Aim. To study the characteristics of the fatty acid (FA) profi le of blood serum and erythrocyte membranes in patients with two forms of fatty liver disease (metabolic + alcoholic): steatosis and steatohepatitis with normal transaminase activity. Materials and methods. We examined 33 men (50.7 ± 9.6 years) with fatty liver disease (metabolic and alcoholic) with fi brosis F ≤ 1 (FibroTest). According to the ActiTest results, patients were divided into groups of steatosis – with minimal (A0–1) activity (n = 17) and steatohepatitis – with moderate/severe (A2–3) necroinfl ammatory activity (n = 16). The FA composition of blood serum and erythrocyte membranes was studied using gas chromatography/mass spectrometry Agilent 7000B (Agilent Technologies, Inc., USA). Methods of unpaired statistics using volcano plot and discriminant analysis based on orthogonal least squares (Orthogonal Partial Least Squares Discriminant Analysis, OPLS-DA), ROC analysis were applied. Results. Volcano plot analysis showed that in patients with fatty liver disease (metabolic and alcoholic) with normal transaminase activity, serum levels of stearic C18:0 (p = 0.016), arachidic C20:0 (p = 0.023), ratio saturated / polyunsaturated fatty acids (PUFA) (p = 0.001) were statistically signifi cantly higher in the steatohepatitis group compared with the steatosis group. The total content in the blood serum of all PUFA (p = 0.003), margaric C17:0 (p = 0.011), the sum of two omega-3 PUFA – eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3) (p = 0.04), the total content of all omega-3 PUFA (p = 0.042) were statistically signifi cantly lower in patients with steatohepatitis. OPLS-DA demonstrated fairly accurate separation of steatohepatitis and steatosis using individual FA and their ratios. When individual FA and their ratios were included in the analysis, a model was obtained with AUC = 0.827 (95% confi dence interval 0.499–1.0), sensitivity 82.2% and specifi city 80.7%. Conclusion. FA in blood serum and erythrocyte membranes appear to be promising biomarkers of steatohepatitis with normal levels of transaminases.

Aim . To analyze the results of the GastroPanel and GastroScreen-3 tests over a 15-year follow-up and determine the incidence of autoimmune gastritis (AIG) in clinical practice and in a random sample of Novosibirsk residents. Materials and methods . Biomarkers were analyzed in two groups: 1,742 people, average age of 50.0 ± 13.53 years (GastroPanel test, Biohit Oy, Finland), and 170 people, average age of 53.8 ± 12.89 years (GastroScreen-3 test, Vector-Best, Russia), from 2007 to 2022. The AIG incidence was calculated in current clinical practice and in a random sample of Novosibirsk residents aged 45–69 years. The PGI level of 160 µg / l was taken as the upper limit of normal, PGI of 31–50 µg / l indicated moderate atrophy, PGI < 30 µg / l and the PGI / PGII ratio ≤ 3 indicated severe gastric fundus atrophy. AIG was considered at PGI ≤ 10.1 μg / l, the PGI / PGI ratio ≤ 1.3, and gastrin-17 ≥ 42.4 pmol / l (GastroPanel) and at PGI ≤ 16.8 μg / l and the PGI / PGII ratio ≤ 1.5 (GastroScreen-3). The H. pylori IgG level > 42 EIU was considered to be positive. Antibodies to CagA protein were determined using the HelicoBest Antibody test (Vector-Best, Novosibirsk). Results . Serological signs of severe and moderate gastric fundus atrophy were detected in 10 and 9.4% (GastroPanel test) and in 13.3 and 7% (GastroScreen-3 test) of those examined, respectively. Signs of multifocal atrophy were found in 0.7% of cases. Antibodies to H. pylori were detected in 57.7%, CagA+ strain – in 56.1% of cases. Peptic ulcer disease (PGI ≥160 µg / l) was found in 15.3% (GastroPanel test) and 10% (GastroScreen-3 test) of the examined. According to the GastroPanel and GastroScreen-3 tests, the incidence of AIG was 1.6% in a random sample and 2.6 and 3.5% in current clinical practice, respectively. Conclusion . Twenty percent of the examined persons were at risk of developing gastric cancer and 10–15% had peptic ulcer disease, which requires further examination. The incidence of AIG in different study groups based on serological screening was 1.6–3.5%.

