Aim. To investigate polymorphisms of 18 genes as possible molecular genetic markers of predisposition or resistance to development of non-infective (NE) or infective endocarditis (IE).

Materials and methods. The study encompassed 81 patients with NE and 94 patients with IE. The control group included 225 conditionally healthy people. Polymorphisms of 18 genes were tested using polymerase chain reaction (PCR).

Results. For the first time, a statistically significant relationship was identified between gene polymorphisms and valvular vegetations: for genes in the hemostatic system – rs6025 (1691 G > A) of the F5 gene (AG genotype), rs1126643 (807 C > T) of the ITGA2 gene (TT genotype); for folate pathway genes – rs1805087 (2756 A > G) of the MTR gene (AG genotype) and rs11697325 (–8202 A/G) of the MMP9 gene (AA genotype) and rs2476601 (C1858T) of the PTPN22 gene (TT genotype). The protective effect of gene polymorphisms was revealed: for the NOS3 gene (4b / 4b genotype) and G (–572) C of the IL6 gene (CC genotype). For two polymorphisms, an association with thromboembolic complications in NE was revealed: rs1126643 (807 C > T) of the ITGA2 gene and rs1799889 (–675 5G > 4G) of the PAI (SERPINE1) gene. In IE, such an association was detected for the polymorphism rs11697325 (–8202 A/G) of the MMP-9 gene.

Conclusion. The polymorphisms of candidate genes were revealed, that are associated with the clinical and hemostasiological characteristics of IE and NE. In NE, for the first time, the association with thromboembolic complications was identified for two polymorphisms: rs1126643 (807 C > T) of the ITGA2 gene and rs1799889 (– 675 5G > 4G) of the PAI-1 (SERPINE1) gene. In IE, such a relationship was detected for one polymorphism – rs11697325 (8202 A/G) of the MMP-9 gene.

Despite the achieved success in the treatment of neonatal hydrocephalus, the task of restoring circulation, outflow, and absorption of cerebrospinal fluid (CSF) remains urgent.

The aim of the study was to investigate the effectiveness of ventriculosubarachnoid drainage in compensating hydrocephalus without shunt implantation.

Materials and methods. We collected and studied clinical material for the period from 2000 to 2018 according to the data of the Republic of Crimea. We identified groups of premature (n = 184) and full-term (n = 107) infants who underwent standard treatment with lumbar puncture, subgaleal drainage, and ventriculoperitoneal shunting (VPS). In case of ventricular occlusion in 143 premature and 46 full-term infants, at the initial stage of treatment, the option of coronary – lambdoid subarachnoid ventriculostomy (RF Patent No. 2715535) in combination with lumbar punctures was included. With progression of hydrocephalus, ventriculosubarachnoid stenting (RF Patent No. 2721455) with subgaleal drainage was considered as an option.

Results. The inclusion of the proposed options made it possible to increase the rate of hydrocephalus compensation without VPS to 75.5% in premature infants and to 80.4% in full-term infants versus 28.3% and 20.6%, respectively, according to the standard protocol (p < 0.001). In other cases, the imbalance between CSF production and absorption persisted, which required integration of a stent with a peritoneal part of the shunt, without replacing the system.

Conclusion. The obtained result allows to consider the inclusion of the proposed options in the modern treatment algorithm for neonatal hydrocephalus.

Background. Increased consumption of animal fat with food contributes to the accumulation of lipids both in the blood and in individual cell structures. Excess fat initiates oxidative stress reactions, which may result in a violation of the structural and functional integrity of cells, in particular, hepatocytes and endotheliocytes. Cytolysis may release specific liver enzymes and activate synthesis of extracellular matrix components, one of the markers of which is a non-collagen glycoprotein laminin.

The drug sulodexide, having a pronounced angioprotective, hypolipidemic, and fibrinolytic effects, contributes to restoration of a number of metabolic disorders.

Aim. To study the content of lipid metabolism parameters, major enzymes of hepatic cytolysis, and laminin in the blood of rats fed with a high-fat diet against the background of sulodexide administration.

Materials and methods. For the study, outbred rats were selected, which were divided into three groups – two experimental groups and one control group. The rats of the first and second experimental groups were fed with a diet with a high content of animal fat (44% of the daily calorie content) for 35 days. In addition, the rats of the second experimental group were daily subcutaneously injected with sulodexide at a dose of 8.5 LRU / kg in terms of the animal’s body weight for 35 days. Starting from day 36 of the experiment, the rats of the control group, as well as the rats of the two experimental groups were fed with a standard diet of the vivarium. The animals were decapitated and blood was taken on day 21, 35, and 60 of the experiment. In the blood serum, the levels of the main lipid metabolism parameters, specific liver enzymes, and laminin were determined.

