Aim. To determine informative prognostic criteria for assessing the HER2 / neu status in primary breast cancer using ^99mTc-DARPinG3.

Materials and methods. The study included 10 patients with breast cancer (T_1-4N_0-2M₀) before systemic therapy, who underwent a radionuclide study using ^99mTc-DARPinG3 at a dose of 3,000 μg. Five patients were characterized by HER2 / neu overexpression in primary breast cancer, whereas 5 patients were HER2-negative. For all patients, morphological and immunohistochemical studies and fluorescence in situ hybridization (FISH) of the primary tumor nodule were carried out. Single-photon emission computed tomography (SPECT) of the chest was performed for all patients 4 hours after the injection of ^99mTc-DARPinG3.

Results. The total activity of ^99mTc-DARPinG3 was 522.4 ± 341.8 MBq. The comparative analysis showed that higher uptake of the labeled protein in HER2-positive breast cancer was significant (p = 0.0159, Mann – Whitney U test). The analysis of the ratios showed significant differences in the tumor-to-background ratios in patients with HER2-positive breast cancer (p < 0.0159, Mann – Whitney U test). Based on the logistic regression analysis, a mathematical model was developed to predict the status of HER2 / neu in primary breast cancer patients (specificity and sensitivity 100%; p = 0.0004) using ^99mTc-DARPinG3 at a dose of 3,000 mcg 4 hours after the injection of the radiopharmaceutical.

Conclusion. The results of the study allow to consider the tumor-to-background ratio 4 hours after the injection of ^99mTc-DARPinG3 as an additional prognostic parameter for determining the HER2 / neu status in primary breast cancer.

Aim. To assess the effect of iron-rich humic substances on hematological parameters in acute post-hemorrhagic and iron deficiency anemia.

Materials and methods. Materials for the study were samples of iron-rich active pharmaceutical ingredients based on humic substances (Fe(III) hydroxide complexes with humic substances and polymaltose): HA-Fe³⁺, HA-PMFe³⁺, FA-Fe³⁺, and FA-PM-Fe³⁺. The anti-anemic activity of the substances was studied on 53 female Wistar rats of the conventional rat line in the model of acute posthemorrhagic and iron deficiency anemia. Anti-anemic activity was assessed by the hemoglobin level, erythrocyte count, hematocrit, and serum iron level.

Results. The studied substances HA-Fe³⁺ and FA-Fe³⁺ are the most effective in correcting the consequences of both experimental acute posthemorrhagic anemia and iron deficiency anemia. Their effect is comparable to that of the positive control drug Ferrum Lek.

Conclusion. Fe(III) hydroxide complexes stabilized by humic and fulvic acids exhibit anti-anemic activity.

Aim. To compare predisposition to thrombosis caused by administration of known systemic hemostatic agents and fibrin monomer under the conditions of normal coagulation versus drug-induced hypocoagulation in the experiment.

Materials and methods. The prothrombotic effect of intravenous (IV) administration of various systemic hemostatic agents was compared in a series of in vivo experiments. These agents included fibrin monomer (FM) (0.25 mg / kg), prothrombin complex concentrate (PCC) (40 IU / kg) or recombinant factor VIIa (rFVIIa) (270 mcg / kg). The studies were conducted under the conditions of hypocoagulation induced by the administration of warfarin (per os at a dose of 0.4–0.5 mg / kg / day for 14 days) or dabigatran etexilate (per os at a single dose of 15–20 mg / kg). Hemostatic system parameters were evaluated using thromboelastometry and calibrated automated thrombography.

Results. It was found that PCC reversed anticoagulant effects and led to an overcompensated increase in the density characteristics of the blood clot along with an excessive increase in thrombin generation in the groups of animals with warfarin-induced coagulopathy. The use of PCC and rFVIIa in the groups of animals with dabigatran-induced hypocoagulation also resulted in an increase in blood thrombogenic properties. In the administration of PCC, it was manifested though an increased D-dimer level and in administration of rFVIIa – through an increase in the clot density characteristics. At the same time, replacement of these hemostatic agents with FM did not affect the hemostatic system parameters.

Conclusion. FM at a dose of 0.25 mg / kg, as opposed to PCC and rFVIIa, is safer in terms of the risk of thrombosis.

The aim of the study was to identify the features of the cellular composition and cytokine profile of bronchoalveolar lavage fluid in rats in a model of diet-induced metabolic syndrome.

