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452. 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, original scientific article Abstract: 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.
Keywords: ANCA, biomarker, glomerulonephritis, microRNA, vasculitis, epigenetics
Published in DiRROS: 26.11.2025; Views: 110; Downloads: 73
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456. 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, original scientific article Abstract: 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.
Keywords: non-invasive preimplantation genetic testing, aneuploidy, next-generation sequencing, embryo ploidy, male weight, female age, body mass index
Published in DiRROS: 26.11.2025; Views: 118; Downloads: 63
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459. 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, original scientific article Abstract: 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.
Keywords: brown adipose tissue, beige adipose tissue, pancreas resection, tirzepatide, obesity
Published in DiRROS: 26.11.2025; Views: 134; Downloads: 78
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