Spatial-temporal representation of the astroglial markers in the developing human cortex.

Specific spatiotemporal patterns of the normal glial differentiation during human brain development have not been thoroughly studied. Immunomorphological studies on postmortem material have remained a basic method for human neurodevelopmental studies so far. The main problem for the immunohistochemical research of astrogliogenesis is that now there are no universal astrocyte markers, that characterize the whole mature astrocyte population or precursors at each stage of development. To define the general course of astrogliogenesis in the developing human cortex, 25 fetal autopsy samples at the stages from eight postconceptional weeks to birth were collected for the immunomorphological analysis. Spatiotemporal immunoreactivity patterns with the panel of markers (ALDH1L1, GFAP, S100, SOX9, and Olig-2), related to glial differentiation were described and compared. The early S100 + cell population of ventral origin was described as well. This S100 + cell distribution deviated from the SOX9-immunoreactivity pattern and was similar to the Olig-2 one. In the given material the dorsal gliogenic wave was characterized by ALDH1L1-, GFAP-, and S100-immunoreactivity manifestation in the dorsal proliferative niche at the end of the early fetal period. The time point of dorsal astrogliogenesis was agreed upon not later than the 17 GW stage. ALDH1L1 + , GFAP + , S100 + , and SOX9 + cell expansion patterns from the ventricular and subventricular zones to the intermediate zone, subplate, and cortical plate were described at the end of early fetal, middle, and late fetal periods. The ALDH1L1-, GFAP-, and S100-immunoreactivity patterns were shown to be not completely identical.

[Idiopathic membranous nephropathy with focal segmental sclerosis].

AIM: To evaluate the clinical and pathological features and prognosis of idiopathic membranous nephropathy (IMN) with focal segmental sclerosis (FSGS) in a group of Russian patients. MATERIALS AND METHODS: 101 patients with morphologically verified IMN were enrolled in our single-center cohort retrospective study. The patients were divided into IMN group and IMN+FSGS group. The primary and secondary outcomes were analyzed in 59 patients, which had follow-up data for period more than 6 months. RESULTS: At the time of renal biopsy the median age was 46.0 (33.0; 55.0) years and the median follow-up was 6.8 (4.0; 15.6) months. Secondary FSGS was revealed in 15 (14.9%) patients with IMN. The IMN and IMN+FSGS groups did not differ in gender, age of onset IMN and age of renal biopsy. In the IMN+FSGS group proteinuria was higher and estimated glomerular filtration rate was lower than that in the IMN group (p<0.05). The systolic arterial pressure and creatinine levels in the IMN+FSGS group were slightly higher than in the IMN group, but the difference was not significant. Anti-PLA2R positivity was similar in both groups. Chronic kidney disease (CKD) progression was observed in 10/52 (19.2%) and 5/7 (71.4%) patients in IMN and IMN+FSGS groups, respectively. In a multivariate Cox regression model, age of renal biopsy (odds ratio - OR 1.12, 95% confidence interval - CI 1.03-1.22; р=0.07), FSGS (OR 0.05, 95% CI 0.01-0.34; р=0.002) и response to initial course of immunosuppression (OR 0.33, 95% CI 0.12-0.95; р=0.039) were associated with the CKD progression. CONCLUSION: In patients with IMN secondary FSGS is associated with a greater severity of proteinuria and a decrease in estimated glomerular filtration rate, and is also an independent factor of the CKD progression.

[Resolution of the national interdisciplinary council of experts "High-dose vitamin D (Devilam) in the practice of an obstetrician-gynecologist"].

On March 28, 2024, the Council of Experts "High-dose vitamin D (Devilam) in the practice of obstetrician-gynecologist, gynecologist and endocrinologist" was held in Moscow with the participation of leading experts gynecologists, endocrinologists and obstetricians-gynecologists, during which new possibilities for the use of high-dose vitamin D in patients of various ages who need correction of existing vitamin D deficiency or insufficiency.

