Luteolin and delphinidin are the flavonoids with known protective roles. They inhibit genotoxic effects induced by halogenated boroxine (HB) in vitro. Statistically significant decrease in the frequency of micronuclei and nuclear buds and suppression of the occurrence of aberrant cells were observed before, but mechanism of its anti-genotoxic activity is still not clear. In our experiment we aimed to quantify HB effects on the relative expression of CAT (catalase) gene and explore antioxidative effects of luteolin and delphinidin via restoration of CAT gene activity. Cell cultures from peripheral blood lymphocytes of five healthy donors were established and treated with independent and concomitant treatments of HB with luteolin or delphinidin. Total RNA was isolated from harvested cells and reverse-transcribed. SYBR based Real-Time PCR amplification method was used. Analysis of results included normalization of ratio of target (CAT) and housekeeping (GAPDH) gene and statistical analysis (REST®). Luteolin itself lead to downregulation of relative CAT gene expression as well as HB. But simultaneous treatment of HB and bioflavonoids lead to upregulation. Delphinidin as independent treatment and as simultaneous treatment caused upregulation of relative CAT gene expression. Obtained results may indicate protective role of delphinidin and luteolin to oxidative damage caused by HB, and also that new approaches to the treatment applications of HB should include bioflavonoids and monitoring corresponding antioxidant system. Our findings indicate that there is a quantifiable effect of luteolin and delphinidine on antioxidant genes which could be used in exact monitoring of oxidative stress related events.

Current standard treatments for osteosarcoma have not been changed for decades and have limited and variable success. The advancement of precision medicine technologies, along with the drug-repurposing and fast drug-screening methodologies available, has opened new avenues for the development of more effective therapeutic strategies. In this study, we evaluated the effectiveness of halogenated boroxine (HB) and dextran-coated cerium oxide nanoparticles—DexCeNPs (SD2)—in an in vitro osteosarcoma model. Both agents were tested individually and in combination. The research encompassed assessments of treatment-related cytotoxicity and cell viability, oxidative stress, and apoptotic and necrotic responses, as well as the effects on 3D spheroid models. The results demonstrated that the effects of HB and SD2 were strongly influenced by the dose, exposure time, and cell type. Both exhibited distinguished antitumor activity through cytotoxicity and specific reactive oxygen species (ROS) induction. The combined treatment produced modulated responses that were dependent on the treatment ratio and cell line, suggesting potential synergistic or selective interactions. Notably, the outcomes of the analysis conducted in 3D models revealed reduced toxicity toward non-tumor cells. These findings suggest the improved efficacy of HB and SD2 used in combination as a selective and novel antitumor strategy and underscore the need for further mechanistic studies at the transcriptomic and proteomic levels to elucidate the underlying pathways and clarify the mechanisms of action.

Climate change poses an increasing challenge to livestock production, making the identification of thermally resilient breeds crucial. This study investigated the expression patterns of eight thermal stress-related genes (HSP90AA1, HSPA8, HSPA1A, IL-6, IL-10, TNF-α, NOS-3, and SOD-2) in two strains of indigenous Pramenka sheep (Hercegovačka and Dubska) under different climatic conditions. Blood samples were collected from 96 sheep across four locations during summer and winter seasons. Gene expression was analyzed using RT-PCR and evaluated against comprehensive environmental data, including the temperature–humidity index (THI). Principal component analysis revealed distinct gene expression patterns between strains and seasons. The Hercegovačka strain showed consistently higher expression of HSP90AA1 compared to the Dubska strain in both seasons (summer: 5.81 vs. 2.47; winter: 4.38 vs. 1.19, p < 0.05), with all individuals exhibiting upregulation during summer and 95.8% showing upregulation during winter. Both strains demonstrated reduced expression of pro-inflammatory cytokines (IL-6, TNF-α) and increased expression of anti-inflammatory IL-10, suggesting maintained immunocompetence under thermal stress. The expression patterns of oxidative stress-related genes (SOD-2, NOS-3) indicated effective management of oxidative stress in both strains. These results suggest superior thermal adaptation in the Hercegovačka strain, particularly through HSP-mediated cellular protection mechanisms, while both strains show favorable immune and oxidative stress responses. These findings provide valuable insights for climate-resilient sheep breeding programs and the conservation of adaptive genetic resources.