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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 FROM AUTHOR]

Meloidogyne incognita Kofoid et White is one of the most dangerous root-knot nematodes in greenhouses. In this study, we evaluated two Bacillus strains (Bacillus velezensis BZR 86 and Bacillus velezensis BZR 277) as promising microbiological agents for protecting cucumber plants from the root-knot nematode M. incognita Kof. The morphological and cultural characteristics and enzymatic activity of the strains have been studied and the optimal conditions for its cultivation have been developed. We have shown the nematicidal activity of these strains against M. incognita. Experiments with the cucumber variety Courage were conducted under greenhouse conditions in 2016–2018. We determined the effect of plant damage with M. incognita to plants on the biometric parameters of underground and aboveground parts of cucumber plants, as well as on the gall formation index and yield. It was found that the treatment of plants with Bacillus strains contributed to an increase in the height of cucumber plants by 7.4–43.1%, an increase in leaf area by 2.7–17.8%, and an increase in root mass by 3.2–16.1% compared with the control plants without treatment. The application of these strains was proved to contribute to an increase in yield by 4.6–45.8% compared to control. Our experiments suggest that the treatment of cucumber plants with two Bacillus strains improved plant health and crop productivity in the greenhouse. B. velezensis BZR 86 and B. velezensis BZR 277 may form the basis for bionematicides to protect cucumber plants from the root-knot nematode M. incognita. [ABSTRACT FROM AUTHOR]

The phytopathogenic fungus Pyrenophora tritici-repentis is a causal agent of tan spot. Antagonistic microorganisms can be used as a non-chemical alternative treatment against the tan spot of wheat. Bacillus velezensis BZR 336 g and BZR 517 stains were selected as the most active microorganisms and potential biocontrol agents. We found that B. velezensis strains BZR 336 g and BZR 517 exhibited antagonistic activity against P. tritici-repentis Kr-15/2016 in vitro: they inhibited mycelium growth by 72.4–94.3% and caused its degenerative changes. Treatment of seeds and plants with strains BZR 336 g and BZR 517 provided a biological efficiency of 31.2–38.4% against tan spot, while artificial inoculation of plants provided only 28.4–43.8% biological efficiency. Treatment of seeds and plants with BZR 336 g and BZR 517 in a three-year field trial demonstrated 24.6–50% biological efficiency. BZR 336 g and BZR 517 provided 5.0–7.6% additional yield. We conclude that BZR 336 g and BZR 517 are promising options for novel bioproducts that can control P. tritici-repentis tan spot. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that a cytology–histology correlation (CHC) with discrepancy detection can both evaluate errors and improve the sensitivity and specificity of the cytologic method. We aimed to analyze the errors in cytologic–histologic discrepancies according to the CHC protocol guideline of the American Society of Cytopathology (2017). This retrospective study included 273 patients seen at the National Medical Research Center of Obstetrics, Gynecology and Perinatology (Moscow, Russia) between January 2019 and September 2021. The patients' mean age was 34 ± 8.1 years. The cytology–histology agreement was noted in 158 cases (57.9%). Major discrepancies were found in 21 cases (7.6%), while minor discrepancies were noted in 93 cases (34.1%). The reason for 13 (4.8%) discrepancies was a colposcopy sampling error and, in 46 (16.8%) cases, the reason was a Papanicolaou (PAP) test sampling error. The discrepancy between primary and reviewed cytology was due interpretive errors in 13 (4.8%) cases and screening errors in 42 (15.4%) cases. We demonstrated that the ASC guidelines facilitate cervical CHC. A uniform application of these guidelines would standardize cervical CHCs internationally, provide a scope for the inter-laboratory comparison of data, and enhance self-learning and peer learning. [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]

The influence of the teacher on the pupil is immeasurably greater when it is supported by the family, when the friendly, joint cooperation of the school and family has been established. And this is understandable, for then the demands made on the children are coordinated and a single policy is pursued in influencing the child. [ABSTRACT FROM AUTHOR]