[Outcomes of hemi-Descemet membrane endothelial keratoplasty and phacoemulsification for the treatment of primary Fuchs' endothelial corneal dystrophy combined with cataract]. / Rezul'taty transplantatsii destsemetovoi membrany s endoteliem i fakoemul'sifikatsii pri pervichnoi endotelial'noi distrofii rogovitsy Fuksa, sochetannoi s kataraktoi.

PURPOSE: This study evaluates the long-term results of surgical treatment of patients with Fuchs' endothelial corneal dystrophy and cataract. MATERIAL AND METHODS: The study included 24 patients (24 eyes) with primary Fuchs' endothelial corneal dystrophy and cataract, who underwent cataract phacoemulsification with IOL implantation and of Descemet's membrane endothelial keratoplasty with a semicircular graft (hemi-DMEK). The effect of treatment was assessed by best corrected visual acuity (BCVA), central corneal thickness (CCT) and endothelial cell density (ECD). RESULTS: In total, surgical treatment involved 14 donor corneas that were divided in half during the preparation and isolation of the Descemet's membrane (DM). By month 12 after the surgery an increase in visual functions and graft transparency were observed in 23 patients (23 eyes) out of 24. Repeated keratoplasty was required in one case due to fibrosis of the posterior layers of recipient's corneal stroma. At 12 months postoperatively, the study group showed an increase in BCVA from 0.16±0.1 to 0.75±20, a decrease in CCT from 650.9±4.5 µm to 519.6±43.9, and a decreased in ECD from 2850.5±84.7 cells/mm2 up to 1285.5±277.2 cells/mm2. Thus, the loss of endothelial cells at one year after surgery amounted to 54.9%. CONCLUSIONS: The developed method for transplantation of a semicircular DM fragment provides a tissue-saving approach to endothelial keratoplasty, and considering the high percentage of transparent engraftment of grafts and complete visual rehabilitation, it can be recommended in the treatment of patients with cataract and Fuchs' endothelial corneal dystrophy.

[Endocrine and psychosomatic disorders in patients with amenorrhea].

The article presents data on the relationship of pathogenetic mechanisms for the development of menstrual disorders of functional and organic origin in connection with mental disturbances from the point of view of the psychosomatic concept. According to the latter, functional disorders of the menstrual cycle are considered as psychosomatic, in which gynecological pathology develops as a result of psychopathological illness. A striking example of such a disorder is functional hypothalamic amenorrhea. At the same time, endocrinopathies, such as polycystic ovary syndrome and premature ovarian insufficiency, can also be considered in the paradigm of psychosomatic illnesses of ovarian function due to the high prevalence of anxiety and depressive disorders in this cohort of patients. This review highlights the importance of interdisciplinary collaboration between a gynecologist and a psychiatrist for the most effective reproductive rehabilitation of patients with amenorrhea. Literature search was carried out in national (eLibrary, CyberLeninka.ru) and international (PubMed, Cochrane Library) databases in Russian and English. The priority was free access to the full text of articles. The choice of sources was prioritized for the period from 2018 to 2023.However, taking into account the insufficient knowledge of the chosen topic, the choice of sources dates back to 1985.

[Replicative and biochemical ageing mechanisms among females with Turner syndromes].