Aim: to examine the characteristics of mixed (metabolic + alcoholic) fatty liver disease (FLD) in relation to Helicobacter pylori infection Patients and Methods: the study included 30 men with signs of hepatic steatosis detected by ultrasound. The patients underwent a com- prehensive clinical and laboratory examination, which included a detailed history of their drug use, an interview about their gastrointestinal symptoms, their alcohol consumption and smoking habits, a complete blood count, and blood biochemistry. H. pylori infection was diagnosed by one-step immunochromatography to detect specific H. pylori antigens in feces. The criteria of the All-Russian Scientific Society of Cardi- ologists were applied to diagnose metabolic syndrome (MS). Indirect liver elastometry was performed using the FibroScan® 502 (Echosens, France) to assess the severity of liver fibrosis (in kPa) with rating of fibrosis stage according to the METAVIR score (F0–F4). Results: MS was identified in 96.7% of patients. Systematic alcohol consumption, defined as consumption of alcohol at least once a week, was common (87%) in these patients. The mean single dose was 103.1±62.86 g, and the mean weekly dose was 211.0±133.8 g (pure ethanol). H. pylori infection was detected in 56.7%. In 18 (60%) patients, liver elastography showed no fibrosis (F0). Stages F1-3 were revealed in 40% of patients, with F1 observed in 26.7%, F2 in 6.7%, and F3 in 6.6%. No significant differences in the parameters were identified based on H. pylori infection status Conclusion: all patients exhibited signs of FLD of mixed origin, associated with both metabolic disorders and systematic alcohol consumption. A greater proportion of patients (56.7%) were found to be infected with H. pylori. The analysis of MS manifestations, alcohol consumption style, smoking, liver tests, liver elasticity, and fibrosis stage revealed no significant differences depending on H. pylori infection. This may be due to the relatively small sample size in this pilot study. KEYWORDS: fatty liver disease, nonalcoholic fatty liver disease, metabolic syndrome, Helicobacter pylori, fibrosis, insulin resistance. FOR CITATION: Belkovets A.V., Kruchinina M.V., Galanova A.V., Shcherbakova L.V. Helicobacter pylori infection and fatty liver disease (results of a pilot study). Russian Medical Inquiry. 2024;8(5):253–259 (in Russ.). DOI: 10.32364/2587-6821-2024-8-5-2.

Aim. To study changes in the electrical and viscoelastic parameters of erythrocytes using the method of dielectrophoresis in patients with manifestations of the metabolic syndrome who underwent COVID-19, when exposed to the drug citicoline in an in vitro experiment to reduce the severity of microcirculatory disorders. Materials and methods. 31 men were examined with manifestations of metabolic syndrome (50.6±9.9 years), COVID-19 convalescences, within 8 to 12 months after the disease, the diagnosis was confirmed by PCR, ELISA. The electrical and viscoelastic parameters of erythrocytes were studied by dielectrophoresis twice: the initial levels of indicators were determined and after 30 minutes of exposure with after 30 minutes of exposure to a solution of the drug Ronocyte (oral solution with the active substance citicoline sodium – 104.50 mg., which is equivalent to 100.00 mg citicoline at a concentration of 0.01 µl per 0.3 µl of red blood cell suspension in 0.3M sucrose solution (pH 7.36). Results. Exposure of erythrocyte suspension of patients with Ronocyte solution led to change in the levels of electrical, viscoelastic parameters: an increase in the average cell diameter (p=0.0003), the proportion of discocytes (p=0.0004), the amplitude of cell deformation at high frequencies of the electric field (p=0.000002), cell capacity (p=0.000007), the velocity of erythrocytes to the electrodes (p=0.003), dipole moment (p=0.002), polarizability at 106 and 0.5×106 Hz (p=0.000019 and p=0.0015, respectively), relative polarizability (p0.05) and, conversely, to reduce summarized rigidity (p=0.000003), viscosity (p=0.000002), electrical conductivity (p0.000001), aggregation indices (p=0.00003), destruction at frequencies of 106 Hz (p=0.003), 0.5x106 Hz (p=0.00002), 0.1×106 Hz (p0.00001), polarizability at low frequencies of the electric field (p=0.02). Under the influence of the drug, the equilibrium frequency of erythrocytes shifted to the low-frequency range compared to the initial values (p0.0000001). The revealed changes indicate an increase in the surface charge of erythrocytes, their ability to deform, and cell resistance under the action of citicoline. Conclusion. For the first time, the effect of the drug with the active substance citicoline, improving the rheological properties of erythrocytes, was discovered. Preparations with the active substance - citicoline should be considered promising for conducting a full-fledged clinical study to study the reduction of circulatory disorders at the microcirculatory level in patients with manifestations of metabolic syndrome who have undergone COVID-19 coronavirus infection.

