Инсулин-позитивные клетки печени и экзокринной части поджелудочной железы у животных с экспериментальным сахарным диабетом

Aim. To compare the number of insulin+ cells in the liver and exocrine part of the pancreas with the type of experimental diabetes, blood glycose and glycated hemoglobin (HbA1c) level and with the number of Pdx1+ cells. Materials and methods. The experiment was carried out on 25 male Wistar rats (weighting (303.0 ± 25.3) g) that were divided into 3 groups: The first group consisted of intact animals, the second had animals with experimental diabetes type 1, and the third with animals with experimental diabetes type 2. Biochemical, immunohistochemical, ELISA methods and statistical analysis were used. Results. Insulin+ and Pdx1+ cells of rats with experimental diabetes were found in the liver and exocrine part of pancreas. The highest number of insulin+ cells in the liver was detected in type 2 diabetes (T2D). A strong positive correlation between the number of insulin+ cells in the liver and level of glycosylated hemoglobin in theblood was revealed in both type 1 and type 2 diabetes. Conclusion. Insulin+ cells are detected in the liver and acinar part of pancreas of both intact rats and rats with experimental diabetes. Group with T2D is characterized by the highest number of insulin+ cells in the liver compared with type 1 diabetes (T1D). The localization of insulin+ cells in the liver changes depending on the type of diabetes. In T2D insulin+ cells are located in all parts of liver acini, meanwhile in animals with T1D such cells are mainly detected in the periportal area. The expression of Pdx1+ in acinar cells of pancreas and liver cells is likely a mechanism for their reprogramming into insulin+ cells in experimental diabetes mellitus. © 2020 Siberian State Medical University. All rights reserved.This work was financially supported by the Russian Science Foundation, grant No. 16-1500039-P and the budget project No. АААА-А18-118020590108-7 of the Institute of Immunology and Physiology, UB RAS

Karl Marx is a Thinker and Creator of the Future

The article considers Karl Marx, an outstanding thinker, who thanks to his knowledge of philosophy, history, and economics has managed to predict the stages and forms for economic, social and, substantially, spiritual development of peoples. His vision of the future is based on the thoughtful, real, and significant understanding of the economic activity of human society. Generally, the scientific community with rather deep and sincere respect paid attention to his ability to expect the future for centuries forward. This article is not just a tribute to the 200 anniversary since the birth of the genius. Now in the 21st century, K. Marx’s anniversary is, first of all, the recognition of his genius. Living now, we see the economic, social and spiritual development of humanity in the conditions of convergence of science, education, quality of life, human health, warm-heartedness and credibility in overcoming even small challenges. We strive for a careful attitude to nature, rational use of its gifts and natural wealth. Only in such harmony, the mankind will have a happy future

SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19

The review aims to consolidate research findings on the molecular mechanisms and virulence and pathogenicity characteristics of coronavirus disease (COVID-19) causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and their relevance to four typical stages in the development of acute viral infection. These four stages are invasion; primary blockade of antiviral innate immunity; engagement of the virus’s protection mechanisms against the factors of adaptive immunity; and acute, long-term complications of COVID-19. The invasion stage entails the recognition of the spike protein (S) of SARS-CoV-2 target cell receptors, namely, the main receptor (angiotensin-converting enzyme 2, ACE2), its coreceptors, and potential alternative receptors. The presence of a diverse repertoire of receptors allows SARS-CoV-2 to infect various types of cells, including those not expressing ACE2. During the second stage, the majority of the polyfunctional structural, non-structural, and extra proteins SARS-CoV-2 synthesizes in infected cells are involved in the primary blockage of antiviral innate immunity. A high degree of redundancy and systemic action characterizing these pathogenic factors allows SARS-CoV-2 to overcome antiviral mechanisms at the initial stages of invasion. The third stage includes passive and active protection of the virus from factors of adaptive immunity, overcoming of the barrier function at the focus of inflammation, and generalization of SARS-CoV-2 in the body. The fourth stage is associated with the deployment of variants of acute and long-term complications of COVID-19. SARS-CoV-2’s ability to induce autoimmune and autoinflammatory pathways of tissue invasion and development of both immunosuppressive and hyperergic mechanisms of systemic inflammation is critical at this stage of infection

Acute and Chronic Systemic Inflammation: Features and Differences in the Pathogenesis, and Integral Criteria for Verification and Differentiation

