[Use of the antioxidant complex Androdoz in men with fertility impairments].

INTRODUCTION: Infertility is a global problem, affecting more than 15% of sexually active couples worldwide. The frequency of the male factor reaches 40-50% and continues to increase. Fertility problems with unknown causes are referred as idiopathic. AIM: To evaluate the possibility of using the Androdoz antioxidant complex in men with infertility. MATERIALS AND METHODS: A retrospective analysis of the medical records of 32 infertile men aged 21 to 45 years (average of 27.8 +/- 6.7 years) with pathospermia was carried out. Antioxidant complex Androdoz was prescribed 2 capsules bid with meals according to the package insert for up to 3 months. The results were assessed after 3 and 12 months (follow-up period) from the start of therapy. In addition to ejaculate analysis, all patients underwent digital rectal examination, transrectal ultrasound of the prostate and ultrasound of the scrotum, microscopic examination of ejaculate and expressed prostate secretions, and PCR-based assay of urethral swab (Androflor). The zinc concentration in seminal plasma, as well as the total antioxidant capacity of sperm, was also evaluated. Damage to sperm chromosomes was characterized by DNA fragmentation using an assessment of sperm chromatin dispersion. RESULTS: Based on the results of a comparative analysis of ejaculate, it was revealed that taking Androdoz complex not only had a positive effect on sperm motility and viability, but also led to a decrease in the percentage of sperm with DNA fragmentation to a level of less than 15%, and significantly increased the total antioxidant capacity of the ejaculate. CONCLUSIONS: The use of Androdoz antioxidant complex in men with reproductive disorders improves the qualitative and quantitative markers of the sperm analysis and the morphological state of the male reproductive system, and allows to replenish the lack of vitamins. The most important effect of Androdoz complex appears after 3 months.

[The role of antioxidants in the therapy of metabolic syndrome in men].

INTRODUCTION: Metabolic syndrome (MetS) is a combination of hormonal, metabolic and clinical disorders. Currently, MetS in men is considered as one of the main risk factors for the development of cardiovascular diseases, insulin resistance, and pathology of the reproductive system. AIM: To study the effect of a complex of folic acid, L-carnitine, vitamin E, zinc and selenium, which are part of the biologically active food supplement "Speroton", on the parameters of carbohydrate and lipid metabolism in men with MetS, especially in the early stages of its development, as well as on erectile function and quality of life of patients. MATERIALS AND METHODS: A total of 64 patients aged 30 to 51 years with MetS of varying severity were included in the study. The main group consisted of 34 patients aged 32 to 51 years (mean age 46.2+/-2.1 years), while in the control group, there were 30 patients aged 30 to 49 years (mean age 45.4+/-3.4 years). The standard therapy in the main group was supplemented by taking the dietary supplement "Speroton" for 3 months. In the control group, patients received only standard therapy for MetS. The results were evaluated after 3 and 6 months from the start of treatment. All patients underwent laboratory evaluation of sex hormones, carbohydrate metabolism and lipid profile. In addition, the concentration of zinc in the spermatozoa was measured, as well as the level of total antioxidant capacity of the sperm. The uroflowmetry, ultrasound of the bladder with the measurement of the postvoid residual, and transrectal ultrasound of the prostate were also performed. RESULTS: An addition of the antioxidant complex "Speroton" to the combination treatment of MetS in the main group allowed to decrease the parameters of oxidative stress by almost two times. By the 6th month of follow-up, the level of insulin improved, which was accompanied by a decrease in the level of HbA1c by 16.3%, suggesting the stabilization of carbohydrate metabolism. A decrease in body mass index by almost 14% (p<0.05) in the main group was found, as well as normalization of the lipid profile. According to the analysis of the erectile function in patients of the main group after 6 months from the beginning of therapy, there was a decrease in the total score to a moderate erectile dysfunction (12.5+/-2.1 points). There was a decrease in storage symptoms and, in part, voiding symptoms in patients in the main group, who received antioxidant therapy. In addition, a positive correlation between the concentration of zinc and the level of total antioxidant capacity in the ejaculate was seen. CONCLUSIONS: Our results suggest the high therapeutic efficiency of dietary supplement "Speroton" as an antioxidant complex for the treatment of patients with MetS of varying severity. The addition of antioxidants "Speroton" to the standard therapy of MetS contributes to the improvement of the sensitivity of insulin receptors, the normalization of carbohydrate and lipid metabolism, endothelial function and blood pressure, which is accompanied by a significant decrease in LUTS severity, as well as an improvement in the erectile function of patients.