Aim: creation of diagnostic models including electrical, viscoelastic parameters of erythrocytes to distinguish fatty liver disease of mixed etiology (metabolic + alcoholic) from non-alcoholic and alcoholic fatty liver disease.Materials and methods. We examined 46 men with non-alcoholic fatty liver disease (NAFLD), 43 men with alcoholic fatty liver disease (AFLD), as well as 54 men with fatty liver disease (FLD) of mixed genesis (metabolic + alcohol-related); average age of the patients included in the study made 48.4 ± 9.6 years. The diagnosis was established on the basis of liver ultrasound findings and FLI liver steatosis index with a fibrosis grade of F1 or less (FibroScan® 502, Echosens, France). The electrical and viscoelastic parameters of erythrocytes were investigated by the diagnostic technique of dielectrophoresis using an electrooptical cell detection system.Results. The most significant parameters for differentiating fatty liver disease of mixed genesis (metabolic + alcoholic) from NAFLD using the Volcano plot have turned out to be cell polarizability at a frequency of 106 Hz (p = 6.49 ×10-5), erythrocyte cell membrane capacity (p = 0.00077), relative polarizability (p = 0.001), the levels of which were higher in patients with NAFLD. On the contrary, the index of red blood cells destruction at 105 Hz was higher in FLD of the mixed genesis (p = 0.047) and the crossover frequency was shifted to the high frequency range more than in NAFLD (p = 0.0005). The discriminant analysis has additionally revealed the significance of the degree of erythrocyte deformation at 5 ×105 Hz in distinguishing between mixed-genesis FLD and NAFLD. In differentiating FLD of mixed genesis from NAFLD, a diagnostic model incorporating the above red blood cells parameters has provided an AUC of 0.829 (confidential interval: 0.742–0.916), sensitivity of 80.9 %, and specificity of 83.3 %. Two indicators of red blood cells have been established that statistically significantly distinguish the mixed-genesis FLD from the AFLD (Volcano plot); these are the index of red blood cells destruction at a frequency of 5 ×105 Hz, which was higher with AFLD (p = 0.0007), and the capacity of cell membranes, the value of which prevailed in mixed-genesis FLD (p = 0.011). When distinguishing the mixed-genesis FLD from the AFLD, the combined model with the inclusion of three parameters of red blood cells, namely the index of red blood cells destruction at a frequency of 5 ×105 Hz, the capacity of erythrocyte membranes, and polarizability at a frequency of 106 Hz, has shown the highest levels of diagnostic accuracy, namely AUC = 0.751 (confidential interval: 0.611–0.908) with a sensitivity of 79.5 %, specificity of 74.7 %.Conclusion. The electrical and viscoelastic parameters of erythrocytes studied using the diagnostic technique of dielectrophoresis should be considered as promising biomarkers for the diagnosis of diffuse liver disease.

Introduction. Fatty liver disease is the largest contributor to the burden of chronic liver disease worldwide. Current approaches do not allow sufficient differentiation between alcoholic and non-alcoholic etiology of the process.Aim. Create diagnostic panels including electrical and viscoelastic parameters of erythrocytes to differentiate fatty liver disease of alcoholic and non-alcoholic genesis.Materials and methods. The study included 38 men (47.5 ± 2.9 years) with NAFLD; 31 men with alcoholic fatty liver disease (AFLD) (45.1 ± 3.1 years) according to ultrasound of the abdominal organs, the degree of fibrosis did not exceed F1 (FibroScan® 502). Electrical and viscoelastic parameters of erythrocytes were studied by dielectrophoresis using an electro-optical cell detection system. To determine the parameters of erythrocytes – biomarkers for distinguishing between AFLD and NAFLD, a system of machine learning methods – Random Forest was used.Results. Electrical, viscoelastic parameters of erythrocytes, which are biomarkers for distinguishing between AFLD and NAFLD, were established: cell membrane capacity (p = 1.21E-11), the degree of change in the deformation amplitude at a frequency of 5 x 105 Hz (p = 2.38E-08), cell polarizability at a frequency of 106 Hz (p = 9.38E-08), the speed of erythrocyte movement to the electrodes (p = 4.32E-06), the magnitude of the dipole moment (p = 1.66E-05), relative polarizability (p = 2.35E-05), the index of erythrocyte destruction at a frequency of 5 x 105 Hz (p = 0.016), the position of the crossover frequency (p = 2.13E- 06). The diagnostic model, including five parameters – the position of the crossover frequency, cell polarizability at a frequency of 106 Hz, cell electrical conductivity, membrane capacity, the degree of change in the deformation amplitude at a frequency of 5 x 105 Hz, provided the highest diagnostic accuracy with an AUC of 0.975, a sensitivity of 96.3%, and a specificity of 91.8% in differentiating between AFLD and NAFLD.Conclusion. Thus, systematic exposure to alcohol modifies the structure of erythrocyte membranes, leading to a decrease in the surface charge, the barrier function of membranes, reducing the resistance of cells, their ability to deform, which determines the key role of the identified electrical, viscoelastic parameters of erythrocytes in differentiating between AFLD and NAFLD.

