Medicine

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Medicine

#16 Autoantibody spectrum and blood cytokine profile in children with juvenile idiopathic arthritis and unspecified reactive arthropathy

Abstract: The research deals with the problem of increasing the number of children with chronic inflammatory joint disease, in particular with juvenile idiopathic arthritis (JIA), to diagnoze which the determination of antibodies against citrullinated peptide (ACP) is increasingly used. However, contradictory diagnostic data in children with such joint diseases [...] Load More determine the relevance of assessing the prevalence of autoantibodies (AAB), the level of cytokines (CK) in whole-blood cell culture supernatants. The research purpose is to evaluate the frequency of determination of AAB, the features of the production of pro- and anti-inflammatory CK in children with JIA and unspecified reactive arthropathy (nReA). The work was carried out according to the general scientific methodology based on a systematic approach applying formal-logical and specific methods. An integrated approach was used, including the analysis of outpatient records, laboratory and statistical methods. The frequency of occurrence of antinuclear antibodies (ANA) was studied; spontaneous and stimulated production of pro- and anti-inflammatory CK by peripheral blood cells, as well as the level of these proteins in blood serum, were evaluated. A comparative analysis of the obtained data with the results of the reference group was applied. The study found the frequency of antibodies against modified citrullinated vimentin (AMCV) and ANA in the reaction of indirect immunofluorescence in patients with JIA and with nReA; the most common types of substrate fluorescence. The research discovered that in patients with JIA there is an imbalance in spontaneous cytokine production, and in patients with nReA there is an increase in spontaneous production of both pro-inflammatory and anti-inflammatory CK by blood cells; when mitogen stimulated blood cells in children with JIA and nReA, there is an increase in TNF-α production, a decrease in the secretion of IL-1β, IL-8, IFN-γ, IL-1ra, compared to conditionally healthy children; in children with JIA, there are no differences between groups with positive and negative values of AMCV in clinical, radiological parameters and CK production, as well as between groups with positive and negative results of the determination of antinuclear factor (ANF). It is recommended to use the obtained data on AAT production and cytokine profile in chronic inflammatory joint diseases in children, rheumatology, and physiology. It is not required to determine the level of AMCV in nReA patients. It is proposed to simultaneously evaluate spontaneous and stimulated production of pro- and anti-inflammatory CK by blood cells in scientific and clinical practice. For the first time, a research of the frequency of detection of ANA and ACP in children with nReA was conducted; the production of pro- and anti-inflammatory CK by peripheral blood cells in patients with nReA was studied; a comprehensive study of spontaneous and stimulated synthesis of pro- and anti-inflammatory CK by peripheral blood cells in patients with JIA, nReA and in healthy children was carried out using a common methodological framework. The methodological approach with the use of mitogen stimulation made it possible to characterize the features of CK production by blood cells, which were not manifested in the study of their spontaneous synthesis. The methodological approach with the use of mitogen stimulation allowed characterizing the features of CK production by blood cells, which were not manifested in the study of their spontaneous synthesis.
Keywords: autoantibody; arthropathy; vimentin; peptides; cytokines
Date of publication: March 2025 / Deadline: 10 January 2025

Journal title: available for those who has paid.

Region of the journal publication: Europe.

Scientific field: Medicine.

Indexing of the journal: Scopus (Q2); WoS (Science Citation Index Expanded; Social Sciences Citation Index ).

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#43-med Whole genome analysis of primary open-angle glaucoma associations with polymorphic loci of the LOXL1 gene

