@misc{Duda-Wiewiórka_Magdalena_Kinga_2024,
 author={Duda-Wiewiórka, Magdalena Kinga},
 address={Kraków},
 howpublished={online},
 year={2024},
 school={Rada Dyscypliny Nauki medyczne},
 language={pol},
 abstract={Endometrial hyperplasia belongs to the most common pathological changes occurring within the uterine cavity. Post-menopausal vaginal bleeding is the standard reason for patients to seek gynecological advice and – simultaneously – it is also the most frequent symptom shared by patients with endometrial hyperplasia and endometrial cancer. Endometrial hyperplasia may be contributing or underlying factors to the development of endometrial cancer. More and more evidence from research confirms the significance of vitamin D (VD) in the development of endometrial pathologies. Apart from the wellknown role of VD in regulation of calcium levels, VD acts as modulator to many genes involved in cell growth, immunological functions and protein synthesis. Research suggests that the mechanism of action of VD may also occur through epigenomic pathways. So far, research has focused mainly on one vitamin D metabolism, 25- hydroxyvitamin D, and as is known, there are numerous metabolites that are collectively referred to as the VD metabolome. The newest research shows that VD acts multidirectionally and its common deficiency has a causal link to the pathogenesis of many gynecological and cancerous conditions. It is postulated that VD affects the endometrium via various mechanisms. The discovery that most tissues have VD receptors was ground-breaking in understanding its role in various medical con},
 abstract={ditions, including the neoplasmal development mechanism, but the degree, to which the VD metabolism in the eutopic endometrium during pathological conditions is impaired, has not yet been explained Objectives: 1. To determine the relationship between the level of VD and its metabolites in the serum of postmenopausal patients with abnormal growth of the uterine mucosa with and without atypia. 2. Determination of differences in the expression level of individual lncRNAs in the study group. 3. Determination of the expression level of miRNAs in individual groups and miRNAs associated with cytochrome P450. Methods: Peripheral blood was collected from each study participant in tubes with EDTA and RNA stabilizer (the PAXgene Blood RNA Tube). Blood samples were frozen at -80 °C until further analysis.A Waters Xevo TQ - MS mass spectrometer with ESI ionization coupled with a Waters Acquity UPLC liquid chromatograph was used to study vitamin D metabolites. The operation of the device was controlled using massLynx programming. The chromatograms were analyzed using TargetLynx computer software. Chromatographic separation was performed using a Waters column with fluoro-phenyl packing. Functional analysis of lcnRNA and gene expression was performed using Agilent microarray technology. Sequencing was performed on the Illumina platform (NGS next generation sequencing). Genetic material in the},
 abstract={form of DNA for DNA damage analysis and telomere length analysis was isolated using a commercially available kit (NucleoSpin). DNA damage analysis was performed using a NanoDrop ND- 1000 spectrophometer and Qubit 4 fluorimeter. 8-OHdG level was measured using the EpiQuick 8-OHdG DNA damage quantification direct kit. Digital PCR technology was used to determine the absolute length of telomeres (TL). PCR amplification was performed on a Qiagen Qiacuity Digital PCR Machine. The dPCR thermal profile was adapted based on the qPCR method developed by Cowton. Results: In the study group, there was no clear relationship between the level of vitamin D and the presence of endometrial hyperplasia with atypia. No significant differences were found in the levels of two other tested VD metabolites (25-OH vit D2 and 1,25-diOH vit D3) in patients with EH with and without atypia. lncRNAs such as KCNMB2-AS1, MIR205HG, RP11-357H14.17 showed significantly higher expression in the group of patients with atypia. In the group of patients with atypia, overexpression of hsa-miR-26a-5p and miR- 27b was demonstrated, which may be related to the inhibition of cytochrome P450 gene enzymes and be associated with a lower level of active VD metabolites. The analysis of telomere length, despite the lack of statistical significance, showed a tendency to shorten in the group of patients with EH with atypia, whic},
 abstract={h may indicate a higher risk of malignant transformation in this group. Conclusions: 1. In the study group, there was no clear relationship between the level of vitamin D and the presence of endometrial hyperplasia with atypia, however, a significant VD deficiency was found in the study group at baseline. 2. lncRNAs such as KCNMB2-AS1, MIR205HG, RP11-357H14.17 showed significantly higher expression in the group of patients with atypia, which may be related to their potential role as diagnostic biomarkers for endometrial hyperplasia with atypia and may also indicate their prognostic value of cancer transformation. 3. In the group of patients with atypia, overexpression of hsa-miR-26a-5p and miR- 27b was demonstrated, which may be related to the inhibition of cytochrome P450 gene enzymes and to the lower level of active VD metabolites.},
 type={Praca doktorska},
}