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BACKGROUND. There is enough evidence of the negative impact of excess weight on the formation and progression of res piratory pathology. Given the continuing SARS-CoV-2 pandemic, it is relevant to determine the relationship between body mass index (BMI) and the clinical features of the novel coronavirus infection (NCI).AIM. To study the effect of BMI on the course of the acute SARS-COV-2 infection and the post-covid period.MATERIALS AND METHODS. AKTIV and AKTIV 2 are multicenter non-interventional real-world registers. The АКТИВ registry (n=6396) includes non-overlapping outpatient and inpatient arms with 6 visits in each. The АКТИВ 2 registry (n=2968) collected the data of hospitalized patients and included 3 visits. All subjects were divided into 3 groups: not overweight (n=2139), overweight (n=2931) and obese (n=2666).RESULTS. A higher BMI was significantly associated with a more severe course of the infection in the form of acute kidney injury (p=0.018), cytokine storm (pCONCLUSION. Overweight and/or obesity is a significant risk factor for severe course of the new coronavirus infection and the associated cardiovascular and kidney damage Overweight people and patients with the 1st and 2nd degree obesity tend to have a high risk of death of SARS-CoV-2 infection in both acute and post-covid periods. On top of that, in case of morbid obesity patients this tendency is statistically significant. Normalization of body weight is a strategic objective of modern medicine and can contribute to prevention of respiratory conditions, severe course and complications of the new coronavirus infection.

Blood pressure (BP) and its level are indicators of human health and the object of research in recent decades. However, not only elevated BP, but also reduced BP (acute and chronic) are one part of the J-shaped curve of increased risk of cardiovascular diseases [1, 2]. Nevertheless, the problem of arterial hypotension (AH) remains poorly understood today. The article discusses the diagnostic criteria of AH, its pathophysiological mechanisms and approaches to diagnosis and treatment.

Aim. To analyze newly diagnosed diseases and features of the post-COVID course in patients after a coronavirus disease 2019 (COVID-19) within 12-month follow-up.Material and methods. A total of 9364 consecutively hospitalized patients were included in the ACTIV registry. Enrollment of patients began on June 29, 2020, and was completed on March 30, 2021, corresponding to the first and second waves of the pandemic. Demographic, clinical, and laboratory data, computed tomography (CT) results, information about inhospital clinical course and complications of COVID-19 during hospitalization were extracted from electronic health records using a standardized data collection form. The design included follow-up telephone interviews with a standard questionnaire at 3, 6, and 12 months to examine the course of post-COVID period.Results. According to the ACTIV registry, 18,1% of patients after COVID-19 had newly diagnosed diseases (NDDs) over the next 12 months. Hypertension (HTN), type 2 diabetes and coronary artery disease (CAD) prevailed in the NDD structure. Comparison of the age-standardized incidence of NDDs (HTN, CAD, diabetes) in the post-COVID period in the ACTIV registry with NDD incidence in 2019 according to Rosstat and the expected incidence of NDDs according to the EPOHA study revealed that HTN, diabetes, CAD in patients after COVID-19 were registered more often as follows: HTN by 7,0 and 4,4 times, diabetes by 7,3 and 8,8 times, CAD by 2,3 and 2,9 times, respectively. NDDs most often developed in patients aged 47 to 70 years. Comparison of the actual and expected number of cases of newly diagnosed HTN, CAD and diabetes depending on age showed that the actual number of cases in the population of patients in the ACTIV register is significantly higher than expected for patients aged 45-69 years and for patients with hypertension or diabetes and aged Conclusion. Available evidence suggests that a strategy for managing COVID-19 survivors should include mandatory screening for early detection of cardiovascular disease and diabetes, which will be key to reducing the risk of further COVID-19 consequences.

