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Background. Epithelial-mesenchymal transition (EMT) is a conserved mechanism in the process of morphogenesis and organogenesis. EMT provides cells with migratory and invasive properties, which is a necessary condition for the formation of endometrioid heterotopias. Aim. To confirm the presence of EMT features in different types of endometriosis. Materials and methods. During a period of five years (2012–2017) we analyzed 43 cases of extragenital endometriosis: appendix (3 case), colon (5 cases), ileum (1 case), abdominal scar endometriosis after caesarean section (24 cases), and inguinal hernia (10 cases). The material was processed according to histological and immunohistochemical technique using monoclonal E-cadherin and polyclonal Vimentin antibodies to assess local invasiveness. Results. In peritoneal endometriosis, the ratio of E-cadherin to Vimentin expression was 10.3, in the colon = 9.1, in the appendix 8.6, in the ileum 5.5, in the hernial sac 4.2. Thus, in diffuse infiltrative forms of endometriosis, the lesion phenotype is characterized by low expression of E-cadherin, while expression of Vimentin is at a high level (p0.05). Conclusion. The results of our study confirmed involvement of the epithelial-mesenchymal transition process in the pathogenesis of extragenital endometriosis lesions, on the one hand, and they certify its invasive potential in these localizations, on the other hand.

Aim. To identify clinical and history features of patients with recurrent deep endometriosis (RDE). Materials and methods. A retrospective study of clinical and history data of 200 patients with DE undergoing surgical treatment at the Department of General Surgery of the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology in 2020–2021. Group 1 included 80 patients with RDE, group 2 included 120 patients with newly diagnosed DE. All patients underwent surgical treatment followed by immunohistochemical examination and DE confirmation. Results. An association was found between the young age of the patient at the time of the first surgery and the type of endometriosis. It was found that women with a history of endometriosis surgery in early reproductive years (29.22±5.3 years) are at risk of recurrent endometriosis. Two or more surgeries were reported in 33.7% of RDE patients. In 90.2% of patients, endometriosis recurred with clinical manifestations; in 9.8%, it was asymptomatic and diagnosed on pelvic ultrasound. The group of RDE patients showed a longer period of infertility (5.432±3.53 years) than the group with newly diagnosed DE (2.953±1.29 years). It was found that the surgeries performed in RDE patients were longer, more complex, and associated with more blood loss. Intestinal resection, ureterolysis, adhesiolysis, and salpingectomy were significantly more common in the RDE group than in patients without a history of endometriosis surgery. Conclusion. In most cases, RDE is clinically manifested, rarely asymptomatic and diagnosed by visualization methods. Patients with a history of surgery at a younger age are at risk of RDE, and their surgical interventions are more complicated with more blood loss. Currently, surgical treatment of DE is the optimal method; however, it has serious disadvantages with severe and even life-threatening postoperative complications.

The use of CpGV strains as the basis for bioinsecticides is an effective and safe way to control Cydia pomonella. The research is aimed at the identification and study of new CpGV strains. Objects of identification and bioinformatic analysis: 18 CpGV strains. Sequencing was carried out on a NextSeq550. Genome assembly and annotation were carried out using Spades, Samtools 1.9, MinYS, Pilon, Gfinisher, Quast, and Prokka. Comparative genomic analysis was carried out in relation to the reference genome present in the «Madex Tween» strain-producer (biological standard) according to the average nucleotide identity (ANI) criterion. The presence/absence of IAP, cathepsin, MMP, and chitinase in the genetic sequences of the strains was determined using simply phylogeny. Entomopathogenic activity was assessed against C. pomonella according to the criterion of biological efficacy. Thus, molecular genetic identification revealed that 18 CpGV strains belong to a genus of Betabaculovirus. For all the strains under study ANI values of 99% or more were obtained, and the presence of the cathepsin, chitinase, IAP, and MMP genes was noted. The strains BZR GV 1, BZR GV 3, BZR GV 7, BZR GV 10, and BZR GV L-8 showed the maximum biological efficacy: 100% on the 15th day of observation. Strains BZR GV 4, BZR GV 8, and BZR GV 13 showed efficacy at the level of the «Madex Tween» preparation: 89.5% on the 15th day of observation. The strains with the highest mortality rate of the host insect were identified: BZR GV 9, BZR GV 10, BZR GV L-6, and BZR GV L-8.

Myeloproliferative neoplasms (MPNs) are subdivided into Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) and Ph-negative MPNs. BCR::ABL1 translocation is essential for the development and diagnosis of CML; on the other hand, the majority of Ph-negative MPNs are characterized by generally mutually exclusive mutations of Janus kinase 2 (JAK2), calreticulin (CALR), or thrombopoietin receptor/myeloproliferative leukemia (MPL). CALR mutations have been described essentially in JAK2 and MPL wild-type essential thrombocythemia and primary myelofibrosis. Rarely coexisting CALR and MPL mutations have been found in Ph-negative MPNs. BCR::ABL1 translocation and JAK2 mutations were initially considered mutually exclusive genomic events, but a discrete number of cases with the combination of these genetic alterations have been reported. The presence of BCR::ABL1 translocation with a coexisting CALR mutation is even more uncommon. Herein, starting from a routinely diagnosed case of CALR-mutated primary myelofibrosis subsequently acquiring BCR::ABL1 translocation, we performed a comprehensive review of the literature, discussing the clinicopathologic and molecular features, as well as the outcome and treatment of cases with BCR::ABL1 and CALR co-occurrence.

