R. Velichinskii, J. Vavilova, A. Boyko, O. A. Shustova, A. Palamarchuk, G. Yusubalieva, O. N. Kucherova, M. Streltsova, E. Kovalenko
{"title":"Umbilical cord blood as a promising source of NK cells for immunotherapy","authors":"R. Velichinskii, J. Vavilova, A. Boyko, O. A. Shustova, A. Palamarchuk, G. Yusubalieva, O. N. Kucherova, M. Streltsova, E. Kovalenko","doi":"10.15789/1563-0625-ucb-2846","DOIUrl":"https://doi.org/10.15789/1563-0625-ucb-2846","url":null,"abstract":"Currently, a large number of studies on genetic modification of cord blood NK cells (UCB-NK) are carried out at both clinical and preclinical levels. Immunotherapy based on UCB-NK cells has great potential for antitumor therapy. However, despite having known several advantages over peripheral blood NK cells (PB- NK), including a high concentration in cord blood and low virulence rate, UCB-NK cells are predominantly characterized in the scientific literature as immature and low-functioning NK cells. In this work, we studied the phenotypic characteristics of UCB-NK cells and the possibility of stimulatory compensation of the decreased functional activity of UCB-NK cells. Our studies revealed UCB-NK cells can be characterized as poorly differentiated and weakly activated cells with high level of inhibitory receptor NKG2A and low level of activating receptor NKG2C and HLA-DR, accordingly with the literature data. Two types of stimuli were chosen to stimulate freshly isolated UCB-NK cells: 1) 100 units of IL-2; 2) combinations of 100 units IL-2 and K-562 feeder cells expressing membrane-bound IL-21 (K562-mbIL21). It was shown the degranulation (LAMP-1) and proliferative activity was higher than for parallel cultured ex vivo PB-NK cells under the same conditions for UCB-NK cells stimulated for 7 days with IL-2 + K562-mbIL21. Moreover, stimulation in the way of IL-2 + K562-mbIL21 seemed to be a more perspective way to obtain a large number of proliferatively active UCB-NK cells compared to stimulation with IL-2 only. Since genetic modification of NK cells is a promising way to improve the antitumor properties of NK cells, retroviral transduction procedure was performed to study of the stimulated UCB-NK cells. UCB-NK cells stimulated with IL-2 + K562-mbIL21 were transduced on day 8 of cultivation. In this study, we used targeted overexpression of the adaptor molecule DAP12, which is involved in the signaling of activating NK cell receptors. PB-NK cells and UCB-NK cells were transduced under the equal experimental conditions in same volume of viral particles. As a result, the transduction efficiency was found to be more than 4-fold higher for UCB-NK cells compared to PB-NK cells. Thus, UCB-NK cells appear to be a promising tool for further research in cancer immunotherapy.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81306055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. Malashenkova, V. Ushakov, S. Krynskiy, D. Ogurtsov, N. Khailov, A. Ratushnyy, E. Filippova, N. Zakharova, G. P. Kostyuk, N. Didkovsky
{"title":"Associations of IL17A G-197A single nucleotide polymorphism with immunological parameters and structural changes of the brain in schizophrenia","authors":"I. Malashenkova, V. Ushakov, S. Krynskiy, D. Ogurtsov, N. Khailov, A. Ratushnyy, E. Filippova, N. Zakharova, G. P. Kostyuk, N. Didkovsky","doi":"10.15789/1563-0625-aoi-2806","DOIUrl":"https://doi.org/10.15789/1563-0625-aoi-2806","url":null,"abstract":"Schizophrenia is a chronic mental disorder that is caused by a complex palette of genetic, epigenetic and environmental factors. Some of the important components of its pathogenesis are systemic inflammation and the dysfunction of immunity, which lead to neuroinflammation, contributing to development of structural brain changes. Earlier we have shown that increase in interleukin-17A levels is associated with morphometric changes and immune dysregulation in schizophrenia. IL17A G-197A (rs2275913) genetic polymorphism is involved in determining interleukin-17A secretion. The goal of this work was to investigate the associations between rs2275913 polymorphism, immune disorders and structural neurovisualization findings in schizophrenia to provide new insights into the immunopathogenesis of this disease. 60 patients aged 18 to 42 years diagnosed with schizophrenia were enrolled. 