The current literature review covers the role of sympathetic nervous system activation (SNS) and the significance of a new biomarker catestatin (CST), which is a chromogranin A-derived peptide, for assessing prognosis of patients with heart failure (HF). This review details the works devoted to CST metabolism and its role in clinical conditions with excessive catecholamine production, including the ability to counterbalance the adverse effects of SNS on cardiovascular system. The paper also presents the central results of studies on HF patients and shows the correlation of the CST level with HF functional class and stage. In addition, particular attention is paid on the possibilities and potential benefits of assessing the CST in addition to conventional management of patients hospitalized due to acute decompensated heart failure.

The authors’ report presents a brief review of the key studies, providing the reason for the use of vascular endothelial growth factor as a marker for stratification of the risk of cardiovascular complications in patients with essential hypertension.

Survival curves were approximated and analyzed based on experimental data on the effect of different polyphenolic compounds on mouse lifespan with the Gompertz model in its minimal variant, which excludes the parameters of sample heterogeneity and age-independent mortality. Vectors from the control data towards the experimental data were plotted on graphs with coordinates [logμ0 (the logarithm of initial mortality) and γ (the rate of aging)] and compared with a series of control points. The deviations were considered real when the tilt angles of the corresponding vectors differed from those of the logμ0 regressions on the γ coordinate based on the control data. The results of analysis of the published data have shown that resveratrol, tocopherol, polyphenol-containing grape skin extract, SkQ1 antioxidant, and metformin do not result in any differences between the control and experimental data beyond the limits expected in the comparison of different samples of the same control population. Unlike the indicated preparations, the complex polyphenol preparation BP-C3 acts differently and decelerates aging in female SHR mice. It is the antioxidant activity of BP-C3 that may partly be associated with this effect. We have determined its antioxidant capacity in vitro, and demonstrated its ability when administered in vivo to hinder a decrease in the total peroxide-decomposing activity in the erythrocytes of male BALB/c mice treated with 5-fluorouracil.

One of the most important aspects of regenerative medicine is the selection of the scaffold—the biological skeleton of the tissue-engineering structure. To reproduce the structure and properties of damaged tissue and maintain the cell adhesion and proliferation, it is optimal to use scafflds obtained by decellularization of native organs with subsequent recellularization of various cell lines. Using the methods of environmental scanning electron microscopy and scanning pulsed ultrasound microscopy, the microstructure of native and decellularized matrixes of dermal tissues was determined.

New techniques have been developed for the preparation of spongy materials and hydrogels based on triblock copolymers of lactide and ethylene glycol with various molecular structures. The influence of the composition of the initial copolymers and supramolecular structure on their mechanical characteristics and biocompatibility was studied. Cytological studies have shown that all materials have a high level of cell viability (GSP). The possibility of obtaining hydrogels with elastic moduli up to 4460 kPa, a record for such systems, was shown.

It has been established that indicators of the intensity of chemiluminescence in the native and muscle cellized tissues of rat muscular organs, as well as in their decellularized matrices, can serve as one of the express criteria that allows, along with ultrastructural analysis, to quantify the viability of cell structures in biological samples of the diaphragm.

In order to select the optimal method for disinfecting the scaffolds prior to decellularization using morphological methods (studying the biomechanical strength of extracellular matrix fibers) and analyzing chemiluminescence in rats, the effect of octenisept and chlorhexidine was studied at different concentrations on the biological matrices of the lungs before and after decellularization. Chlorhexidine at a dilution of 1:10 possessed the least damaging properties for the matrix and most contributed to the decontamination of the cages for further storage and experimental studies.

Different methods of scanning electron microscopy in combination with different sample preparation techniques have been compared by an example of decellularized rat diaphragm matrices. It is shown that a combination of scanning electron microscopy under natural environmental conditions, allowing one to investigate tissue samples in a state similar to native, with the conventional high-vacuum microscopy of samples obtained by drying at the critical point, provides the most complete microstructural analysis of native and decellularized tissue samples.