Aim. To study intravascular changes in hemostasis and changes in electrical, viscoelastic parameters of erythrocytes in COVID-19 convalescents and to evaluate the effectiveness of the pharmacological composition of nicotinamide, cocarboxylase, trifosadenine, cyanocobalamin for intramuscular administration (Cocarnit® drug) and cytidine diphosphocholine (citicoline, Ronocit® drug) to eliminate hemorheological disorders. Materials and methods. Examined 308 patients (154 men and 154 women), average age 53.1±13.8 years, COVID-19 convalescents, within 2 to 14 months after the disease, 50 people of comparable age and gender who had not suffered COVID-19. 42 patients from the main group who had suffered coronavirus infection received complex therapy (taking the drugs Ronocit® and Cocarnit® (World Medicine Ilac San. Ve Tic. A.S., Turkey), and were re-examined after 8 weeks. The electrical, viscoelastic parameters of erythrocytes were studied by dielectrophoresis using an electro-optical cell detection system; hemostasis parameters were studied by standard methods. Results. COVID-19 convalescents revealed a marked decrease in the surface charge of erythrocytes with an increased tendency to aggregate formation, a decrease in the ability to deform against the background of high summarized viscosity and rigidity, the predominance of immature cells with reduced polarizability, high readiness for hemolysis, with a significantly altered structure of erythrocyte membranes associated with their thickening and increased ability to conduct electric current (p=0.05–0.00001). Changes in the cellular link, endothelium and leukocytes proved to be dominant in the activation of hemostasis and indicated the course of endotheliitis (p=0.00001). Combined therapy with Ronocit® and Cocarnit® drugs for 8 weeks led to an increase in the diameter of erythrocytes, the proportion of discocytes, a decrease in the proportion of deformed cells and spherocytes (p=0.00007–0.003), an increase in the amplitude of deformation of erythrocytes at high electric field frequencies (106, 5×105 Hz), membrane capacity and a decrease of summarized rigidity and viscosity (p=0.0003–0.04), a decrease in the electrical conductivity of cell membranes, an increase in the speed of movement of red blood cells to the electrodes, the magnitude of the dipole moment; there was a mixing of the crossover frequency into the low frequency range (p=0.0001–0.052). A decrease in the degree of hemolysis was revealed, to a greater extent at low frequencies of the electric field (p=0.0004–0.05), an increase in polarizability at frequencies 5×105, 105, and 5×104 Hz (p=0.005–0.05) and relative polarizability (p=0.001). The normalization of the Willebrand factor level (p=0.0001) was noted, reflecting the restoration of the integrity and function of the endothelium. Intravascular coagulation indices, estimated by the level of soluble fibrin-monomer complexes, decreased (p=0.018). Normalization of bleeding duration (p=0.012), prolongation of clotting time (p=0.001) against the background of complex therapy were established. Conclusion. The use of complex therapy with Cocarnit® and Ronocit® drugs made it possible to improve the electrical, viscoelastic parameters of erythrocytes, normalize intravascular disorders and eliminate endotheliitis in COVID-19 convalescents, creating the basis for further development of pathogenetic therapy for postcovid syndrome.

The aim of the work was to study the features of fatty acids of erythrocyte membranes and blood serum in patients with alcoholic fatty liver disease (AFLD) with different necroinflammatory activity to identify biomarkers of steatohepatitis. Material and methods. 43 men (48.5 ± 8.1 years) with AFLD with different degrees of necroinflammatory activity according to the AshTest test were examined: Group 1 (n = 23) with minimal activity of A0–1 (steatosis), Group 2 (n = 20) – with pronounced activity of A2–3 (steatohepatitis). The study of the composition of fatty acids (FAs) of erythrocyte membranes and blood serum was carried out using gas chromatography/mass spectrometry (Agilent 7000B, USA). Results. The levels of arachidonic acid C20:4n-6 (p = 0.000018), total content (C20:5n-3+ C22:6n-3) (p = 0.0027), total content of all omega-3 polyunsaturated fatty acids (PUFA) (p = 0.003), levels of docosahexaenoic acid C22:6n-3 (p = 0.0046), docosapentaenoic acid C22:5n-3 (p = 0.0054), docosatetraenoic acid C22:4n-6 (p = 0.01), eicosapentaenoic acid C20:5n-3 (p = 0.048) in erythrocyte membranes and the same acid in blood serum (p = 0.0015) were statistically significantly higher in patients with alcoholic steatohepatitis. In contrast, the concentrations of α-linolenic acid C18:3n-3 (p = 0.0032), hexadecadienoic acid C16:2 n-6 (p = 0.026), palmitoleic acid C16:1;9 (p = 0.033), pentadecanoic acid C15:0 (p = 0.04), the SFA/PUFA ratios (p = 0.017), SFA/UFA (p=0.029) were lower in patients with alcoholic steatohepatitis compared to steatosis. The use of levels of individual FAs or their total content in erythrocyte membranes provided sufficient levels of diagnostic accuracy in distinguishing the degree of necroinflammatory activity in patients with AFLD: arachidonic acid – AUC 0.940, sensitivity 85.7%, specificity 84.6%; total PUFA content – AUC 0.874, sensitivity 78.6%, specificity 84.6%; docosapentaenoic acid – AUC 0.876, sensitivity 78.6%, specificity 76.9%; sum content (C20:5n-3 + C22:6n-3) – AUC 0.863, sensitivity 71.5%, specificity 84.6%. The combined ᾽panel᾽, including a minimum amount of FAs of erythrocyte membranes – C20:4n-6, C18:3n-3, SFA/PUFA, provided the highest levels of diagnostic accuracy – AUC 0.954; 95% CI 0.8-1.0, sensitivity 92.7%, specificity 90.3%. Conclusion. FAs of erythrocyte membranes, blood serum should be considered as promising pathogenetically substantiated biomarkers for identifying patients with steatohepatitis in AFLD.