Results. An increase in the body weight of animals and the level of the studied lipid metabolism parameters in the blood serum was revealed. It is likely that the structural integrity of hepatocytes was affected with the release of liver enzymes into the bloodstream and an increase in their content in the blood of rats. In addition, synthesis of extracellular matrix components was activated with an increase in the serum level of laminin, which performs important structural and regulatory functions.

Conclusion. The use of sulodexide had a favorable effect on the studied metabolic disorders caused by a high-fat diet. It resulted in the normalization of the synthesis of laminin, one of the major non-collagen proteins of the extracellular matrix.

The aim of this study was to evaluate the effect of treatment with valproic acid, erythropoietin, and dexamethasone on the anti-inflammatory and immunosuppressive activity of the secretome of adipose-derived multipotent mesenchymal stromal cells (MMSCs) in an in vitro experiment.

Materials and methods. MMSCs were isolated from the fat of 6 healthy donors. The cells were grown in the culture up to passage 4. Then they were treated with valproic acid, erythropoietin or dexamethasone for 3 hours, washed from preparations, and incubated in a serum-free medium for 48 hours. Some of the cells were not treated with preparations. Supernatants from the cell cultures were concentrated by ultrafiltration, and protein standardization was performed using a nanophotometer. Then the supernatants were sterilized and added to mononuclear cells from peripheral blood of 8 healthy donors. The mononuclear cells were isolated by Ficoll density gradient centrifugation according to the standard protocol. Concentrations of TNFα, IL-2, IL-4, IL-6, IL-10, and IFNγ cytokines in 24-hour cultures and IL-9, IL-10, IL-17A, and IL-21 cytokines in 48-hour cultures were determined using multiplex analysis.

Results. The production of IL-2, IL-6, TNFα, and IL-10 was reduced by the secretome of MMSCs treated with valproic acid. The production of IL-2, IL-6, and TNFα decreased during incubation of the mononuclear cells with the secretome of MMSCs treated with erythropoietin. The secretome of dexamethasone-treated MMSCs suppressed the production of IFNγ, IL-1β, IL-1ra, IL-2, IL-6, IL-9, IL-10, and IL-17A. No statistically significant differences were revealed in the production of IL-4, IL-5, IL-9, and IL-21.

Conclusion. Among the studied inducers, dexamethasone enhanced the anti-inflammatory and immunosuppressive activity of MMSCs the most, which was manifested through the effect of their supernatants on peripheral blood mononuclear cells.

Aim. To study the prognostic value of high serum concentration of soluble ST2 protein (sST2) in the development of cardiovascular events after endovascular myocardial revascularization and the possibility of using this biomarker as a target for β-blocker therapy in patients with chronic heart failure (CHF) with preserved (HFpEF) and mildly reduced (HFmrEF) left ventricular ejection fraction.

Materials and methods. The study included 72 patients (aged 57–69 years, 81.94% were men) with class I–III CHF of ischemic etiology with HFpEF and HFmrEF. The patients were admitted to the cardiology department for endovascular myocardial revascularization. Before myocardial revascularization, serum concentrations of sST2 and N-terminal pro-brain natriuretic peptide (NT-proBNP) in all patients were analyzed by enzyme-linked immunosorbent assay (ELISA). Doses of β-blockers used in all patients were recalculated into a total daily dose equivalent to metoprolol succinate. Patients were divided into 2 groups depending on the median equivalent dose of metoprolol succinate (“high” ≥ 100 mg / day and “low” < 100 mg / day).

Results. In patients of group 1, the serum concentration of sST2 was 30.7% higher (p < 0.001) than in patients of group 2 (40.26 [34.39; 48.92] ng /ml and 27.9 [23.05; 35.27] ng / ml, respectively), the serum NT-proBNP level in group 1 was 22.8% higher (p = 0.049) than in group 2 (167 [129; 330] ng / ml vs. 129 [125; 147] ng / ml, respectively). In patients receiving an equivalent dose of metoprolol succinate < 100 mg / day, the incidence of cardiovascular events was 34% higher (p = 0.002) than in patients receiving an equivalent dose of metoprolol succinate ≥ 100 mg/day. The ROC analysis showed that serum sST2 level ≥ 34.18 ng / ml (sensitivity 78.0%, specificity 90.0%, area under the curve (AUC) 0.906; p < 0.0001) predicts a high risk of cardiovascular events within one year. However, the serum NT-proBNP level was not an informative predictor of cardiovascular events. 