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]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The early diagnosis of endometriosis in adolescents is not developed. Objective: We aim to conduct clinical, imaging, laparoscopic and histological analyses of peritoneal endometriosis (PE) in adolescents in order to improve early diagnosis. Methods: In total, 134 girls (from menarche to 17 years old) were included in a case–control study: 90 with laparoscopically (LS) confirmed PE, 44 healthy controls underwent full examination and LS was analyzed in the PE group. Results: Patients with PE were characterized with heredity for endometriosis, persistent dysmenorrhea, decreased daily activity, gastrointestinal symptoms, higher LH, estradiol, prolactin and Ca-125 (<0.05 for each). Ultrasound detected PE in 3.3% and MRI in 78.9%. The most essential MRI signs are as follows: hypointense foci, the heterogeneity of the pelvic tissue (paraovarian, parametrial and rectouterine pouch) and sacro-uterine ligaments lesions (<0.05 for each). Adolescents with PE mostly exhibit initial rASRM stages. Red implants correlated with the rASRM score, and sheer implants correlated with pain (VAS score) (<0.05). In 32.2%, foci consisted of fibrous, adipose and muscle tissue; black lesions were more likely to be histologically verified (0.001). Conclusion: Adolescents exhibit mostly initial PE stages, which are associated with greater pain. Persistent dysmenorrhea and detected MRI parameters predict the laparoscopic confirmation of initial PE in adolescents in 84.3% (OR 15.4; <0.01), justifying the early surgical diagnostics and shortening the time delay and suffering of the young patients. [ABSTRACT FROM AUTHOR]

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 (< 7 mm at implantation window) and infertility, who were divided into groups: Group 1 (the control) underwent conservative therapy; Group 2 received intraendometrial PRP injections instead of the conservative therapy; Group 3 received identical injections after conservative therapy; Group 4 received injections of the autologous endometrial cells suspended in PRP. A single injection dose of PRP contained 0.6–0.7 × 1011 of platelets. The levels of PDGF-BB and VEGF in PRP were increased compared with ordinary plasma. The autologous endometrial cells, obtained from pipelle biopsies, constituted heterogeneous cell populations containing stromal and epithelial cells. Intraendometrial PRP injections had significant impact on endometrial thickness and local microcirculation in Group 2 and Group 3. In Group 4, injections of PRP reinforced with endometrial cells also facilitated a significant increase in endometrial thickness. This work describes a novel approach for infertility treatment in patients with refractory thin endometrium. PRP injections and injections of the endometrial cells suspended in PRP into endometrium enhanced cell proliferation and angiogenesis. [ABSTRACT FROM AUTHOR]

Uterine leiomyomas usually arise from the uterine body (95%), and rarely from the cervix (0.6%) or other urogenital sites. Lipoleiomyomas are benign, uncommon variants of leiomyomas (0.03–0.2%), histologically composed of smooth muscle cells and mature adipocytes; they usually occur in the uterine body and exceptionally in the cervix. We performed the first systematic literature review of cervical lipoleiomyomas (PRISMA guidelines), presenting five new cases. Including our series, thirty-one detailed cases were reported in the literature (mainly in Asia). The age range was 35–74 years, revealing a higher mean age than conventional cervical leiomyomas (46.5 vs. 39.4 years). Patients were usually multiparous (94%), typically complaining of vaginal bleeding (11/31, 36%), pelvic/abdominal pain (10/31, 32%), and/or urinary disturbances (6/31, 19%) 1 week to 10 months before presentation. Clinical examination revealed a pedunculated tumor (48%), or prolapse of ≥1 pelvic organs (16%). Twenty-four (77%) patients underwent total hysterectomy ± additional surgery; simple myomectomy/excision was performed in five (16%) cases. Only one (3%) of our cases recurred 2 years after partial excision; no evidence of disease was found 13 years after recurrence excision. Adipocytes occupied ≤50% of the tumor volume. Hyaline or myxoid changes and cartilaginous metaplasia were uncommon histological findings. Surgically challenging cases or pregnant patients may require expert gynecologists. Interventional radiology or conservative treatments were rarely proposed. [ABSTRACT FROM AUTHOR]

The distribution of allele frequencies of polymorphic markers of the genes of the apoptosis and cell cycle control system TP53 (rs1042522), MDM2 (rs2279744), and CDKN1A (rs1801270) was obtained. The relationship of these markers with the risk of ovarian cancer was analyzed in women of the Moscow region. The study included 70 healthy female donors and 66 patients with ovarian cancer. DNA isolated from the blood of healthy donors and tissue and blood of patients with ovarian cancer was studied. The polymorphic markers of genes were analyzed by real-time PCR with fluorescent allele-specific probes. In the work, the odds ratios (OR) of ovarian cancer risk were obtained: OR = 0.94, 95% CI = 0.57–1.65, p = 1.0 for the Pro allele of the Arg72Pro of the TP53 gene; OR = 0.96, 95% CI = 0.49–1.89, p = 0.90 for the G allele of the T(–410)G of the MDM2 gene; OR = 1.53, 95% CI = 0.76–3.09, p = 0.29 for the Arg allele of the Ser31Arg of the CDKN1A gene. Obtained results show no association with ovarian cancer for studied markers. It was revealed that the carriage of minor alleles of the Arg72Pro of the TP53 gene, T(–410)G of the MDM2 gene, and Ser31Arg of the CDKN1A gene did not affect the risk of development of ovarian cancer in women of the Moscow region. [ABSTRACT FROM AUTHOR]