IntroductionHuman papilloma virus (HPV) is the most common sexually transmitted infection worldwide. Cervicovaginal microbiota plays an important role in HPV infection and is associated with the development of squamous intraepithelial lesions (SIL). The natural history of cervical cancer involves reversible changes in the cervical tissue from a normal state, in which no neoplastic changes are detected in the squamous epithelium, to varying states of cellular abnormalities that ultimately lead to cervical cancer. Low-grade SIL (LSIL), like another cytological category - atypical squamous cells of undetermined significance (ASCUS), may progress to high-grade SIL (HSIL) and invasive cervical cancer or may regress to a normal state.MethodsIn this work, we studied cervical canal microbiome in 165 HPV-positive and HPV-negative women of a reproductive age with ASCUS [HPV(+) n = 29; HPV(−) n = 11], LSIL [HPV(+) n = 32; HPV(−) n = 25], HSIL [HPV(+) n = 46], and the control group with negative for intraepithelial lesion malignancy (NILM) [HPV(−) n = 22].Results and DiscussionHPV16 is the most prevalent HPV type. We have not found any differences between diversity in studied groups, but several genus [like Prevotella (p-value = 0.026), Gardnerella (p-value = 0.003), Fannyhessea (p-value = 0.024)] more often occurred in HSIL group compared by NILM or LSIL regardless of HPV. We have found statistically significant difference in occurrence or proportion of bacterial genus in studied groups. We also identified that increasing of the ratio of Lactobacillus iners or age of patient lead to higher chance to HSIL, while increasing of the ratio of Lactobacillus crispatus lead to higher chance to LSIL. Patients with a moderate dysbiosis equally often had either of three types of vaginal microbial communities (CST, Community State Type) with the prevalence of Lactobacillus crispatus (CST I), Lactobacillus gasseri (CST II), and Lactobacillus iners (CST III); whereas severe dysbiosis is linked with CST IV involving the microorganisms genera associated with bacterial vaginosis and aerobic vaginitis: Gardnerella, Fannyhessea, Dialister, Sneathia, Anaerococcus, Megasphaera, Prevotella, Finegoldia, Peptoniphilus, Porphyromonas, Parvimonas, and Streptococcus.

Aim. To analyze the profile of anti-Mllerian hormone (AMH) and the expression level of the transmembrane AMH receptor type II (AMHRII) in the eutopic and ectopic endometrium of patients with deep infiltrative endometriosis (DIE). Materials and methods. A comparative analysis of AMHRII expression in epithelial and stromal cells of eutopic and ectopic endometrial samples and the level of serum AMH in patients of reproductive age with DIE (n=50) and tuboperitoneal infertility (n=9) was performed. Results. AMHRII expression in eutopic endometrial stromal cells of DIE patients was significantly higher compared to glandular cells in all study groups (p0.5). AMHRII expression was found to be significantly higher in glandular cells of the eutopic endometrium compared to the ectopic endometrium of pelvic peritoneal foci in DIE patients: 1.600.77 and 1.090.68 points, respectively (p=0.001). Conclusion. The inhibitory effect of AMH on cell proliferation and the proven expression of AMHRII by eutopic and ectopic endometrioid cells may indicate the role of AMH in the pathogenesis of endometriosis and endometriosis-associated infertility.

Cydia pomonella granulovirus is a natural pathogen for Cydia pomonella that is used as a biocontrol agent of insect populations. The study of granulovirus virulence is of particular interest since the development of resistance in natural populations of C. pomonella has been observed during the long-term use of the Mexican isolate CpGV. In our study, we present the genomes of 18 CpGV strains endemic to southern Russia and from Kazakhstan, as well as a strain included in the commercial preparation “Madex Twin”, which were sequenced and analyzed. We performed comparative genomic analysis using several tools. From comparisons at the level of genes and protein products that are involved in the infection process of virosis, synonymous and missense substitution variants have been identified. The average nucleotide identity has demonstrated a high similarity with other granulovirus genomes of different geographic origins. Whole-genome alignment of the 18 genomes relative to the reference revealed regions of low similarity. Analysis of gene repertoire variation has shown that BZR GV 4, BZR GV 6, and BZR GV L-7 strains have been the closest in gene content to the commercial “Madex Twin” strain. We have confirmed two deletions using read depth coverage data in regions lacking genes shown by homology analysis for granuloviruses BZR GV L-4 and BZR GV L-6; however, they are not related to the known genes causing viral pathogenicity. Thus, we have isolated novel CpGV strains and analyzed their potential as strains producing highly effective bioinsecticides against C. pomonella.