Conclusion. It was confirmed that increased sST2 serum concentration has high prognostic value in the development of cardiovascular events within a year after endovascular myocardial revascularization. The possibility of using this biomarker as a target for β-blocker therapy in patients with HFpHF and HFmrEF was substantiated. Aggressive use of β-blockers in the group of patients with HFpEF and HFmrEF and sST2 overexpression is preferable in order to reduce the incidence of cardiovascular events.

Aim. To evaluate the effect of rectal insufflations of medical ozone on markers of inflammation in experimental ulcerative colitis.

Materials and methods. The experimental study was performed in vivo on 49 white, sexually mature male Wistar rats weighing 250 ± 15 g. The model of ulcerative colitis was reproduced using two-stage oxazolone administration (Sigma-Aldrich, USA). A group of animals received rectal insufflations of medical ozone at a dose of 1.0 mg / l once a day in the volume of 10 ml of ozone / oxygen mixture. The cycle of insufflations lasted 10 days. The ozone / oxygen mixture was obtained using an automated ozone therapy device with an ozone destructor UOTA-60-01“Medozon” (Medozon LLC, Moscow, Russian Federation). According to the disease activity index (DAI) score, the disease activity index was evaluated. The intensity of neutrophil phagocytosis in the blood was detected using polystyrene latex particles. The ability of neutrophils to reduce nitroblue tetrazolium (NBT) was determined using spontaneous and induced NBT tests. The interleukin-17 (IL-17) concentration in the serum was determined by enzyme-linked immunosorbent assay (ELISA) using a test system for rats manufactured by Bender MedSystems (Austria).

Results. Under the conditions of ozone therapy by rectal insufflations in experimental ulcerative colitis, we demonstrated improvement in the clinical presentation of the disease, intensity of phagocytosis, phagocytic index, and spontaneous and induced ability of neutrophils to reduce NBT with normalization of the functional reserve of cells and the level of proinflammatory IL-17 on day 6 of the experiment.

Conclusion. The results obtained allow to verify pronounced anti-inflammatory and immunomodulatory effects of ozone and consider it as one of the most relevant treatment strategies for inflammatory bowel diseases.

The aim of the study was to assess the probability of developing withdrawal syndrome caused by discontinuation of 5-day administration of thiowurtzine with naloxone challenge test in the experiment.

Materials and methods. The test sample of the analgesic “Thiowurtzine, capsule 120 mg” served as the study object. The active pharmaceutical ingredient is an organic, low molecular weight compound 4-(3,4-dibromothiophene carbonyl)-2,6,8,12-tetraacetyl-2,4,6,8,10,12-hexaazatetracyclo [5,5,0,0^3,11,0^5,9]dodecane that was first synthesized according to computer modeling results at the IPCET SB RAS (Biysk).

The likelihood of developing physical dependence was explored by per os administration of thiowurtzine and the reference drug tramadol twice a day for 5 days as follows: 1) at 9 a.m. – thiowurtzine 50 mg / kg and tramadol 10 mg / kg, at 3 p.m. – thiowurtzine 50 mg / kg and tramadol 10 mg / kg; 2) at 9 a.m. – thiowurtzine 50 mg / kg and tramadol 10 mg / kg, at 3 p.m. – thiowurtzine 75 mg / kg and tramadol 15 mg / kg; 3) at 9 a.m. – thiowurtzine 75 mg / kg and tramadol 15 mg / kg, at 3 p.m. – thiowurtzine 75 mg / kg and tramadol 15 mg / kg; 4) at 9 a.m. – thiowurtzine 100 mg / kg and tramadol 20 mg / kg, at 3 p.m. – thiowurtzine 100 mg / kg and tramadol 20 mg / kg; 5) at 9 a.m. – thiowurtzine 100 mg / kg and tramadol 20 mg / kg, at 3 p.m. – naloxone 10 mg / kg subcutaneously.

