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Vol 22, No 6 (2024)
- Year: 2024
- Articles: 9
- URL: https://journals.eco-vector.com/1728-2918/issue/view/12863
- DOI: https://doi.org/10.29296/24999490-2024-06
Reviews
The role of soluble immune checkpoint molecules in hematologic malignancies (review)
Abstract
Introduction. Immune checkpoint (IC) signaling pathways are involved in regulating the functions of T lymphocytes and NK cells, which play a key role in antitumor and antiviral control.
The purpose of our study was to systematically analyze the information presented in current literature on the role of soluble ICs (sICs) in the development of hematological neoplasia.
Material and methods. The review includes data from foreign and domestic articles published in PubMed over the past 15 years, which are devoted to the role of soluble IC molecules in the pathogenesis of hematologic malignancies.
Results. The development of lymphoid and myeloid neoplasia is accompanied by an increase in the level of a number of soluble immunoregulatory molecules (programmed cell death protein 1 (sPD-1) and its ligands sPD-L1 and sPD-L2, cytotoxic lymphocyte antigen 4 (sCTLA-4), T-cell immunoglobulin domain and mucin domain 3 (sTIM-3), costimulatory molecules sCD86, sCD40), which is associated with a poor prognosis, shorter overall and progression-free survival of patients. The established patterns confirm the pathogenetic role of the listed soluble IC molecules in the development of malignant diseases of the blood system, as well as their significance as predictors of response to therapy and risk groups stratification.
Conclusion. The presented analysis demonstrates the significant pathogenetic and prognostic role of sICs in hematological neoplasia of lymphoid and myeloid nature.
3-13
Experimental models of lung sarcoidosis
Abstract
Introduction. Sarcoidosis is a systemic granulomatous disease of unknown origin. The study of its features and the development of new diagnostic and treatment methods are limited by the absence of generally accepted experimental models. The purpose of the review is to evaluate existing models of sarcoidosis. To date, there have been in vitro, in vivo, and in silico models of lung sarcoidosis developed. In vitro models are mainly based on cells obtained from C57BL/6J mice or from patients with sarcoidosis. In vivo models have been developed using Lewis rats and C57BL/6 mice. Granuloma formation in these experimental models occurs under the influence of various infectious (most often M. tuberculosis antigens) and non-infectious triggers (such as introducing nanoparticles like quantum dots and multi-walled carbon nanotubes). In silico models consist of individual studies that combine biological data with mathematical and computational representations of granuloma formation. These models allow researchers to evaluate the interactions between immune cells and various cytokines and predict the effects of drugs on potential targets. However, the quality of these models is closely linked to in vitro and in vivo studies and the information obtained from research on the pathogenesis of sarcoidosis.
Material and methods. Studies published in international research databases over the last ten years were reviewed using the keywords sarcoidosis, lung sarcoidosis, and sarcoidosis models, in silico, in vitro and in vivo models.
Conclusion. None of the models adequately meets the research objectives and does not fully reproduce the disease. The prospects for improving sarcoidosis models lie in the use of genetically engineered mice, the creation of cell lines, and the exploration of in silico models.
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Molecular aspects of pathogenesis of chronic lymphocytic leukemia
Abstract
Introduction. Chronic lymphocytic leukemia (CLL) is the most common leukemia type in adults. CLL is characterized by significant changes in the patient's genome, including both various mutations and epigenetic changes. These changes currently play an important role in the diagnosis, prognosis and treatment of the disease.
The aim of the work is to review the scientific literature on genetic mutations that occur in chronic lymphocytic leukemia.
Material and methods. The following databases were used to search for published studies: PubMed, Web of Science, EBSCOhost and Scopus. The search was performed in the time period from the date of creation of the corresponding databases to October 2024. A study was considered suitable if it was original, included the clinical and pathogenetic features of CLL.
Results. From the presented analysis of sources, it could be concluded that the main genetic changes in CLL are chromosomal mutations. Moreover, the most common anomalies are del(13q14) and del(17p). The microenvironment in CLL is also very important. The behavior of CLL cells depends on signals originating from non-tumor cells in the microenvironment. The tumor genome of many patients with CLL is characterized by the presence of mutations in the genes of the variable region of the heavy chain of immunoglobulins, while in other patients the above-mentioned genes do not contain mutations, which is associated with an unfavorable prognosis of the disease.
Conclusions. The review analyzes various types of anomalies in CLL. The main stages of the pathogenetic mechanism in the evolution of the disease and possible methods of treatment depending on the genetic mutation are also examined.
