361. 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
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363. 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
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367. The role of preconception parental health on embryo quality - preliminary results of a prospective study using non-invasive preimplantation genetic testing for aneuploidyMaja Tomic, Eda Vrtačnik-Bokal, Martin Štimpfel, 2025, izvirni znanstveni članek Povzetek: In this study, we aimed to correlate embryonic ploidy status studied with non-invasive preimplantation genetic testing for aneuploidy with the basic patient characteristics of the infertile couple to gain insight into the effects of parental physical health on embryo ploidy. We recruited 131 couples, who were stratified into 4 groups based on female age. We gathered general patient characteristics of the couple and determined the female’s hormonal status. We included 316 embryos in our study. Embryos were either transferred in the uterus in a fresh cycle or vitrified for later use. We collected spent embryo culture medium on either day 5 or 6 and performed whole genome amplification before using Next Generation Sequencing. Pregnancy outcomes were noted and cross-referenced with patient characteristics and the embryo’s ploidy status in a retrospective manner. While we have indirectly observed a level of maternal contamination, we nevertheless found a significant correlation between embryo ploidy status and cell free deoxyribonucleic acid concentration in spent embryo culture, as well a correlation between female age and embryo ploidy status. We observed a significant correlation between male body mass index and cell free deoxyribonucleic acid concentration in spent embryo culture medium and between male body mass index and pregnancy outcome. We illustrated a connection between male body mass index and cell free deoxyribonucleic acid, independent of female markers. This is the first study to observe not only female but male parameters in correlation to cell free deoxyribonucleic acid.
Ključne besede: non-invasive preimplantation genetic testing, aneuploidy, next-generation sequencing, embryo ploidy, male weight, female age, body mass index
Objavljeno v DiRROS: 26.11.2025; Ogledov: 103; Prenosov: 49
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370. Effect of tirzepatide-induced weight loss on adipose tissue in obesity : rationale and design of the randomized placebo-controlled Tirzepatide Brown and Beige Adipose Tissue Activation (TABFAT) trialRok Herman, Mojca Jensterle Sever, Simon Horvat, Luka Ležaič, Žiga Snoj, Igor Pušnik, Katja Goričar, Andrej Cör, Luka Pušnik, Vid Mlačnik, Lara Hanželič, Andrej Janež, 2025, izvirni znanstveni članek Povzetek: Background Obesity is a complex disease marked by excessive, dysfunctional adipose tissue accumulation. Recent research underscores the pivotal role of brown adipose tissue (BAT) in metabolic health and its potential as a thera- peutic target for obesity management. Emerging preclinical and clinical evidence suggests that second-generation anti-obesity drugs, especially dual agonists such as tirzepatide, may enhance BAT activity. Additionally, beige adipose tissue, derived from white adipose tissue (WAT), may contribute significantly to whole-body thermogenesis, yet its role remains underexplored. Methods This investigator-initiated, randomized, placebo-controlled clinical trial aims to evaluate the effects of tirzepatide on BAT activity and WAT browning in premenopausal women with obesity. Thirty-four participants will be randomized 1:1 to receive either tirzepatide or a placebo for 24 weeks. Primary outcomes include changes in BAT volume and activity, assessed using 18F-FDG-PET/CT, MRI, and infrared thermography, as well as the induction of WAT browning, evaluated through changes in mRNA expression patterns and histomorphometric alterations in subcuta- neous adipose tissue samples. Secondary outcomes will involve the assessment of whole-body composition, resting energy expenditure, and various metabolic health markers, correlated with thermogenic adipose tissue changes. Comparative analysis of BAT assessment methods will refine protocols for research and clinical use. Discussion This study is the first to systematically explore the potential of pharmacological obesity management to enhance BAT activity and induce WAT browning. Results may establish thermogenic adipose tissue augmentation as a novel mechanism of action for second-generation anti-obesity medications.
Ključne besede: brown adipose tissue, beige adipose tissue, pancreas resection, tirzepatide, obesity
Objavljeno v DiRROS: 26.11.2025; Ogledov: 128; Prenosov: 75
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