In all the groups, the intensity of the withdrawal syndrome was studied by specific features in outbred male CD1 mice. During one hour following the naloxone injection, health of mice was assessed according to dominant abstinence components and recessive traits of mild withdrawal syndrome. Two hours after the naloxone injection, the number of mice with negative body weight gain was determined. 24 hours after discontinuation of test compound administration, the open-field test was used to determine the impact on animal behavioral patterns (horizontal and vertical motor and exploratory activity, emotionality and its vegetative manifestations). The hot plate test was carried out to measure the analgesic activity (55˚). The criterion of the withdrawal syndrome severity was a decrease in the number of jumping reactions, changes in the general condition of the animals, stimulation of motor activity, manifestations of hyperalgesia, and a decrease in body weight.

Results. No dominant abstinence components and recessive signs of withdrawal syndrome were detected in animals from the thiowurtzine groups. The data obtained in the study (orientation and exploratory behavior, motor activity, emotionality and its vegetative manifestations, grooming, etc.) allow to conclude that thiowurtzine causes no physical dependence in animals after discontinuation of its 5-day administration with naloxone challenge test, as opposed to the reference drug naloxone. A positive disinhibition effect of this analgesic was revealed due to the activated orientation and exploratory behavior (stress caused by the new environment) in the conditions of the open-field test. The animals showed no manifestations of hyperalgesia in the hot plate test. The animals treated with thiowurtzine did not demonstrate any changes in the body weight.

Conclusion. The obtained results prove that thiowurtzine is a non-narcotic analgesic. It evokes no side effects typical of opioid analgesics (tramadol), including development of physical dependence and withdrawal syndrome following naloxone challenge test. Previous in vivo and in silico studies (docking, molecular modeling, molecular dynamics simulation) on the multi-target mechanism of thiowurtzine explain the absence of its morphine-like effect by the fact that the major targets of the analgesic are TRPA1 receptors and voltage-gated Ca 2+ channels. With a high degree of probability, the conclusions made herein predict no drug abuse development when thiowurtzine is used in the clinical setting. Absence of ulcerotoxicity found earlier will enable to administer thiowurtzine in long-term cycles for chronic pain syndrome.

The aim of the study was to determine the number of lymphocytes, intracellular cytokines produced by lymphocytes, and the cell cycle of lymphocytes isolated from the blood of patients when exposed to various drugs, as well as to assess the functions of cultured lymphocytes when exposed to drugs in vivo and in vitro.

Materials and methods. The study involved lymphocytes isolated from the blood of healthy women under various conditions. At the first stage of the study, T-lymphocytes were isolated from the blood of patients before exposure to the drug. The absolute and relative lymphocyte count, the number of intracellular cytokines, and the cell cycle were determined.

At the second stage, the drugs were added to the nutrient medium, where lymphocytes isolated from the blood of patients who did not receive systemic drugs were cultured. The placental extract preparation was added to the lymphocytes isolated from the first group of patients, while the hyaluronic acid preparation was added to the lymphocytes isolated from the second group of patients.

At the third stage, the lymphocytes isolated from the blood of patients after systemic exposure to the placental extract preparation or hyaluronic acid preparation were isolated and cultured, after which the same lymphocyte parameters were determined.

Results. The number of T-lymphocytes increased with the systemic use of the placental extract and hyaluronic acid preparations and practically did not change compared with the baseline data, when these drugs were added to the nutrient medium. Placental extract and hyaluronic acid had a positive effect on the mitotic activity of cells; it is worth noting that the effect of placental extract was greater than that of hyaluronic acid. Both drugs did not have a negative effect on apoptosis of T-lymphocytes. Under the effect of placental extract, lymphocytes secreted more interleukins, which contributed to proliferation of keratinocytes.

Conclusion. The placental extract and hyaluronic acid preparations have a stimulating effect on keratinocytes. The placental extract preparation has a stimulating effect on T-lymphocytes after systemic exposure of the body to it.

Aim. To determine the differences in self-assessment of social functioning by patients with chronic coronary artery disease (CAD), depending on the presence of comorbid affective disorders (ADs).

Materials and methods. Using the Social Adaptation Self-Evaluation Scale (SASS), which makes it possible to assess the degree of social functioning and satisfaction with various aspects of social life, we studied the features of the social functioning of heart hospital patients with chronic CAD with (n = 248) and without AD (n = 291). In 290 patients (average age 56.6 ± 6.7 years) with chronic CAD, chronic ADs (45%) were revealed; depressive episodes (DEs) were diagnosed for the first time in 24% of patients, and 24.5% of patients had recurrent DEs. Bipolar disorder was found in 6.5% of cases. Qualitative and quantitative parameters were investigated using the Mann – Whitney U test and Student’s t-test. To assess the frequencies, the Pearson’s chi-squared test was used.

