Aim. Investigation of the influence of canceroembryonic antigen (CEA) on the immune cells in patients with breast tumors.

Materials and methods. Peripheral blood of 67 patients with invasive ductal carcinoma (n = 44), fibroadenoma (n = 12) and breast pre-cancer (n = 11). In the supernatants of the blood cells cytokine production induced by CEA was determined by ELISA.

Results. It was found that CEA stimulated production of IL-6, IL-8, IL-10, IL-1β, IL-1Ra, TNFα, G-CSF, GM-CSF and the protein MCP-1 by blood immune cells in patients with fibroadenoma compared with groups of patients with invasive ductal carcinoma and precancerous lesions. Stimulation index of CEA on cytokine production by immunocompetent cells in patients in these groups was lower than in groups of patients with fibroadenoma due to initially high levels of spontaneous cytokine production.

Results.  In  patients  with  fibroadenoma  CEA  was  found  to  stimulate  the  production  of  IL-6,  IL-8,  IL-10,  IL-1β,  IL-1Ra,  TNFa,  G-CSF,  GM-CSF  and  MCP-1  compared  with  groups  of  patients  with  invasive ductal carcinoma and precancerous conditions. Indexes of the influence of CEA on cytokine production by immunocompetent cells in these groups was lower than in the fibroadenoma due to initially high spontaneous production of cytokines.

Conclusion.  Evident  spontaneous  cytokine-producing  function  of  immunocompetent  blood  cells  was revealed in patients with invasive ductal carcinoma and precancerous conditions compared to patients with fibroadenoma.  The  differences  between  the  indices  of  CEA  influence  on  cytokine  production  in  patients with malignant, benign and precancerous conditions can serve as a basis for the development of methods of differential diagnosis of breast tumors.

The aim of this work is the development and demonstration of the method of simultaneous detection of several biomarkers of lung cancer in the blood plasma of patients using a multiplex electrochemical testing system based on DNA aptamers. DNA aptamers are a new class of synthetic affinity probes obtained by in vitro or in vivo selection procedure by the systematic evolution of ligands by exponential enrichment (SELEX).

Materials and methods. A set of aptamers obtained previously by selection for postoperative lung cancer tissue was used to create a multiplex electrochemical biochip. Identification of aptamer target proteins was performed using a modified affinity enrichment method (AptaBID). Molecular targets for the used set of aptamers to lung cancer were defined as vimentin, defensin, a light chain of myosin, tubulin alpha 1-B, neutrophil elastase and A1 elongation factor 1.

Measurements of the presence of these biomarker proteins in blood plasma were carried out using electrochemical detection. The difference between peak heights before and after plasma deposition on the electrodes modified by aptamers was considered as a response of the system to the presence of protein onco-markers in blood plasma. Blood plasma of healthy volunteers was used as control.

Results. Research showed that in the blood plasma of all the patients with lung cancer the content of biomarker proteins that bind to aptamers on electrode surfaces was increased. The increased content of these proteins in the blood plasma of patients suggests the presence of invasiveness and metastasis of tumors and their chemo-resistance.

It is known that desynchronosis and physical stress to the point of fatigue are powerful stressors for the body. Studies indicate a depleting effect of the combined stress factors on the adaptive reserves of the organism, especially when the joint exposure is prolonged. However, the adaptive value of the training process in various activities is also well known. In this regard, it seems important to study these two aspects of adaptation when combined effects of light desynchronosis and physical overwork on the body.

Рurpose of this study was to study the features of adaptive reactions of rats under conditions of light desynchronosis and physical overwork.

Materials and methods. An experimental study was performed on 60 mature male rats of the Wistar breed. For the induction of experimental desynchronosis, the animals of the experimental groups were kept for 10 days in artificial bright illumination (150 LX) or full darkening (2-3 LX). The model of physical overfatigue used the method of forced swimming of rats to complete fatigue in their own modification. At the end of the swim test, all the animals were withdrawn from the experiment and underwent one-step-long decapitation under CO2 with anesthesia. In decapitated animals, to collect serum, the blood was collected in a clean, dry vial. In the blood serum of rats, the biochemical standard method was used to determine the level of lactate. Using the ELISA method and the reagent kit “IBL” (Germany), the concentrations of corticosterone and serotonin were determined. The histological analysis of the stress-realizing organs was carried out according to a standard procedure using light microscopy using the Axioskop 40 microscope from CarlZeiss (Germany).