The Role of Cancer and Somatic Stem Cells in the Anti-Inflammatory and Antitumor Effects of Aconitum baicalense Extract on Experimental Breast Cancer.

We studied the effects of the extract of the terrestrial part of Aconitum baicalense in BALB/c female mice at the early stages after the injection of N-methyl-N-nitrosourea (MNU). The extract reduced inflammatory activity and tumor growth in the mammary gland. The antitumor and anti-inflammatory effects of the extract are based on the inhibition of cancer stem cells, hematopoietic stem cells, and hematopoietic progenitor cells that promote inflammation. The extract of A. baicalense disrupted the recruitment of epithelial progenitor cells and angiogenesis precursors to the mammary gland preventing neovascularization and transformation of epithelial cells into tumor cells.

Early Diagnostic Markers and Therapeutic Targets for Experimental Breast Cancer.

Various stem cells were studied in female BALB/c mice at the early terms after administration of N-methyl-N-nitrosourea to search early diagnostic markers and therapeutic targets. At these terms, damage to the epithelium and endothelium, inflammation, and fibrosis were observed in the mammary gland, but the tumor was not detected. Cancer stem cells, hematopoietic stem cells (HSC), hematopoietic progenitor cells, angiogenic precursors, and epithelial progenitor cells were found in the blood and mammary gland. Cancer stem cells (CD44+CD24-) are proposed as the early diagnostic marker of breast cancer, and short-living HSC, hematopoietic progenitor cells, and angiogenic precursors (CD45-CD117+FLK-1+) as predictors of the formation of tumor microenvironment.

Age-Related Features of the Response of the Liver and Stem Cells during Modeling of Liver Cirrhosis.

We studied the age-related characteristics of the response of stem cells and liver in male Wistar rats to administration of carbon tetrachloride (CCl4) and ethanol. It was shown that modeling of liver cirrhosis caused inflammation, fibrosis, damage to sinusoidal capillaries, necrosis, and disturbances in the functional activity of hepatocytes in young rats. These processes were accompanied by mobilization of profibrotic mesenchymal stem cells (MSC), proinflammatory hematopoietic stem cells (HSC) and lymphocytes (CD45hiCD133+) from the bone marrow into the blood and migration to the liver. On the other hand, the number of hepatocyte precursors expressing Sox9 (cells of Hering's canal), immature cholangiocytes, Ito cells, oval cells, and endothelial cells of the liver sinusoids) sharply increased in the liver. In young rats, mobilization and migration of MSC, HSC, and hepatocyte precursors against the background of liver cirrhosis were more intensive than in old animals. The higher resistance of old rats to exposure is associated with age-related changes in the niches as well as in mobilization and migration of cells.

Genetic Factors as the Basis of Sex Differences in Damage to Lung Endothelium and Regulation of Angiogenesis Cells in Modeling Pulmonary Emphysema in C57BL/6 Mice with Dyslipidemia and Hyperglycemia.

We studied the formation of injuries in lung endothelium and the response of angiogenesis cells during modeling of pulmonary emphysema in male and female C57BL/6 mice with metabolic disorders. Hemodynamic disturbances and reduction in the area of the microvasculature caused by combined pathology in male mice were more pronounced than in females. Mobilization and migration of angiogenic precursors were impaired in both male and female mice. In males, activity of recruiting endothelial progenitor cells, vascular smooth muscle cells, luminal cells of nascent vessels and pericytes into the lungs was additionally reduced. In females, accumulation of endothelial progenitor cells (CD45-CD31+CD34+), vascular smooth muscle cells, and pericytes in the lungs was observed, which indicated activation of endothelial regeneration. Sex differences in the reaction of the lung endothelium and angiogenesis cells can be explained by genetic factors of lipid and glucose metabolism.