The choice of cellular resourses for recellularization of biological scaffolds and synthetic matrices remains a topical issue in regenerative medicine. Isolation of stromal cells from native organs and their utilization for recellularization of biological matrices appears to be a promising alternative for the use of mesenchymal stromal cells. The present work presents modified protocols for obtaining stromal cells from homogenized rat lung and diaphragm tissues. Cell culture typing and cell viability evaluation on the scaffolds was followed by the orthotopic transplantation of a tissue engineered diaphragm construct in rats with histological characteristics of explanted tissue after 24 and 45 days. Recellularized stromal cell scaffolds from native tissues with otherwise equal properties caused less noticeable inflammation reaction compared with recellularized mesenchymal stromal cells (MSCs). The intensity of fibrosis was also lower then when using MSCs for scaffold repopulation.

Aim To study the effect of regular drug therapy for cardiovascular and other diseases preceding the COVID-19 infection on severity and outcome of COVID-19 based on data of the ACTIVE (Analysis of dynamics of Comorbidities in paTIents who surVived SARS-CoV-2 infEction) registry.Material and methods The ACTIVE registry was created at the initiative of the Eurasian Association of Therapists. The registry includes 5 808 male and female patients diagnosed with COVID-19 treated in a hospital or at home with a due protection of patients’ privacy (data of nasal and throat smears; antibody titer; typical CT imaging features). The register territory included 7 countries: the Russian Federation, the Republic of Armenia, the Republic of Belarus, the Republic of Kazakhstan, the Kyrgyz Republic, the Republic of Moldova, and the Republic of Uzbekistan. The registry design: a closed, multicenter registry with two nonoverlapping arms (outpatient arm and in-patient arm). The registry scheduled 6 visits, 3 in-person visits during the acute period and 3 virtual visits (telephone calls) at 3, 6, and 12 mos. Patient enrollment started on June 29, 2020 and was completed on October 29, 2020. The registry completion is scheduled for October 29, 2022. The registry ID: ClinicalTrials.gov: NCT04492384. In this fragment of the study of registry data, the work group analyzed the effect of therapy for comorbidities at baseline on severity and outcomes of the novel coronavirus infection. The study population included only the patients who took their medicines on a regular basis while the comparison population consisted of noncompliant patients (irregular drug intake or not taking drugs at all despite indications for the treatment).ResultsThe analysis of the ACTIVE registry database included 5808 patients. The vast majority of patients with COVID-19 had comorbidities with prevalence of cardiovascular diseases. Medicines used for the treatment of COVID-19 comorbidities influenced the course of the infectious disease in different ways. A lower risk of fatal outcome was associated with the statin treatment in patients with ischemic heart disease (IHD); with angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor antagonists and with beta-blockers in patients with IHD, arterial hypertension, chronic heart failure (CHF), and atrial fibrillation; with oral anticoagulants (OAC), primarily direct OAC, clopidogrel/prasugrel/ticagrelor in patients with IHD; with oral antihyperglycemic therapy in patients with type 2 diabetes mellitus (DM); and with long-acting insulins in patients with type 1 DM. A higher risk of fatal outcome was associated with the spironolactone treatment in patients with CHF and with inhaled corticosteroids (iCS) in patients with chronic obstructive pulmonary disease (COPD).Conclusion In the epoch of COVID-19 pandemic, a lower risk of severe course of the coronavirus infection was observed for patients with chronic noninfectious comorbidities highly compliant with the base treatment of the comorbidity.

The organizer of the registers “Dynamics analysis of comorbidities in SARSCoV-2 survivors” (AKTIV) and “Analysis of hospitalizations of comorbid patients infected during the second wave of SARS-CoV-2 outbreak” (AKTIV 2) is the Eurasian Association of Therapists (EAT). Currently, there are no clinical registries in the Eurasian region designed to collect and analyze information on long-term outcomes of COVID-19 survivors with comorbid conditions. The aim of the register is to assess the impact of a novel coronavirus infection on long-term course of chronic non-communicable diseases 3, 6, 12 months after recovery, as well as to obtain information on the effect of comorbidity on the severity of COVID-19. Analysis of hospitalized patients of a possible second wave is planned for register “AKTIV 2”. To achieve this goal, the register will include men and women over 18 years of age diagnosed with COVID-19 who are treated in a hospital or in outpatient basis. The register includes 25 centers in 5 federal districts of the Russian Federation, centers in the Republic of Armenia, the Republic of Kazakhstan, the Republic of Kyrgyzstan, the Republic of Belarus, the Republic of Moldova, and the Republic of Uzbekistan. The estimated capacity of the register is 5400 patients.