85 healthy volunteers were included into the control group. Multiplex assay was used to determine cytokine and chemokine serum levels. Rs2275913 polymorphism was assessed by polymerase chain reaction with electrophoretic detection of amplification products. A number of relationships between rs2275913 polymorphism and the immune parameters in schizophrenia were revealed. Carriers of G allele showed significant increase in IFNY, a key cytokine of Th1-link of adaptive immunity, and IL-8, an inflammatory chemokine. Also, increased levels of CXCL16 were observed in patients carrying the G allele. CXCL16 activates secretion of other proinflammatory chemokines and is involved in activation of Th1 adaptive immunity. Associations of heterozygous GA genotype with reduced cortical thickness in a number of areas of the frontal cortex in schizophrenia were found. Changes in cortical thickness in some of these areas, including middle frontal gyrus and orbitofrontal cortex, can be relevant to the pathogenesis of schizophrenia. The results highlight the importance of immunogenetic factors in the pathogenesis of schizophrenia and indicate that the rs2275913 polymorphism requires further studies as a potential biomarker of immune dysregulation and morphometric brain changes in schizophrenia.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83257376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Features of the immune status of patients with acute coronary syndrome who underwent СOVID-19, depending on the number of cytotoxic T lymphocytes (CD8+)","authors":"E. Safronova, L. V. Ryabova, A. Zurochka","doi":"10.15789/1563-0625-fot-2834","DOIUrl":"https://doi.org/10.15789/1563-0625-fot-2834","url":null,"abstract":"The 2019 coronavirus disease (COVID-19) pandemic has had an unprecedented impact on health and economies around the world. Direct myocardial injury and cytokine storm, leading to destabilization of preexisting plaques and accelerated formation of new plaques, are two mechanisms that trigger the acute coronary syndrome in COVID-19. There is insufficient data on the immune status of patients with acute coronary syndrome who have undergone COVID-19. The aim of the study was to study T and B cell, humoral immunity depending on the number of cytotoxic T lymphocytes (CD8+) in patients with acute coronary syndrome who underwent COVID-19. Materials and methods of research: 65 men with unstable angina pectoris and acute myocardial infarction (acute coronary syndrome) from 40 to 65 years old, who had previously had COVID-19, were examined. A study of peripheral blood was carried out: complete blood count (Medonic device, Sweden), general and specific IgM, IgG, IgA, compliment fragments (Vector Best, Russia). Subpopulations of T and B lymphocytes were determined by flow cytometry. In persons with acute coronary syndrome who underwent COVID-19 with predominantly normal and elevated levels of cytotoxic T cells, a more severe course of the disease was observed: patients with acute myocardial infarction prevailed, they had longer mortality, longer treatment duration, and stent thrombosis was more common. In patients with elevated cytotoxic T cells, there was a maximum increase in erythrocytes, hemoglobin, hematocrit, lymphocytes of both the total number and subpopulations – T helpers, T-NK lymphocytes, NK lymphocytes, T lymphocytes of early and late activation, B1 and B2 lymphocytes, index of NBT-induced test. In patients with normal levels of NK cells, compared with other groups, there was an increase in spontaneous NBT activity and index, a significant decrease in C3a and C5a complement fragments. Prevalence of stent thrombosis and mortality in the group of patients with normal levels of cytotoxic T cells may indicate torpidity of the immune system in these patients with poor outcomes.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88040488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metalloproteinase 9 and its role in the pathogenesis of allergic diseases in children","authors":"O. Semernik, A. Lebedenko, A. A. Appoeva","doi":"10.15789/1563-0625-mai-2721","DOIUrl":"https://doi.org/10.15789/1563-0625-mai-2721","url":null,"abstract":"Metalloproteinases (MMP) play a significant role in the mechanisms of maintaining chronic inflammation and tissue remodeling. The study of concentration changes in these enzymes in the blood serum of children with allergopathology is of great practical and scientific interest.Objective: to study the role of MMP-9 in the pathogenesis of allergic diseases in children. 