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Innovative approaches to genome editing in the treatment of neurodegenerative diseases
Abstract
The purpose of this review is to analyze current advances in the field of genome editing, their application for the modeling and treatment of neurodegenerative diseases, as well as to discuss current limitations and prospects for overcoming barriers in clinical practice.
Materials and methods. To achieve this goal, a systematic analysis of literature over the past nine years (2016–2024) was conducted in the databases CyberLeninka, eLibrary, PubMed, Cochrane Library, SAGE Premier, Springer and Wiley Journals.
The main provisions. Neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's diseases remain a serious challenge for modern medicine, characterized by progressive loss of neurons and the lack of effective therapeutic methods capable of stopping or reversing the pathological process. In recent years, genome editing technologies, including CRISPR-Cas9, TALEN and ZFN, have opened up new horizons in the treatment of these diseases. However, their clinical application is associated with a number of limitations, including problems of delivering editing tools to cells of the central nervous system, the risk of non-target mutations, and ethical issues. In this regard, the improvement of genome editing methods is one of the key areas. Modern methods such as CRISPR-Cas9, basic and prime editing, as well as epigenomic and RNA editing, have demonstrated high potential for accurate correction of genetic defects and modification of pathogenetic processes. Improvements in delivery systems, including viral and non-viral methods, have made it possible to overcome barriers such as low permeability of the blood-brain barrier and increase the effectiveness of therapy.
Conclusion. In recent years, significant progress has been made in the development of methods aimed at improving the safety of genomic editing in the nervous system. Despite significant advances, genome editing technologies face a number of challenges, including the need to increase specificity, minimize non-targeted effects, improve editing in postmitotic neurons and develop long-term safety monitoring methods, as well as address ethical issues related to the clinical application of these technologies.
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Use of nanotechnology in the creation of targeted drugs for the treatment of oncological diseases
Abstract
Objective. To analyze current advances in nanotechnology applications for the development of targeted drugs in oncology, including their mechanisms of action and clinical application prospects.
Material and methods. A comprehensive analysis of scientific literature on nanotechnology applications in anti-cancer drug development was conducted. PubMed, Scopus, and Web of Science databases were used for the period 2000–2024.
Results. The main types of nanoparticles used in oncology, their physicochemical properties, and tumor delivery mechanisms were systematized. The principles of the EPR effect and strategies for improving targeted drug delivery were described. Modern approaches to nanoparticle modification for enhancing their therapeutic efficacy were analyzed.
Conclusion. Nanotechnology represents a promising direction in the development of anti-cancer drugs, enabling improved therapy efficacy and safety. The use of drug delivery nanosystems helps overcome biological barriers and enhance pharmacokinetic parameters of drugs.
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Original research
Molecular mechanisms of the geroprotective action of magnesium hyaluronan in inflamaging human skin fibroblasts
Abstract
Introduction. The study of the molecular mechanisms of skin aging is one of the key problems of dermatocosmetology. Inflamaging is a chronic low–level inflammation that occurs with age. This condition is characterized by a change in the expression of proteins involved in the processes of aging and skin regeneration. Hyaluronic acid preparations containing metals have shown their geroprotective effect in the conditions of inflamaging.
The aim of the studyto identify key biomarkers of cell aging (the development of inflamaging), as well as to study the effect of a hyaluronic acid-based drug with the presence of magnesium in chelated form (Magniderm-09) on human skin fibroblasts in an inflamaging model to assess its possible geroprotective effect.
Material and methods. The study was performed on a culture of skin fibroblasts in a model of inflamaging induced by genotoxic stress. To assess the expression of molecular markers, immunohistochemical analysis of levels of Ki-67, collagen I, III and IV, LOX, ubiquitin, CCN1, IL-8, MMP-3, NF-kB, SIRT1, CD44 was performed.
Results. The modeling of inflamaging revealed a decrease in the expression of Ki-67, all types of collagen, LOX, CCN1, SIRT1, CD44, as well as an increase in proinflammatory cytokines – IL-8, NF-kB, MMP-3 and ubiquitin. Administration of the drug "Magniderm-09" returned expression levels to normal values, which indicates its geroprotective effect.
Conclusion. A correlation has been revealed between the chemical composition of a hyaluronic acid-based hydrogel preparation with the presence of magnesium in chelated form and the molecular biological changes accompanying the process of cellular aging.
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Pathomorphological analysis of salinomycin and nanodiamonds efficacy on Lewis lung carcinoma in mice
Abstract
Relevance. The search for new antitumor drugs and their selective delivery directly to the tumor site is an important task of modern oncology. For these purposes, currently, the use of various nanoparticles as carriers of medicinal substances is of great importance. The pathomorphological features of tumor cells under the action of salinomycin and nanodiamonds have not been studied enough.
