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365. Heterogenous mitochondrial ultrastructure and metabolism of human glioblastoma cells : differences between stem-like and differentiated cancer cells in response to chemotherapyUrban Bogataj, Metka Novak, Simona Katrin Galun, Klementina Fon Tacer, Miloš Vittori, Cornelis J. F. van Noorden, Barbara Breznik, 2025, izvirni znanstveni članek Povzetek: Background[:] Glioblastoma stem-like cells (GSCs) contribute to the resistance of glioblastoma (GBM) tumors to standard therapies. The background of the resistance of GSCs to the chemotherapeutic agent temozolomide is not yet fully understood in the context of cellular metabolism and the role of mitochondria. The aim of this study was to perform a detailed ultrastructural characterization of the mitochondria of GSCs prior and post temozolomide exposure and to compare it to differentiated GBM cells. Materials and methods[:] Patient-derived and established GBM cell lines were used for the study. The ultrastructure of the mitochondria of the examined cell lines was assessed by transmission electron microscopy. The microscopic analysis was complemented and compared by an analysis of cell metabolism using Seahorse extracellular flux analysis. Results[:] We found that the metabolic profile of GSCs is quiescent and aerobic. Their elongated mitochondria with highly organized cristae are indicating increased biogenesis and mitochondrial fusion and corresponds to a more oxidative phosphorylation (OXPHOS)-dependent metabolism. The metabolism of GSCs is dependent on OXPHOS and there are no changes in defective mitochondria fraction after the treatment with temozolomide. In contrast, differentiated GBM cells with fragmented mitochondria, which have less organized cristae, are more energetic and glycolytic. Temozolomide treatment induced ultrastructural mitochondrial damage in differentiated GBM cells. Conclusions[:] We demonstrated differences in mitochondrial ultrastructure and cellular metabolism between GSCs and differentiated GBM cells in response to temozolomide, suggesting that mitochondria play an important role in the resistance of GSCs to temozolomide. This study provides a basis for further studies addressing GSC chemotherapy resistance in the context of mitochondrial structure and function.
Ključne besede: glioblastoma, mitochondria, metabolism, chemotherapy, stem cells
Objavljeno v DiRROS: 26.11.2025; Ogledov: 111; Prenosov: 57
 Celotno besedilo (1,35 MB)
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367. Circulating miRNAs as potential non-invasive biomarkers for ANCA-associated glomerulonephritisMatic Bošnjak, Željka Večerić-Haler, Živa Pipan Tkalec, Jakob Tomšič, Emanuela Boštjančič, Nika Kojc, 2025, izvirni znanstveni članek Povzetek: Introduction: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by necrotizing small vessel vasculitis that frequently manifests as glomerulonephritis (AAV-GN). An accurate noninvasive biomarker reflecting active AAV-GN remains elusive. The knowledge of microRNAs (miRNAs), which have been considered as disease-specific biomarkers, is scarce and lacks validated data in AAV. Methods: This study validated a renal tissue expression profile of candidate miRNAs specific to AAV-GN selected through prior screening using independent cohorts. The analysis was extended to serum samples to explore the potential of a circulating miRNA panel as a noninvasive biomarker for active AAV-GN. To substantiate the findings, we correlated the molecular data with clinical and histologic markers of AAV-GN activity. Results: We identified miR-21-3p, miR-181a-5p, and miR-181d-5p as potential biomarkers distinguishing AAV-GN from non-AAV renal diseases and healthy controls. In addition, miR-21-3p and miR-181d-5p correlated with the presence of active AAV-GN, while miR-181a-5p differentiated AAV-GN subtypes based on ANCA antigen specificity. ROC curve analysis demonstrated that the combined serum expression of miR-21-3p and miR-181a-5p reliably distinguished AAV-GN from other renal pathologies, including ANCA-positive cases without histologic evidence of AAV-GN. Conclusion: Our findings highlight the potential of circulating miRNA expression signature as a noninvasive biomarker for ongoing AAV-GN in the appropriate setting. Larger confirmatory studies are essential to support the clinical application of miRNA-based biomarkers in AAV-GN diagnostics and disease monitoring.
Ključne besede: ANCA, biomarker, glomerulonephritis, microRNA, vasculitis, epigenetics
Objavljeno v DiRROS: 26.11.2025; Ogledov: 102; Prenosov: 71
Celotno besedilo (2,00 MB)
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