammatory bowel disease and erectile dysfunction. Inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode were utilized to estimate the causality. The top single nucleotide polymorphisms (SNPs) associated with inflammatory bowel disease cases (n = 25,800) and erectile dysfunction cases (n = 1,154) were extracted from the summary genome-wide association study (GWAS) data obtained from a publicly attainable database. MR-PRESSO global outlier test and MR-Egger regression were utilized to explore the horizontal pleiotropy and outlier instrumental variables. Cochran's Q statistic was utilized to detect the heterogeneity. Results: In the forward MR study, the IVW approach demonstrated that genetically determined inflammatory bowel disease exhibited a suggestively causal association with an increased risk of erectile dysfunction (OR: 1.11, 95% CI: 1.02-1.21, p = 0.019), and also the genetically determined Crohn's disease was found to be causally associated with an increased risk of erectile dysfunction (OR: 1.09, 95% CI: 1.02-1.17, p = 0.014). However, the MR analysis results showed no significant evidence supporting a causal effect of ulcerative colitis with erectile dysfunction (OR: 1.02, 95% CI: 0.92-1.14, p = 0.679). Furthermore, the reverse MR analysis showed no causal effects of genetically determined erectile dysfunction on inflammatory bowel disease. Additionally, sensitivity analysis demonstrated no pleiotropy and heterogeneity. Conclusion: Our MR analysis substantiated causal links of inflammatory bowel disease and Crohn's disease on erectile dysfunction, which may further elucidate how inflammatory bowel disease impacted the initiation and development of erectile dysfunction, and facilitated the prevention and clinical management of inflammatory bowel disease in individuals with erectile dysfunction.

Associations of genetically predicted circulating levels of cytokines with telomere length: a Mendelian randomization study.

Background: Telomere length (TL) has been regarded as a biomarker of aging, and TL shortening is associated with numerous chronic illnesses. The mounting evidence has shown that inflammatory cytokines are involved in maintaining or shortening TL, the causality of cytokines with TL remains unknown. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to estimate the underlying correlations of circulating inflammatory cytokines with TL. Methods: Genetic instrumental variables for inflammatory cytokines were identified through a genome-wide association study (GWAS) involving 8,293 European individuals. Summary statistics of TL were derived from a UK Bio-bank cohort comprising 472,174 samples of individuals with European descent. We employed the inverse-variance weighted (IVW) approach as our main analysis, and to ensure the reliability of our findings, we also conducted additional analyses including the weighted median, MR-Egger, MR pleiotropy residual sum and outlier test, and weighted model. Lastly, the reverse MR analyses were performed to estimate the likelihood of inverse causality between TL and the cytokines identified in the forward MR analysis. Cochran's Q test were employed to quantify the degree of heterogeneity. Results: After applying Bonferroni correction, a higher circulating level of Interleukin-7 (IL-7) was suggestively associated with TL maintaining (OR:1.01, 95%CI:1.00-1.02, P=0.032 by IVW method). The study also revealed suggestive evidence indicating the involvement of Interleukin-2 receptor, alpha subunit (IL-2Rα) level was negatively associated with TL maintaining (OR:0.98, 95%CI:0.96-1.00, P=0.045 by IVW method), and the weighted median approach was consistent (OR:0.99, 95%CI:0.97-1.00, P=0.035). According to the findings of reverse MR analysis, no significant causal relationship between TL and cytokines was explored. Our analysis did not reveal any substantial heterogeneity in the Single nucleotide polymorphisms or horizontal pleiotropy. Conclusions: Our MR analysis yielded suggestive evidence supporting the causality between circulating IL-7 and IL-2Rα and telomere length, necessitating further investigations to elucidate the mechanisms by which these inflammatory cytokines may impact the progression of telomeres.

Case Report: An extremely rare penile shrapnel injury.

Penile shrapnel injuries are an exceedingly rare occurrence and a medical emergency. Herein, we present a case of penile shrapnel wounds in an adolescent male and discuss the management and complications associated with penetrating injuries to penile. We reported that an 18-year-old Chinese armed police soldier underwent debridement, shrapnel removal and suturing under spinal anesthesia. Six days postoperatively, he was discharged from the hospital smoothly. The patient reported normal erectile function and urination following discharge. With a follow-up of three months, the patient exhibited no symptoms of dysuria or erectile dysfunction. It is explicitly stated that prompt surgery intervention described in this report resulted in optimal prognosis. Penile shrapnel injury is a rare phenomenon typically associated with emergency drill and military training involving explosive shells. With regard to penetrating penile injury, timely surgical exploration is essential because it avoids penile plaque formation, penile fibrosis and angulation, and accelerates the return to erectile and urination function.

Responses of Nonprotein Thiols to Stress of Vanadium and Mercury in Maize (Zea mays L.) Seedlings.

The heavy metal pollution in ecosystems is of increasing global concern. This study investigated firstly the responses of phytochelatins (PCs), glutathione (GSH) and other nonprotein thiols (NPT) in maize seedlings under vanadium (V), mercury (Hg) or their combined stress. With V or V-Hg combined stress, the contents of PCs, GSH and NPT in shoots and roots both increased with increasing the V stress level, and reached the maximum when the V stress level was 5 mg/L. Accumulation of V in all organs of maize seedlings was in sequence as follows: roots ≫ shoots, while Hg inhibited the accumulation of V. Results show that the root of plant has stronger tolerance to V, and the low V stress level can promote the synthesis of thiol groups to reduce the toxicity of Hg for plants.

Chrysin induces cell growth arrest, apoptosis, and ER stress and inhibits the activation of STAT3 through the generation of ROS in bladder cancer cells.

Chrysin is a natural flavone that has various biological activities, including antitumor effects. However, the effect of chrysin on bladder cancer cells remains elusive. The present study investigated the effects of chrysin on bladder cancer cells and its underlying mechanisms. The results demonstrated that chrysin induced apoptosis via the intrinsic pathway, as evidenced by activation of caspase-9 and caspase-3, however not caspase-8. In addition, chrysin reduced the expression of anti-apoptotic B cell lymphoma (Bcl) proteins including Bcl-2, Mcl-1, Bcl-xl, and promoted the protein expression of pro-apoptotic Bcl-2 associated X, apoptosis regulator. Chrysin also induced endoplasmic reticulum stress via activation of the unfolded protein response of PRKR-like endoplasmic reticulum kinase, eIF2α and activating transcription factor 4 in bladder cancer cells. Additionally, chrysin inhibited the signal transducer and activator of transcription 3 pathway. Furthermore, the generation of reactive oxygen species (ROS) was detected following treatment with chrysin. The ROS scavenger N-acetylcysteine inhibited the antitumor effect of chrysin. Collectively, these results indicate chrysin may act as a promising therapeutic candidate for targeting bladder cancer.