BACKGROUND: 2025 is going to be the 100th anniversary of the first historical description of Turner syndrome - complex of  genomic abnormalities, congenital gonadal disruption and hypergonadotropic hypogonadism. Total estrogenic deficiency triggers development of age-related comorbidities. There is no doubt that personalized search for replicative markers of cellular aging among females with Turner syndrome is needed. AIM: To evaluate features of replicative (telomere length) and biochemical (lipid profile, calcium-phosphate album, thyroid hormones, markers cytolysis and cholestasis, carbohydrate metabolism, nitrogenic metabolism, electrolytes, FSH) markers among females with Turner syndrome. MATERIALS AND METHODS: Research has been provided in collaboration between Endocrinology Research Centre of the Russian Ministry of Health and Lomonosov Moscow State University Medical Research and Educational Centre in the period since 10.01.2021 until 01.08.2022. Females with non-iatrogenic hypergonadotropic hypogonadism caused by Turner syndrome (45,X0; 45,X/46,XX; 45,X/46,X,r(X); 13-40 y.o.; n=26) and primary ovarian insufficiency (18-39 нyears=26); healthy females of reproductive age (15-49 y.o.; n=24). Patients have undergone laboratory genetic (leucocyte telomere length), biochemical (fasting glycaemia, urea, creatinine, common/conjugated bilirubin, ALT, AST, gamma-glutamyl transferase, triglycerides, HDL-P, LDL-P, common cholesterol, common/ionized calcium, phosphate, vitamin D, sodium/potassium/chlorides, FSH, HbA1c) analyses. Body measurements - body mass, body height. DNA extraction - provided with Qiagen DNA blood mini kit (Germany). Leukocyte telomere length - with real-time polymerase chain reaction PCR (Flow-fish). Soft program IBM SPSS Statistics (version 26,0 for Windows). RESULTS: 1. Females with Turner syndrome have significantly lower mean telomere length (8,22 kB [6,63-9,30]) than with primary ovarian insufficiency (10, 34 кБ [8,41-13,08], p<0,001) and healthy reproductive age females (10,77 kB [9,95-13,16], р>0,05).2. Telomere length correlates directly and significantly with longevity of menopausal hormonal therapy among females with primary ovarian insufficiency (ρ = 505; p<0,001).3. Patients with Turner syndrome are inclined to vitamin D deficiency (р<0,001), dyslipidemia (р=0,01); increase of levels of aminotransferases, cholestasis markers, phosphate and FSH (р<0,001). CONCLUSION: Turner syndrome is serious genetic disease that leads not only to infertility but to significant decrease of quality/life longevity out of "healthy aging" conception.

Alteration of PBMC transcriptome profile after interaction with multipotent mesenchymal stromal cells under "physiological" hypoxia.

Multipotent mesenchymal stromal cells (MSCs) have demonstrated a pronounced immunosuppressive activity, the manifestation of which depends on the microenvironmental factors, including O2 level. Here we examined the effects of MSCs on transcriptomic profile of allogeneic phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMCs) after interaction at ambient (20%) or "physiological" hypoxia (5%) O2. As revealed with microarray analysis, PBMC transcriptome at 20% O2 was more affected, which was manifested as differential expression of more than 300 genes, whereas under 5% O2 220 genes were changed. Most of genes at 20% O2 were downregulated, while at hypoxia most of genes were upregulated. Altered gene patterns were only partly overlapped at different O2 levels. A set of altered genes at hypoxia only was of particular interest. According to Gene Ontology a part of above genes was responsible for adhesion, cell communication, and immune response. At both oxygen concentrations, MSCs demonstrated effective immunosuppression manifested as attenuation of T cell activation and proliferation as well as anti-inflammatory shift of cytokine profile. Thus, MSC-mediated immunosuppression is executed with greater efficacy at a "physiological" hypoxia, since the same result has been achieved through a change in the expression of a fewer genes in target PBMCs.

[Clinical significance of the determination of antibodies to thrombospondin type 1 containing domain 7A (THSD7A) in membranous nephropathy].