[Display omitted] • Phenotypic plasticity and cancer microbiome were added to "Hallmarks of cancer". • Some metal complexes showed selectivity towards cancer stem cells over cancer bulk. • Endogenous transition metals are important for maintaining intestinal microbiome. • Some metal complexes inhibited oncogenic bacteria and modulated cancer microbiome. • Metal complexes are undervalued therapeutic options for cancer treatment. In this last decade, our understanding of the complex factors and processes that drive cancer development and progression has broadened in scope and grown in depth. Today it is widely held that as a disease, cancer can be characterized in terms of specific hallmarks that normal cells need to acquire to transform into malignant cells. Because it is both logical and intuitive, the hallmarks of cancer concept have been adopted by both the scientific and medical community as an organising principle to understand cancer and to develop new therapeutic approaches. Several new hallmarks have emerged in recent years arising from a better understanding of the crosstalk between cancer cells and their surrounding tumor microenvironment. There is evidence of the so-called "metallic" crosstalk that is linked to neoplastic cell transformation. The current review is based on the collaborative efforts of bioinorganic chemists, molecular biologists and medical doctors. It summarizes the therapeutic strategies developed for targeting phenotypic plasticity and cancer microbiome arising from interactions with transition metals and discusses whether transition metal complexes might offer therapeutic advantages compared to current treatment options. [ABSTRACT FROM AUTHOR]

[Display omitted] • The development of many cancer types is associated with global epigenetic changes. • Metal complexes were shown to interfere with the function of DNMTs, HMDs and HDACs. • Metal prodrugs can be activated upon intracellular triggers. • Selective release of epigenetic modulators might translate into lower toxicity. • Transition metal complexes represent a promising alternative to existing epitherapies. In this last decade, our understanding of the complex factors and processes that drive cancer development and progression has broadened in scope and grown in depth. Today, it is widely held that as a disease, cancer can be characterized in terms of specific hallmarks that normal cells need to acquire to transform into malignant cells. Because it is both logical and intuitive, the hallmarks of cancer concept has been adopted by both the scientific and medical community as an organising principle to understand cancer and to develop new therapeutic approaches. Several new hallmarks have emerged in recent years arising from a better understanding of the crosstalk between cancer cells and their surrounding tumor microenvironment. The current review is based on the collaborative efforts of bioinorganic chemists, molecular biologists and medical doctors. It focuses on the use of transition metals as therapeutic drugs to treat malignancies arising from epigenetic dysregulation and compares the therapeutic approaches of transition metal complexes over existing drugs in clinical use. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Zanelli, Fragliasso, Loscocco, Sanguedolce, Broggi, Zizzo, Palicelli, Ricci, Ambrogi, Martino, Aversa, Coppa, Gentile, Gozzi, Caltabiano, Koufopoulos, Asaturova, Cimino, Cavazza, Orcioni and Ascani.)

Background: Vulvar lichen sclerosus (VLS) is a chronic and recurrent dermatosis of an inflammatory nature with severe focal atrophy of the skin. Connective tissue changes are polymorphic and are still not taken into account in histological diagnostics due to the difficulty of interpreting routine histological methods. In this work, we use multiphoton microscopy (MPM) as a new imaging technique that provides detailed information about the organization of collagen fibers in the dermis based on a non-linear second harmonic generation (SHG) process., Objective: To determine the degree of connective tissue damage in lichen sclerosus using standard histological techniques and to reveal the diagnostic capabilities of multiphoton microscopy., Material and Methods: We studied 42 biopsies with a histopathological diagnosis of VLS and 10 biopsies of normal vulvar skin. Histological, histochemical and immunohistochemical evaluation was used in comparison with MPM data. Quantitative analysis included the determination of the thickness, length of collagen fibers and the average intensity of the SHG signal., Results: A comprehensive study of the skin showed 4 groups of changes that can be regarded as the degree of the dermis damage: initial, mild, moderate, severe. The affected area at the initial and mild degree has subtle changes, however, it is reliably identified by quantitative analysis of the SHG signal. So, the initial degree is characterized by thin (1.3-1.8 µm) long (56-69 µm) collagen fibers, with a moderate degree, the fibers are thickened (3.4-4.3 µm) and fragmented (22-37 µm). The affected area in moderate and severe cases undergoes homogenization, which is associated with the deposition of extremely thin (0.6-0.9 μm) short (16-28 μm) collagen fibers and the expression of type V collagen., Conclusion: Multiphoton microscopy in the second harmonic generation mode is a reliable method for identifying collagen fibers in tissues. The study made it possible to identify 4 degrees of the dermis damage in vulvar lichen sclerosus.