Results. It was found that physical fatigue in rats after daily swimming activities (5 days) was accompanied by a decrease in the level of corticosterone in the blood serum and destructive changes in the adrenal and femoral muscles in comparison with intact animals. In comparison with the intact group, dark deprivation and physical activity did not alter the content of corticosterone, serotonin, and lactate in the blood and caused minor destructive processes in the adrenal glands. Light deprivation and fatigue lowered the level of corticosterone in the blood, caused destructive changes in the adrenal glands and muscles, and increased serotonin levels in serum, but did not change the level of lactate.

Conclusions. The features of adaptive reactions of rats under conditions of light desynchronosis and physical overfatigue are determined by the nature of deprivation or the direction of the phase shift (deprivation of light or darkness). Dark deprivation followed by physical overfatigue causes the development of the resistance phase of the general adaptation syndrome, and light deprivation followed by physical overwork is the phase of exhaustion.

Objectives. To evaluate the immediate results of surgical treatment of patients with large incisional hernia of the anterior abdominal wall with the use of the mesh implants.

Materials and methods. The data were retrospectively collected and analyzed. The study included patients with a large and / or complex incisional hernia. There were 108 patients who underwent incisional hernia repair with mesh reinforcement in the period from 2012 to 2016. In all cases the repairs were made with mesh implants. The average age of patients was (56.4 ± 10.4) years. The body mass index (BMI) was on average (32.6 ± 6.24) kg/m2. The medial localization of the hernia was 102 (94.44%). The width of the hernia defect averaged (12.2 ± 3.7) cm. Implants were placement in onlay positions – 19 (17.6%), sublay – 49 (45.37%), IPOM (Intraperitoneal onlay mesh) – 30 (27.77%) patients, the component separation technique (CST) with mesh reinforcement was used in 10 (9.25%) patients. Active aspiration drainage was performed in 72 (66.66%) patients.

Results. The average time for draining the postoperative wound was (5 ± 2.2) days. The number of wound complications was 23 (21.3%), the number of seromas of the postoperative wound prevailed was 16 (14.8%) patients, of which 2 (1.85%) were chronic abdominal wall seromas, hematoma occurred in  2 patients (1.85%), the number of prolonged serous exudation was 7 (6.5%), necrosis of the wound edges occurred in 4 (3.7%) patients. There was no mortality. Reliably more often wound complications occurred in patients with large hernia defects (p = 0.006), and also with an increase in the duration of surgical intervention (p = 0.01). The hospital-stay in patients with complications was significantly greater (p < 0.001), the need for analgesics also increased (p < 0.001).

Conclusion. Prevention of wound complications after large and complex incisional hernia repair with mesh reinforcement is an important direction in improving the results of surgical treatment in this category of patients.

Aim. Evaluate the effectiveness of ultrasonic elastography in the differential diagnosis of pancreatic cystic lesions.

Materials and methods. Seventy patients with pancreatic cystic lesions were examined. Structure of clinical forms is the following: cystadenoma – 30 (serous cystadenoma – 23, mucinous cystadenoma – 2, mucinous cystadenocarcinoma – 5), pseudocysts – 40. Diagnosis of pancreatic cystic lesions was conducted with the help of transabdominal ultrasound examination (with 3D-reconstruction) and ultrasonic elastography.

Results. The parameters of ultrasonic elastography for various types of pancreatic cystic lesions were determined. Sensitivity, specificity, positive predictive value, negative predictive value, the overall accuracy of the technique accounted for 97, 75, 74, 97 and 84% respectively. The superiority of the elastography technique over the standard transabdominal ultrasound in differential diagnosis of cystic pancreatic formations was illustrated.

Conclusions. Ultrasonic elastography is an effective, non-invasive method of differential diagnosis of pancreatic cystic lesions and can be widely used in clinical practice.

The purpose of the study was to study the influence of complex peroral nimesulid administration and intraarticular etoxidol injection on lipid peroxidation processes and activity of the endogenic antioxidant system on cytological composition of synovial fluid in experimental post-traumatic arthritis.

Materials and methods. The experiments were carried out on 108 white nonlinear rats of both sexes and with a body weight of 180–200 g. The animals were divided into 4 series and excluded from the experiment on the 28^th day.

Conclusion. It was established that peroral catheter nimesulid injection in combination with intra-articular etoxidol injection has a significant impact on lipid peroxidation processes, on activity of the endogenic antioxidant system and on cytological composition of synovial fluid.

