Ашық рұқсат
Рұқсат берілді
Тек жазылушылар үшін
Том 22, № 4 (2024)
Reviews
Functional characteristics of the RAGE molecule in intercellular interactions in normal and lung pathology
Аннотация
Introduction. The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor that is highly expressed in healthy lungs and performs homeostatic function there. However, the exact mechanisms of development of these diseases remain unknown in most cases.
Purpose of the study. Analysis of information about the role of RAGE and its signaling cascades in the pathogenesis of inflammatory, fibrotic and oncological lung diseases for a deeper understanding of signal modulation of this receptor.
Material and methods. The review highlights the results of clinical and experimental studies obtained using methods for determining the quantitative expression of the receptor for advanced glycation end products (RAGE) and its ligands. When preparing materials, sources were used from international and domestic databases Scopus, Web of Science, Pub Medline, eLibrary, mainly over the past 15 years.
Results. By binding the wide range of ligands, RAGE is directly involved in the inflammatory response to injury, fibrosis processes in the lungs and the occurrence of malignant neoplasms, thereby playing an important role in the development of many lung diseases.
Conclusions. To obtain an informative picture of the pathogenesis of lung diseases, it is necessary to conduct a comprehensive assessment of the expression levels of both the RAGE signaling molecule itself and its isoforms and ligands.
3-11
The role of filaggrin in the formation of skin barrier dysfunction
Аннотация
Dysfunction of the epidermal barrier plays an important role in the development of skin inflammatory processes. Pathological changes in the intracellular composition of keratinocytes are an integral part of the modern understanding of the pathogenesis of atopic dermatitis (AD). One of the significant proteins involved in the formation of the skin barrier is filaggrin (FLG).
The purpose of our review is to summarize the available data on the role of FLG in the formation of skin barrier dysfunction in AD.
Material and methods. An analysis of domestic sources was carried out using the scientific electronic libraries Cyberleninka and Elibrary, and foreign sources using the PubMed/Medline databases.
Results. Excessive accumulation of FLG monomers in keratinocytes during skin barrier dysfunction induces premature cell death. Intracellular vesicles/exosomes remove FLG from keratinocytes for further transport through the bloodstream. Staphylococcus aureus is able to influence intracellular vesicles, enhancing FLG transport. More than 140 variants of FLG gene mutations are known, leading to a deficiency of the protective skin protein. In AD there is an increased level of FLG in the blood serum. The level of FLG increases with the severity of the skin inflammatory process. Pregnant women with AD have higher serum FLG levels compared to nonpregnant women with AD, healthy pregnant women, and nonpregnant women.
Conclusion. FLG plays a significant role in maintaining the skin barrier function. Pronounced changes in the level of FLG in the blood serum in AD allow us to consider FLG as a biomarker of exacerbation of this disease. Given the transport of FLG into the blood, further in-depth study of the role of FLG in localizations distant from the skin is necessary.
12-17
Key markers of ferroptosis
Аннотация
Introduction. Ferroptosis is a type of programmed cell death associated with excessive accumulation of endogenous iron in the cell, accompanied by the production of reactive oxygen species and, as a result, lipid peroxidation. The literature review examines the key markers of ferroptosis, which is one of the types of programmed cell death other than apoptosis, necroptosis, pyroptosis, etc.
Purpose: to collect and process information on the main markers of ferroptosis, which will allow to adapt and optimize the processes of its study.
Material and methods: analysis of literary sources of domestic and foreign origin on a given topic.
Results: articles have been found and analyzed, including those from the last 5 years, confirming the prospects of ferroptosis as a potential pharmacological target. Conclusion. Understanding the main signs of the launch of this process is an integral part of the research work aimed at finding new therapeutic targets associated with the launch of ferroptosis, which, in turn, represents a promising pharmacological model, since It has a high potential for the future treatment of drug-resistant types of pathologies.
18-27
Original research
The study of beta-glucan immunomodulating effect in the organotypic culture of rat immune tissue
Аннотация
Introduction. An urgent problem in biology and medicine is the identification of biologically active molecules that affect the cellular processes of proliferation and apoptosis in various tissues of the body.
Purpose of the study. The purpose of this study was to identify the effect of combinations of immunomodulating beta-glucan with immunodepresive preparation cycklophosphamide in organotypic immune tissue of kidney and thymus of 5-months rats.
Material and methods. The method of organotypic cultivation of immune tissues of kidney and thymus was used for rapid screening of the biological activity of the studied beta-glucan.
Results. It has been established that by the combined use of beta-glucan and cycklophosphamide the immunodepresive effect is eliminated.
