Sodium alginate is one of the most frequently used materials in biomedicine. However, alginate-based scaffolds have extremely low adhesive properties and have to be improved. The authors have proposed combined hydrogels of gelatin and sodium alginate which have been modified by peroxynitrite in heterophasic conditions using ethanol. It has been determined that thus modified sodium alginate contains an increased level of carbonyl, carboxyl and nitro groups. Authors have developed chemically and chemical-enzymatically cross-linked hydrogels with better adhesive properties and absence of cytotoxicity. Moreover, sodium alginate modification has a positive impact on cell morphology in comparison with control group of non-adhesive alginate-gelatin hydrogels. It allows the further improvement and application of the biomaterial which have been developed by the authors for bioengineering scaffold production and 3D culturing.

The article presents the results of a study of the level of inducible and endothelial NO syn-thase, nitric oxide metabolites, the concentration of nitrothyrosine and bityrosine in the blood serum of patients with varicose veins of the lower extremities compared with healthy donors

Introduction. PSGL-1 is a complex protein, that provides contacts between blood cells and endothelial cells by connecting with cell-adhesion mole-cules selectins, and it is a universal participant in the processes of leukocyte adhesion, inflammation and immune response. The study of the possible regulation of its functioning is an urgent topic, since the process of its interactions with selectins can be a point of therapeutic application. Aim of the study. Evaluation of the relationship between the concentration of universal ligand selectins PSGL-1, inducible (iNOS) and endothelial (eNOS) NO synthases and final metabolites of nitric oxide (II) in the blood serum of patients with acute arterial thrombosis. Material and methods. The concentrations of PSGL-1, iNOS and eNOS in blood serum were determined, using enzyme immunoassay on an enzyme immunoassay analyzer Stat Fax 2100. The total concentration of the final stable metabolites of nitric oxide(II) (nitrates and nitrites) was determined by the spectrophotometric method modified by V.A. Metelskaya, by coloring in the reaction of diazotization with nitrite of sulfonamide present in the com-position of the Griss reagent. The results were processed, using nonparametric statistics methods of Microsoft Office Excel 2016 and IBM SPSS Statistics 26 (StatSoftInc., USA). Results. The study revealed a statistically significant increase in the level of endothelial nitric oxide synthase and the final stable metabolites of nitric oxide in the blood of patients with acute arterial thrombosis, compared with the control group. A direct correlation of moderate severity was also found between the level of eNOS and the concentration of nitrates and nitrites. A low positive correlation was found between the concentration of PSGL-1 and the level of eNOS, and a low negative correlation was found between PSGL-1 and iNOS. Conclusions. According to the results of the study, it can be concluded that nitric oxide, which generated by endothelial NO synthase in patients with arterial thrombosis, may have a regulatory effect on the expression or functioning of the universal glycoprotein ligand of selectins – PSGL-1, which re-quires more in-depth study.

Introduction. The study of the effect of peroxynitrite, as a product of nitric oxide (II), on the culture of endothelial cells in vitro can contribute to fundamental ideas about the violation of the adhesive function of the endothelium when changing the synthesis of nitric oxide. The aim of the study. To study the effect of peroxynitrite in various concentrations on the metabolic and migration activity of endotheliocytes, as well as on the expression of endothelium-specific proteins-selectin Р and Е, as an indicator of the adhesive function of the endothelium. Methods. The cytotoxicity of peroxynitrite in various concentrations was assessed using the MTT test. The migration and proliferative activity of endotheliocytes was studied by a scratch test. The concentration of sP- and sЕ-selectins was determined using the ELISA sandwich method in the supernatant of endotheliocytes culture. Results. A statistically significant increase in the metabolic activity of endothelial cells was revealed during a 30-minute incubation with peroxynitrite at concentrations of 0,0025, 0,0075 and 0,01 mM. A statistically significant decrease in the migration activity of endothelial cells was revealed after a 30-minute incubation with peroxynitrite at concentrations of 0,0025 and 0,1 mM, both in the first 12 and within 24 hours. A multidirectional effect of peroxynitrite at various concentrations on the level of sP and sE selectins in the cell culture supernatant was revealed: a statistically significant decrease in sE-selectin after 30-minute incubation with peroxynitrite solutions at concentrations of 0,0025, 0,1 and 1,0 mM; as well as a statistically significant increase in sP-selectin during 30-minute incubation with peroxynitrite solutions of 0,0025 and 0,1 mM. Conclusion. Peroxynitrite for endothelial cells can act as a signaling molecule, stimulating or suppressing mitochondrial and migratory activity, and also as a cytotoxic agent, causing cell death. In addition, at various concentrations it is capable of influencing either the synthesis of endothelium-specific selectin proteins or the proteolytic shedding of the extracellular domains of these proteins, which requires further study.