Impact of Covid-19 on farming systems in Europe through the lens of resilience thinking.

Context: Resilience is the ability to deal with shocks and stresses, including the unknown and previously unimaginable, such as the Covid-19 crisis. Objective: This paper assesses (i) how different farming systems were exposed to the crisis, (ii) which resilience capacities were revealed and (iii) how resilience was enabled or constrained by the farming systems' social and institutional environment. Methods: The 11 farming systems included have been analysed since 2017. This allows a comparison of pre-Covid-19 findings and the Covid-19 crisis. Pre-Covid findings are from the SURE-Farm systematic sustainability and resilience assessment. For Covid-19 a special data collection was carried out during the early stage of lockdowns. Results and conclusions: Our case studies found limited impact of Covid-19 on the production and delivery of food and other agricultural products. This was due to either little exposure or the agile activation of robustness capacities of the farming systems in combination with an enabling institutional environment. Revealed capacities were mainly based on already existing connectedness among farmers and more broadly in value chains. Across cases, the experience of the crisis triggered reflexivity about the operation of the farming systems. Recurring topics were the need for shorter chains, more fairness towards farmers, and less dependence on migrant workers. However, actors in the farming systems and the enabling environment generally focused on the immediate issues and gave little real consideration to long-term implications and challenges. Hence, adaptive or transformative capacities were much less on display than coping capacities. The comparison with pre-Covid findings mostly showed similarities. If challenges, such as shortage of labour, already loomed before, they persisted during the crisis. Furthermore, the eminent role of resilience attributes was confirmed. In cases with high connectedness and diversity we found that these system characteristics contributed significantly to dealing with the crisis. Also the focus on coping capacities was already visible before the crisis. We are not sure yet whether the focus on short-term robustness just reflects the higher visibility and urgency of shocks compared to slow processes that undermine or threaten important system functions, or whether they betray an imbalance in resilience capacities at the expense of adaptability and transformability. Significance: Our analysis indicates that if transformations are required, e.g. to respond to concerns about transnational value chains and future pandemics from zoonosis, the transformative capacity of many farming systems needs to be actively enhanced through an enabling environment.

Blockade of Dopamine D2 Receptors as a Novel Approach to Stimulation of Notch1+ Endothelial Progenitor Cells and Angiogenesis in C57BL/6 Mice with Pulmonary Emphysema Induced by Proteases and Deficiency of α1-Antitrypsin.

We studied the effects of spiperone, a selective blocker of dopamine D2 receptors, on the model of pulmonary emphysema provoked by administration of elastase and D-galactosamine hydrochloride to female C57BL/6 mice and characterized by activation of proteases in the lungs and systemic deficiency of its inhibitor α1-antitrypsin. In this model, spiperone prevented the development of inflammatory reaction and reduced the area of emphysematous expanded alveolar tissue. The expression of angiogenic marker CD31 in the lungs increased under these conditions. Regeneration of the damaged microvascular bed under the action of spiperone resulted from recruiting of Notch1+ endothelial progenitor cells (CD45-CD31+CD34+) into the lungs and blockade of the inhibitory effect of dopamine on phosphorylation of VEGF-2 receptors in endothelial cells of different maturity. In addition, spiperone produced a protective effect on hepatocytes and restored the production and secretion of α1-antitrypsin by these cells.

Pericytes and Smooth Muscle Cells Circulating in the Blood as Markers of Impaired Angiogenesis during Combined Metabolic Impairments and Lung Emphysema.

The changes in endothelial progenitor cells and progenitor cells of angiogenesis, pericytes and smooth muscle cells, were studied in female C57BL/6 mice with a combination of metabolic impairments induced by injections of sodium glutamate and lung emphysema modeled by the administration of cigarette smoke extract. It was observed that sodium glutamate significantly enhances pathological changes in the lungs (inflammation and lung emphysema) induced by the administration of cigarette smoke extract. Recruiting of endothelial progenitor cells (CD45-CD31+CD34+ and CD31+CD34+CD146-) and progenitor cells of angiogenesis (CD45-CD117+CD309+) was registered in the injured lungs. Angiogenesis impairment induced by combined exposure is related to altered migration of pericytes (CD31-CD34-CD146+) and smooth muscle cells (CD31-CD34+CD146+) in emphysema-like enlarged lung tissue.

