In 2020 the whole world was faced with an epidemiological outbreak caused by a new coronavirus SARS-CoV-2. The information available to date suggests that the newly isolated SARS-CoV-2 coronavirus should be assigned to superantigens, the main manifestations of which, as it is known, are suppression of nonspecific resistance factors and suppression of innate immunity mechanisms associated with the formation of a systemic inflammatory response in the form of cytokine storm and pathological activation of phagocytes in the lung tissue with its alteration and subsequent fibrosis. In this case, it is quite difficult and sometimes even impossible to observe the formation of fully-fledged specific immune answer on the effect of such antigens. This, along with the high infectious nature of the disease and the associated mortality, requires special attention to the underlying immunopatomechanism(s). Perhaps that is why little information has been obtained regarding the immunogenic properties of the newly isolated SARS-CoV-2 coronavirus so far, as well as, most importantly, about the structures of the virus itself responsible for the formation of specific immunity to it. The latter will serve as the basis for patient management and vaccine development. Nevertheless, a certain point of view on this issue is already beginning to form, as tools for detecting specific antibodies are being actively developed, as well as modern diagnostic tests for coronavirus, which include real-time polymerase chain reaction, real-time reverse transcription polymerase chain reaction and isothermal amplification mediated by reverse transcription. The presented analysis makes it possible to expand the understanding of the issue concerning the immunopathogenesis of COVID-19, the mechanisms of the onset and development of the disease in a living organism, the formation of an immune response to the new coronavirus, and also to determine the therapeutic tactics of managing patients with severe coronavirus infection. Elucidating the mechanisms of the emergence and development of a new coronavirus infection can help scientists, general practitioners, clinicians, and laboratory physicians respond correctly to the COVID-19 pandemic.
The results of three-year research on the use of allogeneic mesenchymal stem cells of adipose tissue (AMSCs) in the treatment of skin burns of II-III degree are presented. in a complex with wounds dressing of nanofibers chitosan and copolyamide, hyaluronic acid. It was found that with surgical necrectomy, introduction of AMSCs and substitution of defects with natural polymer coatings, the healing time is reduced by 89% (p < 0.05). Isolated administration of MSC reduces the healing period by no more than 5% (p > 0.05). The combined use of wounds dressings of nanofibers chitosan and copo lyamide with MSC accelerates the regeneration process by 26% (p < 0.05), with the introduction of AMSCs accelerating the development of granulation tissue by the fifth day of observation by 83% (p < 0.01). Joint use of wound coverings on the basis of hyaluronic acid with AMSCs is accompanied by an increase in the number of vessels of the microcirculatory bed in the defect area by 185% (p < 0.01). Clinical evaluation of the effectiveness of drugs with stem cells – a gel for topical application and a suspension of MSC LC for injection administration demonstrate their ability to optimize regeneration in the burn zone. Application of gel with AMSCs reduces the duration of epithelialization of border (dermal) burns by 2.2-2.4 times, with the final healing period being reduced by 59% (p < 0.01) and the suppuration frequency by 30% (p < 0.05). The introduction of a suspension of AMSCs into the zone of deep burn increases the frequency of engraftment of autografts, stimulates angiogenesis and proliferation of fibroblasts in the superficial and deep layers of the dermis. In the area of MSC administration, the LC perfusion level and the amplitude of blood flow fluctuation are twice as high as the values in the zones without the introduction of cells.
The characteristic of population Т-lymphocytes is presented. The variety of effects of these cells is connected with presence of many subpopulations which name small subpopulations helper T-lymphocytes: Тh1, Тh2, Тh3, Тh9, Тh17, Тh22. Mechanisms of activation of these cells and their role in development of mechanisms of the adaptive immune answer, and also possible variants of development of immune dysfunctions and an immune pathology are described. However, the leading part is allocated to the characteristic regulatory T-lymphocytes. From all subpopulations regulatory lymphocytes subpopulation CD4+CD25+high-Т-lymphocytes. Regulatory function autoimmunity а from these cells is most well investigated is shown already at early age. Given subpopulЫation Т-lymphocytes is capable to render suppressor influence on various types immunocompetent the cells providing functioning both congenital, and got immunity. Very important role in functioning CD4+CD25+high-Т-lymphocytes belongs transcriptional to factor FoxP3. It is established, that FoxP3 renders negative effect on activation of T-cells, possibly, owing to oppression efferent functions interleukin 2. Suppressor the effect of these cells is not limited to the T-cells specific to self-antigens. Their influence extends on all microenvironment lymphocytes. Regulatory function CD4+CD25+high-Т-lymphocytes is carried out by means of rendering cytotoxic effect on a cell-target by means of perforins, granzyme A and CD18 without participation of a Fas-receptor. CD4+CD25+high-Т-lymphocytes can render suppressor effect through production transforming growth the factor and expression him on a membrane of a cell. Except for these cells are described Тh3-lymphocytes and inducible regulatory cells. Effects which they cause, are connected with production transforming growth the factor, interleukins 4 and 10. The given biological functions lead to oppression of production of antibodies plasmacytes and modulate presenter activity of macrophages and dendritic cells.