Abstract: Under modern conditions, primary open-angle glaucoma continues to occupy a leading place in the structure of visual disabilities, despite the success in early diagnosis, a wide range of conservative and surgical methods of treatment. The etiology of glaucoma has not been fully studied, because a multifactorial concept with the involvement of various [...] Load More genetic and non-genetic factors prevails in explanation of its origin and development. Therefore, the selection of polymorphic loci to find associations with the studied phenotype is important for a genetic and epidemiological survey. The purpose of this research was a whole genome analysis and substantiation of associations of primary open-angle glaucoma with polymorphic loci localized in the region 15q24.1. The 246 men with a clinical diagnosis of primary open-angle glaucoma made up an experimental sample of observations, 176 of which formed a control group. The control sample of the observed men has been formed on the principle of nationality homogeneity and lack of any kindred relationships among men. With the use of the phenol-chloroform extraction method, the genomic DNA has been isolated based on the generated panel of peripheral blood samples of the observed men. A sample of seven polymorphic gene loci was formed, whose reaction with the level of expression previously proven in other studies. For the purpose of the genotype comparative analysis of each of the observed patients on the basis of the method of the polymerase chain reaction of DNA synthesis, genotyping of the investigated polymorphic loci has been performed. Determination of the regulatory potential of polymorphisms using contingency tables with the phenotype under investigation has been performed on the platform of the HaploReg software package. The analysis and evaluation of the association in accordance with the Hardy-Weinberg law of genetic equilibrium have been performed using Pearson's chi-squared test. The method of multivariate logistic regression analysis was used in the framework of this research to study the relationship of reference and alternative alleles to the change in regulatory DNA motifs of recipients. The reflective research has confirmed the proactive value of polymorphic loci of the LOXL1 gene (GG rs893818 and GG rs4886776) in the development of primary open-angle glaucoma among men. The results of this research are valuable for understanding the specificity of particular genes in the development of visual defects across various ethno-territorial population groups and environmental conditions. Keywords: genotype, primary open-angle glaucoma, polymorphic loci, expression, whole genome analysis, LOXL1 gene.
Keywords: genotype, primary open-angle glaucoma, polymorphic loci, expression, whole genome analysis, LOXL1 gene.
Date of publication: April 2025 / Deadline: 10 January 2025

Journal title: available for those who has paid.

Region of the journal publication: Europe.

Scientific field: Medicine.

Indexing of the journal: Scopus (Q2); WoS (Science Citation Index Expanded) IF 3.5.

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#39-med Effect assessment of monocyte subpopulations on the immunopotentiating and tolerogenic properties of dendritic cells generated by them

Abstract: Dendritic cells perform important immunoregulatory functions while being easily generated from a population of peripheral blood monocytes. The lack of research in the field of monocyte effect in the context of monocyte subpopulations on the properties of the dendritic cells generated by them determines the relevance of the research. The purpose of this [...] Load More paper is to assess the effect of monocyte subpopulations on the immunopotentiating and tolerogenic properties of dendritic cells. The basis of the study was the data concerning the functional activity indices of dendritic cells generated by CD16- and CD16+ (CD16-Mo-DK and CD16+Mo-DK, respectively) monocytes of 39 healthy donors. The dendritic cell reaction was studied under standard conditions and experimental conditions by adding dexamethasone to dendritic cell culture. The Wilcoxon Rank-Sum Test and correlation analysis in Statistica 6.0 software package have been used for statistical data processing. The statistical significance of differences in the level of immunopotentiating and tolerogenic properties of dendritic cells has been assessed using the Wilcoxon Rank-Sum Test. The strength of the relationship between the stimulant activity of T cells and the pro-inflammatory and anti-inflammatory cytokine production has been assessed by the Spearman's rank correlation. According to the results of the assessment for standard conditions, it was found that for the CD16+Mo-DK population the endocytosis has a lower level compared with CD16-Mo-DK but is more elastic under the effect of dexamethasone. The assessment of the proliferative response has demonstrated that dendritic cells have a stimulating effect on the proliferation of T cells. At the same time, CD16+Mo-DK has a higher ability to stimulate the proliferation of allogeneic T cells. Differences in the response level of autologous T cells are not statistically significant. The dendritic cells under study are equally capable of producing pro-inflammatory and anti-inflammatory cytokine. Based on the results of the experiment, the character of the dexamethasone effect on the investigated characteristics of immunopotentiating and tolerogenic properties of dendritic cells was determined, which is stimulating for the ability of endocytosis and production of pro-inflammatory cytokine and, at the same time, discouraging for the power of proliferative response and production of pro-inflammatory cytokine. The results of the correlation analysis made it possible to determine the feedback between the stimulant activity of T cells and the production of cytokine. The exception is the direct relationship between the activity of CD16-Mo-DK and the production of the pro-inflammatory cytokine. The findings of the research have been confirmed by statistical indicators and present the basis for using regularities of monocytes' effect on the properties of dendritic cells generated by them in practical immunology.
Keywords: monocytes, dendritic cells, T cells, endocytosis, proliferation, population.
Date of publication: April 2025 / Deadline: 10 January 2025

Journal title: available for those who has paid.

Region of the journal publication: Europe.

Scientific field: Medicine.

Indexing of the journal: Scopus (Q2); WoS (Science Citation Index Expanded).