Materials and methods. In an experiment on animals (rats), a model of metabolic syndrome (MS) induced by a high-fat and high-carbohydrate diet was reproduced. To assess the viability of the reproduced model, biochemical and morphometric methods were used, such as measurement of body weight, specific gravity of liver and visceral fat, and blood pressure, determination of glucose concentration in the blood (including a glucose tolerance test), as well as determination of blood lipid parameters. To assess the intensity of the inflammatory response in the blood, the concentration of total protein, the total number of leukocytes, and the levels of immunocytokines (interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)α, monocyte chemoattractant protein (MCP)-1) were determined. Open bronchoalveolar lavage was performed on the isolated heart – lung complex. The concentration of protein, immunocytokines (IL-6, IL-10, TNFα, MCP-1), the total number of leukocytes, and the ratio of their morphological types were determined in the bronchoalveolar lavage fluid (BALF).

Results. In animals with MS, an increase in the total number of leukocytes in the blood due to granulocytes and a rise in the concentration of protein, TNFα, and IL-10 were revealed compared with the parameters in the controls. BALF analysis revealed an increase in the concentration of protein, the total number of leukocytes, and the absolute number of alveolar macrophages, neutrophil granulocytes, and lymphocytes. The levels of IL-6 and MCP-1 were more than 1.5 times higher.

Conclusion. Changes in the qualitative and quantitative parameters of BALF are inflammatory in nature and are formed during a systemic inflammatory response accompanying metabolic disorders in modeling MS in rats in the experiment.

The aim of the study was to create a patient-derived xenograft (PDX) model of human colorectal cancer and to determine its histologic and molecular characteristics, such as the status of KRAS, NRAS, and BRAF genes and the presence of microsatellite instability.

Materials and methods. First generation xenograft models in vivo were created using tumors from patients with colorectal cancer (n = 4) and immunodeficient Balb/c Nude mice (n = 20); second, third, and fourth generation models were created in the same mouse line (n = 3 for each generation). A caliper was used to measure subcutaneous xenografts; their size was calculated by the ellipsoid formula. Cryopreservation involved immersing the samples in a freezing medium (80% RPMI 1640, 10% fetal bovine serum, 10% dimethyl sulfoxide (DMSO)) and storing them at –80 °C. The histologic analysis was performed according to the standard technique (preparation of paraffin blocks and staining of microsections with hematoxylin and eosin). Mutations in the KRAS, NRAS, and BRAF genes were determined by direct Sanger sequencing; microsatellite instability was determined by the fragment analysis at five loci: Bat-25, Bat-26, NR21, NR24, and NR27.

Results. Stable, transplantable xenografts of colorectal cancer were obtained from two out of four patients. The average waiting time from the implantation to the growth of the first generation xenograft was 28 days. The latency phase after cryopreservation was comparable to that at the creation of the first generation PDX model. The model reproduced the histotype, grade and mutational status of the KRAS, NRAS, and BRAF genes, as well as microsatellite instability of the donor tumor.

Conclusion. The developed model of human colorectal cancer was characterized in terms of growth dynamics, cryopreservation tolerance, and histologic and molecular genetic parameters.

Aim. To evaluate the role of polymorphisms in adrenoceptor beta 1 (ADRB1) (Arg389Gly, rs1801253) and angiotensin-converting enzyme (ACE) (I/D, rs4343) genes in assessing the effectiveness of β-blocker (carvedilol) and ACE inhibitor (enalapril) therapy in women with anthracycline-induced cardiotoxicity (AIC) without prior cardiovascular diseases (CVD) during 12-month follow-up.

Materials and methods. A total of 82 women (average age 45.0 (42.0; 50.0) years) with AIC and without prior CVD were included in the study. Echocardiography was performed and serum levels of NT-proBNP were determined at baseline and at 12 months after the enrollment. Gene polymorphisms in ADRB1 and ACE genes were evaluated by polymerase chain reaction at baseline.

Results. Carriers of the G/G genotype in the ADRB1 gene and G/G genotype in the ACE (I/D, rs4343) gene showed a significant increase in left ventricular ejection fraction (LVEF), a decrease in the size of the left ventricle (LV) and left atrium (LA), and a fall in the NT-proBNP level. Carriers of other genotypes had further progression of AIC which was manifested through a decrease in LVEF and an increase in the size of LV and LA.

