Search Results (11)

Endometrial cancer is becoming increasingly common, highlighting the need for improved diagnostic methods that are both effective and non-invasive. This study investigates the use of urinary fluorescence spectroscopy as a potential diagnostic tool for endometrial cancer. Urine samples were collected from endometrial cancer patients (n = 77), patients with benign uterine tumors (n = 23), and control gynecological patients attending regular checkups or follow-ups (n = 96). These samples were analyzed using synchronous fluorescence spectroscopy to measure the total fluorescent metabolome profile, and specific fluorescence ratios were created to differentiate between control, benign, and malignant samples. These spectral markers demonstrated potential clinical applicability with AUC as high as 80%. Partial Least Squares Discriminant Analysis (PLS-DA) was employed to reduce data dimensionality and enhance class separation. Additionally, machine learning models, including Random Forest (RF), Logistic Regression (LR), Support Vector Machine (SVM), and Stochastic Gradient Descent (SGD), were utilized to distinguish between controls and endometrial cancer patients. PLS-DA achieved an overall accuracy of 79% and an AUC of 90%. These promising results indicate that urinary fluorescence spectroscopy, combined with advanced machine learning models, has the potential to revolutionize endometrial cancer diagnostics, offering a rapid, accurate, and non-invasive alternative to current methods. Full article

Despite advances in the genomic classification of breast cancer, current clinical tests and treatment decisions are commonly based on protein-level information. Nowadays breast cancer clinical treatment selection is based on the immunohistochemical (IHC) determination of four protein biomarkers: Estrogen Receptor 1 (ESR1), Progesterone Receptor (PGR), Human Epidermal Growth Factor Receptor 2 (HER2), and proliferation marker Ki-67. The prognostic correlation of tumor-infiltrating T cells has been widely studied in breast cancer, but tumor-infiltrating B cells have not received so much attention. We aimed to find a correlation between immunohistochemical results and a proteomic approach in measuring the expression of proteins isolated from B-cell lymphocytes in peripheral blood samples. Shotgun proteomic analysis was chosen for its key advantage over other proteomic methods, which is its comprehensive and untargeted approach to analyzing proteins. This approach facilitates better characterization of disease-associated changes at the protein level. We identified 18 proteins in B cell lymphocytes with a significant fold change of more than 2, which have promising potential to serve as breast cancer biomarkers in the future. Full article

Peripheral blood CD8⁺ T lymphocytes play a crucial role in cell-mediated immunity and tumor-related immune responses in breast cancer. In this study, label-free quantification analysis and gene set enrichment analysis (GSEA) of CD8⁺ T lymphocytes in the peripheral blood of benign patients and patients with different breast cancer (BC) subtypes, i.e., luminal A, luminal B, and triple-negative breast cancer (TNBC), were performed using nano-UHPLC and Orbitrap mass spectrometry. Differential protein expression in CD8⁺ T lymphocytes revealed significant downregulation (log₂ FC ≥ 0.38 or ≤−0.38, adj. p < 0.05), particularly in proteins involved in cytotoxicity, cytolysis, and proteolysis, such as granzymes (GZMs) and perforin 1 (PRF1). This downregulation was observed in the benign group (GZMH, GZMM, and PRF1) and luminal B (GZMA, GZMH) subtypes, whereas granzyme K (GZMK) was upregulated in TNBC in comparison to healthy controls. The RNA degradation pathway was significantly downregulated (p < 0.05, normalized enrichment score (NES) from −1.47 to −1.80) across all BC subtypes, suggesting a potential mechanism for regulating gene expression during T cell activation. Also, the Sm-like proteins (LSM2, LSM3, and LSM5) were significantly downregulated in the RNA degradation pathway. Proteomic analysis of CD8⁺ T lymphocytes in peripheral blood across different breast cancer subtypes provides a comprehensive view of the molecular mechanisms of the systemic immune response that can significantly contribute to advancements in the diagnosis, treatment, and prognosis of this disease. Full article

Oxidative stress (OS) has an important role in female reproduction, whether it is ovulation, endometrium decidualization, menstruation, oocyte fertilization, or development andimplantation of an embryo in the uterus. The menstrual cycle is regulated by the physiological concentration of reactive forms of oxygen and nitrogen as redox signal molecules, which trigger and regulate the length of individual phases of the menstrual cycle. It has been suggested that the decline in female fertility is modulated by pathological OS. The pathological excess of OS compared to antioxidants triggers many disorders of female reproduction which could lead to gynecological diseases and to infertility. Therefore, antioxidants are crucial for proper female reproductive function. They play a part in the metabolism of oocytes; in endometrium maturation via the activation of antioxidant signaling pathways Nrf2 and NF-κB; and in the hormonal regulation of vascular action. Antioxidants can directly scavenge radicals and act as a cofactor of highly valuable enzymes of cell differentiation and development, or enhance the activity of antioxidant enzymes. Compensation for low levels of antioxidants through their supplementation can improve fertility. This review considers the role of selected vitamins, flavonoids, peptides, and trace elements with antioxidant effects in female reproduction mechanisms. Full article