180 children aged from 1 to 18 years passed a comprehensive clinical and laboratory examination. This study included patients suffering from bronchial asthma (BA) (n = 54), atopic dermatitis (AD) (n = 54) and combination of these pathologies (n = 72). Serum levels of MMP9 were determined by enzyme immunoassay using Cloud-CloneCorp® test systems (USA).The analysis of the obtained data showed that among patients with the established diagnosis of BA, the maximum concentration of this cytokine was registered in children with a moderate course of the disease. The conducted correlation analysis showed the presence of a significant correlation between the severity of asthma and the level of control over the disease (r = 0.63). Similar data was obtained in patients with a combination of BA and AD. In children of this group, there was also a significant increase in serum MMP-9 compared with healthy patients (p = 0.015). The concentration of this matrix metalloproteinase in serum was slightly higher among children with polyvalent sensitization than in patients with monoallergic etiology of the disease (p = 0.272). The values of MMP-9 in patients with only skin manifestations of atopy were significantly higher than in the control group (p = 0.025).The data we obtained showed that all the patients we examined had a significant increase in the level of MMP-9 in the blood serum, which indicates an important role of this cytokine in the pathogenesis of allergic diseases in children.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89652767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. A. Markov, E. G. Kostolomova, T. Kh. Timokhina, G. S. Solovyev, Ya. I. Paromova, E. D. Polyanskih, K. A. Voronin
{"title":"Effect of <i>Bifidobacterium bifidum</i> supernatant on the morphological and functional characteristics of human fibroblasts in real time during an <i>in vitro</i> experiment","authors":"A. A. Markov, E. G. Kostolomova, T. Kh. Timokhina, G. S. Solovyev, Ya. I. Paromova, E. D. Polyanskih, K. A. Voronin","doi":"10.15789/1563-0625-eob-2720","DOIUrl":"https://doi.org/10.15789/1563-0625-eob-2720","url":null,"abstract":"Currently, there is an active search for exogenous stimulators of repair and regeneration processes. In the recent decades, some data on the immunotropic activity of bifidobacteria have been accumulated. The key role in healing of wound defects belongs to fibroblasts due to the secretion of the extracellular matrix components, metabolites, signal factors for the surrounding cells, and tissue metabolism regulation. The paper presents the results of the study of the effect of Bifidobacterium bifidum supernatant (10 ml/mL) on the morphological and functional properties of human fibroblasts in real time during the in vitro experiment. In our work, we used the reference strain B. bifidum 791 (All-Russian Collection of Industrial Microorganisms of the State Research Institute for Genetics and Selection of Industrial Microorganisms “Genetika”, Deposit No. AS-1247) used in the production of the probiotic product “Bifidumbacterin” (ZAO “Ecopolis”, the city of Kovrov), and adult human fibroblasts (cell line LECH-4 (81)) (laboratory of cell cultures ENIIVI, the city of Yekaterinburg). Structural and functional studies were conducted on co-culture days 1, 3, 7, 14, 21, and 28. The products of B. bifidum secondary metabolism have a stressful effect on the morphological and functional state of fibroblasts on the first day. The processes of proliferation are stimulated in the culture in the experiment (2.67±0.24) compared with the control group (0.75±0.15) (p < 0.01) without blocking apoptosis in the cell. This leads to the increase in the production of extracellular matrix proteins, both collagen (pg/mL) (400±19 against 110±25 in the control group), and elastin (ng/mL) 395±30 and 125±29). Co-culture of fibroblasts within 24 hours in the experimental sample leads to a massive “release” of the CD44 receptor (p < 0.05), compared to the control group which is confirmed by phenotypic changes (r = 0.66). The decrease of CD105 + , CD44 + receptors (p < 0.05), compared with the control group and the increase of CD29 + expression (p < 0.05) is observed on days 1 and 3. Activated fibroblasts have an altered secretory phenotype that produces cytokines of various types such as TGF-b (r = 0.78), IL-6 (r = 0.57), IL-1b (r = 0.75), IL-8 (r = 0.63). The maximum adaptation of cells in the experimental system is registered on the 7th day, which correlates with morphometric (r = 0.59) and cytometric (r = 0.71) studies. The received data contribute to understanding of the mechanisms of the immunoregulatory influence of normal biota (in the bifidobacteria model) on the repair and regeneration processes.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135165196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Gorbunov, A. Zhakhov, I. N. Gorbunova, A. M. Milichkina, I. Drozd, A. V. Gubanova, E. M. Danilova, R. N. Kuznecova, T. V. Savin, A. G. Burtseva, N. Pigareva, A. Ischenko, A. Totolian