The aim of the work was to study the pathomorphological features of the tumor in mice with transplanted Lewis lung carcinoma, who were treated with the ionoform antibiotic salinomycin and a combination of salinomycin with nanodiamonds.
Material and methods. 20 mice were divided into 4 groups. 1 – control group; 2 – mice received salinomycin; 3 – salinomycin and nanodiamonds; 4 – nanodiamonds. A morphometric study of histological and immunohistochemical tumor preparations stained for PCNA was carried out.
Results. Salinomycin is established to have an antineoplastic action. The use of nanodiamonds did not significantly affect the morphofunctional characteristics of Lewis lung carcinoma and did not change the antitumor activity of salinomycin.
Conclusion. Salinomycin has an antitumor effect and requires further research.
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The effect of mexidol on the pro- and antioxidant status of blood cells at the stages of anesthesia and in the postoperative period during cystectomy and nephrectomy
Abstract
Introduction. In clinical experiments with various pathologies leading to the activation of POL, it was found that one of the most important areas of correction of oxidative stress is the use of drugs with the properties of antioxidants and antihypoxants [6, 7]. Among these drugs, succinic acid and its derivatives deserve special attention, one of which is the synthetic antioxidant mexidol.
Objectives. To study the effect of antioxidant drug Mexidol on the dynamics of indicators of lipid peroxidation in pre and postoperative phase in patients, which was shown cystectomy and nephrectomy.
Methods. For the study we have chosen two groups of patients, which included patients with pathology of bladder, mostly with tainted tumors. The second group of patients included patients with cancer of the kidney, which was shown nephrectomy. In both groups used different types of anesthesia and premedication with Mexidol. Mexidol was used in the postoperative phase of treatment.
To assess the state of the antioxidant system of the organism of patients was determined the activity of antioxidant enzymes – superoxide dismutase and catalase, as well as the intensity of free radical oxidation at the level of accumulation of malondialdehyde. All of these parameters were determined in plasma and in red blood cells at the following stages: 1 – before surgery, prior to sedation; 2 – traumatic phase on the background of anesthesia, 3 in the postoperative period for 7–10 days.
Results. When comparing the results of the study between groups of patients with malignant tumors of the bladder and oncological diseases of the kidneys, a unidirectional change in the balance of POL /AOS was found: against the background of intensification of free radical oxidation processes, inhibition of the activity of erythrocyte SOD and catalase and an increase in the activity of the same enzymes in blood plasma were recorded. The development of oxidative stress caused by changes in the activity of AOS enzymes was more pronounced in group 2 patients.
Conclusion. Patients with malignant tumors of the bladder and kidneys discovered inhibition of the activity of erythrocyte enzymes of the first line of antioxidant defense against increase the intensity of the FLOOR.
The use of Mexidol as a protective means during operative intervention, the effects of epidural and endotracheal anesthesia, as well as during postoperative treatment caused stabilization of antioxidant enzymes in blood cells and in plasma, exerting a positive effect on the status of cellular membranes.
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Genotoxic effect of SARS-CoV-2 on immunocompetent cells
Abstract
Introduction. In present, the medical community continues to study the impact of coronavirus infection on various organs and systems of the body. Infection with the SARS-CoV-2 virus causes multifaceted pathological processes and, among other things, affects the cells of the circulatory system.
Objective: To assess the degree of DNA damage in peripheral blood lymphocytes of patients infected with the SARS-CoV-2 virus.
Material and methods. 200 patients took part in the study. The control group consisted of conditionally healthy individuals matched by gender and age (n=50). The degree of DNA damage was assessed using the DNA comet assay in an alkaline medium. The assessment parameters included: tail length (TL) (pc), percentage of damaged DNA in the tail (Tail DNA, %), tail moment (conventional units) and Olive moment (conventional units).
Results. The average values of the parameters of comet DNA of patients in the acute period of coronavirus infection were: TL 95.18±5.7 pc, percentage of damaged DNA in the tail (Tail DNA%) 70.82±7.12%, tail moment 68.52±8.58 conventional units, Olive moment 41.11±4.46 conventional units. When comparing the parameters of comet DNA of lymphocytes of conditionally healthy individuals and patients in the acute period of coronavirus infection associated with the SARS-CoV-2 virus, a significant increase (p < 0.001) in these parameters is noted, which indicates an increase in the content of fragmented and damaged DNA in peripheral blood lymphocytes in sick individuals.
Conclusion. The obtained results prove the powerful genotoxic effect of the SARS-CoV-2 virus on human cells.
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