Relevance. To identify new markers of early diagnosis and prognosis of head and neck squamous cell carcinoma (HNSCC) it is necessary to study the molecular features of this disease.

Purpose. The aim of the study was to analyze blood serum protein spectrum in patients with HNSCC and in healthy volunteers using the methods of mass spectrometry and to evaluate the selected serum protein markers as candidates for early detection of HNSCC.

Materials and Methods: The blood serum of HNSCC patients before therapy with metastases, without metastases and healthy volunteers was studied by proteomic methods. Validation of the results of proteomic analysis was carried out by ELISA in serum of 52 patients with HNSCC (T1-4N0-3M0), 10 patients with chronic hyperplastic laryngitis, dysplasia DII-DIII and 10 healthy volunteers. The statistical analysis was carried out using Statistica 6.0. Software package.

Results. Blood serum proteome of HNSCC patients with metastases, without metastases and healthy volunteers are different and contain proteins of different classes. Adenylyl cyclase-associated protein 1 (CAP1) and protein phosphatase 1B (PPM1B) were selected to validate the obtained results. It was shown that the serum level of CAP1 and PPM1B differed in control and dysplasia groups and dysplasia and cancer groups (p ≤ 0,05). In patients with HNSCC (T1N0M0) the serum CAP1 and PPM1B levels were higher than in patients with dysplasia and healthy individuals (p ≤ 0,05). It was noted the positive correlation of the CAP1 level in the serum with the presence of metastases and the PPM1B level.

Conclusion. Candidates for serum markers of HNSCC prognosis were identified. The difference in serum levels of CAP1 and PPM1B depending on the prevalence of primary tumors and the difference in serum level of CAP1 depending on the presence of regional metastases was shown. Determination of CAP1 level in the serum can be useful for early diagnosis and prognosis of HNSCC.

Purpose of the study: working out an easy-to-use complication development index (CDI), designing a program for post morbidity rehabilitation of patients with surgical infection to improve the results of its treatment and reduce lethality.

Materials and methods. A retrospective results analysis of treatment of 320 patients for purulent peritonitis and abdominal sepsis was carried out, including 268 patients (the comparison group) and 52 (the core group) with whom the complications development index was calculated. While studying this group of patients, the same protocol was used to prevent and treat complications on the basis of a complex individual program. In the comparison group, the patients were divided according to the severity of their condition in compliance with generally accepted clinical criteria: medium-heavy (98), severe (86) and extremely severe (84 patients, respectively).

We have studied general clinical and biochemical indices, as well as the results of instrumental studies of the function of vital organs and body systems. The following indices were calculated:  the prothrombin index; the integral index of thromboelastography (IIT), J = [R (min) × K (min)] : mA (mm), where R is the clotting time, K is the clot formation time, mA is the clot density); the general condition severity APACHE II (Acute physiology and chronic health evaluation); the degree of organ dysfunction SOFA (Sepsis organ failure assessment); leukocyte index of intoxication (LII). The PIRO concept (predisposition, infection, response, organ dysfunction) was used for clinical interpretation of the received research results.

Results. The prediction index of complications of surgical infection was proposed. It is based on the results of clinical analysis the results of patient treatment and calculated by using the severity of the underlying pathological process, as well as the number of concomitant diseases, pathological syndromes and aggravating factors.  As a result of the complication development prediction index use along with the implementation of the complex program for prevention and treatment of complications, the number went down from 50% to 90% in different groups under observation.

The purpose of the study was to analyze the expression of CCL11/eotaxin, CCR3 receptor to eotaxin and eosinophil peroxidase (EXP) in tumor tissue and its relation to tissue eosinophilia in gastric and colon cancers.

Materials and methods. 52 patients with gastric cancer and 55 patients with colon cancer were examined. The material of the study was samples of malignant tumors of the stomach and large intestine obtained during a surgery. The expression of CCL11/eotaxin, CCR3 and EXP in the tumor tissue was evaluated by immunohistochemical method. For statistical processing of the results, one-factor dispersion and correlationregression (by Spearman) methods of analysis were used.

Results. High expression of CCL11/eotaxin by tumor cells is typical of stomach and colon cancers with eosinophilic infiltration of the tumor tissue. The CCR3 receptor to eotaxin on the cell membrane of infiltration of the tumor tissue in gastric and colon cancers is found in 100% of cases. Expression of CCR3 (at stomach cancer) and EXP (at stomach and colon cancers) by cells of the tumor microenvironment with eosinophilic granulocytes infiltration is significantly higher than in the cells of the tumor microenvironment without eosinophilic infiltration.