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#30-med The assessment model of gene expression of early and delayed responses in the process of adaptation of muscle cells to aerobic physical activity

Abstract: Physical activity leads to changes in gene expression, which promotes the development of metabolic activity and functional capacities of skeletal muscles, improving the functional state of the body. Despite the awareness of the importance of physical activity in the development of the organism, there is no complete analytical description of the impact [...] Load More of physical activity on the processes of genetic regulation in muscle cells in the scientific literature. The purpose of this paper was to build a model and determine parameters influencing gene expression of early and delayed responses in the process of adaptation of muscle cells to physical activity. As a result of the research, a model of Ca2+-dependent signaling pathway has been built. This pathway leads to gene expression of early and delayed responses in the process of adaptation of muscle cells to physical activity. The model represents a system of ordinary differential equations, for the construction of which mechanisms of mono- and bimolecular reactions and generalized Hill's functions have been used. Sensitivity analysis has been performed to assess the effect of changes in model parameters on changes in mRNA gene concentrations. For the modeling, the BioUML software package was used with the help of which the system of differential equations has been solved (by VODE method), and the sensitivity of the developed model to changes in the rates of Ca2+-dependent signal transmission reactions and transcription regulation processes (local search algorithm) has been assessed. The model was tested using the RNA-sequencing method based on the evaluation of changes in gene expression between working and non-working skeletal muscle of seven men participating in the experiment, the matter of which was to measure the transcriptomic response in the human muscle to aerobic physical activities. The results of the simulation have demonstrated that the mRNA concentration of early response genes depends on the parameters that characterize the reaction of activation of Ca2+-dependent signaling pathway and the processes of genetic regulation, which is confirmed by the highest sensitivity indicators. The concentration of mRNA of delayed response genes is sensitive to the constitutive rate of expression and the rate of mRNA degradation. The built model serves as a diagnostic tool for taking into account the activating mechanism of aerobic physical activity impact on muscle cell gene expression.
Keywords: expression, genes, aerobic physical activities, muscle cells, adaptation, transcriptional response.
Date of publication: April 2025 / Deadline: 10 January 2025

Journal title: available for those who has paid.

Region of the journal publication: Europe.

Scientific field: Medicine.

Indexing of the journal: Scopus (Q2); WoS (Science Citation Index Expanded) IF 3.5.

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#28-med Improvement of differential diagnostics of sarcomatoid renal cell carcinoma

Abstract: Sarcomatoid carcinoma is a malignant tumor that grows from the renal tubular epithelial cells. Today, sarcomatoid renal cell cancer ranks first in the mortality rate of patients and third in the prevalence rate among all urological tumors. It occupies the leading position by the level of growth among onco-urological diseases. The survival rate is directly [...] Load More proportional to the presence of metastases in human lymph nodes, which necessitates early and effective diagnosis of the disease. Therefore, clinical diagnostics of space-occupying lesion of kidneys at an early stage is still an urgent task. The purpose of this study was to evaluate the predictive value of expression of a group of proteins associated with tumor progression, depending on the sarcomatoid differentiation of renal cell carcinoma. The clinical data for the study were the archive panel of the incisional biopsy material of 49 patients of the average age category of 67 years formed between 2011 and 2019. Based on a histopathological examination, the degree of malignancy of sarcomatoid transformation in chromophobe renal cell carcinoma, according to ISUP classification 2018, has been assessed and analyzed. The assessment has been performed by determining the percentage ratio of sarcomatoid cells to the total number of mutant pathological cells. With the use of the international TNM system, four neoplasm classes have been formed depending on the level of sarcomatous component and intervals of their variation. Four modifications of antigen expression in carcinomatous and sarcomatoid components have been substantiated for immunohistochemical reaction research and analysis. According to the results of immunohistochemical research of spindle-cell mesenchymal kidney tumors, the expression of specific markers of renal cell carcinoma in various histological modifications of sarcomatoid renal cell carcinoma has been systemized and analyzed. Distinguishing characters of expression for each marker in carcinoma and sarcomatoid components depending on the histological variant of sarcomatoid carcinoma have been determined by statistical data processing using electronic tables in Statistica10 software package based on the calculation of the Pearson's chi-square test and Fischer’s exact test (χ2). The results obtained will be useful for the development of algorithms to diagnose sarcomatoid carcinoma, which will improve the effectiveness of the research of urological tumors depending on their histological type.
Keywords: immunohistochemical research, sarcomatoid carcinoma, diagnostics, kidneys, tumor, expression, proteins.
Date of publication: April 2025 / Deadline: 10 January 2025

Journal title: available for those who has paid.

Region of the journal publication: Europe.

Scientific field: Medicine.

Indexing of the journal: Scopus (Q2); WoS (Science Citation Index Expanded).