The aim of the study was to develop a method for diagnosing pre-nosological changes in the electrophysiological state of the myocardium in patients with somatoform dysfunction of the autonomic nervous system (SDANS) and risk factors for cardiovascular diseases using the ECG dispersion mapping method. Materials and Methods. The study involved 109 male patients, 58 of them with SDANS, and 51 were healthy subjects. The patients with SDANS had the following risk factors for cardiovascular diseases, in decreasing order: stress (71% of cases), low physical activity (59%), smoking (57%), overweight and obesity (43%), anxiety (41%), low consumption of vegetables and fruit (36%), lack of extra aerobic physical activity (36%), excessive alcohol consumption (34%), depression (26%), total cholesterol ≥5 mmol/L (23%), and heart rate ≥80 (9% of the cases). All the subjects underwent clinical examination, laboratory investigation, ECG, ECG dispersion mapping, heart rate variability monitoring. Results. Using the method of ECG dispersion mapping allowed a way for diagnosing pre-nosological changes in the electrophysiological state of the myocardium in male patients with SDANS, the basis of the pathogenesis of which is formed by the tension of the regulatory systems. Correlation between the total score according to the developed method, the RRNN value after 4 min of staying in orthostasis, and the “Myocardium” integral index has been proved. The diagnostic sensitivity of the proposed method with a threshold score of 8 was 80%, specificity — 70.8%. Conclusion. The developed method for assessing pre-nosological changes in the electrophysiological state of the myocardium which includes cardiovascular risk factors with a reclassifying potential, proves the development of pre-nosological changes in patients with SDANS in response to daily physical strain. The changes are associated with the tension of the electrophysiological state of the myocardium, an increased activity of the sympathetic division of the ANS being one of its pathogenetic mechanisms.
Objects and modern methods of genome editing are considered. The immune system of prokaryote and their protective mechanisms that prevent the purposeful editing of the genome for the benefit of the researcher is characterized. This mechanism in prokaryotes are cluster regulatory interspatial short palindrome repetitions. The number of such repetitions varies from object to object, which ultimately makes it impossible to get the perfect standard model. Three types of such systems that have their own mechanism for generating proteins have now been identified. The proteins, which are now most commonly used to edit the genome and identify areas of proto-special adjacent motifs, are described. Detailed characteristics of the organization of the immune system prokaryote and phases of its activity are given. Three types of short-palin re-recurrence systems have now been identified, and the teams are being identified as cluster regulatory interspatial short palindrome repetitions-Cas9. Each system uses its own mechanism to generate proteins that catalyze the fission of nucleic acids. The type II cluster regulatory interspatial short palindrome repetitions system is most commonly used, better adapted to edit the genome because of its simplicity. It has been established that the cluster regulatory interspatial short palindrome repetitions-Cas9 system can be used for point editing of the genome and in eukaryotes. This is done either through non-homological annexation of the end, or by homologically directed reparation. A promising variant of genetic modeling is the use of the enzyme-endonuclease Cpf1, which is the effector protein of the cluster regulatory interspatial short palindrome repetitions-Cas V type systems. Cpf1 is smaller than the enzyme protein Cas9 and for the system to function only require specers of ribonucleic acid, without additional ribonucleic acid. Unlike Cas9, which cuts both chains of deoxyribonucleic acid in the same place, Cpf1 generates an incision, creating ticky ends that can be used to insert interesting sequences by complementing and ligation. It is likely that the system using the enzyme-endonuclease Cpf1 will be more convenient than the system where the protein is used Cas9, as the range of editing of the controlled genome of ribonucleic acid is expanded to make the necessary edits.
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