Conclusion. Evaluation of gene polymorphisms in ADRB1 (Arg389Gly, rs1801253) and ACE (I/D, rs4343) genes may be recommended before treatment initiation for AIC in women without prior CVD to determine who will benefit from carvedilol and enalapril therapy, as well as to identify a priority group of patients for personalized intensification and optimization of treatment for decreasing development of adverse cardiovascular events.

Aim. To assess external respiration (ER) and its relationship with the activity of enzymes involved in purine metabolism in patients with acute and chronic forms of pulmonary tuberculosis (TB).

Materials and methods. In patients with acute and chronic TB, we assessed the activity of adenosine deaminase (ADA)-1, 2 in the blood serum (eADA), mononuclear cells, and neutrophils, the concentration of ecto-5’-nucleotidase (eNT5E) in the blood serum, the level of CD26 (dipeptidyl peptidase-4, DPPIV) in the blood serum and mononuclear cells, production of reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) in mononuclear cells and neutrophils, as well as parameters of ER.

Results. Patients with TB were found to have an increase in the concentration of eNT5E and eADA-2 activity in the blood serum, stimulated production of ROI in neutrophils, a decrease in the concentration of DPPIV (CD26) in mononuclear cells, and a fall in the production of RNI in mononuclear cells and neutrophils. In patients with chronic TB, a decrease in the activity of ADA-1 in mononuclear cells and a fall in the concentration of DPPIV (CD26) in the blood serum were noted. In patients with acute TB, a decrease in the activity of eADA-1 in the blood serum and ADA-1 in neutrophils, reduced production of ROI in mononuclear cells, and an increase in spontaneous production of ROI in neutrophils were revealed. Correlations were found between the parameters of ER and the concentration of eNT5E in the blood serum, spontaneous production of ROI in mononuclear cells and production of RNI in neutrophils in chronic TB, as well as between eADA-2 in the blood serum, ADA-1 in neutrophils, DPPIV (CD26) activity in mononuclear cells, and ROI and RNI production in mononuclear cells and neutrophils.

Conclusion. The data obtained make it possible to associate regulation of external respiration with parameters of purine metabolism, in particular with the concentration and activity of enzymes responsible for generation and metabolism of adenosine, that determine its level outside cells and inside mononuclear cells and neutrophils, with expression of cofactor molecules, as well as with the duration of activation of cells in innate immunity, neutrophils, and monocytes/ macrophages, determined largely by the potential of adenosine regulation.

The aim of the study was to investigate local biocompatibility and systemic effects of nonwoven polylactide (PLA) matrices on blood and liver parameters after their subcutaneous implantation in Wistar rats.

Materials and methods. Bioabsorbable fibrous PLA matrices were produced by electrospinning and had dimensions (10 × 10 mm², thickness of no more than 0.5 mm; fiber diameter in the matrix ~1 μm) appropriate for subcutaneous implantation in white laboratory rats. Polymer implants were sterilized in ethylene oxide vapor. Thirty days after the implantation of PLA matrices, local biocompatibility according to GOST ISO 10993-6-2011, cellular parameters (total leukocyte count, hemogram, erythrocyte count, hemoglobin concentration), and biochemical blood parameters (lactate concentration, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels) were studied, and a standard histologic evaluation of the liver was performed.

Results. PLA matrix samples were mild local irritants on a scale of 1–1.9 points according to GOST ISO 10993-6-2011 criteria 30 days after the subcutaneous implantation. The median density of distribution of multinucleated giant cells (MNGCs) in the connective tissue around and in PLA matrices was 1,500 (1,350; 1,550) per 1 mm² of a slice. Pronounced leukocytic reaction due to lymphocytosis was noted (an increase by 1.7 times compared with a sham-operated (SO) control group, р < 0.02). The absence of a significant neutrophil count in the blood revealed sterile inflammation proceeding in the subcutaneous tissue around the PLA materials. Normalization of hepatic cytolysis markers (ALT and AST activity) in the blood without pronounced changes in the structure of the liver and the number of binuclear hepatocytes was noted. These markers were increased in SO controls (ALT up to 123% and AST up to 142%, p < 0.001 compared with values in the intact group).

Conclusion. Nonwoven PLA matrices are biocompatible with subcutaneous tissue, undergo bioresorption by MNGCs, and have a distant protective effect on the functional state of the liver in laboratory animals. Hypotheses on the detected systemic effect during subcutaneous implantation of PLA matrices were discussed; however, specific mechanisms require further study.

Aim. To identify the effect of preterm birth on proliferation and hyperplasia of cardiomyocytes in the early postnatal period of ontogenesis in rats.