Aim. To study the regulation of apoptosis in the endometrium of women with chronic endometritis (CE) and external genital endometriosis (EGE) based on the study of the expression of its regulators such as transcription factor (NF-), Bcl-2 and Caspase-8. Materials and methods. The study evaluated the expression of apoptosis factors such as Caspase-8, NF-B transcription factor, and Bcl-2, in patients with chronic endometritis (CE, n=23), external genital endometriosis (EGE, n=20), and intact endometrium (control group; n=7). Statistically significant differences were found for all test markers (p0.05). Results. The increased expression of apoptosis factors is probably related to high endometrial pro-inflammatory activity in both CE and EGE. For EGE, this effect is more pronounced at the transcription level in the form of an increase in the expression of the transcription factor NF-B in both glandular and stromal endometrial cells. It is probably due to the systemic nature of the chronic inflammatory process. For CE, despite the antiapoptotic activity of Bcl-2, an increase in Caspase-8 expression in the endometrium may also indicate a predominance of innate immunity activation. Conclusion. The imbalance of pro- and antiapoptotic factors can be an inducer of both cytotoxic and cytoprotective mechanisms of EGE and CE. However, it requires further research.

A 12-year-old adolescent was diagnosed with a right-sided solid mass in the round ligament of the uterus. The chief complaints were abdominal pain and pelvic discomfort. She underwent laparoscopic tumor resection. Histological examination demonstrated a trabecular growth pattern of epithelioid cells with mitotic activity (3 per 50 HPF), which expressed melanocytic and myoid markers. Due to aforementioned findings, a final diagnosis of perivascular epithelioid cell tumor (PEComa) with uncertain malignant potential was made. To the best of our knowledge, this localization of PEComa is considered to be infrequent with only occasionally reported cases.

Aim. To assess the reproducibility of cytological diagnoses in evaluating liquid cervical smears and immunocytochemical co-expression of p16/Ki-67 using manual and automatic methods. Materials and methods. Cytological smears prepared using the liquid cytology method on the Becton Dickinson device (SurePath technology) were studied. An immunocytochemical study was carried out using a Ventana BenchMark Ultra automatic immunostainer with a commercial CINtec kit (determination of p16/Ki-67 co-expression). In total, 100 cytological slides (50 pairs of Pap-smears and immunocytochemical slides) were studied. The diagnostic kit was reviewed by five cytologists independently, and the cytologic slides were evaluated using four categories according to the Bethesda system (2014) and according to the categories of normal/abnormal. The co-expression of p16/Ki-67 was assessed per the manufacturer's recommendations (Roche) using the manual method (light microscope) and the automatic Vision Cyto Pap ICC system. Statistical processing of the results was performed using the SPSS software package version 26.0.0.0 with the calculation of the reproducibility indices of Cohen's kappa and Fleiss' kappa. Results. When assessing the reproducibility of four categories of cytological diagnoses according to the Bethesda system (2014), Cohen's kappa was 0.0480.265. The overall Fleiss' kappa between all cytologists was 0.103. When only two categories (normal/abnormal) were used, the reproducibility ranged from 0.058 to 0.377. When assessing the co-expression of p16 and Ki-67, Cohen's kappa reproducibility was from 0.196 to 0.574, while the overall Fleiss' kappa was 0.407. When comparing the evaluation results of each of the cytologists with the neural network, Cohen's kappa reproducibility ranged from 0.103 to 0.436. Conclusion. The reproducibility of cytological diagnoses according to the Bethesda system (2014) and two categories (normal/abnormal) based on the Pap smear study was low. Such results are primarily due to a large number of abnormal smears in the study. The immunocytochemical method has diagnosis reproducibility three times higher, indicating the need to measure the co-expression of p16 and Ki-67 to increase the sensitivity and specificity of the cytological method. Similar reproducibility when comparing the manual and automatic evaluation of the "double label" suggests that the neural network algorithm can currently help in decision support rather than replace the cytologist at the diagnostic stage.

Abstract The aim of this study was to evaluate the efficacy of hysteroscopically controlled injections of autologous platelet-rich plasma (PRP) and autologous endometrial cells as a treatment for infertile women with thin endometrium. The study enrolled 115 patients with thin endometrium (

Aim. To analyze the incidence and types of adverse outcomes and complications of laparoscopic myomectomies. Materials and methods. This work is a retrospective study based on data from the Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology. We analyzed 711 case histories of patients diagnosed with uterine myoma who received surgical treatment in the Department of Innovative Oncology and Gynecology from 2015 to 2019. The frequency of malignant neoplasms, verified by pathomorphological examination, and the characteristics of surgical interventions performed in these patients were comparatively evaluated. Results. Surgical interventions for uterine myoma are leading in gynecology due to the high prevalence of such disorders. Conservative myomectomy remains the "gold standard" in organ-sparing surgery. However, during surgeries for suspected benign neoplasms, there is a risk of morcellation of the malignant tumor, significantly worsening patient survival outcomes. In our study, the incidence of uterine leiomyosarcoma in suspected benign neoplasms was 0.98%. The probability of parasitic myomas or disseminated perineal leiomyomatosis after myomatous nodule morcellation is 0.19%. Conclusion. No reliable information about the malignant potential of the tumor and its proliferative activity can be obtained until a definitive pathomorphological examination. The above considerations warrant the routine use of prophylactic measures to prevent tumor cell dissemination.

