Aims: This study aimed to determine the expressions of TGR5 (G protein-coupled bile acid receptor 1) and NADPH oxidase 5 (NOX5) in renal cancer subtypes. Methods: In formalin-fixed, paraffin-embedded tissue sections of renal tumor subtypes, TGR5 and NOX5 protein expressions were measured by immunohistochemical staining and mRNA expressions were measured by RT-PCR. Results: Our results showed that TGR5 and NOX5 exhibited differences in their expression levels in RCC subtypes, and that TGR5 expression was upregulated in papillary RCC (r=0.53, p<0.01). A positive correlation of TGR5 with NOX5 was detected in the same subtype (r=0.49, p<0.01). After COCOR analysis, a statistically significant difference was found in the TGR5-NOX5 correlation between papillary RCC and clear cell RCC subtypes (z=1.92, p=0.02). At the same time, expression profiles showed that TGR5 was highly expressed in all groups except clear cell RCC compared to normal kidney tissue, but among these, TGR5 had the diagnostic power to distinguish papillary RCC from other groups (AUC=0.94, 95% CI: 0.64–0.95, p=0.005). Conclusion: The present findings indicate the potential of TGR5 as a diagnostic biomarker for papillary RCC, while suggesting that it may have a functional role in regulating the tumor microenvironment together with NOX5.

Breast cancer (BC) is a heterogeneous disease with distinct molecular subtypes that exhibit variable immune responses and metabolic profiles. Recent studies have suggested that immunometabolic pathways play a role in tumor progression and treatment resistance. This study investigates the expression patterns of ALKBH7 and NLRP3 across BC molecular subtypes and explores their relationships with clinicopathological parameters and potential immunometabolic profiles. A total of 118 BC patients were classified into HER2+, TNBC, Luminal A, and Luminal B subtypes. Gene expression levels of ALKBH7 and NLRP3 were analyzed using quantitative real-time PCR (qRT-PCR), and correlations with clinical markers were assessed. ALKBH7 and NLRP3 expression levels varied significantly between subtypes, with the highest expression observed in HER2+ tumors. Strong positive correlations were found between ALKBH7 and NLRP3 in all subtypes, particularly in HER2+ (r = 0.812, p < 0.001). Additionally, NLRP3 correlated with Ki-67 in Luminal B tumors, indicating a link between inflammation and proliferative capacity. These findings suggest that ALKBH7 may function as a dual-role biomarker involved in metabolic adaptation and immune signaling in BC. The strong co-expression of ALKBH7 and NLRP3 suggests a functional association between these molecules that may be critical in shaping the tumor microenvironment. This co-expression set, particularly in aggressive subtypes (HER2+ and TNBC), warrants further mechanistic validation as a potential prognostic marker and a novel therapeutic vulnerability.

The aim of present study, to evaluate the genotoxic potential of 1-(4-(3,3-dimethyl-1,6-dioxo-2,3,4,6,11,13-hexahydro-1H-indazolo[1,2b] phthalazine-13yl)phenyl)-2-phenylazetidine-3-yl-acetate which was synthesised assuming that it may be a pharmaceutical raw material and found to inhibit human carbonic anhydrase I, II isozymes. To determine the genotoxic potential of this phthalazine substituted β-lactam compound, chromosomal aberration (CA) and micronucleus (MN) tests were implemented in human peripheral blood lymphocytes. In these tests, lymphocyte cultures were treated with four concentrations (30, 15, 7.5, 3.75 μg/mL) of test compound and simultaneously with negative control (sterile distilled water), solvent control (DMSO) positive control (MMC). According to our results, CA frequencies were significantly increased in two high applied concentrations (30, 15 μg/mL) compared with negative and solvent control. MN frequencies were significantly increased in three applied concentrations (30, 15, 7.5 μg/mL) except lowest concentration (3.75 μg/mL) compared with solvent control. Mitotic indices were also affected by treatment with test compound. The obtained results provide evidence to demonstrate that new phthalazine substituted β-lactam derivative can exert genotoxic and cytotoxic effects in peripheral human lymphocytes especially at high concentrations.