Conclusion. Tissue eosinophilia in gastric and colon cancers develops due to the ability of transformed malignant cells to produce CCL11/eotaxin that mediates the attraction of CCR3-expressing eosinophil granulocytes in the tumor tissue. High level of EPX (marker enzyme of eosinophils) expression by cells of tumor microenvironment in the gastric and colon cancers with tissue eosinophilia suggests the expressed cytotoxic potential of eosinophilic granulocytes, which can be directed against tumor cells.

Aim. To develop and verify a method for diagnosis of peptic ulcer based on neural network analysis of data on patients’ risk factors.

Materials and methods. This article presents the results of a study based on materials on risk factors of 488 patients. The data was analyzed using internally developed artificial neural network (Certificate of State Registration of Program for Computers (RU) no. 2017613090).

The results of the study. The proposed approach demonstrated the levels of sensitivity of 74.4%, m = 4.3 and specificity of 93.3%, m = 2.46 during clinical testing.

The prediction of the age of probable hospitalization ensured the generation of an array of data for which the Mean Absolute Error (MAE) of the prognosis was 1.8 years, m = 0.11 in the training set and 1.9 years,  m = 0.15 in the clinical testing set. The maximum of absolute prognosis error in the clinical testing set did not exceed 2.2 at p = 0.95 and 2.3 years at p = 0.99.

Conclusion.  A new method is proposed for diagnosis of peptic ulcer based on a neural network analysis of data on patients’ risk factors. During clinical testing of the model, this approach demonstrated Area Under the Curve (AUC) levels reaching 0.943. The use of the artificial neural network also made it possible to predict the age of probable hospitalization. The use of the neural network demonstrated additional advantages including: non-invasiveness, the lack of need to prepare the patient for the study and the possibility to obtain results immediately after the onset of the disease without a time delay for sample processing.

Introduction. One of the crucial tasks in medicine is studying the molecular mechanisms of selective management of tumor cell apoptosis following conformational changes in protein molecules (ubiquitination).

The purpose of the study. The aim of the project is to establish the role of ubiquitin and ubiquitinligase in dexamethasone-induced apoptosis in Jurkat cells.

Materials and methods. The study was carried out on the Jurkat tumor cell line (intact cells and cells cultured in the presence of an apoptosis inducer dexamethasone in the final concentration of 10 µmol. In intact and dexamethasone-affected Jurkat cells, implementation of apoptosis and the amount of FAS-, TNF Receptor 1 and cells with reduced mitochondrial membrane potential were assessed by flow cytometry using FITC-conjugated Annexin V and Propidium Iodide. The levels of NF-κB, Apaf-1, ubiquitin and ubiquitin ligase were determined by Western blot analysis. The activity of caspase-3 was measured by spectrofluorometry.

Results. When adding the apoptosis inducer dexamethasone to the Jurkat cell culture, we registered a fall in the concentration of ubiquitin and a rise in the level of ubiquitinligase against the backdrop of activated receptor(an increase in the amount of Annexin V positive cells, FASand TNF Receptor 1) and mitochondrialmediated (an increase in the number of cells with reduced mitochondrial membrane potential and elevation of Apaf-1 level) pathways of apoptosis, as opposed to the intact cell culture. We estimated the completion of apoptosis by determining the activity of caspase-3 in the investigated tumor cells.

Conclusion. The obtained findings allow the conclusion that ubiquitination of regulatory and effector proteins in programmed cell death is one of the molecular mechanisms that regulates and selectively controls apoptosis in Jurkat cells.

Objectives. To assess the impact of obesity on health-related quality of life (HRQoL) in Mongolian and Caucasian adolescents living in rural areas of Buryatia, Russia.

Materials and methods. The study included 77 overweight and obese adolescents aged 11–17 years from rural areas of Buryatia, Russia. Forty-six of them were Mongolians (13 were Soyots (minor ethnic group), 33 were Buryats) and 31 were Caucasians. To compare, we recruited seventy-three adolescents from the same community-based sample with normal weight, comparable with the overweight group in gender, age and race/ ethnos.

Height, weight and waist circumference were objectively measured using standardized methods. BMI and waist circumference Z-scores were calculated using the age and sex specific reference. HRQoL was measured by the self-report version of the Pediatric Quality of Life Inventory 4.0.

Results. Being overweight was associated with poorer adolescent-reported HRQoL totals and in each domain in comparison with the control group of Caucasian adolescents (all р < 0.01), but not Mongolians.