BACKGROUND: Membranous nephropathy (MN) is an immunocomplex glomerular disease, which is the most common cause of nephrotic syndrome in adults. Numerous studies have established that autoantibodies against the target podocyte autoantigens, including the thrombospondin type 1 domain containing 7A (THSD7A), play a leading role in the development of idiopathic MN. AIM: To evaluate the prevalence of anti-THSD7A autoantibodies (anti-THSD7A AB) in a group of Russian patients with MN. MATERIALS AND METHODS: Serum titers of anti-THSD7A AB were tested in 61 patients with biopsy-proven MN and 12 healthy controls. RESULTS: The prevalence of anti-THSD7A AB was not differing significantly in patients with MN and in the control group (110.9 [71.63; 210.62] and 159.25 [125.64; 231.97] pg/ml, respectively; p=0.111). When comparing subgroups of anti-PLA2R-negative patients and patients who did not receive immunosuppressive therapy with the control group, there were also no statistically significant differences in the Anti-THSD7A AB levels (p>0.05). In the MN group, 1 (1.6%) patient was anti-THSD7A-positive: a 60-year-old man with anti-PLA2R-negative MN and the presence of hormonally inactive adenomas of both adrenal glands and colon polyps (villous adenoma with focal moderate dysplasia, tubulo-villous and tubular adenoma with focal moderate severe dysplasia). CONCLUSION: THSD7-associated MN is a rare variant of MN and is usually detected in PLA2R-negative patients. Screening for malignancies in THSD7A-positive MN patients is proposed.

[Molecular and cellular mechanisms of ageing: modern knowledge (literature review)].

Ageing (as known as eldering, senescence) is a genetically and epigenetically programmed pathophysiological process. Velocity of biological ageing is defined as balance between alteration and reparation of body structures. According to last World Health Organization (WHO) highlights ageing still stays an extremely actual scientific, social and demographic problem: in 2020 total number of people older than 60 years and older was 1 billion people; in 2030 future number may be 1,4 billion people, in 2050 - 2,1 billion people. Absence of single universal theory of aging nowadays is reason for scientifical and clinical collaboration between biologists and doctors, including endocrinologists. Designing of potentially effective newest anti-ageing strategies (such as natural/synthetic telomerase regulators, mesenchymal stem cells etc.) is of interest to scientific community. The aim of present article is a review of modern omics (genomic, proteomic, metabolomic) ageing mechanisms, potential ways of targeted prevention and treatment of age-related disease according to conception of personalized medicine. Present review is narrative, it does not lead to systematic review, meta-analysis and does not aim to commercial advertisement. Review has been provided via PubMed article that have been published since 1979 until 2022.

[Neuroendocrine features of the pathogenesis of polycystic ovary syndrome (literature review)].

Polycystic ovary syndrome (PCOS) is one of the most pressing problems in endocrine gynecology. The main signs of the disease are hyperandrogenism, menstrual and/or ovulatory dysfunction, and polycystic ovarian structure according to ultrasound. Women with PCOS are at risk for developing metabolic syndrome, type 2 diabetes, cardiovascular disease, and endometrial cancer. In this connection, the pathogenetic mechanisms of the occurrence of this syndrome are continuously studied and new methods of treatment are being sought. PCOS is characterized by a wide range of various disorders of the neuroendocrine regulation of the reproductive system. The main focus of the review is aimed at summarizing information about the etiological role of neuropeptides and neurotransmitters, such as phoenixin, galanins, orexins, GABA, in the pathophysiology of PCOS and about the possibility of their use for diagnostic and therapeutic purposes. In recent decades, the interest of scientists has been focused on the study of KNDy neurons, because it is the kisspeptin synthesized by them that is one of the main regulators of the hypothalamic-pituitary-ovarian axis. This article discusses data on the significance of KNDy neurons in the pathogenesis of the syndrome. Information is provided on the effect of elevated levels of androgens and anti-Müllerian hormone on GnRH neurons. Also analyzed are studies on functional and structural disorders in the hypothalamus in PCOS. Literature search was carried out in national (eLibrary, CyberLeninka.ru) and international (PubMed, Cochrane Library) databases in Russian and English. The priority was free access to the full text of articles. The choice of sources was prioritized for the period from 2018 to 2023.However, taking into account the insufficient knowledge of the chosen topic, the choice of sources dates back to 1998.

[Russian eligibility criteria prescribing menopausal hormonal hormones therapy for patients with cardiovascular and metabolic diseases. Consensus document of the Russian Cardiological Society, Russian Society of Obstetricians and Gynecologists, Russian Association of Endocrinologists, Eurasian Association of Therapists, Association of Phlebologists of Russia].