Aim. To study the metabolomic profile of bacterial strains of the genus Bacillus promising for the development of biofungicides using thin layer chromatography (TLC), bioautography and high performance liquid chromatography with mass spectrometry (HPLC‐MS).Materials and Methods. The objects of study are strains of bacteria of the genus Bacillus. Exometabolites were isolated from the liquid culture and their metabolomic profile was analyzed by TLC, bioautography, and HPLC‐MS.Results. By the method of bioautography with a test culture of the fungus F. oxysporum var. orthoceras BZR F6 metabolites of bacterial strains of the genus Bacillus surfactin, iturin and fengycin were identified. Quantitative analysis using HPLC‐MS analysis allows us to state that the B. velenzensis BZR 336g and B. amyloliquefaciens BZR 277 strains produce more surfactin than the others. An increased content of ituric lipopeptides was found in strains B. velezensis BZR 517 and B. velenzensis BZR 336g. According to the ability to produce fengycins, strains of B. velezensis BZR 517 and B. velenzensis BZR 336g are ahead of other strains.Conclusion. Studies using two analytical methods reveal that the strains produce all three antifungal lipopeptides. This is important, since metabolites are able not only to suppress phytopathogenic fungi, but also to enhance the antifungal effect due to synergism. The results obtained allow us to state the possibility of using all four strains as producers of effective biofungicides.

H-score is a semi-quantitative method used to assess the presence and distribution of proteins in tissue samples by combining the intensity of staining and the percentage of stained nuclei. It is widely used but time-consuming and can be limited in terms of accuracy and precision. Computer-aided methods may help overcome these limitations and improve the efficiency of pathologists’ workflows. In this work, we developed a model EndoNet for automatic H-score calculation on histological slides. Our proposed method uses neural networks and consists of two main parts. The first is a detection model which predicts the keypoints of centers of nuclei. The second is an H-score module that calculates the value of the H-score using mean pixel values of predicted keypoints. Our model was trained and validated on 1780 annotated tiles with a shape of 100 × 100 µm and we achieved 0.77 mAP on a test dataset. We obtained our best results in H-score calculation; these results proved superior to QuPath predictions. Moreover, the model can be adjusted to a specific specialist or whole laboratory to reproduce the manner of calculating the H-score. Thus, EndoNet is effective and robust in the analysis of histology slides, which can improve and significantly accelerate the work of pathologists.

Introduction. The main function of the endometrium is to create the optimal environment for embryo implantation, controlled by multicomponent signaling pathways. They are modulated by progesterone and estradiol acting through related estrogen receptors (ER) and progesterone receptors (PR). Alteration in steroid hormone, follicle-stimulating hormone (FSHR), and luteinizing hormone (LGHR) receptor expression are underlying factors in the development of various reproductive disorders. Therefore, understanding the physiological features of receptors expression and localization in tissues is extremely important for a proper comprehensive assessment of the endometrial condition. Materials and methods. The expression of ER, PR, FSHR, and LGHR in endometrial samples of healthy females from different menstrual periods, who applied for assisted reproductive technologies (ART) due to male infertility, was assessed by immunofluorescence. Results. The increase in immunoreactivity of ER, PR, FSHR, and LGHR in the glands and stroma of the endometrium is initiated during the early proliferation stage and reaches its maximum during the late proliferation stage. Subsequently, ER expression in the glands and stroma gradually decreases throughout the early and middle stages of secretion; PR immunoreactivity in the stroma and FSHR and LGHR in all endometrial components persists throughout the secretion stage. Conclusion. The correspondence between the change of the studied receptors' expression and endometrium structural features at different stages of the menstrual cycle was demonstrated. The increased expression of ER, PR, FSHR, and LGHR in the endometrium at the proliferation stage coincides with the growth period of the uterine body mucosa, and the increased immunoreactivity of PR, FSHR, and LGHR during the secretion stage is associated with its decidual transformation and seems to create conditions for successful implantation and embryo development if pregnancy occurs.

Aim – to study the biocontrol properties of B. velezensis BZR 336g and B. velezensis BZR 517 strains against Fusarium pathogens using the fungus Fusarium graminearum as an example and to reduce the accumulation of deoxynivalenol (DON) and zearalenone (ZEN) in vitro.Materials and Methods. A study of the toxinogenicity of F. graminearum fungal strains was undertaken on rice and wheat grains and the effect of B. velezensis BZR 336g and B. velezensis BZR 517 strains on the growth of the fungus was studied on wheat grains and by the double cultures method. An experiment to study the effect of a liquid culture and supernatant of bacteria was carried out on wheat grains and the content of DON and ZEN in wheat grains was analyzed by HPLC and enzyme immunoassay.Results. It was found that two strains of the fungus F. graminearum were able to produce a high level of mycotoxins, while the strain F. graminearum 60318 had a higher growth rate. The B. velezensis BZR 336g and B. velezensis BZR 517 strains produced lipopeptide exometabolites and inhibited the growth of the F. graminearum 60318 strain. in vitro, while the content of ZEN remained at the control level.Conclusion. The ability of two strains of bacteria B. velezensis BZR 336g and B. velezensis BZR 517 to suppress the growth of the fungus F. graminearum 60318, as well as to inhibit the accumulation of mycotoxins in wheat grain in vitro, suggests that an increase in the content of antagonist bacteria B. velezensis BZR 336g and B. velezensis BZR 517 in the wheat microbiota can contribute to the suppression of the growth and harm of the fungus F. graminearum 60318.