Materials and methods. Preterm birth (on day 21 and 21.5 of gestation) in Wistar rats was induced by subcutaneous administration of mifepristone. Immunohistochemistry was used to identify and calculate the number of Ki67-positive and Mklp2-positive cardiomyocytes in the left ventricle of preterm and full-term rats on days 1, 2, 3, 4, 5, and 6 of postnatal ontogenesis. Statistical analysis of morphometric parameters was performed using the Shapiro – Wilk test and Mann – Whitney test with the Bonferroni correction.

Results. We revealed an increase in the number of Ki67-positive cardiomyocytes in the left ventricle of the rats: on day 1 of postnatal ontogenesis (in the rats born on day 21 of gestation) and on days 3–5 of postnatal ontogenesis (in the rats born on day 21.5 of gestation). Preterm birth in rats did not result in a change in the number of Mklp2-positive cardiomyocytes in the left ventricular wall.

Conclusion. A change in the pattern of Ki67 expression by cardiomyocytes in the rats born 12 or 24 hours before full term was demonstrated in the early postnatal period of ontogenesis. An isolated increase in Ki67 expression without a change in Mklp2 expression by cardiomyocytes in the left ventricular wall of preterm rats indicates acceleration of cardiomyocyte hypertrophy. Shorter duration of prenatal development is associated with more pronounced morphological and functional rearrangements in the rat myocardium.

Background. Cytogenetic damage (СD) in lymphocytes induced by low doses (up to 0.1 Sv) of ionizing radiation (IR) is the main cytogenetic sign of individual radiosensitivity of the human body. In addition to DNA repair and cell death, which affect the formation of СD and its elimination, IR effects on the cell can be manifested through changes in proliferation of cells with unrepaired DNA damage. The system of cyclins and cyclin-dependent kinases (CDK), which provide coordination of mitotic events during passage of a cell through the cell cycle, plays a crucial role in regulation of cell proliferation.

Aim. To evaluate the relationship of single-nucleotide polymorphisms (SNPs) of cell cycle genes with an increased frequency of СD in workers of a nuclear power plant affected by chronic occupational radiation exposure in the dose range of 100–500 mSv.

Materials and methods. The object of the study was blood of 55 conditionally healthy workers of Siberian Chemical Plant (SCP) who were affected by chronic occupational radiation exposure (gamma radiation) in the dose range of 100–500 mSv. A standard cytogenetic analysis of blood lymphocytes was performed for all examined individuals. Genomic DNA was isolated from the blood of the workers using the QIAamp DNA Blood Mini Kit (QIAGEN, Germany). DNA was genotyped using 257 SNPs of cyclin genes and neighboring intergenic regions using DNA microarrays from the high-density CytoScan HD Array (Affymetrix, USA).

Results. Taking into account the Bonferroni correction, only statistically significant associations of SNPs with the frequency of dicentric chromosomes were found; all other types of chromosomal aberrations did not show statistical significance. The rs803054 CCNI2 was associated with an increased frequency of dicentric chromosomes arising under the influence of chronic occupational radiation exposure.

Conclusion. The discovered SNP (rs803054), whose recessive genotype is associated with an increased frequency of dicentric chromosomes in workers of SCP exposed to radiation at doses of 100–500 mSv over a long time, can be considered as a potential marker of individual radiosensitivity. To confirm the identified associations, further validation studies are needed on an expanded sample of people affected by chronic occupational radiation exposure.

Aim. To evaluate the relationship between coronary microvascular dysfunction (CMD), biomarkers of cardiac fibrosis and cardiac remodeling (soluble ST2 (sST2), fibroblast growth factor-23 (FGF-23), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), and NT-proBNP), parameters of diastolic dysfunction (DD), and the presence of heart failure with preserved ejection fraction (HFpEF) in symptomatic patients.

Materials and methods. Study participants were 59 patients with non-obstructive coronary artery disease (CAD) and preserved left ventricular ejection fraction (LVEF) of 62 (56; 67) %. Non-obstructive CAD was verified by coronary computed tomography angiography. Stress-and rest-myocardial blood flow (MBF) and coronary flow reserve (CFR) parameters were evaluated by CZT SPECT. Serum levels of cardiac biomarkers were measured by the enzyme immunoassay. Two-dimensional transthoracic echocardiography was used to assess DD parameters.