Correction to: Role of ß Cell Precursors in the Regeneration of Insulin-Producing Pancreatic ß Cells under the Influence of the Pegylated Form of Glucagon-Like Peptide 1.

The title of the article should read:"Role of ß Cell Precursors in the Regeneration of Insulin-Producing Pancreatic ß Cells under the Influence of the Pegylated Form of Glucagon-Like Peptide 1".

Endothelial Progenitor Cells and Notch-1 Signaling as Markers of Alveolar Endothelium Regeneration in Pulmonary Emphysema.

We studied the effects of elastase, cigarette smoke extract, D-galactosamine hydrochloride, and tyrosine kinase inhibitor SU5416 on endothelial progenitor cells and angiogenesis precursors, as well as on Notch-1 expression by immature endothelial cells. Simultaneously with pulmonary emphysema, different damaging factors with diverse mechanisms of action caused pathological changes in the microvascular network of the lungs and destroyed the alveolar endothelium in female C57Bl/6 mice. D-galactosamine hydrochloride disturbed mobilization of endothelial progenitor cells expressing VEGFR (CD45-CD309+) and angiogenesis progenitors (CD45-CD309+CD117+) and their migration into emphysema expanded lungs. Elastase inhibited VEGFR-expressing endothelial progenitor cells, while cigarette smoke extract inhibited cells with CD45-CD31+CD34+ phenotype. In pulmonary emphysema provoked by elastase or D-galactosamine hydrochloride, angiogenesis was provided by endothelial cells with CD45-CD31+CD34+ phenotype, whereas in emphysema modeled with SU5416 or cigarette smoke extract, it was provided by the endothelial VEGFR-expressing cells and mature CD31+ endothelial cells, respectively. Replenishment of immature endothelial cells damaged by elastase and SU5416 involved Notch-1+ angiogenesis precursors and Notch-1+ endothelial progenitor cells with VEGFR.

Role of ß Cell Precursors in the Regeneration of Insulin-Producing Pancreatic ß Cells under the Influence of Glucagon-Like Peptide 1.

The effects of the pegylated form of glucagon-like peptide 1 (pegGLP-1) on oligopotent ß cell precursors (CD45-TER119-CD133+CD49flow) in the pancreas were studied in C57Bl/6 mice. Under conditions of streptozotocin-induced type 1 diabetes mellitus, intraperitoneal injection of pegGLP1 increased the content of ß cell precursors and dithizone-stained cells in the pancreas. ß Cell precursors of mice with diabetes demonstrated high self-maintenance potential. In contrast to pegGLP-1, native GLP-1 did not affect ß cell precursors in diabetic animals. Treatment of a culture of ß cell precursors from mice with diabetes induced the yield of dithizone-stained mononuclears. In conditioned mediums of dithizone-positive cells obtained as a result of differentiation of ß cell precursors from mice with diabetes, insulin was detected after administration of pegGLP-1 (10-7 M) and glucose (3 mmol/liter); the level of insulin increased with increasing glucose concentration (to 20 mmol/liter). The in vitro effect of pegGLP-1 did not differ from the effect of GLP-1 (10-7 M).

[Laparoscopic segmental ureteral resection with ileal-ureter substitution for ureteral urothelial carcinoma].

Ureteral resection for the mid-ureter urothelial carcinoma is the operation of choice in patients with low-grade tumors. However, extensive excision within normal tissues may lead to difficulty in appropriate apposition of the ends of the ureter, while incomplete resection increases the risk of oncological progression. This article describes the first experience with laparoscopic segmental ureteral resection with the ileal - ureter substitution for mid-ureter urothelial carcinoma. In this case, a short non-reconfigurated segment of the ileum was interposed between the distal and proximal ends of the resected ureter. Operative time was 230 min, and blood loss was less than 100 ml. No complications were observed. The patients postoperative hospital stay was seven days. Follow-up examination 12 months after surgery showed no evidence of the disease progression and preserved normal renal function. The proposed method may be considered as an alternative treatment for carefully selected patients.

