21 years have passed since the signing of the order on the establishment of the Department of Molecular Genetic Technologies of the Scientific Research Center (order № 118 was signed by Academic N. A. Yaitsky on June 5, 2001) and 20 years have passed since the beginning of the Department's activities. The leading scientist in the field of molecular medicine, Professor Evgeny Iosifovich Schwartz, not only headed the Department, but also brought there his team — the team of the Laboratory of Human Molecular Genetics of the Petersburg Nuclear Physics Institute named by B. P. Konstantinov of National Research Centre «Kurchatov Institute». The team was the first in the country to use the polymerase chain reaction (PCR) method to diagnose human hereditary diseases, and at that time had experience both in mapping mutational damage in monogenic human diseases and in its research in the field of multifactorial pathology. The department creation marked the beginning of molecular genetic technologies at the University and became the basis for fundamental scientific researches and the development of modern methods of molecular genetics. The review describes the history of Department and its main achievements.

Introduction. Changes in the expression of the dopamine transporter (DAT) have been identified in patients with a number of neuropsychiatric disorders, but their significance for pathogenesis remains unclear. DAT knockout rats are a promising model of frontostriatal dysfunctions involved in adapting learning processes to current organism's needs, motivation, and experience.

The objective was to evaluate the effect of DAT disruption on the interaction of classical and instrumental conditioning processes (associative learning).

Methods and materials. Rats from a local colony were used: knockouts (n=31), heterozygotes (n=32), and wild type rats (n=24). DAT knockout (Slc6a3) was detected by PCR followed by restriction analysis. The rats were kept individually with limited access to food and unlimited access to water. In the operant chambers equipped with a MED-PC interface (MED Associates, USA), 3 experiments were performed: 1) classical conditioning; 2) autoshaping of operant responding; 3) reward learning based on secondary reinforcement. Statistical analysis was performed using SigmaPlot 12.5 (Systat Software Inc., USA) and SPSS Statistics 21 (IBM, USA).

Results. We revealed that DAT disruption in rats did not affect the formation of conditioned reflex connections in classical conditioning (1) but was accompanied by impairments in the autoshaping of the operant response (2) and learning based on secondary reinforcement (3).

Conclusion. The observed impairments of associative learning might be associated with a decreased incentive value of stimuli in hyperdopaminergic state.

Introduction. In recent years, much attention has been paid to the study of extracellular microparticles (microvesicles and exosomes) and their role in the pathogenesis of human diseases.

The objective of this study was to determine the number and size of plasma extracellular microparticles (PEMP) in patients with severe and extremely severe COVID-19 and correlate these data with the markers of hemostasis activation, inflammation, and tissue damage.

Methods and Materials. The study included 29 patients with severe and extremely severe COVID-19. Concentration and size of PEMP were determined by nanoparticle trajectory analysis (NTA). All patients underwent the complete blood count and the thromboelastometry (TEM). Hemostatic, biochemical, and immunological parameters were assessed including fibrinogen, prothrombin time, activated partial thromboplastin time, D-dimer, C-reactive protein, lactate dehydrogenase, procalcitonin, von Willebrand factor antigen, interleukin 6, and interleukin 18.

Results. There were 14 patients (48.3 %) discharged from the ICU with improvement (group 1— survived patients), and 15 patients (51.7 %) with lethal outcomes (group 2 — lethal outcome); the PEMP concentration did not differ between these groups. In group 2, there were heterogeneity of PEMP population, and a tendency to the larger PEMP size (p=0.074). In all patients, the PEMP concentration correlated negatively with both prothrombin time and the number of large platelets; the size of PEMP correlated negatively with the level of von Willebrand factor antigen, and positively with the fibrinogen. In group 1, the PEMP concentration had a direct correlation with both the level of interleukin 18 and maximum clot lysis in TEM; the PEMP size had a direct correlation with the maximum clot lysis in TEM and an inverse correlation with both the level of procalcitonin and maximum clot density in TEM.

Conclusion. Our study confirms the importance of the process of extracellular microparticles formation in the COVID-19 pathogenesis. Our findings are consistent with the hypothesis that the parameters of PEMP population can be predictive biomarkers of the COVID-19 severity.

The objective of the study was to validate our previous results obtained during the transcriptome analysis of the primary culture of peripheral blood macrophages in patients with Parkinson's disease associated with mutations in the GBA gene (GBA-PD) in that reduced expression of the neurogenesis genes EGR1 (early growth response protein 1), NR4A2 (nuclear receptor 4A2), JUNB (transcription factor jun-B) in patients with GBA-PD.

Methods and materials. The study included 14 patients with GBA-PD, 15 GBA-carriers, 30 patients with Parkinson's disease (PD) and 44 persons of the control group. The assessment of relative mRNA level of neurogenesis genes EGR1, NR4A2, JUNB in peripheral blood mononuclear cells were carried out by real-time quantitative polymerase chain reaction (PCR) using TaqMan fluorescent probes or EvaGreen fluorescent DNA dye.