Aim. To study the lipid profile in hospitalized patients with coronavirus disease 2019 (COVID-19) depending on the outcome of its acute phase according to the AKTIV international registry.Material and methods. The AKTIV registry included men and women over 18 years of age with a diagnosis of COVID-19, who were treated in a hospital. A total of 9364 patients were included in the registry, of which 623 patients were analyzed for levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides on days 1-2 of hospitalization. The level of high-density lipoprotein cholesterol (HDL-C) was calculated using the Friedewald equation.Results. We found that a decrease in LDL-C level was significantly associated with an unfavorable prognosis for hospitalized patients with COVID-19. This pattern persisted in both univariate and multivariate analyses. LDL-C levels in the final multivariate model had a significant relationship with the prognosis (an increase in the death risk by 1,7 times with a decrease per 1 mmol/l). In addition, we found that the survival of patients with an indicator level of Conclusion. A decrease in LDL-C in the acute period is significantly associated with an unfavorable prognosis for hospitalized patients with COVID-19. Determination of LDL-C can be included in the examination program for patients with COVID-19. However, the predictive value of this parameter requires further study in prospective clinical studies.

History of heart transplantation in combination with immunosuppressive therapy and acute viral respiratory infection overlay makes the patient difficult to manage. In case of COVID-19, the setting is complicated by unknown pathogenesis, including its effect on blood, coagulation system, and lung tissue. Current case report discusses the 60-year-old patient with a COVID-19 infection occurred in the immediate postoperative period after heart transplantation.

Aim. To study the catestatin plasma level in patients with primary hypertension of different cardiovascular risk and to assess its relationship with heart rate variability (HRV) parameters.Material and methods. One hundred eighty men aged 30-50 years were divided into groups: group 1 (n=28) — hypertensive patients with medium risk of developing cardiovascular complications (CVC), group 2 (n=76) — hypertensive patients with high risk of CVC, group 3 (n=31) — hypertensive patients with very high risk of CVC. The control group consisted of healthy men with normal blood pressure (BP) (n=45). We determined plasma catestatin (ng/ml) and conducted Holter monitoring.Results. A pattern was found to reduce the concentration of catestatin with increasing risk of CVC in hypertensive patients, but there were no significant differences between the studied groups (p>0,05).We determined corrections between catestatin levels and echocardiography thickness of left ventricular posterior wall (r=-0,523; p=0,045) and interventricular septum (r=-0,523, p=0,045) in diastole in group 2; thickness of left ventricular posterior wall (r=0,258; p=0,035) and interventricular septum (r=0,254; p=0,038) in systole in group 3. In patients of group 2, direct correlations of catestatin levels and sympathicotonia LF/HF were revealed during the whole observation period (r=0,301; p=0,019) and during wakefulness (r=0,308; p=0,019); inverse correlations — with parameters of parasympathetic tone: nHF during the whole observation time (r=-0,318; p=0,013) and during wakefulness (r=-0,342; p=0,007), pNN50 in the afternoon (r=-0,270; p=0,037).Conclusion. A decrease in catestatin concentrations in hypertensive patients is associated with the progression of disease and an increase in cardiovascular risk. It is assumed that catestatin is involved in the formation of HRV in patients with primary hypertension.