Role of Sertoli and Leydig Cells in the Regulation of Spermatogonial Stem Cell and Development of Reproductive Disorders in Male C57Bl/6 Mice with Type 1 Diabetes Mellitus.

Course administration streptozotocin to male C57Bl/6 mice induces a complex of symptoms typical of type 1 diabetes mellitus: hyperglycemia and insulin deficiency, focal inflammatory infiltration of the pancreas, destructive changes in the Langerhans islets, damage to the insular apparatus (reduced number of PDX1+ cells and insulin expression by the secreting cells). Male reproductive disorder are serious complications of type 1 diabetes mellitus. In "diabetic" mice, interstitial edema with inflammatory infiltration and microvascular disorders in the testicular tissue are observed, the number of endothelial precursors (CD45-/CD31+) and the total number and percentage of motile spermatozoa decreased, immature spermatogenic epithelium cells are desquamated of into the lumen of the tubules. Disturbances in the proliferation and differentiation of various spermatogonial stem cell populations (c-kit-/CD90+, c-kit+/CD90+, and CD51-/CD24+/CD52+) in diabetes can be explained by the inhibitory influence of inflammatory factors on testosterone-producing Leydig cells.

Spatially resolved spectroscopic ion temperature measurements at plasma edge of the T-10 tokamak.

Spectroscopic diagnostics of the edge ion temperature were developed on the T-10 tokamak. Spatially resolved measurements of C5+ and other ionization states of carbon spectral line shapes are provided. Spectra were measured with high spectral resolution using 14 lines of sight in one poloidal section of the tokamak. Each measured line-integrated spectrum contains a combination of multiple local spectra with corresponding values of ion temperature. Modeling of spatial distribution of line emissivity and spectral line shapes along the lines of sight allows the reconstruction of the ion temperature profile on the basis of the closest match of measured and modeled spectra. The fine structure of spectral line, Zeeman effect, and apparatus function are taken into account during data processing. Obtained ion temperature profiles, Ti(r), at the plasma edge are in good agreement with ion temperature profiles measured by Charge eXchange Recombination Spectroscopy (CXRS) diagnostics of T-10. Use of the CXRS equipment for measurements of passive spectra can provide additional information on the temporal evolution of the edge ion temperature. Developed diagnostics provide necessary data for the research of geodesic acoustic modes, which are strongly dependent on plasma edge ion temperature.

Effects of Pegylated Glucagon-Like Peptide-1 Analogue in C57Bl/6 Mice under Optimal Conditions and During Streptozotocin-Induced Diabetes.

Biological activity of a new pegylated form of an of glucagon-like peptide-1 (GLP-1) analogue pegGLP-1 was studied in C57Bl/6 mice under normal conditions and during modeling of streptozotocin-induced type I diabetes mellitus. pegGLP-1 differs from GLP-1 (7-37) by polyethylene glycol residue covalently bound to His7, Lys26, and Lys34 of the GLP-1 molecule. It was shown that single intragastrical administration of pegGLP-1 induced an increase in GLP-1 level in blood serum of healthy mice. The maximum level of this parameter was observed in 4-8 h. pegGLP-1 elimination half-time was 8.5 h and mean retention time was 15 h. Administration of pegGLP-1 to animals with modeled type I diabetes mellitus was followed by an increase in the levels of GLP-1 and insulin in blood serum, produced a hypoglycemic effect, and improved the parameters of glucose-tolerance test. Biological activity of pegGLP-1 was higher than activity of GLP-1.

Regenerative Potential of Spermatogonial Stem Cells, Endothelial Progenitor Cells, and Epithelial Progenitor Cells of C57Bl/6 Male Mice with Metabolic Disorders.

