First-void urine usually contains exfoliated cells of the debris and mucus from the female genital organs and cervix, i.e., high concentration of human papillomavirus deoxyribonucleic acid (HPV DNA). We conducted a meta-analysis of published data and determined an accuracy of HPV detection in first-void urine compared to the women’s cervix. According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we carried out a comprehensive literature search. Eligible articles published from 2011 until 2021 were gathered by searching Embase, PubMed and Cochrane Library Central databases. The patient selection, index test, standard test, and patient flow were the factors involved in quality evaluation. A meta-analysis of 15 studies (3412 women) based on 5054 potential records was conducted. Pooled sensitivity for high-risk HPV detection in urine of 78% (70–84%) and specificity of 89% (81–94%) were calculated. Any HPV detection in urine of 87% (74–94%) and 91% (83–96%) were pooled sensitivity and specificity, respectively. HPV 16 and 18 had a pooled sensitivity of 77% (76–77%) and specificity of 98% (98–98%). Meta-analysis indicated variations between the pooled specificities and sensitivities. In meta-regression analysis, a heterogeneity in accuracy by using covariates (bias in patient selection, purpose, sample timing, storage temperature and HPV detection method) were not detected. Our meta-analysis demonstrates the accuracy of detection of HPV in urine for the presence of cervical HPV. Although progress is continuously made in urinary HPV detection, further studies are needed to evaluate and to improve the accuracy of the first-void urine test in order to be comparable with other screening methods.

Background: Transforming RhoA proteins (RHOA) and their downstream Diaphanous homolog 1 proteins (DIAPH1) or mDia1 participate in the regulation of actin cytoskeleton which plays critical role in cells, i.e., morphologic changes and apoptosis.Methodology: To determine the cell viability the real time cell analysis (RTCA) and flow cytometry were used. To perform proteomic analysis, the label-free quantitative method and post-translation modification by the nano-HPLC and ESI-MS ion trap mass analyser were used.Results: The results of the cell viability showed an increase of dead cells (around 30 %) in MCF-7/DOX-1 (i.e., 1μM of doxorubicin was added to MCF-7/WT breast cancer cell line) compared to MCF-7/WT (control) after 24 h doxorubicin (DOX) treatment. The signalling pathway of the Regulation of actin cytoskeleton (p<0.0026) was determined, where RHOA and mDia1 proteins were up-regulated. Also, post-translational modification analysis of these proteins in MCF-7/DOX-1 cells revealed dysregulation of the actin cytoskeleton, specifically the collapse of actin stress fibbers due to phosphorylation of RHOA at serine 188 and mDia1 at serine 22, resulting in their deactivation and cell apoptosis.Conclusion: These results pointed to an assumed role of DOX to dysregulation of actin cytoskeleton and cell death.

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.

Breast cancer is the most prevalent cancer type in women worldwide. It proliferates rapidly and can metastasize into farther tissues at any stage due to the gradual invasiveness and motility of the tumor cells. These crucial properties are the outcome of the weakened intercellular adhesion, regulated by small guanosine triphosphatases (GTPases), which hydrolyze to the guanosine diphosphate (GDP)-bound conformation. We investigated the inactivating effect of ARHGAP1 on Rho GTPases involved signaling pathways after treatment with a high dose of doxorubicin. Label-free quantitative proteomic analysis of the proteome isolated from the MCF-7 breast cancer cell line, treated with 1 μM of doxorubicin, identified RAC1, CDC42, and RHOA GTPases that were inactivated by the ARHGAP1 protein. Upregulation of the GTPases involved in the transforming growth factor-beta (TGF-beta) signaling pathway initiated epithelial–mesenchymal transitions. These findings demonstrate a key role of the ARHGAP1 protein in the disruption of the cell adhesion and simultaneously allow for a better understanding of the molecular mechanism of the reduced cell adhesion leading to the subsequent metastasis. The conclusions of this study corroborate the hypothesis that chemotherapy with doxorubicin may increase the risk of metastases in drug-resistant breast cancer cells.

The movement of teeth by orthodontic treatment with the Invisalign (IN) system and fixed orthodontic appliances (FOA) is characterized by the reconstruction of periodontal ligaments, alveolar bone, and gingiva. A reflection of these phenomena can be found in the composition of gingival crevicular fluid (GCF). A total of 90 samples from 45 participants (45 whole saliva and 45 GCF), including 15 patients with FOA, 15 patients with IN, and 15 patients with oral health, were subjected to matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF/MS) analysis. Mass fingerprints were generated for each sample. Three models were tested: a quick classifier (QC), a genetic algorithm (GA), and a supervised neural network (SNN). For both groups of samples (saliva and GCF), the GA model showed the highest recognition abilities of 88.89% (saliva) and 95.56% (GCF). Differences between the treated (FOA and IN) groups and the control group in saliva and GCF samples were determined using cluster analysis. In addition, we monitored the effect of long-term orthodontic treatment (after 6 months) in the lag phase of orthodontic tooth movement. The results show increased levels of inflammatory markers (α-defensins), which may indicate an ongoing inflammatory process even after 21 days from force application.