OBJECTIVES:To investigate the association between p53 gene expression, prostate-specific antigen (PSA), and oxidative stress markers (sialic acid and vitamin C) in infertile men. METHODS:This case-control study involved 150 infertile men and 150 fertile controls from Kerala, India. Serum sialic acid, PSA, and vitamin C were measured by ELISA, and p53 expression was quantified by real-time PCR (2-ΔΔCt method). Non-parametric tests, correlation analyses, regression models, and ROC curves were used to assess associations, predictive value, and diagnostic performance. RESULTS:Infertile men showed significantly lower serum sialic acid and vitamin C levels and higher PSA concentrations and p53 gene expression than fertile controls (all p<0.05). p53 expression was significantly associated with PSA, sialic acid, and vitamin C in infertile men. Although no biomarker independently predicted infertility in logistic regression, robust linear regression identified vitamin C as a strong negative predictor and PSA as a positive predictor of p53 expression. ROC analysis revealed moderate discriminative ability for vitamin C, PSA, and sialic acid, while p53 expression alone showed limited diagnostic accuracy. CONCLUSIONS:The concurrent elevation of p53 expression, increased PSA levels, and antioxidant depletion in infertile men reflects activation of cancer-related cellular stress and genomic surveillance pathways rather than evidence of malignancy.
Diabetes mellitus (DM) is a major global health concern closely associated with cardiovascular diseases, particularly diabetic cardiomyopathy (DCM), which can develop independently of hypertension or coronary artery disease. Chronic hyperglycemia in DM promotes oxidative stress and inflammation, driving myocardial dysfunction and fibrosis. The NLRP3 inflammasome, a cytosolic multiprotein complex, is a central mediator linking metabolic stress to innate immunity. In both type 1 and type 2 DM, it senses injurious stimuli including mitochondrial reactive oxygen species (ROS), ATP, and advanced glycation end-products (AGEs) activating caspase-1 and triggering the release of pro-inflammatory cytokines IL-1β and IL-18, thereby promoting inflammation and pyroptotic cell death. This review focuses on NLRP3 inflammasome activation in the diabetic heart, emphasizing upstream regulators such as thioredoxin-interacting protein (TXNIP) and NF-κB and downstream consequences including cardiomyocyte death, fibrosis, and contractile maladaptation. Therapeutic approaches targeting NLRP3 range from conventional drugs, including metformin and SGLT2 inhibitors, to specific inhibitors such as MCC950 and colchicine, highlighting their cardioprotective potential. Emerging evidence on microRNA-mediated regulation, exosomal signalling, and inter-organ communication further elucidates how systemic inflammation contributes to heart failure in diabetic patients. Despite progress, significant gaps remain regarding the cell-type specificity, temporal dynamics, and epigenetic control of NLRP3 activation in the diabetic myocardium, limiting translation of preclinical findings into effective therapies. Understanding these mechanisms may enable precise, targeted interventions to mitigate inflammation-driven cardiac injury in DM.
Abstract Objectives To evaluate biochemical, hormonal, genetic, and mitochondrial alterations associated with cardiovascular risk in SCH, emphasizing the interplay between NT-proBNP, succinate dehydrogenase (SDH) complex activity, and thyroid-stimulating hormone receptor (TSHR) gene expression. Methods A case–control study was conducted involving SCH patients and age-matched euthyroid controls. Serum thyroid profiles, NT-proBNP, and SDH complex activity were quantified by standard assays, and TSHR gene expression was measured using RT-PCR. Receiver operating characteristic (ROC) analyses assessed diagnostic performance, and multiple linear regression identified independent predictors of TSHR expression. Results Compared with controls, SCH cases showed significantly higher TSH and NT-proBNP levels, reduced SDH complex activity, and upregulated TSHR gene expression (p<0.05). ROC analysis demonstrated excellent diagnostic accuracy for NT-proBNP, SDHA, and TSHR expression. After adjustment for confounders, SDH complex activity remained the only independent predictor of TSHR expression, whereas NT-proBNP lost independent significance, suggesting an indirect or interaction-mediated effect. Conclusions SDHA serves as a robust independent predictor of cardiovascular risk in SCH, highlighting mitochondrial dysfunction in thyroid receptor regulation. NT-proBNP showed predictive potential but not independent significance, indicating secondary modulation by hormonal or metabolic factors. Larger longitudinal studies are warranted for validation.
OBJECTIVES:This study aimed to investigate the association between thyroid hormone disturbances, obesity-related parameters, and the expression profiles of Y-linked spermatogenic genes (AZFa, AZFb, and AZFc) in infertile men, and to determine whether endocrine and metabolic alterations predict AZF gene dysregulation. METHODS:A case-control study included 150 infertile men and 150 fertile controls. Anthropometric indices and hormonal, biochemical, and inflammatory markers were assessed. Relative expression levels of AZFa, AZFb, and AZFc genes were quantified using qRT-PCR and the 2ˆ-ΔΔCT method. Correlation analysis, LASSO regression, and ROC curve modeling were performed to identify predictors of AZF gene downregulation. RESULTS:Infertile men had significantly higher BMI, waist circumference, and thyroid-stimulating hormone (TSH) levels, with reduced triiodothyronine (T3) and thyroxine (T4) concentrations (p<0.001). AZFa, AZFb, and AZFc expression levels were significantly decreased and negatively correlated with TSH, BMI, and inflammatory cytokines. A combined model of TSH, BMI, and interleukin-6 demonstrated the highest diagnostic accuracy (AUC=0.88), with 86 % sensitivity and 80 % specificity. CONCLUSIONS:Thyroid dysfunction, obesity, and systemic inflammation synergistically downregulate AZF gene expression and impair spermatogenesis. Integrating endocrine, metabolic, inflammatory, and molecular markers may improve diagnostic precision and personalized management of male infertility.
Male infertility accounts for nearly half of all infertility cases worldwide but remains under-recognised. This review summarises the current genetic and molecular determinants of male infertility and their clinical implications. A comprehensive narrative review was conducted on chromosomal abnormalities, Y-chromosome microdeletions, single-gene mutations, epigenetic alterations, mitochondrial dysfunction and syndromic conditions affecting spermatogenesis. Advances in high-resolution genomic tools, including whole-exome sequencing (WES), next-generation sequencing (NGS) and genomic microarrays, were evaluated alongside assisted reproductive technologies (ARTs) such as intracytoplasmic sperm injection (ICSI) and pre-implantation genetic testing (PGT). Modern genomic technologies enhance diagnostic accuracy and enable personalised reproductive management. Molecular mechanisms, including sperm DNA fragmentation, non-coding RNA regulation and environmentally influenced epigenetic changes, are major contributors to infertility. Integrating molecular diagnostics with ART supports precision-based treatment and genetic counselling. Genetic and molecular insights are transforming male infertility care through individualised diagnostics and targeted interventions. Continued genomic and molecular research will further refine diagnosis, optimise ART outcomes and advance personalised reproductive medicine.