Subgroup analysis for overweight adolescents indicated that after controlling for gender, age, Tanner stage of adolescents, education and social status of their mothers, HRQoL scores were significantly lower in the Caucasians compared with the Mongolians regardless of BMI z-score in all domains. Moreover, abdominal obesity was independently associated with poorer scores in the domains of emotional (β = –0.26; р = 0.018), school (β = –0.23; р = 0.03) and psychosocial (β = –0.24; р = 0.028) functioning and total HRQoL scores  (β = –0.22; р = 0.04).

Conclusion. In the rural community-based sample, overweight Caucasian adolescents have significantly poorer HRQoL than their non-overweight peers of the same race, and they have worse HRQoL than obese Mongolian adolescents with comparable anthropometric characteristics.

When developing health improvement programs for adolescents from rural Buryatia, it should be considered that the improvement of quality of life may become a good motivation to lose weight for Caucasian adolescents but not for Mongolian adolescents.

The aim of the study is to assess the effect of changes in the body in men and women with type 1 diabetes on the state of bone mineral density and metabolic rate and determine the directionality of changes in serum markers of bone remodeling and bone mineral density in both sexes with this disease.

Materials and methods. Bone mineral density (with (DXA) and serum bone remodeling markers [ALP, P1NP and b-CTx] were measured in 57 women and 41 men with type 1 diabetes (n = 98) and in a group control, consisting of 43 women and 39 men (n = 82).

Results. Analysis of the obtained results showed lower values in all the surveyed areas in patients with diabetes, compared with the control group. It was found that the studied bone formation markers (ALP, P1NP) behave differently; while the P1NP level is significantly reduced in women with T1DM vs control patients (p < 0.001), the level of ALP was comparable between the groups of patients with T1DM and control (p > 0.05). b-CTx showed a significant negative correlation with the T-score of the MIC of the lumbar spine (r = –0.431; p = 0.000).

Conclusions. Based on the results of studying the T-score it was found that in men and women with diabetes, in comparison with the control, the bone density in the vertebrae was reduced. In men with type 1 diabetes changes in the T-score in the spine were found to be less intense than in women.

The aim of this investigation was to reveal the expression TRIM16, ERα, ERβ and AR in prostate cancer tissues compared to benign hyperplasia and clinical and morphological parameters.

Materials and methods. Fifty patients with locally advanced prostate cancer with T2-3N0M0 and twenty patients with benign hyperplasia were included in the study. Prostate cancer patients were divided into subgroups according the Gleason score. Nine patients had Gleason score of 6, eighteen patients had 7 Gleason score, seven patients got 8 Gleason score and seven patients got 9 Gleason score. PSA level was from 4 to 100 ng/ml. TRIM16, ERα, ERβ and AR expression was determined by PCR in real time.

Results. Increase of TRIM16 expression in prostate cancers was accompanied by high AR and ERα expression. The onco-suppressor ERβ was not changed in cancer tissues compared to benign hyperplasia. The Gleason score level was dependent on AR/ERβ relation. Associations between the PSA, AR, ERβ and TRIM16 were found in prostate cancers

Conclusion. Transcription factor TRIM16 participated in prostate cancer development. The connection between the ER and AR expression and clinical and morphological factors was found.

The aim of the investigation was to assess histochrome’s anabolic effect as a consequence of treatment of various doses in rats in conditions of prolonged physical training.

Materials and methods. The experiments were performed on the Wistar’s rats. Experimental Group 1 was subcutaneously injected with histochrome in a dose of 1 mg/kg (n = 20) within 10 days, experimental group 2 was treated subcutaneously at a dose of 10 mg/kg (n = 20), and control group 3 received equivolume injections of isotonic sodium chloride (n = 20). Rat musclehypertrophy was induced using the method of forced swimming. A piece ofmuscle  was takenfor morphological examination a day after the first and last period of swimming. Hypertrophy of muscle fibers was evaluated by the cross-sectional diameter of muscle fibers, the average quantity of argyrophilic nucleolar organizer region (AgNOR) proteins and the percentage of nuclei with 1, 2, 3 or more AgNOR compared to intact (control) animals.

Results. Microscopic morphological examination of M. gastrocnemius registered increase in diameter of muscle fiber by 19,4% (1 mg/kg) and by 60% (10 mg/kg). In the control group of rats an increase in a transverse section of muscle fibers was not found to be statistically significant.