The article presents the results of a study of the level of E-selectin, NO-synthase in the blood serum of patients with acute venous thrombosis compared with healthy donors, and their re-lationship.

The present review considers current data on the structure, functions and role of interleukin-13 in the pathogenesis of vascular wall varicose transformation in terms of proteolysis and inflammatory response. It is known that interleukin-13 is able to interact with transforming growth factor-1 in diseases associated with fibrosis. The latter activates fibroblasts and excessive formation of the extracellular matrix, thereby inducing fibrosis of the vascular wall, which is one of the links in the pathogenesis of varicose veins. Also, to date, there is evidence of the interleukin-13 participation in the induction of certain proteolytic enzymes synthesis, such as matrix metalloproteinases. For the latter, participation in the transformation of the venous wall has been proven to date. The remodeling of the venous wall itself can lead to an increase in the expression of proteinases, providing a proteolytic mechanism for changing the structural organization of the venous wall in varicose veins of the lower extremities. At the same time, the involvement of lysosomal cysteine proteinases remains poorly understood. The expression and production of individual cathepsins are regulated by biologically active molecules: interleukin-1, interleukin-6, tumor necrosis factor , which are directly involved in inflammatory reactions in the wall of varicose veins. In particular, venous pathology develops in a vicious circle of inflammation with the formation of abnormal venous blood flow, chronic venous hypertension and dilation, and the recruitment of leukocytes. This leads to a further, deeper, remodeling of the walls and valves of the veins, an increase in blood pressure and the release of pro-inflammatory mediators chemokines and cytokines. In connection with the above, in order to understand the mechanisms of proteolysis in the vascular wall in varicose veins of the lower extremities, it is important to have an idea about the possible interactions of interleukin-13 with transforming growth factor-1, inflammatory cytokines, and cathepsins.

Endothelial cells (ECs), which form the inner surface of the blood vessels, contact the blood, withstand mechanical pressure, and demonstrate heterogeneous reactions to exogenous and endogenous stimuli. ECs have unique properties in accordance with their niches and play an important role in regulating vascular homeostasis. Endothelial cells may undergo a dynamic phenotypic switch in terms of its heterogeneity, which may lead to endothelial dysfunction and a number of associated pathologies. Endothelial-mesenchymal transition (EndMT) is one of the possible molecular and cellular mechanisms of this kind. EndMT is characterized by phenotypic changes in ECs through which endothelial cells acquire new properties, i.e., start producing mesenchymal markers such as alpha-SMA and vimentin, change morphology, and become able to migrate. EndMT is a complex biological process that can be induced by inflammation, hypoxia, or oxidative stress and be involved in pathogenesis of cardiovascular disease. This review describes the key markers, inhibitors, and inducers of endothelial-mesenchymal transition and overall state-of-the-art of EndMT in cardiovascular diseases.

Introduction. In the publications of many authors, there is evidence that the mechanism of development of chronic prostatitis and varicocele is oxidative stress, leading to a decrease in male fertility. This problem requires a deeper study. The aim of the study. To evaluate the carbonylation of spermоplasm’s proteins in patients with chronic prostatitis III B and varicocele II and III degrees with concomitant asthenozoospermia in the anamnesis. Methods. Determination of the total protein concentration in the spermoplasm was carried out by the biuretic method using commercial kits of the company (Mindrey, China) on a biochemical analyzer (Mindrey BS 120, China). Carbonylated proteins in the spermoplasm were evaluated using the R.L. Levine method modified by E.E. Dubinina. Results. In the course of our study, it was found that in patients with chronic prostatitis III B, accompanied by asthenozoospermia and in patients with varicocele II and III degrees with concomitant asthenozoospermia, an increase in carbonylated proteins in the spermoplasm is noted at all absorption maximum (λ356, λ370, λ430, λ30), on three of them statistically significant; at the same time, the reserve-adaptive potential in relation to the oxidative effect is reduced. Thus, the established decrease in fertility in patients with the studied pathology is associated with an increase in carbonylated proteins in the spermoplasm