A biosensor based on field-effect transistors on silicon-on-insulator structures (SOI-biosensor) is a high-potential device for detection of biological molecules, for instance, such as troponin I; the biosensor allows conducting label-free real-time analysis.The aim of the study is the development of SOI-biosensor design for detection of acute myocardial infarction marker -troponin I.A notable feature of this design was the integration of two grounding electrodes directly onto the biosensor surface, which effectively nullified the static potential of the liquid sample and minimized physical breakdowns of biosensor elements.Materials and Methods.The highly specific anti-troponin I DNA aptamer was used as a receptor for specific detection of protein marker.Aptamer immobilization on the biosensor surface was carried out by physical adsorption.The analyzed range of target troponin I molecules concentration in the sample varied within 10 -11 to 10 -9 mol/L, mirroring clinical levels observed in myocardial infarction cases.During the experiment, a constant voltage of V ds =0.15 V was maintained.Results.The developed SOI-biosensor successfully detected target troponin I molecules at a concentration of 10 -11 mol/L.The detection process exhibited an effective time of approximately 200-300 s per sample.Moreover, analysis of the detection process revealed a noticeable decrease in current within the source-drain circuit, indicative of the negatively charged complex formed by troponin I and anti-troponin I DNA-aptamer at the "liquid sample-nanowire" phase interface.

Научно-исследовательский институт терапии и профилактической медициныфилиал Федерального государственного бюджетного научного учреждения «Федеральный исследовательский центр Институт цитологии и генетики

The purpose of the work: to investigate the possibilities of combined models including electrical, viscoelastic parameters of erythrocytes, fatty acid levels of erythrocyte membranes, blood serum to improve the accuracy of early colorectal cancer (CRC) diagnosis. Materials and methods. 65 patients with stages 1-2 of CRC (mean age 63.3±9.6 years), 25 people with adenomatous polyps (AP) and 35 people of the comparison group were examined. The electrical and viscoelastic parameters of erythrocytes were studied by dielectrophoresis in the frequency range 5x10 4 -10 6 Hz; the levels of fatty acids (FA) in erythrocyte membranes, blood serum - using gas chromatography/mass spectrometry (Agilent 7000B (USA). When creating combined models, machine learning methods were used, for their interpretation and assessment of the degree of contribution of parameters to their composition, the method of constructing SHAP diagrams was used. Results. The use of combined models made it possible to achieve high diagnostic accuracy of distinction: for the pair “healthy versus patients with AP” during ROC analysis, the AUC was 1,0 (sensitivity 1,0, specificity 1,0). This model included parameters: diameter of erythrocytes at a frequency of 10 6 Hz, proportion of deformed cells, summerized rigidity, amplitude of cell deformation at a frequency of 10 6 Hz, speed of movement of erythrocytes to electrodes, electrical conductivity of cells, level of arachidonic acid, aggregation index at a frequency of 5x10 4 Hz, polarizability at a frequency of 10 6 Hz, total content of eicosapentaenoic and docosahexaenoic (n3), level of docosatetraenoic FA (n6). For the pair “healthy vs patients with 1-2 stages of CRC”, the AUC also reached 1,0 (an increase in AUC from 0.916 when using only FA to 1.0 in combined models) (sensitivity 1,0, specificity 1,0); the most significant for the distinction were: electrical conductivity, cell capacity, erythrocyte level of palmitooleiс C16:1;9 FA, the position of the crossover frequency, summerized rigidity, the amplitude of cell deformation at a frequency of 10 6 Hz, the degree of cell deformation at a frequency of 5x10 5 Hz, the level of the dipole moment, the total content of serum saturated FA, the proportion of deformed cells, serum levels myristic, palmitic FA, the rate of movement of erythrocytes to the electrodes, the level of docozapentaenoic C22:5n-3 in the blood serum. For the pair “patients with 1-2 stages of CRC versus patients with AP”, the AUC was 0,98 (sensitivity 0,92, specificity 1,0). This model consisted of indicators: the diameter of erythrocytes at different frequencies of the electric field, the level of decadienic FA (n6) in erythrocyte membranes, the proportion of discocytic forms, the content of stearic FA in erythrocytes, the serum level of palmitoleic C16:1;9 FA, the total content of saturated FA, aggregation indices at low frequencies of NUAEF, the level of pentadecanoic FA in erythrocyte membranes, serum stearic acid content and cell polarizability at a frequency of 10 6 Hz. Conclusion. The creation of combined models consisting of electrical, viscoelastic parameters of erythrocytes, fatty acid levels of erythrocyte membranes, blood serum using machine learning methods and the construction of SHAP diagrams ensures high accuracy in the diagnosis of precancerous and early colorectal cancer.