Results. The mean total SASS score in the patients with chronic CAD with AD corresponded to difficult social adaptation (33.7 [29.5; 39]), while the patients without AD had good social adaptation score of 40.8 ± 6.3 (p < 0.05). In the group without AD, patients with normal social adaptation prevailed (n = 215; 73.8%), while patients with AD more often had difficulties with social adaptation (n = 148; 59.7%). In the CAD patients, depending on the presence of AD, the frequency of disturbances in various spheres of social adaptation differed: employment, interest in and pleasure from activities, disposition of income, pleasure from and interest in seeking information, social support (p = 0.001).

Conclusion. Higher frequency of pronounced impairment in social functioning in patients with chronic CAD with AD determines the need for taking this fact into consideration when planning rehabilitation measures in this group of patients.

Aim. To assess the impact of autologous activated T-lymphocyte immunotherapy on clinical parameters and quality of life in patients with allergic bronchial asthma (BA) in comparison with patients with allergic BA who received standard therapy.

Materials and methods. A non-randomized, pilot study included 19 patients with allergic BA of moderate severity (7 men and 12 women aged 23–61 years, average age – 38.5 ± 4.3 years) who received the T-cell vaccine (n = 12) and standard therapy with inhaled glucocorticoids, short- and long-acting β2-adrenergic agonists (n = 7). After signing an informed consent, the patients were subcutaneously injected with autologous activated T-lymphocytes with a frequency of 4 injections 1 time / week, and then 6 injections 1 time / month. The research methods included asthma control measurement according to the ACQ-5 questionnaire and quality of life assessment according to the AQLQ(S) questionnaire. Clinical data were collected during lung function tests and by measuring the total immunoglobulin E (IgE) level.

Results. In the course of the study, the immunotherapy was well tolerated, no systemic adverse reactions were noted. The treatment approach in the patients who received the T-cell vaccine resulted in significant improvement of asthma control parameters (according to the ACQ-5 questionnaire) and parameters of the patients’ quality of life (according to the AQLQ(S) questionnaire) within all 4 categories. Besides, their lung function improved by the end of treatment, and the total IgE level decreased. No significant changes in these parameters were observed during the follow-up in patients who received standard therapy. The study was conducted before immunotherapy, after 2 months (after 5 injections), and after 7 months (after 10 injections).

Conclusion. Evaluation of the impact of immunotherapy with autologous activated T-lymphocytes on the clinical parameters and quality of life in patients with BA indicates effectiveness of treatment in patients with allergic BA.

Aim. To study anti-inflammatory, analgesic, and possible ulcerogenic effects of a novel aminoguanidine derivative in adjuvant arthritis (a model of rheumatoid arthritis) in rats.

Materials and methods. The experiments were carried out on 42 outbred male Sprague Dawley rats. After modeling arthritis (starting from day 7 after the administration of complete Freund’s adjuvant), intramuscular injections of the aminoguanidine derivative (code LIS-M) at a dose of 2.5, 5, and 10 mg / kg or the reference drug diclofenac at a dose of 4 mg / kg were performed once a day for 22 days. The volume of the inflamed limb was measured twice a week, pain threshold was measured every week. After finishing the administration of the compounds, the levels of interleukin (IL) 1, IL-6, and tumor necrosis factor-α (TNFα) were measured in rat plasma, the ankle joint was histologically studied, and the gastric mucosa was studied to detect damage, ulcers, and scarring.

Results. The aminoguanidine derivative, an inhibitor of inducible nitric oxide synthase, was more effective at the dose of 10 mg / kg than diclofenac at the dose of 4 mg / kg. It had anti-inflammatory and analgesic effects in the joint affected by complete Freund’s adjuvant, promoted restoration of the histologic structure in the synovial membrane and articular cartilage, and reduced the plasma concentration of IL-1, IL-6, and TNFα by 1.4–1.5 times. The LIS-M compound did not damage the gastric mucosa in rats with adjuvant arthritis.

Conclusion. The aminoguanidine derivative LIS-M exerts potent anti-inflammatory and analgesic effects in adjuvant arthritis in rats (a model of rheumatoid arthritis). LIS-M has no ulcerogenic effect on the gastric mucosa in rats.