One of the major social and public health problems in the world is adolescent pregnancy. Adolescent pregnancy is strongly associated to less favorable results for both the mother and the newborn. We conducted this research to ascertain the impact of teenage age on neonatal outcomes and also observed the lifestyles of pregnant teenage girls. We conducted a study of 2434 mothers aged ≤19 years (n = 294) or 20–34 years (n = 2140) who gave birth in 2019–2020 at the Department of Gynaecology and Obstetrics of Louis Pasteur University Hospital in Košice. The data on mothers and newborn infants have been reported from the reports on mothers at childbirth. Women between the ages of 20 and 34 served as the reference group. The teenage mothers were more likely to become pregnant if they were unmarried (OR = 14.2; 95% CI = 9.3–21.6; p < 0.001) and had a basic education or lack of education (OR = 16.8; 95% CI = 11.5–24.6; p < 0.001). Additionally, they were more likely to smoke when pregnant (OR = 5.0; 95% CI = 3.8–6.6; p < 0.001). Low birth weight was more common in newborns born to adolescent mothers than in those born to adult mothers (p < 0.001). Our findings showed that infants of teenage mothers often had lower birth weights (−332.6 g, p < 0.001). Adolescent mothers were associated with lower Apgar scores at the first minute (p = 0.003). As compared with the control group, pregnant teenage girls had a greater prevalence of preterm deliveries in our research (p = 0.004). This study finds significant age-related disparities in neonatal outcomes between mothers. These results might be used to identify vulnerable groups who need special assistance and actions to reduce the probability of negative outcomes for such groups. Full article

Human papillomavirus (HPV)-associated lesions and malignancies exhibit alterations in the composition and functionality of the extracellular matrix (ECM) that represent the complex molecular pathways present between infection and disease. A total of 20 urine samples were used, including from 10 patients with cervical intraepithelial neoplasia grade 3 (CIN3) and 10 healthy controls to perform the label-free quantitative analysis using the nano-HPLC and ESI-MS ion trap mass analyzer and matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-TOF/MS) fast screening. Among 476 identified/quantified proteins, 48 were significantly changed (log₂-fold change ≥1.0 or ≤−1.0, −log10 (bbinominal, p-value ≥ 1.3), of which were 40 proteins (down-regulated) and 8 proteins (up-regulated) in CIN3, in comparison to healthy controls. The biological function and key pathway enrichment of the gene set using gen set enrichment analysis (GSEA) were analyzed. The ECM-receptor interaction pathway (NES = −1.64, p = 0.026) was down-regulated by 13 proteins (HSPG2, COL6A1, COL6A3, SPP1, THBS1, TNC, DAG1, FN1, COMP, GP6, VTN, SDC1, and CD44; log₂ FC range from −0.03 to −1.48) for the CIN3 group in the KEGG database. The MALDI-TOF/MS screening showed the difference of protein profiles between the control and CIN3 groups, i.e., using the scatter plot with a well-separated shape, as well as effectively distinguishing both groups (control and CIN3) using genetic algorithms (GA) with cross-validation (51.56%) and recognition capability (95.0%). Decreased levels of ECM-receptor interaction proteins may cause disturbances in the interactions of cells with the ECM and play an important role in the development and progression of cervical cancer. Full article

The increased interest in assisted reproduction through in vitro fertilization (IVF) leads to an urgent need to identify biomarkers that reliably highly predict the success of pregnancy. Despite advances in diagnostics, treatment, and IVF approaches, the 30% success rate of IVF seems insurmountable. Idiopathic infertility does not have any explanation for IVF failure especially when a patient is treated with a healthy competitive embryo capable of implantation and development. Since appropriate intercellular communication is essential after embryo implantation, the emergence of the investigation of embryonic secretome including short non-coding RNA (sncRNA) molecules is crucial. That’s why biomarker identification, sncRNAs secreted during the IVF process into the blastocyst’s cultivation medium, by the implementation of artificial intelligence opens the door to a better understanding of the bidirectional communication between embryonic cells and the endometrium and so the success of the IVF. This study presents a set of promising new sncRNAs which are revealed to predictively distinguish a high-quality embryo, suitable for an embryo transfer in the IVF process, from a low-quality embryo with 86% accuracy. The identified exact combination of miRNAs/piRNAs as a non-invasively obtained biomarker for quality embryo determination, increasing the likelihood of implantation and the success of pregnancy after an embryo transfer. Full article