Results. Decreased CFR was defined as CFR ≤ 2. Therefore, CMD was defined as the presence of decreased CFR in the absence of flow-limiting CAD. Distribution of patients was performed by CFR values: group 1 included patients with preserved CFR (>2, n = 35), and group 2 encompassed patients with decreased CFR (≤2, n = 24). In 87.5% of cases, patients with CMD were diagnosed with HFpEF, whereas in patients with preserved CFR, heart failure was diagnosed only in 51.4% of cases (p < 0.0001). CFR values were correlated with the left atrial volume (r = –0.527; p = 0.001), E / A ratio (r = –0.321, p = 0.012), and E / e’ (r = –0.307; p = 0.021). Following the ROC analysis, the levels of sST2 ≥ 31.304 ng / ml (AUС = 0.730; р = 0.004) and NT-proBNP ≥ 0.034 pg / ml (AUС = 0.815; р = 0.034) were identified as cut-off values for the presence of CMD in patients with non-obstructive CAD.

Conclusion. The obtained data suggest that CMD may play an essential role in HFpEF. The values of CFR were correlated with DD parameters, and decreased CFR was associated with overexpression of biomarkers of cardiac fibrosis and cardiac remodeling. Serum levels of sST2 and NT-proBNP were identified as cut-off values for the presence of CMD in patients with non-obstructive CAD.

Aim. To study the effect of a high-fat, high-carbohydrate diet on retinal morphology of young and old rats in the experiment.

Materials and methods. The study was carried out on male Wistar rats aged 60 and 450 days at the beginning of the experiment. The animals were divided into 4 groups: group 1 (n = 14) included intact rats aged 150 days at the end of the experiment; group 2 (n = 14) encompassed rats (60 days old) fed with a high-fat, high-carbohydrate diet (HFHCD) for 90 days; group 3 (n = 14) included intact rats (450 days old) receiving a standard diet for 90 days; group 4 (n = 14) included rats (450 days old) fed with HFHCD for 90 days. Immunoassay and histology were used in the work.

Results. HFHCD resulted in an increase in glucose concentration in animals of both age groups. In old animals, it caused a pronounced increase in the content of insulin, TGFβ, and fibronectin in the blood serum, neovascularization of outer retinal layers, as well as karyopyknosis and death of neurosensory cells, leading to destruction of photoreceptors and drastic thinning of the outer nuclear and outer plexiform layers. In young rats fed with HFHCD, no pronounced histologic disorders of the retina were noted.

Conclusion. HFHCD enhances age-related retinal changes in old (450-day-old) rats.

Aim. To analyze risk factors in the group of patients with Parkinson’s disease (PD) and compare them with the literature data.

Materials and methods. The study included 439 patients with PD and 354 controls, comparable by gender and age. For each individual, a registration card was filled in containing demographic, epidemiological, clinical, and neuropsychological data. The severity of the disease was studied according to the MDS-UPDRS scale; the stage of PD was determined according to the Hoehn and Yahr scale. Cognitive functions were assessed by the MoCA test and MMSE. The length of the (CAG)n repeat region in the HTT gene was determined using fragment analysis on the ABI 3730 DNA analyzer. The obtained results were analyzed using GeneMapper Software v4.1 (Applied Biosystems, USA).

Results. When comparing patients with PD and the control group, the odds ratio (OR) for PD in individuals with traumatic brain injury was 3.13 (95% confidence interval (CI): 2,27–4.34; p = 4.94 × 10^–13), which showed the significance of this risk factor for PD. Consumption of coffee in the anamnesis distinguished the group of PD patients from the control group (OR = 0.41 (95% CI: 0.30–0.56); p < 0.0001), confirming its neuroprotective effect. Analysis of the variability in the length of the (CAG)n repeat regions in the HTT gene showed that patients whose genotype contained an allele with 17 repeats in combination with any allele other than an allele containing 18 repeats had a protective effect (OR = 0.50 (95% CI: 0.27–0.92); p = 0.025). All genotypes containing an allele with 18 repeats were predisposed to PD (OR = 2.57 (95% CI: 1.66–4.28); p = 0.007). The predisposing effect of the allele to PD, unrelated to the expansion of CAG repeats in the HTT gene, was revealed for the first time.

Conclusion. Traumatic brain injury and the allele with 18 CAG repeats in the HTT gene are risk factors for PD. Coffee consumption can be attributed to protective factors in relation to PD.

The aim of the study was to evaluate the effect of plasma acid on the uterine tissue of laboratory animals in vitro.