Aim. To assess the effect of melatonin (MT) on the content of lipid peroxidation (LPO) and protein oxidation (PO) products in the tissue homogenate from the burn wound in experimental thermal injury (TI).

Materials and methods. Third-degree (IIIA) TI with a relative area of 3.5% was modeled on male Wistar rats via contact of the skin with boiling water. Intraperitoneal administration of MT (10 mg / kg) was performed once a day for 5 days. On days 5, 10, and 20, LPO products in the heptane and isopropanol phases of lipid extraction and PO products were determined in the tissue homogenate from the burn wound.

Results. The content of secondary and end products of LPO in the heptane phase and end products in the isopropanol phase increased in the wound. The content of primary and secondary PO products of neutral nature increased on days 5, 10, and 20, and the level of secondary PO products of neutral nature elevated on days 10 and 20. Administration of MT reduced the content of LPO end products in the heptane phase, secondary and end products of LPO in the isopropanol phase, and the total amount of PO products due to primary and secondary products of neutral nature.

Conclusion. In the 20-day follow-up, LPO and PO products accumulated in the burn wound. The administration of MT at a total dose of 50 mg / kg led to reduction and partial restoration of the content of LPO and POM products, which can limit secondary alterations and accelerate healing of the burn wound.

Aim. To evaluate the possibility of using lung ultrasound for diagnosing COVID-19 pneumonia in patients of the respiratory hospital of Siberian State Medical University (SSMU).

Materials and methods. An analysis of lung ultrasound data was carried out in 39 patients (17 men and 22 women aged 33–78 years) with COVID-19 pneumonia. Lung ultrasound was performed in all patients in addition to radiography performed at the prehospital stage and in 15 patients who underwent computed tomography (CT) of the lungs.

Results. In the majority (61.6%) of cases, during the ultrasound examination, COVID-19 pneumonia manifested itself as interstitial lung disease. The white lung phenomenon and a combination of the aforementioned interstitial changes were recorded with the same frequency (5.1%), while pulmonary consolidation in addition to interstitial changes was visualized in 10.2% of cases. Interstitial lung disease was bilateral in 83.3% of patients and unilateral in 16.7% of cases. The inferior lobes of the lungs were affected in 60.0% of cases, middle lobe – in 30.0% of cases, and superior lobes – in 15.0% of patients. The ultrasound examination detected changes in the lungs in 32 patients, while radiographic changes were present in 35 cases. Bilateral inflammation was more often detected by radiography than by ultrasound. When comparing the data of lung ultrasound and CT, the agreement between the methods was found in 66.7% of cases, and the discrepancy between the findings of the two methods was observed mainly in patients with a large number of affected segments of the lungs and localization of the disease in the superior lobes according to CT.

Conclusion. Lung ultrasound is a valuable tool that can be used to stratify risk in patients at any stage of diagnosis and treatment in the context of the COVID-19 pandemic due to availability, speed of implementation, and the absence of a need for patient transportation.

Background. SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has one of the largest genomes. It encodes 16 non-structural proteins that are necessary for replicating and overcoming host defense mechanisms. Flavonoids are of interest as research objects in developing drugs for comprehensive COVID-19 therapy. This group of compounds is characterized by a wide range of biological activity and a high safety profile.

Aim. To perform virtual screening of flavonoids for possible inhibition of proteins of the SARS-CoV-2 infection.

Materials and methods. Structural proteins of SARS-CoV-2 infection, such as ADP-binding domain NSP3, main protease NSP5, RNA-dependent RNA-polymerase NSP12, and endoribonuclease NSP15, were obtained from Protein Data Bank (PDB). Flavonoid structures were obtained from the ZINC database. Protein models were processed using AutoDockTools software, and ligands were processed in Raccoon | AutoDock VS. Virtual screening and re-docking were performed in AutoDock Vina.

Results. Validation showed agreement between native and re-docked conformations, indicating the applicability of the virtual screening method. Flavonoids interacted with the key amino acid residues in all the studied proteins. The highest binding energy was demonstrated by 3,7-dihydroxyflavone and 6S-coccineone B, the latter having a multimodal effect.

Conclusion. The results of the study may be used for the development of phytomedicines for comprehensive therapy for COVID-19.

Aim. To review the current progress in the use of remote health monitoring (RHM) technologies for chronic noncommunicable diseases (CNCD).