Menopausal symptoms can disrupt the life course of women at the peak of their career and family life. Currently, the most effective treatment for these manifestations is menopausal hormone therapy (MHT). The presence of cardiovascular and metabolic diseases in itself does not exclude the possibility of prescribing MHT to relieve menopausal symptoms and improve quality of life. However, often an obstacle to the use of this type of hormonal therapy is the fear of doctors who are afraid of doing more harm to patients than good. Caution is especially important when it comes to women with underlying health conditions. Moreover, it should be recognized that there is a lack of high-quality research regarding the safety of MHT for major chronic non-infectious diseases and common comorbid conditions. The presented consensus document analyzed all currently available data obtained from clinical trials of various designs and created a set of criteria for the acceptability of prescribing MHT to women with concomitant cardiovascular and metabolic diseases. Based on the presented document, doctors of various specialties who advise women in menopause will receive an accessible algorithm that will allow them to avoid potentially dangerous situations and reasonably prescribe MHT in real practice.

[Russian Eligibility Criteria for Prescribing Menopausal Hormone Therapy to Patients With Cardiovascular and Metabolic Diseases. Consensus Document of RSC, RSOG, RAE, EUAT, RAP].

Menopausal symptoms can impair the life of women at the peak of their career and family life. At the present time, the most effective treatment for these manifestations is menopausal hormone therapy (MHT). The presence of cardiovascular and metabolic diseases in itself does not exclude the possibility of prescribing MHT to relieve menopausal symptoms and improve quality of life. However, often an obstacle to the use of this type of hormone therapy is the fear of physicians to do more harm to patients than good. Caution is especially important when it comes to women with concurrent diseases. Moreover, it should be recognized that there is a shortage of high-quality research on the safety of MHT for underlying chronic non-infectious diseases and common comorbidities. The presented consensus analyzed all currently available data from clinical trials of various designs and created a set of criteria for the appropriateness of prescribing MHT to women with concomitant cardiovascular and metabolic diseases. Based on the presented document, physicians of various specialties who advise menopausal women will receive an accessible algorithm that will allow them to avoid potentially dangerous situations and reasonably prescribe MHT in real-life practice.

In Vivo and In Vitro Analysis of Toxicity of a Prospective Magnetic Resonance Contrast Agent Based on Arabinogalactan and Gadolinium Nanocomposite.

We studied the cytotoxic effect of gadolinium nanocomposite on cultured mouse fibroblasts 3T3-SV40 and histological changes in the liver tissue of albino rats after its administration. For in vitro experiment, gadolinium nanocomposite on the natural matrix of arabinogalactan (nGd-AG) was dissolved in DMEM nutrient medium to concentrations of 0.005, 0.02, 0.5, 2, and 5 mM. In in vivo experiment, a nGd-AG solution was orally administered to rats through a tube in a dose of 500 µg Gd/kg in 1 ml of 0.9% NaCl for 10 days. The pattern and degree of influence of the gadolinium nanocomposite on the studied cell culture depended on the concentration and duration of exposure. IC50 of nGd-AG determined after cell incubation for 24, 48, and 72 h were 616 µg/kg (3.9 mM), 302 µg/kg (1.9 mM), and 222 µg/kg (1.4 mM), respectively. Histological changes in the liver of white rats induced by exposure to nanocomposite attested to the development of a compensatory reaction of the organ.

[The comparative analysis of surgical procedures a in patients with benign prostatic hyperplasia and type 2 diabetes mellitus].