Results. Relative mRNA level of the JUNB gene in peripheral blood mononuclears was decreased in the group of patients with GBA-PD compared to controls (p=0.034). We found out that the relative mRNA level of the NR4A2 gene in peripheral blood mononuclears was increased in the group of patients with GBA-carriers compared to GBA-PD, patients with PD and controls (p=0.0029, p=0.00045, p=0.0024 respectively). There were no statistically significant differences in the mRNA level of the EGR1 gene between all the study groups (p>0.05).

Conclusion. GBA-PD is characterized by reduced expression of the JUNB gene compared to control and of the NR4A2 gene compared to GBA-carriers.

Introduction. Obesity is associated with a high risk of developing concomitant diseases such as: metabolic syndrome, type 2 diabetes mellitus (DM2), cardiovascular pathology. FABP4 (fatty acid binding protein) is the specific lipid chaperone and an important protein for the function of adipose tissue and is one of the adipocytokines secreted by adipose tissue.

The objective of the study was to investigate the FABP4 gene expression in subcutaneous and visceral adipose tissue (SAT and VAT) in patients with obesity and DM2.

Methods and materials. SAT and VAT samples were obtained during bariatric surgery (N=43, BMI>35): obese with DM2 (N=21), obese without DM2 (N=22). Samples for the control group without obesity (N=15, BMI<30) were obtained during planned operations on the abdominal cavity. FABP4 mRNA level was estimated by real-time PCR.

Results. It has been demonstrated that the mRNA level of the FABP4 gene in SAT and VAT is reduced in obesity, regardless of the manifestation of DM2 (p<0.01). A negative correlation was observed between the mRNA level of the FABP4 gene in adipose tissue and the BMI index (for SAT: r=—0.327, p = 0.016; for VAT: r=—0.304, p = 0.024).

Conclusion. The expression level of FABP4 gene in AT can act as a marker of AT dysfunction in obesity.

The objective of the study was to evaluate structural changes in the margin of gastroduodenal ulcers complicated by perforation, bleeding or penetration in terms of the features of ulcer healing.

Methods and materials. Histological and IHC studies were performed on 25 patients of the main group with perforated gastroduodenal ulcers and 23 patients of the control group with chronic recurrent ulcers complicated by bleeding and penetration. Histological sections were stained with hematoxylin and eosin, and Van Gieson's picrofuchsin. Immunohistochemical reactions were performed with antibodies to Ki-67, CD68, CD138, and CD34.

Results. On macroscopic evaluation, a clear even margin of the perforation was noted. Histological examination with the background of acute dyscirculatory changes clearly shows a zone of necrosis and a weakly expressed layer of granulation tissue, which in majority of the cases was practically absent. The margin of a perforated ulcer consists of a minimally presented, clearly delimited zone of tissue detritus and a practically unchanged muscle layer. Plasma cells dominated in the cell infiltrate, and the index of proliferative activity in the epithelium of the ulcer margins was about 45 %, distributed fairly evenly.

Conclusions. Perforated ulcers can be considered as a special group of ulcers with the most pronounced changes of infiltration by plasmatic cells and eosinophils, edema and acute dyscirculatory changes, uniform and fairly high proliferative activity of the epithelium. Changes in the margins of the perforated ulcer allow for complete regeneration without excessive scarring with precise suturing of the perforation.

Introduction. The high frequency of the use of assisted reproductive technologies and the inconsistency of information about the parameters of the cognitive development of IVF children determined the formulation of the research problem.

The purpose of the work is to assess the originality of the speech development of children and adolescents conceived using the IVF procedure. The age of the children at the time of the survey was from 5 to 15 years.

Methods and materials. A sample of 51 children (29 boys), mean age (7.9±2.8) years, 14 children had psychiatric diagnoses (ASD, mental retardation, etc.). Research methods: speech therapy assessment of speech development, neuropsychological diagnostics according to L.S. Tsvetkova, WICS, descriptive statistics, correlation analysis.

Results. 41% of children had mild variants of speech development delay under 3 years old, 59 % of children had normal speech development. With age, the frequency of detected deviations in speech development decreases, so that in older age group (from 11 to 15 years old), 85 % have normotypical development of speech. Correlation analysis showed the originality of the correlations of the parameters of speech development, neuropsychological assessment, and scores on Wechsler subtests.

Conclusions. An unambiguous conclusion about the violation of speech development in children conceived by IVF cannot be drawn, however, in the presence of mental pathology and taking into account the age of the mother and the number of ART procedures, attention should be paid to the provision of speech therapy and neuropsychological correction from an early age.