The aim of our study was to establish the predictive value of pelvic floor muscle morphometry using 3D/4D ultrasound in relation to the success of pelvic floor muscle training (PFMT) for 12 weeks in women with stress urinary incontinence (SUI). A total of 86 women with SUI from regional gynaecological and urological outpatient clinics were enrolled on this cross-sectional study. SUI symptoms were assessed by the International Consultation on Incontinence Questionnaire (ICIQ-UI SF). Pelvic floor muscle function was evaluated using a perineometer. Pelvic floor muscle morphometry (PFMM) was evaluated by the size of the urogenital hiatus (HA in cm²) at rest (R), at contraction (C) and during the Valsalva manoeuvre, i.e., a strong push (V), by 3D/4D USG. The intervention was PFMT for 12 weeks. After PFMT, we noted significant improvement in SUI symptoms, pelvic floor muscle function and morphometry. Moderately significant (0.001) negative correlations were confirmed between the total ICIQ-UI SF score and strength (−0.236 **) and endurance (−0.326 **) of the maximal voluntary contraction (MvC), the number of MvC lasting 3 s (−0.406 **) and 1 s (−0.338 **). Moderately significant (0.001) positive correlations were confirmed between the total ICIQ-UI SF score and R (r = 0.453 **), C (r = 0.533 **) and V (r = 0.442 **). The predictive value of PFMM reached a positive prediction of a decrease with an ICIQ-UI SF score below 8. HA during V was most strongly associated with SUI reduction, with an area under the curve (AUC) of 0.87 (p ≤ 0.001), a positive predictive value of 83.3%, a negative predictive value of 75.0%, sensitivity of 78.9% and specificity of 80.0%. The predictive values of pelvic floor muscle morphometry using 3D/4D USG confirmed the success of PFMT in women with SUI. Full article

Background: Health characteristics associated with uric acid (UA) in the Roma minority remain less well known. The study sought to determine the ethnicity- and sex-specific associations of serum UA with health factors in Eastern Slovakian Roma and non-Roma populations. Methods: Data from the comparative cross-sectional HepaMeta study conducted in Slovakia in 2011 were used. The study enrolled 452 Roma subjects (35.2% men) and 403 non-Roma individuals (45.9% men) aged 18–55 years. Results: All study parameters differed between the sexes in both the Roma and non-Roma participants (p < 0.05). UA was related to sex with odds ratio for female sex 0.873, 95% CI 0.853–0.893 (p < 0.0001) per 10-unit increase of UA. Average level of UA ± standard deviation was lower in Roma than in non-Roma (226.54 ± 79.8 vs. 259.11 ± 84.53 umol/L; p < 0.0001). The Roma population presented with greater levels of high-sensitivity C-reactive protein (hsCRP) (3.07 ± 4 mg/L vs. 1.98 ± 2.83 mg/L; p < 0.0001) and ferritin in Roma males (403.78 ± 391.84 vs. 302.67 ± 236.26 mg/L; p < 0.0001). Conclusions: Serum UA is sex- and ethnicity specific. Elevated levels of hsCRP and ferritin particularly in Roma males can reflect low-grade systemic inflammation and thus serve as a marker of an increased cardiovascular risk. Full article

In the present study we evaluated the anti-angiogenic activities of β-escin (the major active compound of Aesculus hippocastanum L. seeds). Human umbilical-vein endothelial cells (HUVECs) were used as an in vitro model for studying the molecular mechanism underlying the anti-angiogenic effect of β-escin. We investigated the in vitro effects on proliferation, migration, and tube formation of HUVECs and in vivo anti-angiogenic activity was evaluated in a chick chorioallantoic membrane (CAM) angiogenesis assay. Moreover, the effect on gene expressions was determined by the RT2 ProfilerTM human angiogenesis PCR Array. It was found that β-escin exerts inhibitory effect on the basic fibroblast growth factor (bFGF)-induced proliferation, migration and tube formation, as well as CAM angiogenesis in vivo. The inhibition of critical steps of angiogenic process observed with β-escin could be partially explained by suppression of Akt activation in response to bFGF. Moreover, the anti-angiogenic effects of β-escin could also be mediated via inhibition of EFNB2 and FGF-1 gene expressions in endothelial cells. In conclusion, β-escin affects endothelial cells as a negative mediator of angiogenesis in vitro and in vivo and may therefore be considered as a promising candidate for further research elucidating its underlying mechanism of action. Full article

This study was designed to examine the in vitro antiproliferative effect of brassinin and its derivatives on human cancer cell lines. Among seven tested compounds, homobrassinin (K1; N-[2-(indol-3-yl)ethyl]-S-methyldithiocarbamate) exhibited the most potent activity with IC₅₀ = 8.0 μM in human colorectal Caco2 cells and was selected for further studies. The flow cytometric analysis revealed a K1-induced increase in the G₂/M phase associated with dysregulation of α-tubulin, α₁-tubulin and β₅-tubulin expression. These findings suggest that the inhibitory effect of K1 can be mediated via inhibition of microtubule formation. Furthermore, simultaneously with G₂/M arrest, K1 also increased population of cells with sub-G₁ DNA content which is considered to be a marker of apoptotic cell death. Apoptosis was also confirmed by annexin V/PI double staining, DNA fragmentation assay and chromatin condensation assay. The apoptosis was associated with the loss of mitochondrial membrane potential (MMP), caspase-3 activation as well as intracellular reactive oxygen species (ROS) production. Moreover, the antioxidant Trolox blocked ROS production, changes in MMP and decreased K1 cytotoxicity, which confirmed the important role of ROS in cell apoptosis. Taken together, our data demonstrate that K1 induces ROS-dependent apoptosis in Caco2 cells and provide the rationale for further in vivo anticancer investigation. Full article