The properties of spermatogonial stem cells, endothelial progenitor cells, and the epithelial progenitors of C57Bl/6 mice under conditions of metabolic disorders were studied using the model of busulfan-induced suppression of spermatogenesis and in vitro culture technique. Spermatogonial stem cells CD117-CD90+ and epithelial progenitors CD45-CD31-Sca-1+CD49f+ derived from the testes of mice with metabolic disturbances demonstrated 17- and 28-fold increase in the respective cell mass and generated cell colonies in vitro. In contrast, spermatogonial stem cells with immune phenotype CD51-CD24+CD52+ had reduced selfrenewal capacity. Spermatogonial stem cells CD117-CD90+ and CD117+CD90+ as well as endothelial progenitors CD45-CD31+ derived from the testes of donor mice with metabolic disorders demonstrated high transplantation capacity in C57Bl/6 mouse testes damaged by cytostatic busulfan.

Regenerative Potential of Stem and Progenitor Cells from Ischemic Testes of C57Bl/6 Mice in Culture and in the Model of Spermatogenesis Suppression Caused by Busulfan.

The regenerative potential of stem and progenitor cells from ischemic testes of C57Bl/6 mice was studied in vitro (cell culture) and in vivo (mouse model of busulfan-induced suppression of spermatogenesis). Spermatogonial stem cells with phenotypes CD117-CD90+ and CD51-CD24+CD52+ from ischemic testes demonstrated 33-fold and 7-fold increments of cell mass and generated colonies in vitro. Epithelial (CD45-CD31-Sca-1+CD49f+) and endothelial (CD45-CD31+) precursors exhibited lower self-renewal capacity. On day 30 after injection of stem and progenitor cells from ischemic testes to the rete testis zone of the testes of busulfantreated animals, an increase in the count of CD117-CD90+ spermatogonial stem cells, total count, and mobile sperm count in the testes of recipient mice was observed. In addition, we observed an increase in Sca-1+ cell count, recovery of the spermatogenic epithelium in the seminiferous tubules, and appearance of immature Leydig cells in "busulfan" testes; the level of tissue testosterone and fertility index also increased.

Role of Tissue-Specific Stem and Progenitor Cells in the Regeneration of the Pancreas and Testicular Tissue in Diabetic Disorders.

Using the model of hypogonadism in C57Bl/6 male mice, we showed that injection of streptozotocin to newborn animals and high-fat diet induced serum IFN-γ and IL-17 elevation, glucose metabolism disturbances, insulin resistance, destructive changes of the Langerhans islets (deficit of PDX1+ß cells), while the number of oligopotent ß cell precursors (CD45-TER119-CD133+CD49flow) increased. Diabetes played the role of an inducer of testicular tissue inflammation (pan-hemopoietic cell infiltration, increase of IL-2, IL-17, and IL-23 content) and reproductive system disturbances in mice (decrease in free testosterone concentration, suppression of spermatogenesis, and infertility). The development of hypogonadism was paralleled by an increase in the count of spermatogonial stem cells (CD117+CD29+CD90+), multipotent mesenchymal stromal cells (CD45-CD31-CD90+CD106+), hemangiogenesis precursors (CD45-CD117+Flk1+), and epithelial cells (CD45-CD31-CD49f+CD326+).

Response of Stem and Progenitor Cells to Testicular Ischemia.

Stem and progenitor cells were studied on mouse model of testicular ischemia. Testicular ischemia led to a decrease in free testosterone concentration. Hemodynamic changes, interstitial edema, and destruction of spermatogenic epithelium, Leydig, and Sertoli cells were observed in the testicular tissue. Accumulation of degenerative germ cells was accompanied by reduction in the count of spermatogonial stem cells with immunophenotype CD117(-)CD29(+)CD90(+) and CD117(+)CD29(+)CD90(+). Simultaneously with pathomorphological changes in the testes and suppression of spermatogenesis, ischemia reduced the count of hematopoietic progenitor cells, hematopoietic stem cells with immunophenotype Lin(-)CD117(+)Sca-1(+)c-kit(+)CD34(+) and Lin(-)CD117(+)Sca-1(+)c-kit(+)CD34(-), and multipotent mesenchymal stromal cells (CD45(-)CD31(-) CD90(+)CD106(+)) in the testicular tissue. The population of CD45(-)CD31(+)-endothelial cells in ischemic testicular tissue increased.