The use of CpGV strains as the basis for bioinsecticides is an effective and safe way to control Cydia pomonella. The research is aimed at the identification and study of new CpGV strains. Objects of identification and bioinformatic analysis: 18 CpGV strains. Sequencing was carried out on a NextSeq550. Genome assembly and annotation were carried out using Spades, Samtools 1.9, MinYS, Pilon, Gfinisher, Quast, and Prokka. Comparative genomic analysis was carried out in relation to the reference genome present in the «Madex Tween» strain-producer (biological standard) according to the average nucleotide identity (ANI) criterion. The presence/absence of IAP, cathepsin, MMP, and chitinase in the genetic sequences of the strains was determined using simply phylogeny. Entomopathogenic activity was assessed against C. pomonella according to the criterion of biological efficacy. Thus, molecular genetic identification revealed that 18 CpGV strains belong to a genus of Betabaculovirus. For all the strains under study ANI values of 99% or more were obtained, and the presence of the cathepsin, chitinase, IAP, and MMP genes was noted. The strains BZR GV 1, BZR GV 3, BZR GV 7, BZR GV 10, and BZR GV L-8 showed the maximum biological efficacy: 100% on the 15th day of observation. Strains BZR GV 4, BZR GV 8, and BZR GV 13 showed efficacy at the level of the «Madex Tween» preparation: 89.5% on the 15th day of observation. The strains with the highest mortality rate of the host insect were identified: BZR GV 9, BZR GV 10, BZR GV L-6, and BZR GV L-8. [ABSTRACT FROM AUTHOR]

Simple Summary: Our research integrates two key areas of focus. We first focus on a comparative biostatistical analysis of the agreement between three laboratory methods for genotyping gene copy number variations, and then we explore new characteristics of the distribution of this type of genetic aberration among cancer-associated genes. The results could be used to help molecular oncologists pick the smallest set of methods that will allow for accurate CNV genotyping in personalized cancer prognosis and drug-response prediction. We see the following strengths of our research: (1) We employ various methods for the detection of CNVs, such as CoreExome microarrays, nCounter v2 Cancer CN Assay panel, and digital droplet PCR; (2) This study sets out an interpretable comprehensive biostatistical analysis of the agreement using the PABAK score and Passing–Bablok regression; (3) This study presents the detection of CNVs in 12 paired tumor ovarian cancer/normal samples with clinical data; and (4) The research has translational potential. Objective: The goal of this study was to compare the results of CNV detection by three different methods using 13 paired carcinoma samples, as well as to perform a statistical analysis of the agreement. Methods: CNV was studied using NanoString nCounter v2 Cancer CN Assay (Nanostring), Illumina Infinium CoreExome microarrays (CoreExome microarrays) and digital droplet PCR (ddPCR). Results: There was a good level of agreement (PABAK score > 0.6) between the CoreExome microarrays and the ddPCR results for finding CNVs. There was a moderate level of agreement (PABAK values ≈ 0.3–0.6) between the NanoString Assay results and microarrays or ddPCR. For 83 out of 87 target genes studied (95%), the agreement between the CoreExome microarrays and NanoString nCounter was characterized by PABAK values < 0.75, except for MAGI3, PDGFRA, NKX2-1 and KDR genes (>0.75). The MET, HMGA2, KDR, C8orf4, PAX9, CDK6, and CCND2 genes had the highest agreement among all three approaches. Conclusions: Therefore, to get a better idea of how to genotype an unknown CNV spectrum in tumor or normal tissue samples that are very different molecularly, it makes sense to use at least two CNV detection methods. One of them, like ddPCR, should be able to quantitatively confirm the results of the other. [ABSTRACT FROM AUTHOR]

Aim. To study the structure of bacteria exometabolites of the Bacillus velezensis BZR336g strain using the GC×GC‐MS method when cultivated on nutrient media differing in the content of microelements.Material and Methods. The object of the study is the B. velezensis BZR336g bacterium strain. It shows promise for the development of a biopreparation on its basis for protecting plants against phytopathogenic fungi. Exometabolites were isolated from the liquid culture and their metabolomic profile was analysed with the GC×GC‐MS method using a LECO Pegasus BT‐4D device.Results. Among the identified compounds one can see the precursors of biologically active metabolites of bacteria of the strain B. velezensis BZR336g. Analysis of the total accumulation of fatty acids and their analogs, as well as of amino acids and peptides, by B. velezensis BZR336g bacteria on nutrient media differing in the content of metal ions, shows that Co2+ ions in combination with Mn2+ and Zn2+ ions play an important role in inducing their synthesis. The presence of the Co2+ ion in the nutrient medium has the greatest influence on the synthesis of peptide components. If it is removed from the nutrient medium, the amount of amino acids and peptides decreases by almost two times. Benzene compounds can act as precursors of aromatic hydrocarbons, which are also of interest in the analysis of bacterial metabolism, since they have antimicrobial activity.Conclusions. The number of compounds that are precursors of lipopeptide metabolites depends on the content of metal ions in the nutrient medium. This fact may vary depending on the combination in which the metals are present.