The study of biosynthetic nuclei activity of myosimplastus registered increase the AgNOR proteins in both examines groups of animals in comparison the less dynamics in control one. By 10th day of observation the quantity of myosimplastus with two AgNOR increased in a control group of rats by 10%. The maximum AgNOR proteins gained was marked in case of the prolonged use of histochrome in a dose 1 mg/kg.

Conclusion. Histochrome enables the increase in dose-dependent biosynthetic processes in skeletal muscles of rats, providing the development of anabolic effect.

Aim. The purpose of this study was to examine the association of increasing concentrations of endothelin-1 and soluble forms of ST2 protein (sST2)  in the blood plasma of patients with chronic heart failure (CHF) who underwent implantation of a cardioverter-defibrillator, with the development of cardiovascular events (death from cardiovascular diseases, decompensated CHF, acute coronary syndrome or acute ischemic stroke) to determine whether these biomarkers can be used as predictors of an unfavorable course of the disease.

Material and methods. A 6-month cohort study included 40 patients with CHF who received an ICD 4-12 weeks before their inclusion in the study. At the beginning of the study the concentrations of endothelin-1 and sST2 in plasma by ELISA were analyzed, along with conventional diagnostic techniques typical of a specialized cardiology clinic.

Results. Phenotype with a favorable course of the disease was identified in 21 patients (group 1), and with a unfavorable course was seen in 19 (group 2). The concentration of endothelin-1 and sST2 in the blood plasma of the 2nd group patients was higher than in patients of the 1st group. The link of cardiovascular events with high levels of soluble ST2 protein and endothelin-1 in blood plasma has been identified. Variation of the decision rule threshold on the ROC-curve has allowed sST2 concentration of 34.93 ng/ml to be determined as a cutoff  point.  Accuracy of two-class classification (determination of  the posterior probability of cardiovascular events) after identifying such cut-off  point was characterized by 93%  sensitivity and 72% specificity (area under ROC-curve – 0.87).  If the value of the plasma concentrations of sST2 more 34.93 ng/ml the relative risk of cardiovascular events was 4.4 (95% CI 1.7–11.1). The use of endothelin-1 surplus in plasma (cut-off point – 0.34 fmol/ml) in predicting cardiovascular events was lower: the sensitivity – 88%, specificity – 68% (area under ROC-curve – 0.74). When the concentration of endothelin-1 in blood plasma was more than 0.34 fmol/ml the relative risk of cardiovascular events was 2.7 (95% CI 1.2–6.3).

Conclusion. The increase in the sST2 and endothelin-1 concentration in blood plasma may be considered as a predictor of cardiovascular events in CHF patients after implantation of cardioverter-defibrillator.

The aim is to determine the most significant predictors of the oral lichen planus in patients with gastrointestinal pathology.

Materials and methods. The study was performed of 40 patients aged 41 to 86 years with oral lichen planus. Degree of mucosal damage by oral lichen planus was evaluated. The concomitant pathology of the gastrointestinal tract was established. A discriminant analysis was carried out.

Results. The most significant predictors for a diagnosis of oral lichen planus in patients with  gastrointestinal pathology are revealed. The sensitivity of the method was 100.0%, the specificity was 100.0%, and the errorfreeness was 100.0%.

The conclusion. Discriminant analysis allows us to conduct a diagnosis of the oral lichen planus in patients with gastrointestinal pathology. This model is available in clinical practice.

The goal of the present research is to study the hemocompatibility of magnetic nanoparticles (MNPs)  in model systems in vitro.

Materials and methods. Magnetite nanoparticles and magnetite colloidal solutions were used in 0.9% NaCl in concentrations 0.2, 2.0 and 20.0 mg/ml. The study was performed with heparinized human whole blood, 1 ml of which was mixed with 1 of ml nanoparticles/physiological solution. Measurements were made directly after mixing, and then 1, 2.5 and 5 hours later. The amount of reactive oxygen species (ROS) was measured with luminol-dependent chemiluminiscence (CL). An erythrocyte aggregation index was calculated. For the assessment of hemolytic properties, a hemolysis coefficient was calculated based on optical density of the plasma. The nanoparticless surface protein layer investigation was performed with IR-Fourier spectroscopy.

Results. Nanoparticles decline CL in timeand concentration-dependent manner. Erythrocyte aggregation stability grows, but concentration and/or application time increment leads to significant hemolysis. IR-Fourier spectroscopy data shows albumin as main component of protein crown, whose conformation changes in time.