Currently, there is rationale for separating the systemic manifestations of classical inflammation from systemic inflammation (SI) itself as an independent form of the general pathological process underlying the pathogenesis of the most severe acute and chronic diseases. With this aim in view, we used integral scales of acute and chronic SI (ChSI), including the following blood plasma parameters: interleukins 6, 8, 10; tumor necrosis factor alpha; C-reactive protein; D-dimer; cortisol; troponin I; myoglobin. The presence of multiple organ dysfunction according to the SOFA score was also taken into account. The effectiveness of the scales was tested in groups of intensive care patients during different periods of acute trauma, sepsis, and septic shock. The ChSI scale was applicable under systemic autoimmune diseases, chronic purulent infections, chronic limb threatening ischemia, and end-stage renal disease of various genesis. The number of examined patients was 764 in total. The scales allowed us to verify specific phases of acute SI and identify pathogenetic risk factors of lethal outcomes, as well as the most severe variants of the chronic pathologies course. These scales are open adaptable systems (in terms of the nomenclature and choice of indicators). They are primarily intended for scientific research. However, the SI verification methodology presented in this paper may be useful for developing advanced criteria for assessing both the typical links in the pathogenesis of many diseases and the severity of the overall condition of patients for clinical practice

Lymphopenia-induced proliferation of CD4 T-cells is associated with CD4 T-lymphocyte exhaustion in treated HIV-infected patients

Background & objectives: Under the lymphopenic condition, T-cells divide to maintain their peripheral pool size. Profound chronic lymphopenia in some treated HIV-infected patients, characterized by poor T-cell recovery, might result in intensive homeostatic proliferation and can cause T-cell exhaustion and/or senescence. The present study was undertaken to evaluate the homeostatic proliferation of CD4+T-cells in treated HIV-infected individuals, and to determine the amount of phenotypically exhausted and senescent CD4 T-lymphocytes. Methods: Thirty seven treated HIV-infected patients with suppressed HIV viral load (350/μl (n=21). T-cell subsets [naïve, central memory (CM), and effector memory (EM)] and proportions of cycling (Ki-67+), senescent (CD57+) and exhausted (PD-1+) T-lymphocytes were assessed using flow cytometry. Results: CD4+T-cell cycling rate was higher in INRs than in IRs due to more extensive proliferation of CM, 4.7 vs 2.7 per cent (P 0.05)] was more pronounced in the INR group than in the IR group. The frequency of CD4+Ki-67+ CM T-cells was related to the proportion of CD4+PD-1+ cells of the same subset, r=0.789 (P <0.001). The numbers of CD4+Ki-67+PD-1+ CM and EM T-cells were substantially higher in INRs than in IRs. Interpretation & conclusions: The present data indicated that intensive homeostatic proliferation contributed to the T-cell exhaustion in HIV-infection

Antinuclear Autoantibodies in Health: Autoimmunity Is Not a Synonym of Autoimmune Disease

The incidence of autoimmune diseases is increasing. Antinuclear antibody (ANA) testing is a critical tool for their diagnosis. However, ANA prevalence in healthy persons has increased over the last decades, especially among young people. ANA in health occurs in low concentrations, with a prevalence up to 50% in some populations, which demands a cutoff revision. This review deals with the origin and probable physiological or compensatory function of ANA in health, according to the concept of immunological clearance, theory of autoimmune regulation of cell functions, and the concept of functional autoantibodies. Considering ANA titers ≤1:320 as a serological marker of autoimmune diseases seems inappropriate. The role of anti-DFS70/LEDGFp75 autoantibodies is highlighted as a possible anti-risk biomarker for autoimmune rheumatic disorders. ANA prevalence in health is different in various regions due to several underlying causes discussed in the review, all influencing additive combinations according to the concept of the mosaic of autoimmunity. Not only are titers, but also HEp-2 IFA) staining patterns, such as AC-2, important. Accepting autoantibodies as a kind of bioregulator, not only the upper, but also the lower borders of their normal range should be determined; not only their excess, but also a lack of them or “autoimmunodeficiency” could be the reason for disorders

The global response to the COVID-19 pandemic : how have immunology societies contributed?

The COVID-19 pandemic is shining a spotlight on the field of immunology like never before. To appreciate the diverse ways in which immunologists have contributed,Nature Reviews Immunologyinvited the president of the International Union of Immunological Societies and the presidents of 15 other national immunology societies to discuss how they and their members responded following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For this Viewpoint,Nature Reviews Immunologyasked the presidents of 16 immunology societies from around the world to discuss how their society and its members responded to the COVID-19 pandemic. Their answers highlight the incredible contributions that immunologists around the globe have made following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)