Based on the data of morphological analysis, we performed histological evaluation of rat tissue reaction to subcutaneous implantation of decellularized matrices of intrathoracic organs and tissues. Cell composition of the inflammatory infiltrate was analyzed, and the dynamics of macrophage and T and B lymphocyte content was assessed on days 7 and 14 of the experiment. It was found that the reaction to implantation depended not only on the quality of decellularization and efficiency of removal of antigen molecules, but also on the original histological structure and quality of preimplantation processing of the transplant.

Nicotinamide adenine dinucleotide (NAD) plays a key role in the vital metabolic and regulatory processes in mammals. Disturbance of the NAD level regulation is associated with the development of such serious diseases as pellagra, neurodegenerative and cardiovascular disorders, diabetes, cancer and others. This paper presents an experimental approach that allows to determine the amount of NAD+ in mouse tissues using NMR spectroscopy, as well as the level of NAD+-dependent deacetylation of proteins in the cytosol and mitochondria.

Review of the key studies on antihypertensive, vasodilatatory, angiogenic and antiapoptotic action of catestatin — a peptide resulting from endogenic protease interaction with chromogranin А. Plasma levels of catestatin correlate negatively with the hypertension phenotype. Pathogenetic role is discussed for catestatin in development of essential hypertension and its possible influence as a marker of cardiovascular risk stratification.

Biological compatibility of a tissue engineered construct of the trachea (synthetic scaffold) and allogenic mesenchymal stem cells was studied on laboratory Papio hamadryas primates. Subcutaneous implantation and orthotopic transplantations of tissue engineered constructs were carried out. Histological studies of the construct showed chaotically located filaments and mononuclear cells fixed to them. Development of a fine connective tissue capsule was found at the site of subcutaneous implantation of the tissue engineered construct. The intact structure of the scaffold populated by various cell types in orthotopic specimens was confirmed by expression of specific proteins. The results indicated biological compatibility of the tissue engineered construct with the mesenchymal stem cells; no tissue rejection reactions were recorded; simulation of respiratory disease therapy on Papio hamadryas proved to be an adequate model.

The use of recellularized matrices allows obtaining tissue-engineered structures that largely reproduce the morphofunctional features of native organs and tissues. Doubts as to the advisability of preimplantation recellularization of the scaffold, which are associated with the death of prepopulation cells on the scaffold in vivo, require studying the behavior of cells on plastic and biological implants after recellularization. Rat esophagus that had undergone detergent-enzymatic decellularization was repopulated with GFP-positive cells intensely fluorescing in the green spectrum, which allowed us to trace the status of the initial cell population during cultivation on plastic and after transplantation, determine the viability and metabolic activity of cells, and conduct fluorescent detection of the cells on the scaffold before and after implantation. There were no data on the apparent cell proliferation on the matrix; however, there were indirect indications of metabolic activity and GFP synthesis by the cells that populated the scaffold before implantation.

New techniques were developed for the preparation of spongy materials and hydrogels based on triblock copolymers of lactide and ethylene glycol with various molecular structures. The effect of composition of the initial copolymers and supramolecular structure on their mechanical characteristics and biocompatibility was studied. According to cytological studies, all materials had a high level of cell viability (CV). The possibility of obtaining hydrogels with elastic moduli of up to 4460 kPa, which is a record high value for such systems, was demonstrated.