Oxidative stress plays one of the leading roles in the pathogenesis of varicocele, which affects the quantity and quality of seminal fluid. The research of ejaculate are currently based mainly on chemical-microscopic methods. Biochemical parameters of sperm are determined in insufficient volume, therefore, the introduction of new biochemical markers in order to diagnose a decrease in male fertility is an urgent issue. Oxidatively modified proteins can be considered as a marker of decreased fertility in men with varicocele. The aim of the work was to research the carbonylation of spermоplasm proteins in patients with varicocele II and III degrees with accompanying asthenozoospermia in the anamnesis. Material and methods. The study shows results of 60 men medical examination. The patients weredivided into two groups. The first group consisted of 30 men diagnosed with grade II and III varicocele with accompanying asthenozoospermia. The second group consisted of 30 patients with normozoospermia and without impaired reproductive function. The material for the study was spermoplasm. Spermoplasm was obtained by centrifugation of sperm samples for 10 minutes at a speed of 1000 rpm. Chemical microscopic examination of the ejaculate was carried out on a sperm analyzer (AFS-500-2, Russia) and light microscopy (microscope MS 100 X, Austria). Determination of protein concentration in spermoplasm was carried out by biuretic method with commercial kits of the company (Mindrey, China) on the biochemical analyzer Mindrey BS 120 (China). Determination of oxidative modification of proteins in spermoplasm was carried out by the method of R.L. Levine in modification by E.E. Dubinina. Results. There was a 2-fold increase in ADNPhG at λ 356, and λ 430 by 3.2 times in patients of the first group. It was also noted that the increase in КDNPhG at λ 370 increased by 2 times, and λ 530 by 3.9 times in the spermoplasm, in contrast to patients of the control group. It was also noted that the increase in KDNPhG at λ 370 increased by 2 times, and λ 530 by 3.9 times in the spermoplasm, in contrast to patients in the control group. Conclusion. An increase in oxidatively modified proteins in patients with varicocele may be associated with an increase in oxidative processes, a decrease in the antioxidant defense of the body and damage to the DNA of spermatozoa, which leads to a violation of its functions.

Introduction. glioblastomas multiforme (grade Iv gliomas) are common and the most aggressive primary tumors of the brain with very unfavorable prognosis. In all previously published papers on epileptiform activity in glioblastomas, not enough information on encephalogram results is presented. Aim. To study the features of epileptiform activity in patients with glioblastomas and development of a plan for further study of these patients. Materials and methods. An analysis of articles from Elsevier, Embase, Scopus, The Cochrane Library, global Health, Russian Science Citation Index (RSCI) databases, Scholar, google, web of Science, pubmed search engines and scientific electronic library CyberLeninka was performed. materials were selected considering journal indexing system and citations, scientific novelty of the studies, statistical significance of the results. publications repeating data from previous articles or describing animal experiments were excluded from analysis. Results. During the study, data on mechanisms of epileptiform activity pathogenesis, predisposing factors (tumor location in the temporal, frontal or parietal lobes, IDH-1 and / or IDH-2 gene mutations), treatment options in patients with glioblastomas were systemized. Additionally, and original plan of data accumulation for clinical studied taking into account limitations of the previous studies was developed to increase quality of results interpretation. Conclusion. Epileptiform symptoms in glioblastomas negatively affect patients’ quality of life and lifespan. Currently, researchers actively search for an effective method of treatment of epileptic seizures in patients with glioblastomas. The most effective is combination of temozolomide with valproate and levetiracetam due to good control of seizure frequency, low toxicity, and pharmacological synergy between the drugs.