AIM: To compare the efficiency of two surgical methods, holmium laser enucleation of prostate (HoLEP) and laparoscopic retropubic simple prostatectomy with clamping of internal iliac arteries and vesicourethral anastomosis [LPA+CIIA+VUA]) for treating of patients with benign prostatic hyperplasia (BPH) and type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: A total of 56 men with T2DM who underwent surgical treatment of BPH in the National Research Centre for Endocrinology of the Russian Ministry of Health (director - corresponding member of RAS Mokrysheva N.G..) in a period from 2021 until 2022 were included in the study. Patients with T2DM received two types of antidiabetic drugs: basal-bolus insulin therapy and metformin (1000 mg/day per os). Patients were divided into the group of LPA+CIIA+VUA (n=28) and HoLEP (n=28). Preoperative, intraoperative and postoperative examinations with an evaluation of intraoperative and early postoperative complications (I, II, III, IV grades according to the Clavien-Dindo scale) were performed. After 1 year of follow-up, International Prostatic Symptom Score (IPSS), "Quality of Life" score (QoL), International Index of Erectile Function-5 score (IIEF-5), maximal urine flow rate (Qmax), and postvoid residual volume (ml) were assessed. Efficiency of surgical procedures was estimated according to "trifecta": absence of postoperative complications, urine continence, maximal urine flow (Qmax) >15 ml/sec. RESULTS: In the group of HoLEP, shorter postoperative bladder catheterization time but higher risk of urinary incontinence, bladder neck contracture and urethral strictures was found. LPA+CIIA+UVA leaded to a two-fold decrease in intraoperative hemoglobin loss with no necessity of repeat procedures. CONCLUSIONS: Our preliminary results demonstrated higher efficacy of LPA+CIIA+VUA for treatment of BPH in patients with T2DM than HoLEP. Patients who underwent LPA+CIIA+VUA were more often achieved the "trifecta". In order to implement LPA+CIIA+VUA into clinical practice, multi-center, large-scale, double-blind, placebo-controlled ("scar-surgery") randomized studies are required.

[Features of aging replicative and biochemical aspects among females with non-iatrogenic hypergonadotropic hypogonadism].

BACKGROUND: Estrogenic deficiency is the basic condition of human ageing that leads to hypergonadotropic hypogonadism. The existence of correlation between hypergonadotropic hypogonadism, replicative (leukocyte telomere length) and biochemical data is widely supposed among females with physiological (menopausal) and pathological (primary ovarian insufficiency) estrogenic deficiency is not unreasonable. AIM: To evaluate features of replicative (telomere length) and biochemical (metabolic syndrome) ageing markers among females with physiological (menopausal) and pathological (primary ovarian insufficiency) estrogenic deficiency. MATERIALS AND METHODS: Research has been provided in collaboration between Endocrinology Research Centre of the Russian Ministry of Health and Lomonosov Moscow State University Medical Research and Educational Centre in the period since 10.01.2021 until 01.08.2022.110 females (20-75y.o.) have participated in the present research.Group 1: 26 females receiving menopausal hormonal therapy (MHT) ≥ 5 years with 0,5; 1; 2 mg estrogenic component.Group 2: 27 females in physiological menopause without MHTGroup 3: 33 females with primary ovarian insufficiency and receiving sex-steroid replacement therapy.Group 4: 24 healthy reproductive age females without sex-steroid replacement therapy.Patients have undergone laboratory genetic (leucocyte telomere length), biochemical analyses.DNA extraction - with Qiagen DNA blood mini kit (Germany). Biological material was cito conserved with Ficoll solution. Leukocyte telomere length - with real-time polymerase chain reaction PCR (Flow-fish).Soft program IBM SPSS Statistics (version 26,0 for Windows) has been used for statical analysis. RESULTS: 1.Menopausal females receiving MHT were inclined to highest HDL-P levels (p<0,006).2.Females with primary ovarian insufficiency were inclined to relatively highest serum creatinine level (p<0,001).3.Reproductive age females had relatively highest telomere length (p<0,001).4.FSH level correlates negatively and moderately (ρ= - 0,434) leukocyte telomere length (р<0,001) among females. CONCLUSION: Females with premature ovarian insufficiency are most sensible to ageing due to features of replicative and biochemical markers.

[Features of steroidogenesis and arterial hypertension in men in different types of "physiological" male hyperandrogenism].