The aim of the review is to highlight the main factors affecting the development of liver fibrosis and possible mechanisms of liver damage in patients who have experienced COVID-19. A search was carried out using keywords in the Scopus, Web of Science, and PubMed databases in literary sources of the last three years on factors associated with fibrogenesis in novel coronavirus infection. The review presents the main mechanisms of liver damage in COVID-19: direct effects on hepatocytes and cholangiocytes, hypoxia, and immune-mediated and drug-induced damage. We analyzed the significance of factors affecting fibrosis development in patients with COVID-19: chronic diffuse liver diseases, against which COVID-19 occurs, such as non-alcoholic fatty liver disease, alcohol-associated liver disease, chronic hepatitis B, C, and cirrhosis of the liver.Damage to the liver in coronavirus infection develops by several mechanisms. The development of COVID-19 against the background of diffuse liver pathology of various genesis is associated with progression of these diseases (increased fibrogenesis) and a poorer prognosis.

The purpose of the study: to study the possibilities of using fatty acids of erythrocyte membranes in differentiating patients with fatty liver disease of alcoholic, non-alcoholic and mixed genesis (metabolic + alcohol). Material and methods. 38 men (average age 47.5 ± 2.9 years) with non-alcoholic fatty liver disease (NAFLD); 31 men with alcoholic fatty liver disease (AFLD) (45.1 ± 3.1 years) and 30 men (48.2 ± 3.2 years) with fatty liver disease of mixed genesis (metabolic + alcoholic) were examined. The degree of fibrosis in the groups did not exceed grade I. The composition and levels of the fatty acids (FA) of erythrocyte,s membranes were studied using gas chromatography/mass spectrometry, a system based on three Agilent 7000B quadrupoles (USA). Results. The levels of elaidic, 9-palmitoleic, eicosapentaenoic fatty acids were higher (p = 0.041–0.058), and the content of margaric, stearic and alpha-linolenic acids (p = 0.043–0.05) were lower in alcoholic genesis compared with non-alcoholic. The use of a panel of fatty acids – C18:1;t9, C17:0, C18:0, C18:3 n-3, C16:1;9, C20:5 n-3 – provided high diagnostic accuracy with an AUC of 0.914, sensitivity of 81%, specificity of 93% when distinguishing NAFLD from AFLD. It was found that the total content of unsaturated, monounsaturated, levels of arachidonic (n-6), oleic, eicosapentaenoic (n-3), palmitoleic, elaidic, the total content of two n-3 PUFA – eicosapentaenoic and docosahexaenoic in patients with mixed-genesis fatty liver disease were statistically significantly higher, and the levels of stearic, the total content of saturated, arachinic and the ratios of saturated FA/unsaturated FA, saturated FA/polyunsaturated FA were lower than in patients with non–alcoholic fatty liver disease (p = 0.000004–0.04). In patients with fatty liver disease of mixed genesis, the total content of monounsaturated FA, especially oleic and palmitoleic, linoleic (n-6) and saturated lauric, were significantly higher, and the levels of saturated FA arachinic, stearic, SFA/USFA, SFA/PUFA ratios were lower than in AFLD (p = 0.0009–0.06). Conclusion. The revealed differences in the levels of fatty acids of erythrocyte membranes in patients with fatty liver disease of various origins are probably associated with the main etiological factor and can be used to develop new diagnostic methods and targets for therapy.

Purpose of the work: to analyze the research performed in the last decade on the study of serum markers used to diagnose inflammatory bowel diseases (IBD), differential diagnosis of nosological forms of IBD, to predict the course of the disease, response to ongoing therapy, as well as to predict the recurrence of the disease. Materials and methods. A search was carried out in the text databases “Scopus”, “Web of Science”, “PubMed” using keywords from the literature sources of the last 10 years about blood serum biomarkers used for diagnosis, evaluation of therapeutic efficacy, monitoring of disease activity and evaluation of prognosis in patients with IBD. Results. Information on serological biomarkers of IBD, which are well known and widely used in clinical practice (C-reactive protein), recently discovered biomarkers (cytokines, antibodies and non-coding RNA), as well as recent advances in serological biomarkers (metabolomics, proteomics, oncostatin M, galectins), were analyzed, which are used in various aspects of the diagnosis of IBD. Since intestinal fibrosis significantly affects the prognosis in patients with IBD, data on serum markers of intestinal fibrosis are presented separately. Conclusion. Recently, serum biomarkers in patients with IBD have become the object of close attention, since they are minimally invasive, convenient, and relatively inexpensive than markers in biopsy specimens, other biological fluids, fecal, and respiratory tests. Despite an extensive list of studies conducted over the past 10 years, there are still no ideal serum biomarkers for the diagnosis of IBD. Serum and non-coding RNA profiling techniques are just beginning to develop, but offer great promise for clinical practice. A combination of different biomarkers may be useful to improve the efficiency of IBD diagnosis.