Aim.To study the clinical course specifics of coronavirus disease 2019 (COVID-19) and comorbid conditions in COVID-19 survivors 3, 6, 12 months after recovery in the Eurasian region according to the AKTIV register.Material and methods.The AKTIV register was created at the initiative of the Eurasian Association of Therapists. The AKTIV register is divided into 2 parts: AKTIV 1 and AKTIV 2. The AKTIV 1 register currently includes 6300 patients, while in AKTIV 2 — 2770. Patients diagnosed with COVID-19 receiving in- and outpatient treatment have been anonymously included on the registry. The following 7 countries participated in the register: Russian Federation, Republic of Armenia, Republic of Belarus, Republic of Kazakhstan, Kyrgyz Republic, Republic of Moldova, Republic of Uzbekistan. This closed multicenter register with two nonoverlapping branches (in- and outpatient branch) provides 6 visits: 3 in-person visits during the acute period and 3 telephone calls after 3, 6, 12 months. Subject recruitment lasted from June 29, 2020 to October 29, 2020. Register will end on October 29, 2022. A total of 9 fragmentary analyzes of the registry data are planned. This fragment of the study presents the results of the post-hospitalization period in COVID-19 survivors after 3 and 6 months.Results.According to the AKTIV register, patients after COVID-19 are characterized by long-term persistent symptoms and frequent seeking for unscheduled medical care, including rehospitalizations. The most common causes of unplanned medical care are uncontrolled hypertension (HTN) and chronic coronary artery disease (CAD) and/or decompensated type 2 diabetes (T2D). During 3- and 6-month follow-up after hospitalization, 5,6% and 6,4% of patients were diagnosed with other diseases, which were more often presented by HTN, T2D, and CAD. The mortality rate of patients in the post-hospitalization period was 1,9% in the first 3 months and 0,2% for 4-6 months. The highest mortality rate was observed in the first 3 months in the group of patients with class II-IV heart failure, as well as in patients with cardiovascular diseases and cancer. In the pattern of death causes in the post-hospitalization period, following cardiovascular causes prevailed (31,8%): acute coronary syndrome, stroke, acute heart failure.Conclusion.According to the AKTIV register, the health status of patients after COVID-19 in a serious challenge for healthcare system, which requires planning adequate health system capacity to provide care to patients with COVID-19 in both acute and post-hospitalization period.

The main aim of our investigation was analysis and optimization of the existing protocols of esophagus decellularization in rats, identification of parameters affecting the quality of decellularization and intactness of the native properties of esophageal extracellular matrix (ECM). Materials and methods. We developed a modified decellularization protocol based on detergent-enzymatic method using sodium deoxycholate and DNAse. Results. Morphological evaluation of the obtained decellularized matrices demonstrated the absence of cells and cell elements while mechanical properties of ECM were preserved. Conclusion. The developed protocol of esophagus decellularization is a potential basis for obtaining of tissue-engineered esophagus scaffold constructions.

It was found that the chemiluminescence intensity in native and recellularized tissues of rat muscular organs as well as in their decellularized scaffolds can serve as an express criterion that, along with ultrastructural analysis, makes it possible to perform quantitative assessment of the viability of cellular structures in biological samples of the diaphragm.

Tissue engineering is rapidly growing now and can become a promising alternative to transplantation of organs and tissues, as it is devoid of major shortcomings of transplantology, such as acute shortage, complexity of selection, delivery and storage of donor material, lifelong immunosuppressive therapy. One of the most widely known methods of obtaining biological scaffolds for the subsequent creation of tissue-engineered constructs of organs and tissues is decellularization. The evaluation of the quality of the obtained scaffolds, based on the study of the viability of cell structures in decellularized and recellularized matrices, is one of the priorities of modern regenerative medicine worldwide. In this investigation, the biophysical criteria of decellularization and recellularization of tissue-engineered constructs based on the evaluation of the generation of free radicals in native, decellularized and recellularized tissues by EPR spectroscopy and chemoluminescence in a complex assessment of the quality of biological matrixes obtained are considered using intrathoracic organs and tissues of rats. It has been established that the intensity indices of free radical generation in native and recellularized tissues of animal organs, as well as in decellularized matrices, can serve as one of the express criteria for quantitative assessment of cell structures viability.