This article presents the results of an exploration of the determination of nitrogen oxide me-tabolites in spermoplasm among patients with chronic prostatitis IIIB with asthenozoospermia and patients with varicocele of II and III stages with asthenozoospermia.

Although the relationship between the amount of vitamin B12 and the quality of sperm exists, but results are controversial and require several additional research. The objective of our study was to analyse the amount of vitamin B12 in the sperm samples from patients with chronic prostatitis and varicocele with accompanying asthenozoospermia, and to identify the relationship between the amount of vitamin B12 and asthenozoospermia. The research was carried out of men with chronic prostatitis and varicocele with accompanying asthenozoospermia and infertility at the age of 27±2 years. The material of the investigation was spermoplasm. A chemical microscopic examination of the ejaculate was carried out with a sperm analyzer and with the light microscopy. The amount of vitamin B12 in the spermoplasm was determined by the method of competitive ELISA. It was found that the level of vitamin B12 was 3.6 times lower in patients with chronic prostatitis III B and asthenozoospermia then in the control group. Among patients with varicocele of II and III grade and asthenozoospermia, the level of vitamin B12 was 4.4 times lower than in control group. A positive correlation relationship of average strength was revealed (r=0,683; p=0,001). Additionally, it was revealed that among patients with Chronic prostatitis III B and varicocele of II and III grades with accompanying asthenozoospermia, there was the positive correlation relationship of average strength (r=0,690; p=0,001) between the amount of vitamin B12 and sperm mobility. A decrease in vitamin B12 levels may serve as a marker of reproductive dysfunction in men.

Dysferlin is a transmembrane calcium-binding protein of the ferlin-1-like protein family, which includes myoferlin Fer1L3, otoferlin Fer1L2 and other ferlins Fer1L4, Fer1L5, and Fer1L6 along with dysferlin itself. Dysferlin is synthesized in all cells of the body, but most actively – in the symplasts of striated muscle tissue. The full range of functions performed by this protein is not fully clarified, but the following have been clearly shown: participation in the post-injury repair of sarcolemma and intracellular vesicular systems, generation and maintenance of the correct functioning of the sarcolemmal T-tubule system, regulation of endo- and exocytosis and inflammation, participation in phagocytosis. Mutations in the dysferlin gene lead to the development of a number of neuromuscular diseases of the autosomal recessive type of inheritance called dysferlinopathies: Miyoshi myopathy, limb-girdle muscular dystrophy type 2B, and distal anterior compartment myopathy. These diseases are characterized by the impaired expression of mRNA and/or the function of the protein dysferlin in skeletal muscles, which is caused by mutations in the DYSF (dystrophy-associated fer-1-like) gene. Although rare, dysferlinopathy is characterized by continuous progression causing severe disability, which explains the importance of research and development of appropriate treatments, including gene therapy. The article presents information on the structure of dysferlin, the mechanisms of its normal functions, as well as the biochemical basis of the pathogenesis of dysferlinopathies.