{"title":"Quantification of C1 esterase inhibitor in human serum by enzyme-linked immunosorbent assay: Correlation with turbidimetric immunoassay","authors":"N. Gorbunov, A. Zhakhov, I. N. Gorbunova, A. M. Milichkina, I. Drozd, A. V. Gubanova, E. M. Danilova, R. N. Kuznecova, T. V. Savin, A. G. Burtseva, N. Pigareva, A. Ischenko, A. Totolian","doi":"10.15789/1563-0625-qoc-2794","DOIUrl":"https://doi.org/10.15789/1563-0625-qoc-2794","url":null,"abstract":"C1 inhibitor of serine proteases (C1-INH) performs a regulatory function in the complement system and vascular permeability. Deficiency of C1-INH leads to various forms of angioedema, including hereditary angioedema (HAE). The cause of HAE is a genetically determined violation of the synthesis of C1-INH. A decrease in the level of C1-INH to 50% relative to the norm leads to an increase in the production of bradykinin, which is the basis for the diagnosis of HAE. The development of affordable ELISA for the quantitative determination of C1-INH is a popular direction for clinicians. During the development of a new kit for quantitative determination of C1-INH, two mouse monoclonal antibodies (mAb) with different epitope specificities were obtained. On their basis, a sandwich-type ELISA was developed. The specificity of the obtained mAb's was confirmed using the medical device “Berinert”. To prepare calibrators, C1-INH was affinity purified from human blood plasma using a sorbent with immobilized mAbs. The identity of the C1-INH protein was confirmed by PAGE electrophoresis, immunoblotting, and mass spectrometry on MALDI-TOF/TOF UltrafleXtreme mass spectrometer. To assess the quality indicators of developed reagents kit, studies were carried out in accordance with GOST R 51352-2013 and TU 21.20.23-041-01967164-2022. Values of quality indicators: accuracy — 93.53%; measurement linearity interval — 22.00-176.07 ng/mL. Using the developed ELISA test system, we examined 28 blood sera from healthy donors and 7 blood sera from patients with confirmed HAE. In the same samples, the content of C1-INH was determined by turbidimetric method, using the \"Diagnostic reagents for in vitro immunochemical studies of specific blood proteins. Model: C1-esterase inhibitor (C1 EsteraseInhibitor)\" (Aptec, Belgium). The correlation coefficient was 0.94 (p < 0.05). It was found that the diagnostic sensitivity and specificity of the developed ELISA is 100%. As a result of the study, an original ELISA test system for the quantitative determination of C1-INH was developed \"Reagent kit for enzyme-linked immunosorbent assay of human C1-inhibitor (C1-inh PS)\".","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75265988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Semikina, M. Snovskaya, M. Basargina, A. A. Seliverstova, A. A. Zhuzhula, I. Davidova
{"title":"Evaluation of mediators of fibrosis and angiogenesis in the blood serum of premature infants with bronchopulmonary dysplasia","authors":"E. Semikina, M. Snovskaya, M. Basargina, A. A. Seliverstova, A. A. Zhuzhula, I. Davidova","doi":"10.15789/1563-0625-eom-2789","DOIUrl":"https://doi.org/10.15789/1563-0625-eom-2789","url":null,"abstract":"In premature birth and postpartum damage to the developing lung, the processes of the formation of pulmonary vessels and alveoli are disrupted, leading to bronchopulmonary dysplasia (BPD). BPD is a multifactorial disease and the pathogenesis of lung tissue damage is still not fully understood. Studies of angiogenesis biomarkers can be informative for assessing the development of BPD. In this study we examined the blood serum of 65 premature infants aged 6 to 180 days of life; gestational age at birth was 23-33 weeks, body weight 480-1840 g, APGAR score 5-6. All children in the early neonatal period had respiratory distress syndrome, then 46 children formed and 19 did not form bronchopulmonary dysplasia. The concentration of the factors of angiogenesis and fibrosis was determined in blood serum by ELISA. There were no differences in the levels of angiopoietins 1 and 2, vascular endothelial growth factor VEGF-D, transforming growth factor beta TGF-β, thrombospondin-1. We observed a tendency to increasing the level of VEGF-A, which is a key regulator of angiogenesis and lung maturation; we regard this tendency as a favorable sign of lung formation. We found tendencies to increase of the adhesion molecule of endothelial platelet cells PECAM-1, interleukin 8 and connective tissue growth factor CTGF. CTGF expression is enhanced by artificial lung ventilation and exposure to high oxygen concentrations. We consider an increase of CTGF in BPD to be an unfavorable change, since the binding of CTGF to VEGF inhibits VEGF-induced angiogenesis. In children with BPD, we found a decrease in the level of platelet derived growth factor PDGF-BB, the median concentration was 3180 pg/mL in BPD versus 4782 pg/mL without BPD (p = 0.024). PDGF is an important factor in tissue regeneration and plays an important role in the formation of blood vessels. We assume the decreasing of PDGF concentration in BPD can lead to a violation of the alveolarization necessary for the formation of the structure of healthy lungs. Studies of angiogenesis factors will help to better understand the pathogenesis of lung damage in BPD.