Conclusion. The data obtained create the basis for beta-glucan usage as a protector by the immunodepresive action of different substances. The base is created for creation of new drugs for treatment of the oncological and infection deseases.
28-31
Elastic and hyperelastic properties of the human nail plate
Аннотация
Introduction. As is known, changes in the nail, as an appendage of the skin, can be genetically determined, caused by injuries, diseases, medications or exposure to harmful substances. Installation of partial or complete dentures may be required for any form of growth disorder of the nail plate (onychodystrophy). Prosthetics can act as a means of masking nail abnormalities. In all these cases, knowledge of the mechanical properties of both the replacement materials and the nail plate itself is necessary. However, the latter have not been fully studied; there is no detailed knowledge about the elastic and hyperelastic characteristics of the biomaterial.
The aim of the study. The mechanical properties of the human nail plate are compared with elastic and hyperelastic models of continuum mechanics (large deformations).
Methods. Experimental σ-ε curves obtained from literature data were used. The computer algebra system Mathcad 15.0 and the multifunctional finite element analysis package ANSYS 2022 R2 were used.
Results. The parameters of the linear and 6-hyperelastic models were calculated and their correspondence to the initial data was determined. Among hyperelastic models, the 5-parameter Mooney–Rivlin model and the 2nd order polynomial model are best suited to describe the mechanical properties of the nail plate. These models have the highest correlation coefficient R=0.98 and the following statistical indicators SD=0.005 GPa, δmax=0.011 GPa, δ=12.93%. The greatest discrepancies between the experimental and model data were demonstrated by the Ogden model of the 1st order nail plate (R=0.84) and the simplest hyperelastic neohookean model (R=0.86). The stability of the models (dσ/dε sign) at small deformations was studied.
Conclusion. The results obtained can be useful for podiatrists involved in the development of methods for restoring nail plates using artificial replacement materials and are recommended for use in nail tissue engineering.
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Dacarbazine initiates sirt1-independent overexpression of anti-apoptotic bcl2 in melanoma cells in vivo
Аннотация
Introduction. Cancer cell drug resistance in melanoma is associated with evasion of apoptosis-induced stimuli. Assessing the level of expression of the BCL2 and SIRT1 genes in distant organs and the tumor node makes it possible to assess the resistance of melanoma cells to chemotherapeutic effects associated with the activation of anti-apoptotic mechanisms.
The aim of the study. Relative expression level of the SIRT1 and BCL2 estimation in the tumor node and target organs for distant metastatic (lungs, liver) in B16 melanoma bearing mice under dacarbazine treatment.
Methods. In the in vivo model of B16 melanoma. Intraperitoneal administration of dacarbazine was used in vivo. Subsequently, total RNA was extracted from the cells of tumor node and distant organs (liver, lungs). Relative expression levels of the apoptosis and cell proliferation genes SIRT1, BCL2 were analyzed using real-time PCR (RT-PCR) method.
Results. When exposed to dacarbazine, the relative level of expression of the anti-apoptotic BCL2 in the tumor in B16 melanoma increases by 5.7-fold. The relative expression level of SIRT1 in the lungs after intraperitoneal injections of dacarbazine decreased by 3.8-fold.; in the liver of mice, the relative expression level of SIRT1 increased by 1.94-fold. The relative level of BCL2 expression in the lungs after intraperitoneal injections of dacarbazine decreased by 31-fold. In mouse liver, the relative expression level of BCL2 increased 1.94-fold.
Conclusion. When exposed to dacarbazine as a damaging factor in skin melanoma in vivo, SIRT1-mediated protection against apoptosis of liver cells and SIRT1-mediated activation of apoptosis in lung tissue cells of mice can be replaced, while in the melanoma tumor cell a pattern of SIRT1-independent induction of anti-apoptotic processes by dacarbazine in B16 melanoma bearing mice under dacarbazine treatment.
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Interleukins and metalloproteinases in the lungs of mice with BCG-granulomatosis with the injection of the liposomal form of dextrazide
Аннотация
Introduction. An actual decision of the issue of safety and effective drug therapy improvement is the development of transport systems that allow to provide targeted delivery of drugs to target cells, while reducing their toxic effects. The aim of the work was to carry out a comparative study of the effects of isoniazid, composition of isoniazid with oxidized dextran (dextrazid), and liposomal form of dextrazid (LFD) on the levels of interleukins IL-6 and tumor necrosis factor-α (TNF-α), metalloproteinases MMP1 and MMP9, tissue inhibitor of proteinase TIMP1, volume density of destruction and lymphoid infiltrates in the lung parenchyma of mice with BCG-granulomatosis.