BACKGROUND: Assessing the severity of endothelial dysfunction (ED) and making a prognosis after open reconstructive interventions in patients with peripheral atherosclerosis is complicated due to a limited number of conventional routine methods, including laboratory ones, available for establishing associations between biochemical markers and disease outcomes. AIM: This work is dedicated to the evaluation of nitric oxide (II) metabolites (nitrates and nitrites) in patients with complications following open bypass procedures on the lower extremity arteries using synthetic grafts in order to assess the severity of endothelial dysfunction and its negative sequalae. MATERIALS AND METHODS: The study involved 60 subjects with stage IIb–III chronic lower limb ischemia according to A. V. Pokrovsky–Fontaine classification (categories 3–5 Rutherford) due to atherosclerotic peripheral artery disease. Median age of the subjects was 65 (60–67); the majority of the patients were male (51 (85%). Median value of ankle-brachial index at baseline was 0.32 (0.19–0.42). All participants underwent open bypass grafting procedures using synthetic vascular grafts. Nitric (II) oxide (NO) metabolites level (nitrites and nitrates) was measured before the intervention and three months afterwards by spectrophotocolorimetry using an ELISA analyzer Stat Fax 3200 (Awareness Techonology, Inc., USA) and Griess reagent. The subjects were followed up for a year to determine the rate of development of complications such as restenosis, graft thrombosis, limb loss (major amputation), lethal outcomes, as well as disease progression, myocardial infarction, oncology, and stroke. RESULTS: Performance of a reconstructive procedure on lower extremity arteries was followed by a decrease in NO metabolites level from initial median 76.3 mcmol/ml (48–100.7) to 52.4 mcmol/ml (36.1–93.8) at three months after the intervention (р = 0.015). There was a positive correlation between the NO metabolites level at baseline (0 months) and follow-up visit (3 months) (r = +0.573). Complications within one year after bypass procedures were detected in 66.64% subjects. Baseline level of NO metabolites in patients who required an amputation within one year after the procedure was markedly elevated and reached 116.3 mcmol/ml (90–130.5) (p = 0.025); development of restenosis and lethal outcomes within one year were associated with initially low NO metabolites levels, 35.6 mcmol/ml (p = 0.036) and 33 mcmol/ml (30–36), accordingly (р = 0.043). CONCLUSIONS: Both markedly high and low levels of nitric oxide metabolites (nitrates and nitrites) levels are associated with development of severe complications after open reconstructive procedures in patients with peripheral atherosclerosis. Quantitative determination of the NO metabolites level in serum is a relatively easy and reliable method allowing for the determination of the severity of endothelial dysfunction and its sequalae in subjects after open bypass reconstructive procedures on lower extremity arteries.

Endotheliocytes are the key elements of the vascular wall and are involved in regulation of vascular tone and permeability, inflammation, hemostasis, angiogenesis etc. Impaired function of endothelial cells universally recognized as endothelial dysfunction is associated with a number of common diseases such as ischemic heart disease, arterial hypertension, atherosclerosis, peripheral arterial disease, septic shock, chronic kidney disease, obesity, oncological and autoimmune diseases. Less is known about the role of endothelial cells in pathogenesis of development and progression of rare diseases, such as muscular dystrophies. Muscular dystrophies involve over 30 genetically determined diseases, which are characterized by the development of a progressive muscular weakness and skeletal muscle degeneration. Presence of a nucleotide variant associated with a certain muscular dystrophy is primarily marked by a limited potential of skeletal muscle regeneration due to the impaired structure and function of myogenic cells. Inherited myopathies include a group of severe neuromuscular diseases caused by a mutation in the dysferlin gene DYSF, which leads to the synthesis of a dysfunctional dysferlin. Complex molecular and cellular interactions involved in skeletal muscle damage and endothelial dysfunction play an important role in the pathogenesis of dysferlinopathies. The possibility to produce an effect on different pathological aspects of dysferlinassociated myopathies such as complement system activation, inflammation, impaired function of endothelial cells, damage and necrosis of myofibrils are extensively studied in vitro and in vivo. This article is dedicated to the current understanding of relationship between the endothelium and its dysfunction in myogenesis and skeletal muscle regeneration in normal and pathological conditions caused by a group of inherited progressive myodystrophies, dysferlinopathies in particular, as well as possible clinical application of endothelial cells in treatment of muscular dystrophies.

We studied the effect of nitinol, the most prevalent material for endovascular stents, on metabolic and coagulation activity of a primary culture of human umbilical vein endothelial cells (HUVEC). Metabolic activity was evaluated using MTS-test and by the level of stable NO metabolites in the conditioned medium, coagulation activity was assessed by activity of von Willebrand factor (vWF) and levels of plasminogen activator inhibitor-1 (PAI-1) and soluble endothelial protein C receptors (sEPCR). Exposure to nitinol reduced metabolic activity of the cell culture by 11.1% in comparison with the control (p<0.001). Although absolute activity of vWF and absolute level of sEPCR were elevated, incubation with nitinol did not lead to a statistically significant elevation of these parameters in comparison with the control, which can indicate the absence of substantial hypercoagulation effects of nitinol.

В 2019 году в журнале «Наука молодых» (Eruditio Juvenium) коллективом авторов была опубликована первая часть статьи, посвященная ключевым аспектам гистогенеза, особенностям структуры, цитофизиологии и иммуноцитохимическим маркерам эндотелиоцитов (doi:10