To search for data, we used Web of Science, Scopus, Russian Science Citation Index, Academic Search Complete (EBSCO), Cochrain, and PubMed databases. The date range was 5–10 years. The importance of development of RHM technologies and their further study was shown to confirm the evidence of effect of certain RHM systems.

New approaches to the integration of the medical community into the international telemedicine strategy are considered. It was established that RHM can potentially decrease treatment costs and reduce the burden on medical organizations. The review analyzes the experience in using RHM in patients with cardiovascular diseases, as well as respiratory and endocrine disorders. The review also summarizes and systematizes the findings of studies on assessing the effectiveness of RHM technologies in clinical practice, including their use in the COVID-19 pandemic.

It is noted that despite high interest of the scientific community in the study of RHM technologies, unambiguous results demonstrating the effectiveness of such developments in clinical practice have not been presented.

In recent decades, following cooperation between scientists in various specialties, new unique data on the pathogenesis of ulcerative colitis have been obtained. The role of an impaired immune response to antigens of gut microbiota in genetically predisposed individuals under the effect of certain environmental factors was proven. 

Assessing the interaction between the colonic mucosa and gut microbiota will help to understand the mechanisms of ulcerative colitis and develop new treatment strategies for the disease.

This review presents modern views on the pathogenesis of ulcerative colitis with a focus on the imbalance between local protective and aggressive factors of the gastric and intestinal mucosa. The structure and role of the epithelial barrier both under normal conditions and in ulcerative colitis are considered in detail.

The aim of this review was to summarize the data on resistance of the colonic mucosa and its damage in ulcerative colitis.

The study of sudden cardiac death (SCD) and its etiopathogenesis in cardiology practice remains one of the most pressing public health problems. In Western countries, SCD accounts for 20% of the total mortality and 50% of mortality associated with cardiovascular diseases. Considering the electrical instability in the myocardium as one of the main reasons for the development of life-threatening arrhythmias (ventricular tachycardia / ventricular fibrillation) and SCD, one should be aware of such provoking factors as ischemic heart disease, myocarditis, valvular heart disease, pharmacological influences, cardiomyopathy, and channelopathy. An increase or decrease in the duration of the QT interval, which reflects the work of ion channels, as well as ventricular depolarization and repolarization, increases the risk of SCD.

The aim of this review was to study and analyze the available literature data on the relationship of molecular genetic markers with the duration of the QT interval.

Currently, there is a number of genetic studies that allow to identify a large number of mutations and polymorphisms of known genes that affect the variability of the QT interval, showing their significance in risk stratification of sudden arrhythmic death and choosing the right tactics for managing, preventing, and treating patients, thus reducing the risk of SCD. The predictive value of genetic testing is the highest for long QT syndrome (LQTS), for which a gene-specific risk profile has been established, and lower for other channelopathies. A large amount of genetic data may be a promising approach to quantifying the risk of SCD, especially at a young age, which will be facilitated by further study of this problem.

Involutional hormonal processes characteristic of the postmenopause are accompanied by disorders that deteriorate the quality of life in the female population and lead to an increased risk of developing metabolic diseases of the bones and cardiovascular system. In modern medicine, it is extremely important to understand the pathogenesis of postmenopausal osteoporosis (PMO) in association with cardiovascular diseases, which are the main causes of mortality in the population.

This review is devoted to determining the key aspects of the pathogenesis of PMO and identifying their relationships with cardiovascular pathology. Epidemiological data are assessed, the main mechanisms of PMO and vascular pathology development are considered, the fundamental role of hormone deficiency, immune dysregulation disorders, and disorders of macrophage polarization is described, and data on the association between the pathogenesis links of the studied pathological processes are analyzed.

The obtained data will form a unified approach to reducing the growing prevalence of cardiovascular diseases and complications of PMO and contribute to the development of new research areas in disease prevention.

The review presents an analysis of the scientific literature on comorbidity of coronary artery disease (CAD) and assessment of its impact on the results of coronary artery bypass grafting (CABG). Arterial hypertension (AH), chronic obstructive pulmonary disease (COPD), metabolic syndrome (MS), and diabetes mellitus (DM) have been shown to be the most common comorbidities in CAD patients. Clinical manifestations of cardiovascular comorbidities also include atrial fibrillation, acute cerebral ischemia, atherosclerosis of carotid and lower limb arteries, and chronic heart failure.

