Biology subjects

Pereckova, J.

Publications and source records attributed to Pereckova, J..

3 recordsLinked to original sources

bioRxiv2026

10-Nitro-oleic acid improves survival following gamma irradiation and modulates hematopoietic and intestinal responses

Acute radiation syndrome remains a major consequence of high-dose ionizing radiation exposure, and effective pharmacological countermeasures are limited. Nitro-fatty acids possess anti-inflammatory and cytoprotective properties, suggesting potential effectiveness in radiation injury. Here, we investigated the radioprotective effects of 10-nitro-oleic acid (10-NO2OA) in mouse models of total body irradiation (TBI). C57BL/6 mice were exposed to either sublethal (4 Gy) or LD50-level (7.5 Gy) gamma irradiation and treated with 10-NO2OA according to pre-irradiation, post-irradiation, or combined treatment regimens. Survival, hematological responses, bone marrow cells (BMCs)/colony-forming units (CFU), plasma granulocyte colony-stimulating factor (G-CSF), NRF2-responsive signaling, and intestinal responses were evaluated. Administration of 10-NO2OA before and after irradiation significantly improved 30-day survival following 7.5 Gy TBI (57% vs. 20% in vehicle-treated controls). In contrast, post-irradiation treatment alone was ineffective, whereas pre-irradiation treatment alone produced a non-significant trend toward improved survival. The protective effect was absent in BALB/c mice, indicating strain dependence. Although 10-NO2OA did not prevent long-term radiation-induced cytopenia, it increased neutrophil and platelet counts, elevated plasma G-CSF levels shortly after irradiation, and transiently enhanced BMC counts. In irradiated BMCs, 10-NO2OA activated NRF2-responsive gene expression in vitro and in vivo. Exploratory intestinal analyses revealed improved macroscopic appearance and partial restoration of irradiation-suppressed cytokine and growth factor production. In conclusion, 10-NO2OA improves survival following LD50-level gamma irradiation and is associated with modulation of hematopoietic, cytoprotective, and intestinal responses. These findings identify 10-NO2OA as a promising candidate radioprotective agent and support a multifactorial mechanism of action.

pharmacology and toxicology↗

bioRxiv2026

Hypoxia-conditioned HNSCC cell line secretomes drive phenotypic, functional, and transcriptional reprogramming of human neutrophils

Neutrophils display marked functional plasticity in cancer; however, it remains poorly understood how soluble factors derived from hypoxic and irradiated head and neck squamous cell carcinoma (HNSCC) cells reprogram neutrophil phenotype and function. Here, we employed a well characterized and controlled in vitro model to examine how tumor-conditioned media (TCM) from HNSCC cell lines cultured under ambient (21% O2) or hypoxic (1% O2) conditions, with or without 6 Gy gamma irradiation, modulate human neutrophil phenotype, and functional and transcriptional responses. Initial analyses were performed using TCM from three different HNSCC cell lines, whereas subsequent mechanistic characterization focused on FaDu-derived TCM. We show that TCM prolongs neutrophil survival in a cell line-dependent manner. Among the tested cell lines, hypoxia-conditioned FaDu-derived TCM promoted immunomodulatory neutrophil state characterized by enhanced survival, selective priming of ROS production, and elevated TRAIL-R3/TRAIL-R2 ratio. Induction of classical activation markers (CD11b, CD62L) was not evident. Transcriptomic analysis revealed minimal effects of normoxic TCM. Hypoxia-conditioned TCM induced a pronounced transcriptional program enriched in hypoxia- and stress-associated pathways. In contrast, irradiation of tumor cells had a limited additional impact on neutrophil reprogramming. Together, these findings indicate hypoxia-conditioned tumor secretomes as important drivers of neutrophil functional adaptation in vitro, supporting a model in which soluble factors alone are sufficient to induce a persistent, immunomodulatory neutrophil phenotype. This work provides mechanistic insight into tumor-neutrophil crosstalk, highlighting hypoxia-driven signaling as a potential therapeutic target in radioresistant HNSCC and supporting a role for neutrophil reprogramming in this context.

cancer biology↗

bioRxiv2025

HPV status and oxygen tension shape transcriptomic, inflammatory, and cell cycle responses in HNSCC treated with ionizing radiation

Head and neck squamous cell carcinoma (HNSCC) comprises biologically distinct subtypes defined by human papillomavirus (HPV) status, which may influence treatment outcomes. Hypoxia is a common feature of solid tumors, including HNSCC, and can reduce radiotherapy efficacy by modulating DNA repair, cell-cycle progression, and inflammatory signaling. However, the combined impact of hypoxia and HPV status on cellular radiosensitivity remains poorly defined. We investigated the influence of hypoxia (1% O2) and gamma-irradiation on proliferation, cell cycle, apoptosis, transcriptomic profiles, and cytokine/chemokine secretion in three HNSCC cell lines: HPV-negative FaDu and Detroit-562 (metastatic origin), and HPV-positive 2A3. Cells were cultured under chronic hypoxic or ambient conditions, with or without irradiation. Independent of HPV status or metastatic phenotype, hypoxia prolonged the cell doubling time, while only irradiated cells (under both oxygen conditions) exhibited features of an intermediate epithelial-mesenchymal transition phenotype. Treatment of HPV-positive cells significantly decreased the number of upregulated genes, reduced cytokine secretion (IL-8, SERPINE1), and affected all phases of the cell cycle compared with HPV-negative cells. Furthermore, only the metastatic cell line showed no change in cleaved caspase-3 levels after irradiation in hypoxia and produced higher levels of cytokines (IL-8, SERPINE1). Our findings highlight how tumor oxygenation and HPV status intersect to modulate the radiation response in HNSCC. These insights may guide the development of personalized, biomarker-driven radiotherapy strategies that account for both the tumor microenvironment and viral etiology.

cancer biology↗