👤 Pamela Czajka

Identifying reliable circulating biomarkers is crucial for improving the diagnosis and risk stratification of patients with ischemic stroke. In this study, we evaluated several whole-blood circulating miRNAs (miR-106b-5p, miR-16-5p, miR-15b-5p, let-7e-5p, and miR-125a-3p/-5p) to determine their diagnostic and disease severity in acute ischemic stroke (AIS). Sixty AIS patients and thirty age- and sex-matched controls were included. Whole-blood miRNAs were quantified at admission and on day 7. Statistical analyses included ROC curves, multivariate logistic regression, and SHAP-based machine learning. Bioinformatic analyses assessed predicted miRNA targets, pathway enrichment, and interaction networks. MiR-125a-3p was significantly reduced in AIS at both time points, while miR-125a-5p was elevated at admission and decreased by day 7. Both miRNAs showed moderate diagnostic value (AUC 0.675 and 0.712, respectively). Higher admission levels of miR-16-5p were strongly associated with greater neurological deficit (NIHSS) and unfavorable outcome (mRS ≥ 3). Multivariate analyses confirmed high miR-16-5p and elevated CRP as independent predictors of poor outcome. Bioinformatic analyses revealed that miR-16-5p targets were enriched in pathways relevant to ischemic injury, including hypoxia response, platelet activation, coagulation, TGF-β and BDNF signaling. A target-interaction network highlighted IL6, FN1, TGFB1, ICAM1, and TLR4 as central nodes linking miR-16-5p to ischemia-inflammatory mechanisms in AIS. Circulating miRNAs display distinct expression patterns in the acute phase of AIS. miR-16-5p emerges as a promising biomarker associated with stroke severity and unfavorable outcome, while miR-125a-3p and miR-125a-5p show potential diagnostic utility. These findings strengthen mechanistic links between platelet-derived miRNAs and ischemic stroke biology. Larger, longitudinal studies integrating functional validation are warranted to confirm their clinical value. Show less

Despite the wide range of diagnostic and therapeutic methods, breast cancer is responsible for many deaths each year. One of the original and novel cancer therapeutic approaches is gene therapy based on recombinant adeno-associated viral vectors. Among the molecular factors with the potential to become useful diagnostic biomarkers, microRNA (miRNA) molecules are being considered for personalized therapies. The aim of the study was to examine the utility of miRNA profiling in the design of personalized recombinant adeno-associated virus (rAAV)-based gene therapy for breast cancer patients. The analysis of 754 miRNAs in 7 breast cancer samples and control samples was performed using real-time polymerase chain reaction (PCR) based on TaqMan® Low-density Array (TLDA) cards. Online repositories were used to explore the relationship between miRNAs and genes encoding rAAV receptors (KIAA0319L, HSPG2, FGFR1, c-MET, PDGFRA, ITGB5, and RPSA). Then, we performed a comparative analysis of the results to examine the possibility of using miRNA profiling in the design of rAAV-based therapeutic protocols. Fifty-two percent of tested miRNAs were noted in at least 1 analyzed breast cancer and control tissue. Thirteen miRNAs were selected due to being outliers in the tested samples. In total, 155 miRNAs targeted genes encoding rAAV receptors in the tested samples (29 miRNAs for KIAA0319L, 60 miRNAs for c-MET, 31 miRNAs for HSPG2, 43 miRNAs for FGFR1, 36 miRNAs for PDGFRA, 18 miRNAs for RPSA, and 25 miRNAs for ITGB5). The expression of the selected miRNAs was not homogeneous across the 7 samples. Profiling of microRNA could be a significant factor in the design of rAAV-based personalized gene therapy for breast cancer patients. Show less