Concomitant COPD doubles the risk of postoperative complications after CABG and reduces the 10-year survival rate in patients to 30%. In CAD patients with MS, the risk of postoperative mortality increases by 1.4 times, and the 5-year survival rate decreases by 3 times. Diabetes significantly worsens the long-term survival of patients after CABG and is an independent predictor of acute cardiovascular events after revascularization in the long term. The presence of various comorbidities in CAD patients requires a personalized approach to managing the risks of adverse outcomes after CABG and introduction of modern artificial intelligence (AI) technologies into clinical practice, which significantly increase the accuracy of prognosis.

A review of modern studies on the problem of multimorbidity, its definition, frequency of occurrence, prevalence, medical and social consequences, factors predisposing to its formation, and approaches to diagnosis, therapy, and rehabilitation is presented. According to modern understanding, multimorbidity is the presence of two and / or more chronic diseases that are pathogenetically interconnected and / or coincide in time in one patient.

Currently, multimorbidity is becoming an epidemic, affecting people of different ages and gender and with various diseases. The literature describes multiple adverse medical and social consequences of multimorbidity, such as increased rates of hospitalization, disability, and mortality, decreased functional capabilities and quality of life in patients, as well as increased volume, timing, and cost of medical care. Today, issues of the unified terminology, identification of multimorbidity, and the structure and clinical manifestations of associated pathology are being studied. There are single works on the study of possible factors contributing to the formation of multimorbidity. Approaches to management of patients in conditions of multimorbidity are being developed. A more detailed study of the mechanisms of multimorbidity formation and common pathogenetic links of associated diseases will make it possible to develop more effective strategies for the diagnosis, treatment and rehabilitation of multimorbid patients.

Activation of the estrogen receptor-α (ER-α) signaling pathway is a significant factor in the initiation of carcinogenesis in various types of tumors due to the genomic and non-genomic effects of estradiol in cancer cells. However, data on the expression of ER-α and aromatase on stromal and immune cells in the tumor microenvironment (TME) point to an additional mechanism by which estrogens increase tumor malignancy. There is growing evidence that TME can affect tumor immunity by increasing the immune response or reducing immunoreactivity.

The important role of estrogen and the estrogen receptor signaling pathway in the response of the tumor microenvironment in cancer of various localizations, not only classical hormone-dependent cancers, has been proven. However, the clinical effectiveness of blocking the effect of estrogen on tumor growth has been primarily shown in cancer of the female reproductive system. At the same time, data on the significant role of TME in the development of endocrinotherapy resistance in breast cancer treatment are of great interest.

Despite the possibilities of standard therapy, a more in-depth study on the role of various TME components in cancer evolution, creation of a micrometastatic niche, as well as in the response to therapy may result in development of new strategies for cancer treatment. It is also necessary to study the possibilities of overcoming the immunosuppressive effect of the estrogen receptor signaling pathway on TME in order to increase the survival rates in patients with hormone-dependent cancers, particularly, breast cancer.

Implantable cardioverter-defibrillators (ICDs) are considered to be the most beneficial in preventing sudden cardiac death (SCD), especially in patients with reduced left ventricular ejection fraction (LVEF). However, major large-scale randomized clinical trials on ICD effectiveness were conducted 20 years ago and do not reflect current realities. Modern ICDs and methods for treating heart failure have drastically improved. New clinical reality requires reconsideration of approaches to determining the risk of SCD and indications for ICD, personalization of device selection and programming, and identification of barriers that prevent ubiquitous use of the method in real clinical practice.

The article reviews the available evidence base on the use of ICDs, current clinical guidelines, complications following the device implantation, and any difficulties associated with ICD application in routine clinical practice.

X-linked adrenoleukodystrophy belongs to peroxisomal disorders characterized by combined damage to the nervous system and adrenal glands and often leading to death. This hereditary disease results in mutations in the ABCD1 gene, leading to ineffective β-oxidation of fatty acids following a decrease in the activity of acetyl-CoA synthetase of their long chains. Accumulation of acyl-CoA derivatives of fatty acids takes place, which affect the physicochemical properties of cell membranes.

We have described a clinical case of X-linked adrenoleukodystrophy in a 9-year-old boy with the primary manifestation of the disease at the age of 7 years and 10 months in form of enterovirus encephalitis.

Early diagnosis, prenatal screening of adrenoleukodystrophy for performing gene-specific therapy, slowing the progression of the disease, and prolonging the life of the patient with the diagnosis of a rare hereditary disease are required.