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74127592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. V. Neroeva, O. A. Svitich, V. Neroev, A. R. Kinkulkina, N. Balatskaya, E. Sorozhkina
{"title":"Investigation of local expression of NLRP3 inflammasome complex genes in modeling retinal degeneration in vivo","authors":"N. V. Neroeva, O. A. Svitich, V. Neroev, A. R. Kinkulkina, N. Balatskaya, E. Sorozhkina","doi":"10.15789/1563-0625-iol-2780","DOIUrl":"https://doi.org/10.15789/1563-0625-iol-2780","url":null,"abstract":"Neurodegenerative ophthalmopathology is one of the main causes of irreversible blindness and disability in the world. In the pathogenesis of diseases of this group, more and more attention has recently been paid to the role of local inflammation caused by the activation of innate immunity and the mechanisms of its genetic regulation. In recent years, works have appeared in the field of experimental ophthalmology that have demonstrated the possibility of NLRP1, NLRP3 inflammasome complexes assembling when exposed to hyperglycemia, oxygen deprivation of retinal cells, as well as modeling compressive stress similar to that in glaucoma [15]. However, the mechanism of inflammasome involvement in the development of neurodegenerative eye diseases remains unclear. The aim of the study was to investigate the local expression of genes encoding proteins of the NLRP3 inflammasome complex (NLRP3, CASP-1) in an experimental model of retinal degeneration in rabbits. The studies were performed on samples of tissue complex (TC) of the retina/retinal pigment epithelium (RPE) (retina/RPE TC), isolated from the eyes of 14 New Zealand albino rabbits, in which degenerative retinal lesion was modeled by a single subretinal injection of 0.01 mL of 0.9% sodium chloride solution, and 7 healthy rabbits without eye damage. The formation of retinal degeneration was judged on the basis of changes in morphofunctional parameters obtained during specialized ophthalmological research methods (optical coherence tomography, fundus autofluorescence, electroretinography) at follow-up periods of 1, 3 and 6 months. The level of expression of NLRP3 and CASP-1 genes in the retina/RPE TC was evaluated by reverse transcription polymerase chain reaction (RT-PCR). According to the results of the study, a statistically significant increase in NLRP3 gene expression (p < 0.001) was noted in the retina/RPE TC of experimental animals, which may indicate the involvement of NLRP-3 inflammasome components in the development of neurodegenerative retinal lesions. At the same time, the expression of the gene encoding CASP-1 was detected only in the retina/RPE TC of experimental eyes and is probably due to local inflammatory mechanisms in the retinal tissue.The high level of NLRP3, CASP-1 mRNA, detected in all retina/RPE TC samples of experimental eyes at late stages of the experiment (3 and 6 months), allows us to assume the formation of mechanisms (for example, activated glial phenotype) that support inflammation in retinal tissue. This should be taken into account in actively developing transplantation methods for the treatment of retinal degeneration.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74916711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Pivovarova, I. Voznyuk, I. V. Osipova, O. Ariskina, E. A. Gogoleva, M. V. Prokhorova, N. G. Karpova
{"title":"Hypoxia-induced factor-1α and markers of inflammation in patients with ischemic stroke","authors":"L. Pivovarova, I. Voznyuk, I. V. Osipova, O. Ariskina, E. A. Gogoleva, M. V. Prokhorova, N. G. Karpova","doi":"10.15789/1563-0625-hif-2740","DOIUrl":"https://doi.org/10.15789/1563-0625-hif-2740","url":null,"abstract":"Ischemic stroke (IS) occurs as a result of local disturbance of hemocirculation and hypoxia in the brain tissue. Hypoxia-inducible factor-1α (HIF-1α), which is involved in the regulation of tissue oxygen levels, plays an important role in the pathophysiology of stroke, including neuronal survival, neuroinflammation, angiogenesis, glucose metabolism, blood-brain barrier permeability, and