This paper investigates the antagonistic and plant growth promotion activity of the new indigenous bacteria antagonist strains P. chlororaphis BZR 245-F and Pseudomonas sp. BZR 523-2. It was found that on the 10th day of cultivation, BZR 245-F and BZR 523-2 exhibit an antagonistic activity against F. graminearum at the level of 59.6% and 15.1% and against F. oxysporum var. orthoceras at the level of 50.2% and 8.9%, respectively. Furthermore, the BZR 523-2 strain stimulated the growth of winter wheat seedlings more actively than the BZR 245-F strain. When processing seeds of winter wheat, Pseudomonas sp. BZR 523-2 indicators were higher than in the control: plant height increased by 10.3%, and root length increased by 18.6%. The complex characteristic properties of the metabolite were studied by bioautography and HPLC-MS. Bioautography proved the antifungal activity of phenazine nature compounds synthesized by the new bacterial strains. We qualitatively and quantitatively analyzed them by HPLC-MS analysis of the strain sample metabolites. In the BZR 245-F sample, we found more phenazine compounds of various types. Their total phenazine concentration in the BZR 245-F was more than five times greater than in the BZR 523-2. We defined crucial differences in the quantitative content of the other metabolites. Despite the difference between new indigenous bacteria antagonist strains, they can be used as producers of effective biopesticides for sustainable agriculture management.

The expression level of the progesterone receptor (PGR) plays a crucial role in determining the biological characteristics of serous ovarian carcinoma. Low PGR expression is associated with chemoresistance and a poorer outcome. In this study, our objective was to explore the relationship between tumor progesterone receptor levels and RNA profiles (miRNAs, piwiRNAs, and mRNAs) to understand their biological characteristics and behavior. To achieve this, we employed next-generation sequencing of small non-coding RNAs, quantitative RT-PCR, and immunohistochemistry to analyze both FFPE and frozen tumor samples, as well as blood plasma from patients with benign cystadenoma (BSC), serous borderline tumor (SBT), low-grade serous ovarian carcinoma (LGSOC), and high-grade serous ovarian carcinoma (HGSOC). Our findings revealed significant upregulation of MMP7 and MUC16, along with downregulation of PGR, in LGSOC and HGSOC compared to BSC. We observed significant correlations of PGR expression levels in tumor tissue with the contents of miR-199a-5p, miR-214-3p, miR-424-3p, miR-424-5p, and miR-125b-5p, which potentially target MUC16, MMP7, and MMP9, as well as with the tissue content of miR-16-5p, miR-17-5p, miR-20a-5p, and miR-93-5p, which are associated with the epithelial–mesenchymal transition (EMT) of cells. The levels of EMT-associated miRNAs were significantly correlated with the content of hsa_piR_022437, hsa_piR_009295, hsa_piR_020813, hsa_piR_004307, and hsa_piR_019914 in tumor tissues. We developed two optimal logistic regression models using the quantitation of hsa_piR_020813, miR-16-5p, and hsa_piR_022437 or hsa_piR_004307, hsa_piR_019914, and miR-93-5p in the tumor tissue, which exhibited a significant ability to diagnose the PGR-negative tumor phenotype with 93% sensitivity. Of particular interest, the blood plasma levels of miR-16-5p and hsa_piR_022437 could be used to diagnose the PGR-negative tumor phenotype with 86% sensitivity even before surgery and chemotherapy. This knowledge can help in choosing the most effective treatment strategy for this aggressive type of ovarian cancer, such as neoadjuvant chemotherapy followed by cytoreduction in combination with hyperthermic intraperitoneal chemotherapy and targeted therapy, thus enhancing the treatment’s effectiveness and the patient’s longevity.

Abstract Background Low endometrial receptivity is one of the major factors affecting successful implantation in assisted reproductive technologies (ART). Infertile patients with thin endometrium have a significantly lower cumulative clinical pregnancy rate than patients with normal endometrium. Molecular pathophysiology of low receptivity of thin endometrium remains understudied. We have investigated composition of glycocalyx of the apical surface of luminal and glandular epithelial cells in thin endometrium of infertile women. Methods Thirty-two patients with tubal-peritoneal infertility undergoing in vitro fertilization (IVF) were included in the study. Endometrial samples were obtained in a natural menstrual cycle. Patients were divided into two groups: patients with normal endometrium (≥8 mm) and with thin endometrium (