Цель исследования – выявление жирных кислот (ЖК) мембран эритроцитов, значимых для различения пациентов с неалкогольной жировой болезнью печени (НАЖБП) от здоровых мужчин, исследование их индексов и установление ассоциаций уровней жирных кислот с клинико-биохимическими параметрами. Обследованы 30 мужчин (возраст 48,7 ± 3,4 года) с НАЖБП по данным УЗИ органов брюшной полости, подтвержденной индексом NLFS, степень фиброза печени, установленная методом непрямой эластометрии, не превышала 1-й степени. В качестве группы сравнения обследованы 28 условно здоровых мужчин (возраст 47,3 ± 2,7 года). Уровень ЖК мембран эритроцитов исследован с помощью газохроматографомасс-спектрометрической системы на основе трех квадруполей. Установлено статистически значимо более высокое содержание ряда насыщенных ЖК (НЖК) (лауриновой, маргариновой, пентадекановой), мононенасыщенных ЖК (МНЖК) (пальмитолеиновой, олеиновой, элаидиновой, суммарного уровня мононенасыщенных ЖК), линолевой кислоты, соотношения омега-6 к омега-3 полиненасыщенных ЖК (ПНЖК) у пациентов с НАЖБП по сравнению с группой контроля. Напротив, концентрация двух НЖК (арахиновой, стеариновой), омега-3 полиненасыщенной ЖК (докозагексаеновой, DHA), суммарное содержание эйкозапентаеновой ЖК (EPA) и DHA, а также всех омега-3 ПНЖК и соотношение НЖК и ненасыщенных жирных кислот (НЖК/ННЖК) оказались меньше у больных с НАЖБП, чем у здоровых мужчин. Анализ индексов жирных кислот, отражающих их метаболизм, выявил повышение активности элонгазы (белка ELOVL6) – С18:0/С16:0 ( p < 0,001), показателя липогенеза de novo – C16:0/C18:2n-6 ( p = 0,03) и снижение активности стеароил-КоАдесатуразы-1 (С16:1;7/С16:0 ( p = 0,004); С18:1;с9/С18:0 ( p < 0,0001)), дельта-5-десатуразы (С20:4n-6/С20:3n-6) ( p = 0,022) у пациентов с НАЖБП по сравнению с группой контроля. Использование содержания отдельных ЖК как маркеров для различения пациентов с НАЖБП от здоровых лиц показало высокую диагностическую точность: для пальмитолеиновой кислоты – площадь под кривой AUC 0,877, чувствительность 87 %, специфичность 83 %; для арахиновой кислоты – AUC 0,825, чувствительность 84 %, специфичность 78 %; для суммарного содержания МНЖК – AUC 0,821, чувствительность 81 %, специфичность 78 %. Использование «панели» ЖК (С16:1;9, сумма МНЖК, С20:0, n6/n3 ПНЖК, С18:0) обеспечило повышение чувствительности (91 %) и специфичности (95 %) (AUC 0,915). Выявлены разнонаправленные ассоциации уровня ЖК мембран эритроцитов с проявлениями метаболического синдрома, показателями печеночных проб.

The purpose of the review is to highlight the most significant changes in the parameters of red blood cells associated with the development of thrombosis in patients with coronavirus infection. A search was carried out using keywords in the databases Scopus, Web of Science, PubMed according to literary sources of the last 3 years on changes in erythrocyte indices associated with thrombosis against the background of COVID-19 infection. Information is presented on the main shifts in red blood indicators during SARS-CoV-2 infection associated with the development of thrombosis: virus attachment and amplification of viral proteins in erythropoiesis progenitor cells; activation of stress erythropoiesis with an increase in nuclear erythrocyte cell content up to 45 %; activation of band 3 protein oxidation with its excessive cleavage, oxidation and cleavage of alpha-chains of spectrin, ankyrin; changes in the lipid architecture of the membrane and a decrease in the activity of erythrocyte antioxidant activity, which mediate violations of cell deformability and impaired release of ATP; a decrease in the ability of erythrocytes to secrete nitric oxide; a decrease in the level of sphingolipids of the erythrocyte membrane; excessive production of microvesicles with tissue factor; an increase in the rigidity of erythrocytes with impaired release of intra-erythrocyte nitric oxide due to an attack by the SARS-CoV-2 virus 1-hemoglobin beta chain and porphyrin capture with potential heme inhibition; an increase in activated complement components C3b and C4d, immunoglobulin IgG expression on erythrocyte surface, which worsens cell deformability; attachment of erythrocytes through Toll-like receptor 9 to neutrophil extracellular traps, which promotes thrombosis; increased presentation of phosphatidylcholine on erythrocyte membranes, which facilitates the assembly of the tenase complex and prothrombinase complex, contributing to the production of thrombin, an increase in intracellular calcium levels with stimulation of the formation of microvesicles with prothrombotic potential; activation of oxidative stress in erythrocytes under conditions of hypoxia with generation of reactive oxygen species, hemoglobin autooxidation. Conclusions. The data obtained indicate the active role of erythrocytes in the development of intravascular disorders and microcirculation disorders with the risk of cardiovascular complications in patients with COVID-19. Probably, the involvement of red blood cells causes the development of systemic hypoxia in those patients. A detailed study of the identified shifts makes it possible to identify new targets for therapy and improve the prognosis of patients with COVID-19.