is important in IS outcomes. The purpose of the study was to determine the relationship between blood levels of HIF-1α and the degree of neurological deficit in the acute period of IS and the outcome of the disease. We examined 58 people with IS aged 73 (67-81) years. Patients were divided into two groups – discharged and dead. The severity of stroke (NIHSS), neurological deficit, comorbidity index, blood levels of HIF-1α, p53 protein, interleukin-6, cystatin C, CRP, creatinine, hematological parameters were determined at admission, on days 3 and 10 of the disease. At admission the blood levels of HIF-1α was lower than in the comparison group and remained reduced until the 10th day. On day 10 the association of HIF-1α with neurological deficit, comorbidity index and disease outcome was determined. We observed a feedback of HIF-1α with the content of erythrocytes, hemoglobin and hematocrit, which can be regarded as a reflection of the hemic component of mixed hypoxia. In dead patients, an increased blood level of cystatin C was detected, which was associated with HIF-1α concentrations. In all periods of observation of IS, a correlation between cystatin C and creatinine and CRP levels was noted. These results may indicate dysfunction of endotheliocytes, inflammation associated with hypoxia in IS. The prognostic significance of the blood level of HIF-1α on the 10th day for the outcome of IS was AUC = 0.900. Blood levels of HIF-1α in the acute period was associated with the severity of IS and the outcome of the disease.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76889028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Kovaleva, I. Nesterova, S. N. Pikturno, E. I. Dydyshko, N. S. Prosolypova, А. M. Chulkova
{"title":"Diagnostically significant changes in subsets CD11b+CD64-CD32+CD16+, CD11b+CD64+CD32+CD16+ neutrophilic granulocytes of immunocompromised women with chronic infectious and inflammatory diseases of the genital tract of various etiologies","authors":"S. Kovaleva, I. Nesterova, S. N. Pikturno, E. I. Dydyshko, N. S. Prosolypova, А. M. Chulkova","doi":"10.15789/1563-0625-dsc-2782","DOIUrl":"https://doi.org/10.15789/1563-0625-dsc-2782","url":null,"abstract":"Chronic pelvic inflammatory disease (PID) in women remains a problem due to the importance of medical consequences. The study of the receptor apparatus of neutrophilic granulocytes (NG) involved in anti-infective protection in diseases of various etiologies seems to be relevant. Aim: to clarify the features of variants of quantitative and phenotypic changes in subsets of NG CD11b+CD64-CD32+CD16+, CD11b+CD64+CD32+CD16+ of immunocompromised women during exacerbation of chronic PID of various etiologies. We were tested women 20-40 years: Study Group 1 (SG1, n = 20) – chronic PID during the exacerbation with mono- or mixed latent/recurrent various viral infections (chronic herpes-virus infections, papillomavirus infection, recurrent ARVI); Study Group 2 (SG2, n = 30) – chronic PID of bacterial etiologies; Comparison Group (CG)– 20 healthy women. The number of subsets CD11b+CD64-CD32+CD16+NG (major) and CD11b+CD64+CD32+CD16+NG (minor), receptor expression density (MFI) was determined (FC500, USA). It was found that in PID during the period of exacerbation, diagnostically significant differences in the subset composition of NG were revealed. We got a decrease in the CD11b+СD64-СD32+СD16+NG subset and in 7,6 times increase in the CD11b+CD64+CD32+CD16+NG subset in SG2 with chronic PID of bacterial etiology, in contrast to chronic PID occurring in combination with recurrent/persistent viral infection SG1. Negative transformation of NG subsets is associated with a predominant decrease in the level of expression of the activation CD16. The absence of an adequate response to the infectious and inflammatory process was revealed – the absence of an increase in the expression of the activation CD11b in the major subset in SG1, as well as in the minor subset in groups SG1 and SG2. In the major subset of NG in groups SG2 a decrease in the expression of the activation marker CD11b. In the various viral infections and PID (SG1), in the negatively altered minor subset of NG we got a decrease of expression of CD16, an increase of expression of CD64 and CD32. Determination of subsets of CD11b+СD64-СD32+СD16+, CD11b+CD64+CD32+CD16+NG and their phenotype can be used as diagnostic markers for the differential diagnosis of PID of viral and bacterial etiology, and for the development of new methods of targeted immunomodulatory therapy.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76174859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}