Aim. To conduct a comparative analysis of the results of organ-preserving laparoscopic operations performed for uterine fibroids with the use of plastic containers for morcellation and without it. Materials and methods. We examined 57 patients with a diagnosis of uterine fibroids who were admitted to the Department of Innovative Oncology and Gynecology of the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology for organ-preserving surgical treatment. To achieve the goal of the study, the patients were divided into the following groups: the main group 29 patients who underwent laparoscopic myomectomy and morcellation of removed nodes using plastic containers. The control group consisted of 28 patients who underwent morcellation during laparoscopic myomectomy without the use of plastic containers. Results. The duration of laparoscopic operations performed using plastic containers main group was 85.6925.87 minutes. Laparoscopic conservative myomectomies, performed without the use of limiting systems, took a slightly longer amount of time control group 88.7530.36 minutes. There were no statistically significant differences, but in the second group, more prolonged sanitation of the abdominal cavity and removal of small fragments of myomatous nodes after morcellation outside the sacs were required. Autoinfusion was used in 6 (20.69%) patients in the main group, in 7 (25%) patients in the control group. Blood transfusion was not used in any case. Average blood loss was 120.6967.50 ml in the main group, 125.0099.54 ml in the control. The duration of hospitalization in the main group was 4.661.76 days, in the control group 5.793.62 days. In the main group, histological examination revealed leiomyoma in all cases, leiomyoma was detected in 96.4% (27 patients) of cases in the control group, and leiomyosarcoma in 1 patient (3.6%). Conclusion. In all groups of patients, there was a favorable course of the postoperative period, early activation of patients. In the group of laparoscopic operations, one patient (3.6%) after morcellation of the myomatous node without the use of a plastic container was found to have leiomyosarcoma. The use of plastic containers in our study did not increase the duration of operations and did not affect the volume of blood loss, the frequency of intra- and postoperative complications. In contrast, the operation time was slightly higher among patients who were operated without the use of containers. In all likelihood, this was due to the fact that the morcellation stage itself took longer, since it was required to extract small fragments of myomatous nodes, as well as thorough and prolonged sanitation of the abdominal cavity. It should be noted that the use of plastic containers, of course, requires the development of certain skills from the surgeon, taking less and less time in parallel with the learning curve. Of course, further studies are required to assess the risk of tumor spread in patients undergoing surgery using plastic containers, but preliminary data indicate that ablastic morcellation can and should be used in organ-preserving surgery for uterine myoma.

Aim. To conduct a retrospective analysis and evaluate the morphological methods for HPV-related intraepithelial lesions detection in women of reproductive age. Materials and methods. The data of cytological diagnosis, as well as the results of histological reports were analyzed for the period from 2018 to 2019. A comparative analysis was performed in 415 patients with HPV-related intraepithelial lesions, who applied to the scientific and polyclinic department of the Kulakov National Research Medical Center at the age of 19 to 45 years. Morphological examination was carried out by specialists of the 1st pathology department of the Center. Results. According to the results of a comparative analysis of cytological and histological conclusions, 3 groups were formed: 1 the group of coincidence (agree) of cytological and histological conclusions; 2 group of minor discrepancies (minor under/ over) between cytological and histological finding; 3 group of major discrepancies (major under/ over) between cytological and histological findings. Cytological and histological compliance was achieved in 194 (46.74%) patients. The total number of minor nonconformities was 192 (46%) cases. The total number of significant discrepancies between cytological and histological findings was 29 (6.9%) patients: 20 (4.8%) cases were found in the group NILM, hr. cervicitis HSIL and 9 (2.1%) cases in the group HSIL hr. cervicitis according to the results of histological examination. Conclusion. Cervical screening reduces the risk of breast cancer due to cytological examination of the cervix, but histological examination is crucial in making a correct diagnosis, since its result determines the choice of treatment method. The comparative analysis showed that in all groups there were cases of hypo- and hyperdiagnostics during cytological examination although the major discrepancies which can change treatment algorithm, were found only in 6.8% cases.

Disruption of endometrial regeneration, fibrosis formation, and intrauterine adhesions underlie the development of “thin” endometrium and/or Asherman’s syndrome (AS) and are a common cause of infertility and a high risk for adverse obstetric outcomes. The methods used (surgical adhesiolysis, anti-adhesive agents, and hormonal therapy) do not allow restoration of the regenerative properties of the endometrium. The experience gained today with cell therapy using multipotent mesenchymal stromal cells (MMSCs) proves their high regenerative and proliferative properties in tissue damage. Their contribution to regenerative processes is still poorly understood. One of these mechanisms is based on the paracrine effects of MMSCs associated with the stimulation of cells of the microenvironment by secreting extracellular vesicles (EVs) into the extracellular space. EVs, whose source is MMSCs, are able to stimulate progenitor cells and stem cells in damaged tissues and exert cytoprotective, antiapoptotic, and angiogenic effects. This review described the regulatory mechanisms of endometrial regeneration, pathological conditions associated with a decrease in endometrial regeneration, and it presented the available data from studies on the effect of MMSCs and their EVs on endometrial repair processes, and the involvement of EVs in human reproductive processes at the level of implantation and embryogenesis.