Given data proves safety of studied MNPs in relation to examined parameters in low (0.2 and 2.0 mg/ml) concentrations up to 2.5 hours interaction. This allows us to treat these MNPs as a promising agents for further use in medical practice after completing examinations related to other homeostasis indicators.

The aim of the investigation was to determine the characteristics of the immune response regulation for pulmonary tuberculosis (TB) and to analyze the role of regulatory T cells in the immunopathogenesis of TB with eosinophilia in the blood, depending on the clinical form of the disease and sensitivity of Micobacterium tuberculosis to anti-TB drugs.

Materials and methods. 157 patients who were initially diagnosed with infiltrative and disseminated TB were examined. The material of the study was venous blood and culture of mononuclear leukocytes isolated from venous blood. The content of interleukin (IL) 4, IL-10 and transforming factor beta (TGFβ) in culture suspensions of mononuclear leukocytes in vitro and IL-5 in the blood was determined by enzyme-linked immunosorbent assay (ELISA) test. The expression of surface molecules CD4, CD20, CD25 and intracellular transcription factor Foxp3 by lymphocytes of the blood was evaluated by flow cytometry. The obtained results were analyzed by statistical methods.

Results. It is shown that excessive generation of regulatory T cells in patients with TB is associated with eosinophilia of the blood and imbalance of immune response regulation mechanisms. In TB with eosinophilia, an increase in the number of Foxp3-positive regulatory T cells in the blood is combined with in vitro hypersecretion of anti-inflammatory cytokines TGFβ, IL-10, IL-4 and an increase in the content of CD20+ B lymphocytes and IL-5 in the blood. These changes are most pronounced in the disseminated form of TB in combination with drug resistance.

Conclusion. Characteristics of immunoregulation at TB with blood eosinophilia are associated with activation of immunosuppression mechanisms and polarization of immune response towards Th2-dependent pathway.

The aim of this study was to compare the activity of proteasomes with different variants of tumor progression in luminal and triple-negative breast cancer (BC).

Materials and methods. 132 patients with primary luminal and triple-negative breast cancer in stage Т_1-3N0₂M₀ who had not received neoadjuvant treatment were included in this study. Proteasome chymotrypsin-like (ChTL) and caspase-like (CL) activities were determined by hydrolysis of fluorogenic peptides Suc-LLVY-AMC and Z-LLGlu-AMC in samples of tumor and adjacent tissues. The coefficients of chymotrypsin-like (kChTL) and caspase-like (kCL) proteasome activity were also calculated as the ratio of the corresponding activity in the tumor tissue to activity in the adjacent tissue.

Results: Results. The increased level of ChTL and CL proteasomal activity in the tumor were observed in comparison with adjacent tissues for all molecular subtypes of BC. The process of lymphogenic metastasis of luminal A and luminal B subtypes of breast cancer is associated with significant changes in the CL activity of the proteasome. Caspase-like activity of proteasomes was increased in luminal A breast cancer with extensive lymphogenic metastasis (N2), and on the other hand it was decreased in the luminal B subtype of cancer. For the hematogenic pathway of breast cancer progression the ratio of proteasomal activity in the tumor and adjacent tissues plays a significant role. The increase in proteasome activity in the tumor over the activity of proteasomes in adjacent tissues more than 2 times was associated with poor metastatic-free prognosis of the disease.

Discovery and development of new chemical compounds with putative anti-cancer properties requires reliable predictive preclinical models for in vitro screening of efficacy. Such models mainly include cultures of human cancer cells: two-dimensional (2D) and three-dimensional (3D) cell culture systems. In this review, we discuss the molecular aspects of cells cultured in 2D and 3D, and their relevance to cancer study, focusing on key examples from the recent literature. Advantages, disadvantages and perspectives of described models are also analyzed.