To analyze experimental data on the effect of various polyphenolic compounds on lifespan of mice, we approximated survival curves with the Gompertz model in its minimal form, which does not account for the heterogeneity of samples and the age-independent mortality. The plots of regressions of log0 (logarithm of the initial mortality) on  (the rate of aging) in series of control samples were used to assess the deviations of vectors directed from control to experimental data from the slopes of the control regressions. The analysis of published data suggests that resveratrol, polyphenol-containing grape skin extract, metformin, tocopherol, and the antioxidant SkQ1 do not produce changes beyond those possible upon comparing of different samples of a control population. The effect of the polyphenolic composition BP-C3 on female SHR mice is unique in being associated with a significant decrease in the rate of aging. The effect may be partly contributed to by the antioxidant properties of BP-C3. Its antioxidant capacity determined in vitro is comparable with that of established antioxidants, such as dihydroquercetin. Its effects in vivo include the ability to ameliorate reduction in the peroxide-decomposing activity of RBC lysates from male BALB/c mice treated with 5-fluorouracil.Для анализа экспериментальных данных о влиянии различных полифенольных соединений на продолжительность жизни мышей использована аппроксимация кривых дожития параметрической моделью, основанной на законе Гомпертца в его минимальной форме, не учитывающей гетерогенность выборок и независимую от возраста смертность. На графиках в координатах [lg0 (логарифм начальной смертности);  (скорость старения)] строили векторы от контрольных к экспериментальным точкам и сравнивали их с сериями контрольных точек. Реальными считали изменения, при которых углы наклона соответствующих векторов отличались от углов наклона регрессий lg0 на , построенных по контрольным данным. Результаты анализа опубликованных данных показали, что ресвератрол, токоферол, богатый полифенолами экстракт кожицы винограда, антиоксидант SkQ1 и метформин не вызывают отличия контроля от опыта, выходящие за пределы того, что возможно при сравнении разных выборок одной контрольной популяции. В отличие от указанных препаратов, комплексный полифенольный препарат BP-C3 действует так, что у самок мышей SHR снижается скорость старения. Вклад в этот эффект может вносить антиоксидантная активность BP-C3. Определена его антиоксидантная емкость in vitro и продемонстрирована способность при введении in vivo препятствовать снижению общей пероксидразрушающей активности, происходящему в эритроцитах самцов мышей BALB/c при введении 5-фторурацила.

Development of artificial tissues or organs is one of the actual tasks in regenerative medicine that requires observation and evaluation of intact volume microstructure of tissue engineering products at all stages of their formation, from native donor tissues and decellularized scaffolds to recipient cell migration in the matrix. Unfortunately in practice, methods of vital noninvasive imaging of volume microstructure in matrixes are absent. In this work, we propose a new approach based on high-frequency acoustic microscopy for noninvasive evaluation and visualization of volume microstructure in tissue engineering products. The results present the ultrasound characterization of native rat diaphragms and lungs and their decellularized scaffolds. Verification of the method for visualization of tissue formation in the matrix volume was described in the model samples of diaphragm scaffolds with stepwise collagenization. Results demonstrate acoustic microscopic sensitivity to cell content concentration, variation in local density, and orientation of protein fibers in the volume, micron air inclusions, and other inhomogeneities of matrixes.

s The article is devoted to the development of a method for predicting the nonlinear dielectric properties of layered composites with complex dependences of the dielectric constant on the electric field strength, which consider the effects of a sharp increase and subsequent decrease in the dielectric constant with increasing field strength. The method is based on the use of the theory of asymptotic averaging proposed by N.S. Bakhvalov, E. Sanchez-Palencia, in relation to the nonlinear problem of electrostatics in a layered medium. As a result of applying this method, local nonlinear problems of electrostatics on a periodicity cell are formulated, and an algorithm for calculating effective nonlinear dielectric constants is proposed. It is shown that a layered composite is a transversely isotropic nonlinear dielectric material if its layers are isotropic materials. A numerical example of calculating the nonlinear properties of a 2-layer composite based on barium titanate and ferroelectric ceramic varicond VK4 is considered. Calculations have shown that the developed method for calculating the nonlinear-dielectric ratios of composites is quite effective and makes it possible to predict the dielectric properties of composites at various values of the electric field strength, including the regions where the dielectric permittivities of the layer materials are saturated. The developed technique can serve as a basis for designing new nonlinear dielectric composite materials with unusual properties.