Reparative Spheroids in HPV-Associated Chronic Cervicitis

Background: Spheroid cell structures (SCS) described in cell culture are used to study cell-cell and cell-matrix interactions. However, the role of the SCS in the repair process in vivo remains unexplored. The aim of the study was to examine the cellular composition of the spherical structures and their functional significance in the repair of the squamous epithelium in human papilloma virus-associated chronic cervicitis (HPV-CC). Methods and Results: The cytology and biopsy materials from 223 patients with HPV-CC were subjected to molecular testing for HPV DNA by Real-Time Polymerase Chain Reaction (Real-Time PCR) with genotyping and chromogenic in situ hybridization (CISH), as well as immunocytological and immunohistochemical analyses of p16INK4A, Ki67, SMA, Vimentin, CD34, E-cadherin, Oct4, CD44, CKW markers. In the stem cell niche zone, these spheroid structures were discovered having proliferative activity and showing signs of producing stem cells involved in the repair of the cervical mucosa in HPV-CC. Conclusion: The persistence of the HPV in the stem cell niche zone cells in the cervix determines the chronization of inflammation in this area, with the ability to perform pathological repair. The immunophenotype of the spheroid cell structures in the HPV-CC includes cells with signs of stem cells (‘stemness’) and the mesenchymal-epithelial transition

Observation of grating diffraction radiation at the KEK LUCX facility

The development of linac–based narrow–band THz sources with sub–picosecond, ?J-level radiation pulses is in demand from the scientific community. Intrinsically monochromatic emitters such as coherent Smith–Purcell radiation sources appear as natural candidates. However, the lack of broad spectral tunability continues to stimulate active research in this field. We hereby present the first experimental investigation of coherent grating diffraction radiation (GDR), for which comparable radiation intensity with central frequency fine–tuning in a much wider spectral range has been confirmed. Additionally, the approach allows for bandwidth selection at the same central frequency. The experimental validation of performance included the basic spectral, spatial and polarization properties. The discussion of the comparison between GDR intensity and other coherent radiation sources is also presented. These results further strengthen the foundation for the design of a tabletop wide–range tunable quasi–monochromatic or multi–colour radiation source in the GHz–THz frequency range

Project of Russian Consensus on gestational diabetes mellitus: diagnostics, treatment and postnatal care

Current document presents a coherent viewpoint of Russian Association of Endocrinologists and Russian Association of Obstetriciansand Gynaecologists on diagnostic criteria of gestational diabetes mellitus (GDM) and other glycemic disorders during gestation. Currentapproach is based on analysis of high-profile multinational study HAPO (Hyperglycemia and Adverse Pregnancy Outcomes Study),which included more than 23 000 pregnant women. This project was repeatedly reviewed on workgroup sessions and presented orallyon 6th Russian Congress of Endocrinology with international participation, as well as Russian interdisciplinary educational congressGestational Complications and Premature Delivery

Russian National Consensus Statement on gestational diabetes: diagnostics, treatment and postnatal care

Current document presents the expert consensus of Russian Association of Endocrinologists and Russian Society of Obstetrician- Gynecologists on diagnostic criteria of gestational diabetes and other glycemic disorders of pregnancy. The consensus is based on analysis of HAPO (Hyperglycemia and Adverse Pregnancy Outcomes Study) - a major multinational study, that included more than 23000 patients. Project of current consensus was repeatedly discussed during meetings of the research group and publicly addressed at 6th Pan-Russian Congress of Endocrinology with international participation ?Modern Endocrine Technologies?, as well as Pan-Russian Educational Interscience Conference ?Complicated Pregnancy and Preterm Birth?

MiRNAs Regulating Oxidative Stress: A Correlation with Doppler Sonography of Uteroplacental Complex and Clinical State Assessments of Newborns in Fetal Growth Restriction

Overproduction of reactive oxygen species (ROS) and, as a result, uncontrolled oxidative stress (OS) can play a central role in disorders of fetal hemodynamics and subsequent development of adverse perinatal outcomes in newborns with fetal growth restriction (FGR). Given the epigenetic nature of such disorders, the aim of our study was to evaluate the expression of miRNAs associated with OS and endothelial dysfunction (miR-27a-3p, miR-30b-5p, miR-125b-5p, miR-221-3p, miR-451a and miR-574-3p) in umbilical cord blood using real-time quantitative RT-PCR. ΜiRNA expression was evaluated in patients with FGR delivery before (n = 9 pregnant) and after 34 weeks of gestation (n = 13 pregnant), and the control groups corresponding to the main groups by gestational age (13 pregnant women in each group, respectively). A significant increase in miR-451a expression was detected in late-onset FGR and correlations with fetoplacental and cerebral circulation were established (increase of resistance in the umbilical artery (pulsatility index, PI UA (umbilical artery): r = −0.59, p = 0.001) and a decrease in cerebral blood flow (CPR: r = 0.48, p = 0.009)). The change in miR-125b-5p expression in the placenta is associated with reduced Doppler of cerebral hemodynamics (CPR: r = 0.73, p = 0.003; PI MCA (middle cerebral artery): r = 0.79, p = 0.0007), and newborn weight (r = 0.56, p = 0.04) in early-onset FGR. In addition, significant changes in miR-125b-5p and miR-451a expression in umbilical cord blood plasma were found in newborns with neonatal respiratory distress syndrome (NRDS) (in early-onset FGR) and very low birth weight (VLBW) (in late-onset FGR). A number of key signaling pathways have been identified in which the regulation of the studied miRNAs is involved, including angiogenesis, neurotrophin signaling pathway and oxidative stress response. In general, our study showed that changes of the redox homeostasis in the mother-placenta-fetus system in FGR and subsequent perinatal outcomes may be due to differential expression of oxidative stress-associated miRNAs