Simple Summary: Ovarian serous borderline tumor (SBT) is a known precursor of low-grade serous carcinoma, and it has been reported that about 50% of SBTs are BRAF-mutated and that these tumors have a better prognosis. Therefore, early identification of the mutation is important for accurate treatment and follow-up of patients with SBT. It has been shown that eosinophilic cells (ECs) can be a histologic sign of a BRAF mutation. Therefore, the aim of our retrospective study was to evaluate the interobserver reproducibility for these cells. A BRAFV600E mutation was found in 45% of cases. The interobserver reproducibility in the assessment of ECs was substantial. The sensitivity and specificity for predicting the mutation were 79% and 91%, respectively, so ECs in ovarian SBTs can be used for initial screening of the BRAFV600E mutation to stratify patients and establish a prognosis. According to recent reports, ovarian serous borderline tumor (SBT) harboring the BRAF V600E mutation is associated with a lower risk of progression to low-grade serous carcinoma. Preliminary observations suggest that there may be an association between eosinophilic cells (ECs) and the above-mentioned mutation, so this study aimed to evaluate interobserver reproducibility for assessing ECs. Forty-two samples of SBTs were analyzed for ECs with abundant eosinophilic cytoplasm. Immunohistochemical staining and genetic pro-filing were performed in all cases to verify the BRAF V600E mutation. A BRAF V600E mutation was found in 19 of 42 (45%) cases. Inter-observer reproducibility in the assessment of ECs was substantial (κ = 0.7). The sensitivity and specificity for predicting the mutation were 79% and 91%, respectively. Patients with BRAF-mutated SBTs were significantly younger than those without mutation (p = 0.005). SBTs with BRAF mutation were less likely to be accompanied by non-invasive implants than wild-type SBT: 12% (2/17) versus 33% (6/18). Seven cases were excluded due to incomplete cytoreductive surgery. Nevertheless, Fisher's exact test showed no significant differences between the two groups (p = 0.228). Overall, this study strengthens the idea that ECs in ovarian SBTs may represent a mutation with prognostic significance, which can serve as a primary screening test for BRAF V600E mutation in this pathologic entity. [ABSTRACT FROM AUTHOR]

Ovarian cystadenofibroma (CAF) is a rare ovarian tumor originating both from epithelial and stromal components being, however, classified as epithelial tumors. CAF prevalence among all ovarian tumors does not exceed more than 1.7 %. CAFs are commonly asymptomatic, in extremely rare cases of large tumor or ovarian torsion pain sensation may be noted. External genital endometriosis (EGE) is a chronic gynecological disorder that occurs in women of reproductive age and cause infertility and pelvic pain. EGE prevalence comprises around 10 % in women of reproductive age, 20–50 % in women with infertility, and almost 90 % in women with chronic pelvic pain. Magnetic resonance imaging (MRI) is method of choice in diagnostics of such pathology due to the high natural soft tissue contrast and functional techniques such as diffusion-weighted images (DWI) and dynamic contrast enhancement (DCE). Surgery planning, necessity for systemic therapy or follow-up directly depend on imaging and diagnostic laparoscopy results. Here we present a clinical case of rarely combined serous papillary CAF with extended EGE accompanied with consequences of intra-tumoral hemorrhage. Case study demonstrates main visualization characteristics that provide correct differential diagnosis and exclude malignancy transformation.

Aim. To evaluate the endometrial glyotype in the implantation window in patients with infertility in assisted reproductive technologies (ART) programs and to develop criteria for assessing endometrial receptivity based on the analysis of complex changes in the functional groups of glycans in the main endometrial epithelial to use in clinical practice. Materials and methods. The study included 32 infertile patients who took part in ART programs. Pipelle endometrial biopsy was performed during the implantation window in the cycle preceding the cycle of ovarian stimulation and embryo transfer. Using lectin histochemistry and immunohistochemistry, glycans levels in the glycocalyx of endometrial surface epithelium (SE) and glandular epithelium (GE) was studied. Results. Differences in the expression of mannose-rich glycans in SE and N-acetylgalactosamine--terminated glycans in the GE of the endometrium were revealed, as well as the link between the expression of lectin staining glycans: ConA, VVL, UEA-I, SNA, MAL-II, ECL and monoclonal antibodies: anti-MECA -79 mAb and anti-LeY mAb in SE and GE of the endometrium was assessed in patients with infertility, depending on the outcome of the ART program. The estimated threshold levels in glycan expression and the odds ratio for pregnancy occurrence allow to characterize the diagnostic value for the studied glycomarkers and to develop criteria for assessing endometrial receptivity. Conclusion. Based on a comprehensive evaluation of glycans in the main endometrial epithelial structures in the cycle preceding the ART cycle, criteria for assessment of the likelihood of pregnancy have been developed, which can increase the effectiveness of ART programs in patients with infertility.

It is generally accepted that choriocarcinoma is a trophoblastic tumor of gestational origin during the reproductive period, but this neoplasm can rarely occur after menopause or be non-gestational making diagnosis a real challenge. In addition to this, somatic neoplasms can also undergo trophoblastic differentiation. The last two types of tumors are most often especially aggressive and have a poor prognosis, so they require more aggressive treatment respectively. To distinguish gestational/non-gestational origin that has an important impact on patient’s management, DNA polymorphism study could be provided.We report a clinical case involving a 58-year-old woman with a history of ovarian non-gestational choriocarcinoma, composed of bulky mass with multiple metastasis including contralateral ovary, omentum, peritoneum, pleura, and colon. The microscopic, immunohistochemical, and molecular features are described, including short tandem repeat (STR) genotype via DNA analysis.