Detection of virus in sample is an actual problem in biotechnology, virology, medicine using biosensor. History of problem dates back to middle of last century and is associated with development of an ion-sensitive solid-state device for neurophysiological measurements. Aim of work is theoretical investigation process of detection antibody+antigen (AB+AG) complexes using SOI-FET biosensor. On example of crystal with ten biosensors, estimates of probability detection AB+AG complexes influenza virus are made. In detection process, following four results are possible: – target complex is present in test sample, and it was correctly detected; – target complex is present in sample, but it was not detected; – target complex is absent in sample, but background particles are mistakenly detected as target complex; – target complex is absent in sample, background particles present in sample and are correctly detected as noise.

Early diagnosis of autoimmune gastritis (AIG) is quite difficult in a physician’s daily practice. Since the disease is asymptomatic for a long time, it is often diagnosed already with severe atrophy with the loss of a large number of gastric glands and potentially significant pernicious anemia, and sometimes with the onset of cancer. Morphological and endoscopic changes do not occur immediately and are not specific in patients with AIG. In this case, non-invasive diagnostics play a key role. The diagnostics of AIG are often done in patients with vitamin B12 and iron deficiency. However, the development of these deficiencies can take a long time. The non-invasive technique with the determination of such biomarkers as pepsinogen I, II (PGI, PG II), their ratio, gastrin-17, as well as Helicobacter pylori (H. pylori) infection, including a cytotoxic (CagA +) strain, is used to exclude preclinical stages of AIG. The titer determination of anti-parietal cell antibodies and the anti-intrinsic factor antibodies allows identifying the immune nature of gastritis. But recent studies show that these markers can be negative in some patients. This article actualizes the problem of early diagnosis of AIG and demonstrates the importance of practical application of currently existing non-invasive methods for the diagnosis of stomach diseases.

Aim of the study was to investigate the features of the fatty acid (FA) profile of erythrocyte membranes of patients with fatty liver disease (FLD) of mixed genesis (metabolic + alcoholic) from the point of view of atherogenic changes.Material and methods. 31 men (50.6 ± 9.9 years old) with FLD of mixed genesis, the degree of liver fibrosis corresponded to 0-1 (FibroScan ® 502 Echosens, France), and 28 persons of the comparison group, comparable in age, were examined. The study of the composition of FAs of erythrocyte membranes was carried out using gas chromatography/mass spectrometry – a system based on three quadrupoles Agilent 7000B (USA).Results. Patients with FLD of mixed genesis had higher level of palmitoleic (p = 0.03), pentadecanoic (p = 0.05), omega-6 to omega-3 polyunsaturated fatter acids (PUFA) ratio (p = 0.03) and, conversely, lower level of docosahexaenoic (p = 0.0002), total content of eicosapentaenoic and docosahexaenoic FA (p = 0.0007), of all omega-3 PUFA (p = 0.001) in the membranes of erythrocytes compared to healthy persons. There are trends towards a decrease in the content of omega-3 eicosapentaenoic acid and an increase in the ratio of SFA/PUFA in patients with fibroids of mixed genesis in contrast to healthy individuals. The level of individual FA provided high diagnostic accuracy in differentiating patients with FLD of mixed genesis from healthy individuals: palmitoleic (9-C16:1) (area under ROC (AUC) 0.702, sensitivity 66.7 %, specificity 69.6 %), docosahexaenoic (C22:6n-3) (AUC 0.795, sensitivity 77.3 %, specificity 78.3 %), as well as the total content of eicosapentaenoic and docosegexaenoic FA (C20:5n-3 + C22:6n-3) (AUC 0.777, sensitivity 70.1 %, specificity 82.6 %).Conclusions. The revealed features of the profile of erythrocyte membrane FA in FLD of mixed genesis – increase of saturated, monounsaturated, omega-6 PUFA content and reduce of omega-3 PUFA concentration are atherogenic. The continuation of research in terms of the use of FAs as biomarkers of this pathology and targets for therapeutic effects should be considered promising.