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Background: Treatment failure following androgen deprivation therapy (ADT) presents a significant challenge in the management of advanced prostate cancer. Thus, understanding the genetic factors influencing this process could facilitate the development of personalized treatments and innovative therapeutic strategies. The phosphoinositide 3-kinase (PI3K)/AKT signaling pathway plays a pivotal role in controlling cell growth and tumorigenesis. We hypothesized that genetic variants within this pathway may affect the clinical outcomes of patients undergoing ADT for prostate cancer. Methods: We genotyped 399 single-nucleotide polymorphisms (SNPs) across 28 core PI3K/AKT pathway genes in a cohort of 630 patients with prostate cancer undergoing ADT. We assessed the potential association of the SNPs with patient survival. Functional analyses of the implicated genes were also performed to evaluate their effects on prostate cancer. Results: After multivariate Cox regression analysis and multiple testing correction, GABRB3 rs12591845 exhibited the most significant association with both overall and cancer-specific survivals (P < 0.003). A comprehensive pooled analysis of 16 independent gene expression datasets revealed elevated expression of GABRB3 in prostate cancer tissues compared to that in normal tissues (P < 0.001). Furthermore, gene set enrichment analysis unveiled differential enrichment of pathways such as myogenesis, interferon γ and α responses, and the MYC proto-oncogene pathway in tumors with elevated GABRB3 expression, implying a role for GABRB3 in prostate cancer. Conclusion: Our results suggest that rs12591845 could potentially serve as a valuable prognostic indicator for patients undergoing ADT. The potential role of GABRB3 in promoting prostate tumorigenesis is also highlighted. [ABSTRACT FROM AUTHOR]

Background: The association between occupational noise exposure and hypertension is inconsistent because of an exposure bias caused by outer-ear measurements of noise levels among workers. This study used hearing loss values (HLVs) measured at 4 kHz and 6 kHz in both ears as a biomarker to investigate the chronic effects of noise exposure on hypertension in 790 aircraft-manufacturing workers.Methods: Participants were divided into a high hearing loss (HL) group (n = 214; average HLVs ≥ 30 decibel [dB] at 4 kHz or 6 kHz bilaterally; 83.1 ± 4.9 A-weighted decibel [dBA]), a median HL group (n = 302; 15 ≤ average HLVs < 30 dB at 4 kHz or 6 kHz bilaterally; 83.1 ± 4.4 dBA) and a low HL group (n = 274; average HLVs < 15 dB at 4 kHz or 6 kHz bilaterally; 82.2 ± 5.1 dBA) based on the results of pure tone audiometry. Multivariate logistic regressions were used to estimate the risk of hypertension between groups.Results: The prevalence rates of hypertension were significantly higher in the high HL (43.5%; p = 0.021) and median HL (42.1%; p = 0.029) groups than in the low HL group (33.2%). The high HL and median HL workers had 1.48-fold (95% confidence interval [95%CI] = 1.02-2.15; p = 0.040) and 1.46-fold (95%CI = 1.03-2.05; p = 0.031) higher risks of hypertension relative to the low HL workers. Employment duration was significantly and positively correlated with the risk of hypertension among workers with average HLVs ≥ 15 dB at 4 kHz (p < 0.001) and 6 kHz (p < 0.001) bilaterally.Conclusions: Our findings suggest that high-frequency hearing loss is a good biomarker of occupational noise exposure and that noise-induced hearing loss may be associated with the risk of hypertension. [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies have reported the association between hypertension and exposure to road traffic noise, but the association between noise frequency characteristics is not clear. This study investigated the association between exposure to different frequency components of road traffic noise and the prevalence of hypertension in central Taiwan.Methods: We recruited 820 residents living near main roads for more than 3 years. Frequency components of traffic noise and traffic flow rates during 0900-1700 on weekdays were measured simultaneously in 2008. Multiple logistic regressions were conducted to estimate odds ratios (ORs) for diagnosed hypertension, adjusting for potential confounders and the total traffic flow rate.Results: The high-exposure group (≥ the median of noise levels [decibels, dB]) at 63 Hz, 125 Hz and 1000 Hz had ORs for hypertension of 2.77 (95% confidence interval [CI]: 1.17-6.52), 4.08 (95% CI: 1.57-10.63) and 1.98 (1.00-3.92) (95% CI: 1.00-3.92), respectively, compared to the low-exposure group (< the median of noise levels [dB]). There was an increasing trend in the prevalence of hypertension by exposure to road traffic noise at 63, 125 and 1000 Hz in all subjects and in men. Total subjects exposed to ≥ 51 dB at 125 Hz had an OR of 4.65 (95% CI = 1.46-14.83) compared to those exposed to < 47 dB.Conclusions: With the possible bias of exposure misclassification and a bias from using diagnosed hypertension, these results suggest that exposure to road traffic noise at low and hearing-sensitive frequencies may be associated with hypertension and exposure to noise at 125 Hz may have the greatest risk for hypertension. [ABSTRACT FROM AUTHOR]

Background: Successful reproductive efforts require the establishment of a situation favorable for reproduction that requires integration of both behavior and internal physiological events. TR4 nuclear receptor is known to be involved in male fertility via controlling spermatogenesis, yet its roles in regulating other biological events related to reproduction have not been completely revealed., Methods: Male TR4 knockout (TR4 -/-) and wild type mice were used for the sexual behavior and penile dysfunction studies. Mice were sacrificed for histological examination and corresponding genes profiles were analyzed by quantitative RT-PCR. Reporter gene assays were performed., Results: We describe an unexpected finding of priapism in TR4 -/- mice. As a transcriptional factor, we demonstrated that TR4 transcriptionally modulates a key enzyme regulating penis erection and neuronal nitric oxide synthese NOS (nNOS). Thereby, elimination of TR4 results in nNOS reduction in both mRNA and protein levels, consequently may lead to erectile dysfunction. In addition, male TR4 -/- mice display defects in sexual and social behavior, with increased fear or anxiety, as well as reduced mounting, intromission, and ejaculation. Reduction of ER alpha, ER beta, and oxytocin in the hypothalamus may contribute to defects in sexual behavior and stress response., Conclusions: Together, these results provide in vivo evidence of important TR4 roles in penile physiology, as well as in male sexual behavior. In conjunction with previous finding, TR4 represents a key factor that controls male fertility via regulating behavior and internal physiological events.