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Biology

#14-bio Hydrochemical indicators of drinking water as a threat for morbidity rates for the population

Abstract: The maintenance and increase of safe drinking water supply, hygiene and sanitation, and proper water management are fundamental to human health in all countries and regions of the world. Efforts to improve the chemical composition of drinking water, sanitation, and hygiene interact with each other and actively contribute to the health and public well-being. [...] Load More Because of the topic urgency, the purpose of the study was to justify the maximum permissible limit of component mineral composition of drinking water as an impact factor on the general health status of the population. The object of research has been chosen because the population of this region uses an artesian water supply for more than 30 years. As a result, the hardness level of drinking water permanently increases in comparison with surface water sources. In the framework of this study, using the method of comparative analysis of standards of water quality hydrochemical indicators and level of pollution (specified in sanitary and epidemiological rules), the pollution level and quality of artesian water supply has been justified. Supplied water by its properties (mineralization and ionic composition) meets sanitary standards for drinking water; however, it does not fully meet the optimal physiological parameters due to the reduction of some chemical elements necessary for the body and because of the concentration level of toxic chemicals. With the use of the correlation analysis method, a direct proportion between the disease incidence among the adult population and the level of chemical elements contained in drinking water of artesian well drinking-water supply has been justified. Gradation of disease incidence levels among the adult population of the region to "high level of intensity" and "low level of intensity" depending on maximum permissible regulated norms of concentration of chemical elements in drinking water has been implemented. Quantitative standards of hydrochemical indicators of drinking water quality based on the concentration level of toxic and essential chemical elements were substantiated and recommended. The obtained research results are practical and can be used by sanitary services to improve standards of drinking water quality assessment as well as design, construction, operation of water supply systems, and provision of drinking water to the population.
Keywords: water supply, hydrochemical indicators, drinking water, health, chemical element.
Date of publication: May 2025 / Deadline: 7 January 2025

Journal title: available for those who has paid.

Region of the journal publication: Europe.

Scientific field: Agricultural, Biological Sciences, Environmental Science, Social Sciences.

Indexing of the journal: Scopus (Q1-2); WoS (Science Citation Index Expanded).

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#13-med Features of interaction between elemental homeostasis and the level of human physical activity

Abstract: The problem of homeostasis, despite a large number of homeostatic agents, is still extremely urgent. It is difficult to overestimate the role of the self-regulating system of homeostasis in maintaining the normal functioning of such human systems as immune, cardiovascular, respiratory, etc. Regular physical activity as a stress simulation stimulates [...] Load More the adaptive response of the human body and aims to maintain homeostasis of the whole organism. The purpose of the paper was a comprehensive study of the impact of the relationship between physiological mechanisms of homeostasis and motor activity on the content of micro- and macronutrients in the human body. The qualitative characteristics between elemental homeostasis and the level of human physical activity have been analyzed using the deductive analysis method based on literature sources. It has been found that the consumption of microelements increases with increasing energy consumption. Thus, physically very active people consume more micronutrients than untrained ones. However, the revealed characteristics of the relationship are contradictory, and there is no possibility of quantitative estimates of microelement consumption. Thus, micronutrient requirements among moderately active people are unlikely to be much higher than the levels recommended for the general population. On the basis of the method of analysis and synthesis, the peculiarities of the status of micronutrients for health and functional performance among physically active people, athletes, and those who lead an inactive life, have been revealed. It has been revealed that moderate physical activity does not necessarily affect the daily consumption of microelements. Metabolic peculiarities of the human organism during the longtime physical activity, moderate motor activity, and in conditions of sedentary behavior have been generalized. The features of influencing physical activity and the general state of the human body in the process of accumulation and change of the status of essential and toxic microelements in the human body have been revealed. The main characteristics of their impact on human functional performance depending on the levels of physical activity have been analyzed. The immunological balance of priority microelements in the metabolic correction in the human body in conditions of an active lifestyle and significant physical activity has been generalized. The obtained results of this study are aimed at strengthening knowledge about elemental homeostasis and metabolic networks to offer dietary guidance on metabolism and the communicative role of different products in conditions of various levels of human physical activity.
Keywords: elemental homeostasis, physical activity, micronutrients, essential microelements, toxic microelements, metabolism.
Date of publication: April 2025 / Deadline: 7 January 2025

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Region of the journal publication: Europe.

Scientific field: Medicine, Biology.

Indexing of the journal: Scopus (Q1-2); WoS (Science Citation Index Expanded).