Material and Methods. The study was performed on 100 male BALB/c mice, the tested substances were injected for 2 and 6 months. Lungs were fixed in 10% buffered formalin solution and subjected to standard histologic staging. To estimate the volume density of destructive changes and lymphoid infiltrates, the percent of area occupied by them was determined; in immunohistochemical study, the volume density of positively stained cells was determined.
Results. It was shown that the effectiveness of dextrazide in comparison with isoniazid regarding the reduction of inflammatory processes activity in the lungs is higher, with the greatest effectiveness of LFD injected by inhalation. In response to isoniazid injection into mice, the levels of MMP1 and MMP9 decreased more than twice, and the level of TIMP1 increased; LFD injection intraperitoneally and inhaled caused a more pronounced effect. The level of destructive changes in the lung parenchyma of mice was maximal in mice in the comparison group and minimal in animals injected with LFD regardless of the form of its injection.
Conclusion. The results of the study indicate that oxidized dextran in composition with isoniazid contributes to an additional reduction in the activity of inflammatory processes in the lungs of mice with BCG granulomatosis; placing the composition in liposomes enhances the anti-inflammatory effect and contributes to the reduction of destructive processes by decreasing MMP activity and increasing TIMP1 activity.
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Pathogenetic role of changes serum level interleukin-4 during therapy for ulcerative colitis
Аннотация
Introduction. An important pathogenetic link in systemic inflammation in ulcerative colitis (UC) is dysregulation of the immune response.
The aim of the study: to study pathogenetic changes in the serum level of interleukin (IL)-4 during UC therapy.
Methods. 66 patients with ulcerative colitis were examined, of which 21 patients received genetically engineered biological drugs (GEBD), and 20 healthy volunteers. The amount of IL-4 was determined by enzyme immunoassay.
Results. The content of IL-4 in the serum of patients significantly exceeded the values of the control group. Minimum cytokine values (3–4 pg/ml) were determined in 5 patients with severe UC activity and total intestinal lesions without GEBD therapy. Negative correlations between IL-4 values and the location of colitis and the severity of exacerbation were revealed. Achieving remission was accompanied by an increase in serum IL-4, which was less during GEBD therapy.
Conclusion. A study of the IL-4 content in the blood serum of patients in the dynamics of UC revealed significant quantitative changes at different stages of the disease, exceeding the values of healthy volunteers. Restriction of overproduction of IL-4 as an anti-inflammatory cytokine can serve as a criterion for the effectiveness of therapy.
52-56
Different concentrations of peroxynitrite cause a unique cellular response of endotheliocytes in vitro
Аннотация
Introduction. The study of the effect of peroxynitrite, as a product of nitric oxide (II), on the culture of endothelial cells in vitro can contribute to fundamental ideas about the violation of the adhesive function of the endothelium when changing the synthesis of nitric oxide.
The aim of the study. To study the effect of peroxynitrite in various concentrations on the metabolic and migration activity of endotheliocytes, as well as on the expression of endothelium-specific proteins-selectin Р and Е, as an indicator of the adhesive function of the endothelium.
Methods. The cytotoxicity of peroxynitrite in various concentrations was assessed using the MTT test. The migration and proliferative activity of endotheliocytes was studied by a scratch test. The concentration of sP- and sЕ-selectins was determined using the ELISA sandwich method in the supernatant of endotheliocytes culture.
Results. A statistically significant increase in the metabolic activity of endothelial cells was revealed during a 30-minute incubation with peroxynitrite at concentrations of 0,0025, 0,0075 and 0,01 mM. A statistically significant decrease in the migration activity of endothelial cells was revealed after a 30-minute incubation with peroxynitrite at concentrations of 0,0025 and 0,1 mM, both in the first 12 and within 24 hours. A multidirectional effect of peroxynitrite at various concentrations on the level of sP and sE selectins in the cell culture supernatant was revealed: a statistically significant decrease in sE-selectin after 30-minute incubation with peroxynitrite solutions at concentrations of 0,0025, 0,1 and 1,0 mM; as well as a statistically significant increase in sP-selectin during 30-minute incubation with peroxynitrite solutions of 0,0025 and 0,1 mM.
Conclusion. Peroxynitrite for endothelial cells can act as a signaling molecule, stimulating or suppressing mitochondrial and migratory activity, and also as a cytotoxic agent, causing cell death. In addition, at various concentrations it is capable of influencing either the synthesis of endothelium-specific selectin proteins or the proteolytic shedding of the extracellular domains of these proteins, which requires further study.
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