Preeclampsia: The Interplay between Oxygen-Sensitive miRNAs and Erythropoietin

Changes in the oxygen partial pressure caused by a violation of uteroplacental perfusion are considered a powerful inducer of a cascade of reactions leading to the clinical manifestation of preeclampsia (PE). At the same time, the induction of oxygen-dependent molecule expression, in particular, miRNA and erythropoietin, is modulated. Therefore, the focus of our study was aimed at estimating the miRNA expression profile of placental tissue and blood plasma in pregnant women with preeclampsia using deep sequencing and quantitative RT-PCR, as well as determining the concentration of erythropoietin. The expression of miR-27b-3p, miR-92b-3p, miR-125b-5p, miR-181a-5p, and miR-186-5p, as regulated by hypoxia/reoxygenation, was significantly increased in blood plasma during early-onset preeclampsia. The possibility of detecting early PE according to the logistic regression model (miR-92b-3p, miR-125b-5p, and miR-181a-5p (AUC = 0.91)) was evaluated. Furthermore, the erythropoietin level, which is regulated by miR-125b-5p, was significantly increased. According to PANTHER14.1, the participation of these miRNAs in the regulation of pathways, such as the hypoxia’s response via HIF activation, oxidative stress response, angiogenesis, and the VEGF signaling pathway, were determined

Methylation Profile of Small Breast Cancer Tumors Evaluated by Modified MS–HRM

The DNA methylation profile of breast cancer differs from that in healthy tissues and can be used as a diagnostic and prognostic biomarker. Aim of this study: To compare the levels of gene methylation in small malignant breast cancer tumors (MAST1, PRDM14, ZNF177, DNM2, SSH1, AP2M1, CACNA1E, CPEB4, DLGAP2, CCDC181, GCM2, ITPRIPL1, POM121L2, KCNQ1, and TIMP3. Significant differences in the validation set of samples were found for seven genes; the combination of the four genes GCM2, ITPRIPL1, CACNA1E, DLGAP2 (AUC = 0.99) showed the highest diagnostic value based on logistic regression for all breast cancer samples. Our modified MS–HRM method demonstrated that small breast cancer tumors have a specific DNA methylation profile that distinguishes them from healthy tissues and benign proliferative lesions

Diagnostic Potential of Exosomal HypoxamiRs in the Context of Hypoxia–Sumoylation–HypoxamiRs in Early Onset Preeclampsia at the Preclinical Stage

As the search for non-invasive preclinical markers of preeclampsia (PE) expands, the number of studies on the diagnostic potential of exosomes is growing. Changes in the partial pressure of oxygen caused by impaired uteroplacental perfusion in PE are a powerful inducer of increased production and release of exosomes from cells, which also determine their cargo. At the same time, the expression pattern of oxygen-dependent microRNAs (miRNAs), called “hypoxamiRs”, is modulated, and their packing into exosomes is strictly regulated by sumoylation. In connection therewith, we emphasize the evaluation of exosomal hypoxamiR expression (miR-27b-3p, miR-92b-3p, miR-181a-5p, and miR-186-5p) using quantitative RT-PCR, as well as SUMO 1–4 and UBC9 (by Western blotting), in pregnant women with early-onset PE. The findings show that miR-27b-3p and miR-92b-3p expression was significantly changed at 11–14 and 24–26 weeks of gestation in the blood plasma of pregnant women with early-onset PE, which subsequently manifested. High sensitivity and specificity (AUC = 1) were demonstrated for these miRNAs in the first trimester, and significant correlations with a decrease in hemoglobin (r = 0.71, p = 0.002; r = −0.71, p = 0.002) were established. In mid-pregnancy, the miR-27b-3p expression was found to correlate with an increase in platelets (r = −0.95, p = 0.003), and miR-92b-3p was associated with a decrease in the prothrombin index (r = 0.95, p = 0.003). Specific exomotifs of studied miRNAs were also identified, to which the sumoylated ribonucleoprotein hnRNPA2/B1 binds, carrying out their packaging into exosomes. The expression of conjugated SUMO 1 (p = 0.05), SUMO 2/3/4 (p = 0.03), and UBC9 (p = 0.1) was increased in exosomes at early-onset PE, and the expression of free SUMO 1 (p = 0.03) and SUMO 2/3/4 (p = 0.01) was significantly increased in the placenta, as an adaptive response to hypoxia. Moreover, SUMO 2/3/4 was negatively correlated with miR-27b-3p expression in the placenta. In conclusion, the diagnostic potential of exosomal hypoxamiRs mediated by sumoylation may form the basis for the development of combined specific targets for the treatment of early-onset PE, as hnRNPA2/B1 is a target of miR-27b-3p, and its sumoylation creates miR-27b-3p–hnRNPA2/B1–SUMO 1–4 cross-talk