 

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Medicine

#5-med Enhancing diagnostics of immunogenic mismatch in the process of hematopoietic stem cell transplantation

Abstract: Transplantation of hematopoiesis precursor cells is a rapidly developing technology and a key to the treatment of hematologic malignancies and other hematological diseases. Hematopoietic stem cell (HSC) transplantation is still a complicated procedure. The reason is that the genes encoding the main histocompatibility complex (MHC) are highly polymorphic, [...] Load More and compatibility of donor and recipient by MHC alleles is critical for alloreactivity against malignant clones. However, often in the course of the post-transplantation immune response, healthy tissues of the patient are also affected. Both of these effects have the same nature and depend on the compatibility of the donor and recipient using the main histocompatibility complex. The purpose of this research was to develop a methodological approach to determine the risk of genotyping of polymorphisms and the probability of predicting immunogenic mismatch in the process of HSC transplantation (HSCT). For the statistical analysis, two samples have been formed of potential donors of HSC register and recipients and donors of HSC, who, after filtration, did not have a genotyped pair (365 persons), and donor-recipient pairs (79 persons), for which the allele frequencies have been calculated. With the use of the Fischer's Exact test, the statistical significance of interrelationships between the variable characterizing the allele frequencies of minor lymphocyte stimulatory genes for the population and the allele frequencies corresponding to the five superpopulations from the 1000 Genomes Project has been assessed: European, American, East Asian, African, and South Asian. The Monte Carlo method has been used to calculate the immunogenicity coefficient (the probability that in a donor-recipient pair from the same population, a recipient has at least one immunogenic allele, and the donor must be homozygous for the non-immunogenic allele). In the use of the Monte Carlo method, 100 thousand simulations of related and unrelated allo-HSCT have been performed. Thus, the Monte Carlo method made it possible to calculate the immunogenicity coefficient as the probabilistic characteristic of the process under study based on the generated random values described by the mathematical model. For the implementation of the method, a program has been written using RStudio 1.0.143 software and R 3.5.1 programming language. Fisher's criterion and the Student's t-test were used for the comparison of the number of immunogenic mismatches in real donor and recipient pairs. The results obtained have an applied character and will be useful for the formation of registers of bone marrow donors, as well as for the determination of targets in the immunosuppressive therapy and cell-based therapy.
Keywords: hematopoiesis, hematopoietic stem cells, transplantation, histocompatibility, alloreactivity, donor, recipient.
Date of publication: May 2025 / Deadline: 10 January 2025

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Region of the journal publication: Europe.

Scientific field: Medicine.

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Biology

#1-med Peculiarities of the physiological activity of obestatin in the body's vital activity

Abstract: The problem of metabolic syndrome in the modern world has turned into a global epidemic, affecting millions of people. It poses a threat to public health due to the risk of related diseases and pathologies. At the same time, the issue of finding effective treatment methods, especially obesity, remains open. The purpose of this research was to substantiate [...] Load More the biological, physiological, pathophysiological, and pharmacological aspects of obestatin action for the body's vital activity in the norm and pathology. The basis for identifying the peculiarities was the research that demonstrated the pathogenetic connection and frequent combination of food behavior disorders, essential hypertension, insulin resistance, and lipid metabolism disorders caused by the pathology of the ghrelin-obestatin system. The article analyzes various causes and features of gastrointestinal diseases (diseases of the GI tract). The factors of eating disorder and modern methods of its regulation through endogenous regulators of appetite and body weight have been summarized. Through the inductive generalization method, the peculiarities of ghrelin and obestatin ratio in pathological obesity and among healthy people have been argued. The characteristics of the physiological activity of food hormones in adipogenesis have been generalized. It has been substantiated that obestatin is, as well as ghrelin, regulating hormone in adipocyte metabolism and the transition of pre-adipocytes to adipocytes. Besides, it determines the activity of adipogenesis to a greater degree. This fact suggests that the correct regulation of the obestatin level can accelerate the process of correction of pathologies of the GI tract. Through a literature review, the interaction between body mass index, blood glucose, insulin, and leptin levels and the content of obestatin in the blood has been assessed. The role of obestatin in nutrition regulation has been substantiated. The research also revealed the peculiarities of anorexigenic effects of obestatin, which primarily imply the central action mechanisms, based on the analysis of the modern scientific literature. Its ability to pass the blood-brain barrier (BBB) was also considered, which made it possible to conclude about the ambiguity of the passage mechanisms. Based on the above study, it has been revealed that the data on the central effects of obestatin in the norm and pathology, as well as the assessment of its possible application in clinical practice, are very fragmentary and contradictory. The revealed problems can serve as a basis for the determination of promising scientific research in the field of hormone therapy of cardiometabolic syndrome.
Keywords: cardiometabolic syndrome, obestatin, gastrointestinal tract, pathology, ghrelin, food behavior.
Date of publication: April 2025 / Deadline: 7 January 2025

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Region of the journal publication: Europe.

Scientific field: Medicine.

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