Materials and methods. Treatment of dimethyl sulfoxide – water solution and water for injections with a spark discharge in air resulted in a decrease in pH, which contributed to generation of plasma acid in the solutions. We incubated uterine tissues in vitro in plasma acid at room temperature for 30 minutes. The treated tissues were examined histologically and immunohistochemically.

Results. We showed that plasma acid had pronounced biological activity. Immunohistochemistry was used to show that, depending on the type of a solution, plasma acid altered generation of nitrosative damage products (3-NT) and oxidative DNA damage (8-OHdG) and modulated the number of cells with high proliferative potential (including CD133⁺ cells) and production of vascular endothelial growth factor (VEGF). These effects contributed to the general cytotoxicity of plasma acid solutions.

Conclusion. During 30-minute exposure in vitro, plasma acid prepared from the dimethyl sulfoxide (DMSO) – water mixture exhibits various biological effects in uterine tissue samples obtained from experimental animals. Plasma-treated water exerts cytotoxic effects associated with oxidative DNA damage and promotes induction of pro-angiogenic activity in the uterine tissue. Plasma-treated DMSO does not have a cytotoxic effect. It inhibits cell proliferation, reducing the population of CD133⁺ cells and VEGF production in the tissue.

Aim. To study the associations of blood proteins with the presence of unstable atherosclerotic plaques in the arteries in patients with coronary artery disease using the quantitative proteomic analysis.

Materials and methods. The study included patients with coronary artery disease (n = 40); the average age of patients was 58 ± 7 years. Material for the study was blood serum. Protein concentrations in serum samples were determined using the PeptiQuant Plus Proteomics Kit (Cambridge Isotope Laboratories, USA). Protein fractions were identified using the liquid chromatograph and tandem mass spectrometer Q-TRAP 6500.

Results. Mass spectrometry revealed an increased concentration of proteins, such as fibrinogen, fibulin-1, and complement factor H, in the serum samples of patients with unstable atherosclerotic plaques. It took place with a simultaneous decrease in the levels of α 2-antiplasmin, heparin cofactor II, coagulation factor XII, plasminogen, prothrombin, vitronectin, complement proteins (C1, C3, C7, C9), and complement factor B. The differences were considered significant at p < 0.05. It was revealed that the presence of unstable atherosclerotic plaques was associated with the level of fibulin-1 (Exp(B) = 1.008; р = 0.05), plasminogen (Exp(В) = 0.995; р = 0.027), and coagulation factor X (Exp(В) = 0.973; р = 0.037).

Conclusion. An increased concentration of fibulin-1 can be considered as a potential biomarker of unstable atherosclerotic plaque development in coronary artery disease. The possibility of using the studied proteins as biomarkers of unstable atherosclerotic plaques requires further studies on their potential role in the development of this disease.

Aim. To assess periprocedural dynamics of left ventricular ejection fraction (LVEF) in patients with first acute myocardial infarction (AMI) and percutaneous coronary intervention (PCI) without heart failure (HF) in the medical history, as well as its prognostic value in the development of cardiovascular complications in the postinfarction period.

Materials and methods. A prospective, single-center observational study included 131 patients with first AMI without HF in the past medical history and successful PCI. LVEF was assessed before PCI at admission and before discharge. In patients with reduced baseline LVEF of less than 50%, the criteria for its periprocedural improvement were chosen: 1) LVEF ≥ 50%; 2) ΔLVEF of more than 5%, but EF < 50%. The endpoints were hospitalization for the development of HF and death from cardiovascular disease in combination with the development of HF. The average follow-up period was 2.5 years.

Results. At admission, LVEF was < 50% in 74 (56.5%) patients. At discharge, according to the criteria for LVEF improvement, the proportion of patients in this group was 40.5 and 14.9%, respectively. In 44.6% of cases, no increase in LVEF was noted. The predictors of the absence of periprocedural dynamics in LFEF included impaired regional contractility index > 1.94, left ventricular end-systolic volume > 57 ml, left ventricular end-diastolic diameter > 5.1 cm, pulmonary artery systolic pressure >27 mm Hg, NT-proBNP > 530 pg / ml, and E / A ratio > 1.06. During the follow-up period, 28 (21.4%) patients were hospitalized for the development of HF, 33 (25.2%) patients had a combined endpoint. The absence of periprocedural improvement in left ventricular contractility was independently associated with higher odds of hospitalization for HF (relative risk (RR) 3.5; 95% confidence interval (CI) 1.63–7.55; p = 0.001) and the combined endpoint (RR 2.6; 95% CI 1.28–5.48; p = 0.009) in the postinfarction period.