AIM: To reveal the peculiarities of steroidogenesis and arterial hypertension in «physiological¼ hyperandrogenism in men. MATERIALS AND METHODS: One-stage simultaneous study. The groups of men with hyperandrogenism caused by increased total testosterone (n=34) and those with hyperandrogenism caused by increased dihydrotestosterone (DHT) (n=66) were compared. In determining the type of hyperandrogenism and allocating patients to groups, DHT and total testosterone levels were determined by enhanced chemiluminescence. Subgroups of men with and without arterial hypertension were compared in the group of patients with hyperandrogenism due to an increase in total testosterone. Body mass index, waist circumference, systolic and diastolic blood pressure, pulse, and LH, SBHG, estradiol, blood multisteroid levels by isotope dilution liquid chromatography/tandem mass spectrometry, glucose, blood lipid spectrum, uric acid, creatinine, renin, potassium, sodium, and blood chloride were assessed in all patients. Patients with arterial hypertension additionally underwent daily BP monitoring, albuminuria assessment, electrocardiography, ocular fundus examination. The baseline threshold level of significance was p<0.05. For multiple comparisons, the p significance level was calculated using the Bonferroni correction. RESULTS: Statistically significant differences were found in the levels of 17-hydroxypregnenolone, 17-hydroxyprogesterone, and androstenedione, which were higher in men with elevated levels of total testosterone. No statistically significant differences in other laboratory parameters were found. No cases of increased blood pressure were detected in the group of men with elevated DHT. In the group of men with elevated total testosterone, 23,5% of men with arterial hypertension without targetorgan lesions were identified, while hyperandrogenism was associated with 17,6% of cases. Arterial hypertension associated with hyperandrogenism was characterized by a rise in blood pressure in the early morning hours. Estradiol levels, while remaining within normal limits, were statistically significantly lower in patients with arterial hypertension compared with men with elevated testosterone but without hypertension. CONCLUSION: No cases of arterial hypertension were observed in «physiological¼ hyperandrogenism due to elevated DHT levels, whereas its incidence in «physiological¼ hyperandrogenism due to elevated total testosterone was 23,5%. The features of steroidogenesis were increased production of 17-hydroxypregnenolone, 17-hydroxyprogesterone, and androstenedione in men with testosterone hyperandrogenism and decreased estradiol production in patients with arterial hypertension compared with patients without testosterone hyperandrogenism.

[Replicative and biochemical ageing features among females with primary ovarian insufficiency].

BACKGROUND: One of the most dangerous reproductive pathologies is primary ovarian insufficiency (POI). Except manifestation in the age <40 years old it leads to demographical losses, decrease of chances for healthy aging. POI can be characterized as summary of secondary amenorrhea, total estrogenic deficiency and hypergonadotropic hypogonadism. Hence, POI has probably harmful effect on telomere length. Telomere length determining and sex steroid replacement therapy may be promising and effective to prevent decrease of life quality/ longevity among females with POI. AIM: To evaluate features of replicative (telomere length) and biochemical (metabolic syndrome) markers among females with primary ovarian insufficiency. MATERIALS AND METHODS: Research has been provided in collaboration between Endocrinology Research Centre of the Russian Ministry of Health and Lomonosov Moscow State University Medical Research and Educational Centre in the period since 10.01.2021 until 01.08.2022. Females with non-iatrogenic hypergonadotropic hypogonadism caused by primary ovarian insufficiency (n=33); healthy females of reproductive age (18-49 y.o.; n=24). Patients have undergone laboratory genetic (leucocyte telomere length), biochemical analyses. DNA extraction - with Qiagen DNA blood mini kit (Germany).Leukocyte telomere length - with real-time polymerase chain reaction PCR (Flow-fish). Soft program IBM SPSS Statistics (version 26,0 for Windows). RESULTS: Females with POI due to estrogenic deficiency have slightly shorter mean telomere length (10,0 [7,9-10,7] kB, than healthy females of reproductive age (10,8 [10,0-13,1] кБ, р<0,001). Females with POI due to estrogenic deficiency have higher chances for development of carbohydrate metabolism disturbances (prediabetes) (р<0,043), increasement of FSH level (р<0,001). FSH level correlates moderately and negatively (ρ=0,434) with leukocyte telomere length (р<0,001). CONCLUSIONS: Female with POI and receiving sex steroid replacement therapy have decrease of telomere length and increase of chances for carbohydrate metabolism disturbances in opposite to healthy reproductive females.