The review of the literature is devoted to modern data on the formation of the ovarian reserve of the female sexual organ. The relationship between the size of the ovarian reserve and length of reproductive capacity emphasizes the importance of understanding the regulatory factors and processes that determine its creation. We described ovarian reserve markers and regulators such as oocyte phosphotidylinositol-3-kinase, a stem-cell factor (kit ligand) that promote the survival of follicles during neonatal development, synaptonemic complex (SCP3), which is the marker of the first division of meiosis, as well as genes DMC1 and PTEN, involved in meiotic transformations and recruitment of primordial follicles. Changes in the expression of some genes and factors in the human fetal ovaries during primary follicular assembly now give an idea of the ways controlling early folliculogenesis. Aberrant production of these factors can cause dysfunction, the development of ovarian disorders and a defective follicular reserve. In particular, the degree of change in the number of germ cells at each of the stages leading to the creation of an ovarian reserve should be noted. This change can affect the final size of the follicular stock, and, consequently, the reproductive longevity of a person and health in the postproductive period. In particular, the number of primary follicles during puberty is positively correlated with the number of growing follicles and their response to gonadotropin treatment. The size of the ovarian reserve depends on the genes involved in proliferation and differentiation of germ cells, sexual differentiation, meiosis, germ cell degeneration, the formation of primary follicles, and the potential mechanism for self-renewal of embryonic stem cells. For example, a possible molecular mechanism has been established leading to a meiotic process in oocytes involving the above genes and factors, as well as apoptotic and antiapoptical signals: Bax, Bcl-2, p53, CDK1, Lsd1, Notch, Stra8, Dazl, Dmc1, Rec8, XIAP , PUMA. Therefore, understanding all the subtleties and molecular mechanisms at each stage of laying down and developing the ovaries, sex cells and their environment, and the death of gametes, can help to search for possible regulators and prevent pathological depletion of the follicular stock.

This review examines the epidemiology of drug resistant epilepsy in adults in Russia and abroad. References were taken from Russian and foreign databases for the period from 2010–2017. Only full-text publications (66) were included in this review. We concluded that the despite the achievements of clinical pharmacology and the development of new antiepileptic drugs, the problem of drug resistant epilepsy remains not fully resolved today. The worldwide high prevalence rate of patients with drug resistant epilepsy substantiates the problem. Thus, the average incidence of this disease varies from 30% to 70%, depending on the type of epilepsy and background pathology, which is the cause of symptomatic epilepsy. However, we have faced the problem of the absence both in Russia and abroad of large multicenter studies on the epidemiology of drug resistant epilepsy in the analyzed period of time. We have also revealed the lack of a unified definition of the disease, which is probably one of the reasons for the insufficient number of epidemiological studies of drug resistant epilepsy in different countries of the world.

One of the promising areas is the design and modification of materials for control over the fate of multipotent mesenchymal stromal cells (MMSCs) that will allow stroma of various human and animal organs and tissues to be constructed. However, the discussion about the existence and functioning of microenvironment for the MMSCs is just beginning to develop. The design of artificial materials that are able to reproduce biomimetically the cellular and tissue microenvironment and based on ideas and main elements borrowed from wildlife is current direction in a development of medical materials technology and tissue bioengineering. Scaffold technology is a promising experimental approach to simulate the properties of natural microenvironment of stem cells. Our aim is a short review of key elements of MMSC microterritories, its advanced investigations and the attempts of modeling in application to tissue bioengineering and regenerative medicine.

The article represents a clinical observation describing the case of mechanical obstruction in the respiratory passages with an unusual foreign body, a fir branch. The diagnostic problem lied in the fact that a patient did not notice the fact of aspiration, the respiratory symptoms were non-specific, and the foreign body was radiotransparent. A detailed case history allowed the detection and endoscopic confirmation of the aspiration of a foreign body, a fir branch, and the consideration of the community acquired pneumonia and secondary aspiration pneumonia that required specialized medical care by the thoracic surgery department.

Chondrosarcoma is one of the most common tumors in adults. Correct grading of chondrosarcoma is the most important criterion that defines the course of surgical treatment. A case report of a 56 years old female patient with chondrosarcoma of the pelvic bone is presented. The assistance of magnetic resonance tomography in accurate grading of the tumor is shown.

Decomposition of professional thinking of the human operator in process control, requiring intense attention for a long time, was performed. The problem of assessing the ability of the operator to adapt to mental stress was formulated. The authors proposed a model for calculation of the indicators of the functional state of the body  during the transition from normal to hard work. It is based on a dynamic model of the system, which is not in a stationary state under external forces, but will be changing until the rate of entropy production within the system reaches the minimum in these conditions. It is shown that this model can be used to solve the problem.

This article is devoted to the 70th birthday anniversary and the 45th anniversary of the scientific and educational work of N.A. Kornetov – DM, Professor of the Division of Psychiatry, Narcology and Psychotherapy, the Honored Scientific Worker of the Russian Federation, the Honored Professor of SSMU. The article highlights his interdisciplinary and educational activity in the development of International Academy of Integrative Anthropology, main courses of scientific activity and new data in the field of integrative clinical anthropology, the doctrine of constitutions, and the biological significance of minor physical anomalies.