Conclusion. In patients with first AMI and left ventricular systolic dysfunction, periprocedural evaluation of LVEF is reasonable to stratify the risk of adverse cardiovascular outcomes.

The aim of the study was to evaluate the expression of scavenger receptors (CD163, CD204, CD206) on macrophages in patients with pulmonary tuberculosis, depending on the clinical form of the disease and sensitivity of the pathogen to anti-tuberculosis drugs.

Materials and methods. 64 patients with pulmonary tuberculosis (TB) were examined: 26 patients with disseminated pulmonary tuberculosis (DTB) and 38 patients with infiltrative pulmonary tuberculosis (ITB). Of these, 42 patients secreted Mycobacterium tuberculosis (MBT) sensitive to basic antituberculosis drugs (ATBD), and 22 patients secreted MBT resistant to first-line anti-TB drugs. Material for the study was venous blood. To isolate monocytes from the whole blood in order to transform them into macrophages, Ficoll density gradient centrifugation with a density of 1.077 g / cm³ was used followed by immunomagnetic separation of CD14+ cells. Monocytes were cultured in the X-VIVO 10 medium with gentamicin and phenol red with the addition of macrophage colony-stimulating factor (M-CSF) (5 ng / ml) at a concentration of 1×10⁶ cells / ml with stimulators: interleukin (IL)-4 (10 ng / ml) and interferon (IFN) γ (100 ng / ml). Immunophenotyping of macrophages was performed using monoclonal antibodies to CD163, CD204, and CD206 on the Beckman Coulter CytoFLEX LX Flow Cytometer. The analysis of the obtained data was carried out using the CytExpert 2.0 software. The results were analyzed using statistical methods.

Results. Switching the phenotype of macrophages from the M1-like proinflammatory phenotype to M2-like antiinflammatory one contributes to the chronic course of pulmonary TB, dissemination, and persistence of infection. In the present study, we analyzed the features of the expression of CD163, CD204, and CD206 scavenger receptors on macrophages in patients with pulmonary TB. An increase in the number of macrophages carrying markers of the M2 subpopulation (CD163, CD204, and CD206) on their surface was noted, regardless of the clinical form of pulmonary TB and drug resistance of M. tuberculosis.

Conclusion. Studying the mechanisms underlying M1 or M2 activation of macrophages is necessary for a deeper understanding of the immunopathogenesis of TB and the role of innate immunity cells in protecting the body from mycobacteria. The analysis of the expression of scavenger receptors CD163, CD204, and CD206 on macrophages allowed to conclude that, in pulmonary TB, especially in patients with drug resistant M. tuberculosis and infiltrative TB, regulatory mechanisms that suppress the activation of innate immunity are implemented together with polarization of macrophage differentiation towards the M2 phenotype. It may be the cause of immune deficiency induced by the pathogen.

Over the past decades, lung ultrasound in the diagnosis of lung diseases has become widespread. Ultrasound examination has a number of advantages (no radiation exposure, real-time imaging, clear visualization of the subpleural lung regions and costophrenic angles), which make it possible to use ultrasound to monitor the dynamics of pneumonia in children and pregnant women. Currently, in the context of the COVID-19 pandemic, lung ultrasound is widely used due to its high diagnostic efficiency, which is comparable with classical radiography and X-ray computed tomography (CT) by a number of parameters.

The article describes the method of lung ultrasound and the radiographic pattern of COVID-19-associated pneumonia. It also provides a review of the literature, according to which the severity of pneumonia was determined, depending on the radiographic pattern, and the need for a lung ultrasound was identified.

The article indicates that information on assessment of the radiographic pattern of the lungs at runtime in different variants of the course of coronavirus infection, as well as many methodological issues, including the frequency of second-look lung ultrasound, has not been sufficiently studied.

The article presents a systematic review of publications devoted to the study of genetic markers of severe pneumonia.

The aim of the study was to compile a list of genetic markers that contribute to a severe course of pneumonia on the basis of the published data.

In the current study, we searched for and analyzed articles published between January 2000 and April 2021. Following the search for and subsequent selection of articles, a list of 10 publications was compiled, which demonstrated a clear association of certain gene variants with severe and complicated pneumonia. Finally, we made a list of genetic markers of severe pneumonia consisting of 16 polymorphisms in 12 genes (CD86, IL6, IL10, PAI1, TNFα, HMGB1, ATG16L1, AGTR1, GCLC, CAT, IFNγ, FCGR2A).

