Current data suggest that aristolochic acid (AA) exposure is a putative cause of Balkan endemic nephropathy (BEN), a chronic kidney disease strongly associated with upper tract urothelial carcinoma. The cellular metabolism of AA is associated with the production of reactive oxygen species, resulting in oxidative distress. Purpose: Therefore, the aim of this study was to analyze individual, combined and cumulative effect of antioxidant gene polymorphisms (Nrf2 rs6721961, KEAP1 rs1048290, GSTP1AB rs1695, GSTP1CD rs1138272, GPX3 rs8177412 and MDR1 rs1045642), as well as GSTP1ABCD haplotypes with the risk for BEN development and associated urothelial cell carcinoma in 209 BEN patients and 140 controls from endemic areas. Experimental method: Genotyping was performed using polymerase chain reaction (PCR) and PCR with confronting two-pair primers (PCR-CTTP) methods. Results: We found that female patients carrying both variant GPX3 rs8177412 and MDR1 rs1045642 genotypes in combination exhibited significant risk towards BEN (OR 1 = 3.34, 95% CI = 1.16–9.60, p = 0.025; OR 2 = 3.79, 95% CI = 1.27–11.24, p = 0.016). Moreover, significant association was determined between GPX3rs8174412 polymorphism and risk for urothelial carcinoma. Carriers of variant GPX3*TC + CC genotype were at eight-fold increased risk of BEN-associated urothelial tumors development. There was no individual or combined impact on BEN development and BEN-associated tumors among all examined polymorphisms. The haplotype consisting of variant alleles for both polymorphisms G and T was associated with 1.6-fold increased risk although statistically insignificant (OR = 1.64; 95% CI = 0.75–3.58; p = 0.21). Conclusions: Regarding GPX3 rs8177412 polymorphism, the gene variant that confers lower expression is associated with significant increase in upper urothelial carcinoma risk. Therefore, BEN patients carrying variant GPX3 genotype should be more frequently monitored for possible upper tract urothelial carcinoma development.

Numerous studies point to the significance of cathepsin B (CTSB) in the development of carcinoma. Therefore, the aim of this pilot study was to investigate the levels of cathepsin B (CTSB) and the expression of CTSB mRNA in the plasma of non-Hodgkin lymphoma (NHL) patients. Methods: The study included 44 newly diagnosed NHL patients and 35 healthy volunteers comprising the control group. CTSB in the plasma samples were detected using the enzyme-linked immunosorbent assay (ELISA). Results: The level of CTSB was significantly higher in NHL patients compared to control subjects: 15.28 (11.68–17.23) versus 11.57 (10.12–13.41), p = 0.003. In addition, a positive correlation between plasma CTSB mRNA and CTSB after therapy was observed (rho = 0.591, p = 0.026). Regarding redox parameters, we found a negative correlation between CTSB and the total antioxidant status (TAS) (rho = −0.499, p = 0.035), as well as a positive correlation with the total oxidant status (TOS) (rho = 0.576, p = 0.012). Conclusions: Targeting CTSB might have significant clinical relevance in the diagnostics of NHL.

Background/Objectives: Low-density lipoprotein cholesterol (LDL-C) is a primary therapeutic target in cardiovascular risk assessment. While direct assays are available, LDL-C is frequently estimated using various formulas, whose performance can vary by population and lipid concentration. This study evaluates the analytical agreement and clinical classification performance of four formulas (Spasić–Kotur–Vujović, Friedewald, De Long, and Martin–Hopkins) against directly measured LDL-C. Methods: Lipid profiles from 3935 fasting adult patients were analyzed. LDL-C was directly measured via a homogeneous assay and compared with calculated values using linear regression and Bland–Altman analyses. Analytical bias and classification accuracy were assessed across stratified lipid levels. Results: Among the evaluated equations, the Spasić–Kotur–Vujović formula showed the closest agreement with directly measured LDL-C. It had the lowest mean absolute bias and mean percentage differences across most lipid strata, as well as narrower limits of agreement compared with Friedewald, De Long, and Martin–Hopkins formulas. Although all formulas showed strong correlations with directly measured LDL-C (Pearson’s r correlation coefficient = 0.956–0.958; intraclass correlation coefficient > 0.974), systematic underestimation of LDL-C was observed for all equations and became more pronounced with increasing total cholesterol, LDL-C, triglycerides, and non-high-density lipoprotein cholesterol concentrations. The Spasić–Kotur–Vujović formula achieved the highest overall classification accuracy (70%), followed by De Long (68%), Martin–Hopkins (61%), and Friedewald (58%). Conclusions: Despite strong correlations, clinically relevant differences in bias and classification exist among LDL-C formulas. The Spasić–Kotur–Vujović formula demonstrated superior agreement and accuracy in this population, suggesting it is a more reliable tool for routine laboratory practice. It should be noted that these findings reflect agreement with the specific homogeneous LDL-C assay used on the Alinity c platform (Abbott Laboratories,, Chicago, IL, USA) and may not be directly generalizable to other analytical systems.