TBHP-induced oxidative stress alters microRNAs expression in mouse testis.

PURPOSE: Reactive oxygen species (ROS) and oxidative stress is one of the main reasons of male infertility. MicroRNAs (miRNAs) regulate multiple intracellular processes. Alterations in miRNAs expression may occur in different conditions and diseases. In this study, the effect of oxidative stress induced by tertiary-butyl hydroperoxide (TBHP) on the expression of candidate miRNAs in mouse testis was investigated. METHODS: After determining median lethal dose (LD50), TBHP was intraperitoneally (ip) injected at the dilution of 1:10 LD50 into the adult male mice for 2 weeks, and then testis tissues were removed in order to assay the ROS level. Total RNA was extracted and the expression of five miRNAs was quantified by reverse transcription-real time polymerase chain reaction (RT-qPCR). RESULTS: The flow cytometry analysis showed a significant increase in ROS level in testis. The expression of three out of five selected miRNAs, including miR-34a, miR-181b and miR-122a, showed some degrees of changes following exposure to oxidative stress. These miRNAs are involved in antioxidant responses, inflammation pathway and spermatogenesis arrest. CONCLUSIONS: In conclusion, TBHP alters the miRNA expression profile of testis which might play a potential role in oxidative and antioxidative responses and spermatogenesis.

Development, validation and comparison of two nomograms predicting prostate cancer at initial 12-core biopsy.

AIM: Our aim was to establish, validate and compare two nomograms in an Iranian population for the first time using clinical, laboratory and transrectal ultrasonography (TRUS) findings for predicting prostate cancer at initial biopsy. METHODS: Data were collected on a total of 916 men referred for an initial prostate biopsy in our center in a 7-year period. Variables analyzed included age, prostate-specific antigen (PSA), free/total PSA (%fPSA), digital rectal examination (DRE) findings, prostate volume (PV) and presence of hypoechoic lesion on TRUS. Univariate logistic regression models were fitted to test cancer predictors. Two multivariate logistic regression models were fitted to create nomograms. Both models were internally validated. Calibration of nomograms was assessed graphically. The area under the receiver operating characteristic curve (AUC) was calculated as a scale of discrimination and predictive accuracy and also used to compare models. RESULTS: Prostate cancer was detected in 221/669 (33%) men. Based on univariate logistic regression, all of variables except DRE were significant predictors of prostate cancer, with highest AUC for PV (AUC 0.696, 95% CI 0.653-0.738).AUC of nomogram with and without TRUS findings and PSA alone were 0.791, 0.721 and 0.624, respectively. In internal validation, both nomograms had acceptable calibration plots. CONCLUSION: Our nomogram based on age, DRE, PSA, %fPSA and TRUS finding was significantly more accurate in predicting initial prostate biopsy outcome in men.