These genetic markers of severe and complicated pneumonia are responsible for various innate immune responses. The odds ratio for complicated pneumonia with a risk allele in the polymorphisms in the mentioned genes ranges from 1.39 to 4.28. To understand molecular and genetic mechanisms of severe pneumonia, further investigation of the effect of these genetic factors on the outcomes of pneumonia in different groups of patients with a simultaneous assessment of the cumulative effect of genetic variants and genetic interactions is required.

According to the latest concepts, for micrometastasis to develop into macrometastasis, differentiated cancer cells must revert to a dedifferentiated state. Activation of stemness genes plays a key role in this transition. Suppression of stemness gene expression using microRNAs can become the basis for the development of effective anti-metastatic drugs. This article provides an overview of the existing methods for assessing the effect of microRNAs on stemness genes and cancer cell dedifferentiation.

The pathogenetic mechanisms of progression of chronic periodontitis and psoriatic arthritis have common components in immune and inflammatory responses.

The pathogenesis of chronic periodontitis involves interaction of microbial and immunological components. As a chronic immune-mediated inflammatory disease and a consequence of an infectious trigger that originally affects gingival soft tissue, periodontitis is typically characterized by periodontal destruction and damage to adjacent connective tissues. Neutrophils contribute to the development of periodontitis and participate in its progression by recruiting T helper 17 cells and stimulating synthesis of the receptor activator of the nuclear factor kappa-β ligand (RANKL), contributing to bone resorption.

Macrophages as producers of proinflammatory cytokines (interleukin (IL)-1β, IL-6, IL-22, IL-23, tumor necrosis factor (TNF)), free radicals, and matrix metalloproteinases contribute to the chronic course of the disease. Tissue destruction results in generation of reactive oxygen species by neutrophils, which, against the background of a decrease in the antioxidant potential, leads to development of oxidative stress. These processes together lead to tooth mobility, formation of periodontal pockets, and bone resorption.

The key factors in the formation of psoriatic arthritis against the background of periodontitis are overproduction of proinflammatory cytokines in target tissues (skin, joints, gingival microflora) and development of an excessive systemic immune response to the microbiota inhabiting the epithelial and periodontal tissues. A statistically confirmed correlation of the progression of periodontal destruction with the presence of psoriatic arthritis proves the significance of the effects of inflammation as a background for the progression of a comorbidity. Increased IL-17 synthesis plays a crucial role in the development of immune responses of pathological bone remodeling and bone resorption in periodontitis and psoriatic arthritis.

Aim. Using bioinformatic tools, to perform a pathway enrichment analysis in Alzheimer’s disease and coronary heart disease (CHD).

Materials and methods. Genes contributing to susceptibility to CHD and Alzheimer’s disease were obtained from the public database DisGeNET (Database of Gene – Disease Associations). A pathway enrichment analysis was performed in the ClueGO Cytoscape plug-in (version 3.6.0) using hypergeometric distribution and the KEGG and Reactome databases.

Results. The identified genes contributing to susceptibility to Alzheimer’s disease and CHD are included in 69 common signaling pathways, grouped into the following subgroups: cell death signaling pathways (1); signaling pathways regulating immune responses (2); signaling pathways responsible for fatty acid metabolism (3); signaling pathways involved in the functioning of the nervous system (4), cardiovascular system (5), and endocrine system (6).

Conclusion. Following the performed analysis, we identified possible associations between processes involving genetic factors and their products in CHD and Alzheimer’s disease. In particular, we assumed that susceptibility genes involved in the implementation of these pathways regulate apoptosis, production of inflammatory cytokines and chemokines, lipid metabolism, β-amyloid formation, and angiogenesis.

Cystic fibrosis is one of the urgent medical and social problems of health care systems in most countries due to fairly high prevalence, development of multi-organ lesions, and poor outcomes.

Due to modern advances in the diagnosis and treatment of cystic fibrosis, not only has the average life expectancy of patients increased, but their quality of life has also improved, and it has become possible to maintain pregnancy and childbearing. Since cystic fibrosis can adversely affect the course of pregnancy, childbirth, and health of both mother and child, proper management of women with cystic fibrosis during pregnancy and childbirth is of particular relevance. The presented clinical case is an example of competent supervision at all stages of monitoring of a patient with cystic fibrosis during pregnancy and childbirth.