Simulated microgravity affects stroma-dependent ex vivo myelopoiesis.

Microgravity is known negatively affect physiology of living beings, including hematopoiesis. Dysregulation of hematopoietic cells and supporting stroma relationships in bone marrow niche may be in charge. We compared the efficacy of ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs) in presence of native or osteocommitted MSCs under simulated microgravity (Smg) using Random Positioning Machine (RPM). In comparison with 1 g, a decrease of MSC-associated HSPCs and an increase of floating HSPCs was observed after 7 days of Smg exposure. Among floating HSPCs, primitive progenitors were presented by late CD34+/133-. Total CFUs as well as erythroid (BFU-E) and granulocytic (CFU-G) numbers were lower. MSC-associated primitive HSPCs demonstrated increased proportion of late CD34+/133- in expense of early CD34-/133+. Osteo-MSCs preferentially supported late primitive CD34+ and more committed HSPCs as followed from increase of CFUs, and CD235a+ erythroid progenitors. Under Smg, an increased VEGF, eotaxin, and GRO-a levels, and a decrease in RANTES were found in the osteo-MSC-HSPC co-cultures. IL-6,-8, -13, G-CSF, GRO-a, MCP-3, MIP-1b, VEGF increased in co-culture with osteo-MSCs vs intact MSCs. Based on the findings, the misbalance between primitive/committed HSPCs and a decrease in hematopoiesis-supportive activity of osteocommitted cells are supposed to underline hematopoietic disorders during space flights.

Short-Term Interaction with Endothelial Cells Enhances Angiogenic Activity of Growth-Arrested Mesenchymal Stromal Cells In Vitro and In Ovo.

We compared angiogenic effects of conditioned medium from mesenchymal stromal cell (MSC) monoculture and co-culture of MSC with endothelial cells (EC). Conditioned medium from 24-h EC-MSC co-cultures significantly stimulated the proliferation and migration of EC in monoculture and growth of the vascular network of the chorioallantoic membrane of the quail embryo in ovo in comparison with the conditioned medium from MSC monoculture. Conditioned medium from the co-culture contained increased levels of angiogenic factors (FGF-2, MCP-1, PDGF-AB/BB, IL-6, IL-8, etc.), which could explain the revealed effects. We hypothesized that a similar mechanism of EC-mediated enhancement of functional activity of MSC could be involved in reparative angiogenesis in the target tissues in vivo.

[Fetal mediastinal teratomas. Report of two cases]. / Teratomy sredosteniya ploda. Opisanie dvukh nablyudenii.

Teratomas are one of the most common tumors diagnosed in fetuses and newborns. In this age group, extragonadal teratomas predominate, among which the mediastinum ones accounts for up to 15% of teratomas of the perinatal period. They may be associated with the thymus or thyroid gland; in some cases a clear connection with adjacent organs cannot be identified. Teratomas of the heart, also localized in the mediastinum, are often considered separately from the mediastinal ones; most often the tumor affects the pericardium. The article describes two cases of mediastinal teratomas detected by ultrasound in the second trimester of pregnancy, with signs of rapid growth and compression symptoms typical for this localization of the tumor - hydropericardium and other manifestations of non-immune fetal hydrops. In both cases, immature teratomas (grade 2 and 3) were diagnosed with a predominance of immature neuroectodermal tissue, as well as with the presence of endoderm derivatives, including areas of the hepatoid structure, microglandular structures and cysts lined with mucus-forming epithelium. The mesodermal component was represented by hyaline cartilage. An immunohistochemical study revealed an extremely high proliferative activity in the immature neuroectodermal component - more than 90% of positive nuclei were detected in the neuroepithelium upon reaction with Ki67 antibodies. In all other tissue elements, proliferative activity was low.