Biomeditsinskaya khimiya最新文献

{"title":"Bioinformatic identification of proteins with varying levels of post-translational modifications in a model of atherogenesis in mice.","authors":"Yu V Miroshnichenko, A V Rybina, V S Skvortsov","doi":"10.18097/PBMCR1575","DOIUrl":"https://doi.org/10.18097/PBMCR1575","url":null,"abstract":"<p><p>Mass spectrometric data obtained using a model of tandem carotid artery stenosis in mice with unstable and stable atherosclerosis were analyzed to identify differences in the level of post-translational modifications (PTMs) of proteins. The original proteomic data obtained by Chen et al. [DOI: 10.1038/s42003-023-04641-4] and deposited in the PRIDE repository (identifier PXD030857) were used. Based on results of the bioinformatic analysis, 12 proteins with PTMs (methylation, acetylation, and phosphorylation) were selected; comparison of healthy and atherosclerotic vascular sections showed that the selected proteins were characterized by significant changes in the level of individual modified peptides. According to the literature data, all 12 proteins are involved in the process of atherogenesis. Our study thus revealed putative points of regulation of the atherogenesis processes at the PTM level.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 4","pages":"308-313"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991380","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":"Platelet functional activity in patients with immune thrombocytopenia.","authors":"V V Bodrova, S G Khaspekova, O N Shustova, N V Tsvetaeva, A V Mazurov","doi":"10.18097/PBMCR1596","DOIUrl":"https://doi.org/10.18097/PBMCR1596","url":null,"abstract":"<p><p>Immune thrombocytopenia (ITP) is one of the most common causes of decreased platelet count. Bleeding is the main clinical symptom of ITP; although its severity correlates with the depth of thrombocytopenia, it may also depend on changes in the functional activity of platelets. In this study we have compared platelet functional activity in healthy volunteers (HV) and in ITP patients, as well as in groups of ITP patients with different levels of bleeding. The study included 65 HV and 84 ITP patients. Platelet activity was assessed by flow cytometry. Platelets were activated with thrombin receptor activating peptide (TRAP) or ADP, and the exposure of activation markers, activated form of glycoprotein (GP) IIb-IIIa and alpha-granule membrane protein P-selectin, was determined on their surface by measuring the binding of PAC-1 and CD62P antibodies, respectively. Platelet-associated IgG (PA-IgG, an indicator of the level of antiplatelet autoantibodies), the percentage of \"young\" reticular platelets (RP, %) and platelet light scatter (an indicator of their size) were also assessed using flow cytofluorimetry. Platelet binding of PAC-1 (and, to a lesser extent, CD62P binding) was lower in ITP patients than in HV. In ITP patients, PAC-1 binding inversely correlated with the PA-IgG content. In contrast to HV, in ITP patients, PAC-1 and CD62P binding did not directly correlate with the platelet size and RP, %. In ITP patients with severe bleeding, the platelet count was lower, PAC-1 and CD62P binding was reduced and PA-IgG and RP, % levels were increased. Thus, a decrease in the content of activation markers on the platelet surface was registered in ITP patients; it was more pronounced in patients with severe bleeding. It is suggested that the cause of this decrease may be due to the effect of autoantibodies (PA-IgG) on platelets, and in particular on GP IIb-IIIa.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 4","pages":"288-299"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991478","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":"The inhibitory effect of mometasone and nortriptyline on the production of proinflammatory cytokines by blood mononuclear cells of patients with allergic rhinitis under conditions of stimulated immune response.","authors":"T V Mironova, A D Tahanovich, A G Kadushkin, V V Makarevich, I P Shilovskiy, M R Khaitov","doi":"10.18097/PBMCR1568","DOIUrl":"https://doi.org/10.18097/PBMCR1568","url":null,"abstract":"<p><p>Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa; it develops when the immune system reacts to an allergen. Side effects of topical glucocorticosteroids (GCS) used for AR treatment, the development of steroid resistance in patients and the continuing increase in morbidity explain the clear need to search for new approaches for AR treatment. The tricyclic antidepressant nortriptyline has demonstrated anti-inflammatory properties in a number of experimental studies, as well as its ability to complement the action of corticosteroids. The aim of this study was to compare the effects of nortriptyline and the synthetic GCS mometasone on the culture of mononuclear cells (MNC) of AR patients. Blood MNCs from six AR patients were cultured in the presence of nortriptyline or mometasone, and then type 1, type 2, or type 17 immune response (IR) were stimulated by adding recombinant activator proteins (IL-2, IL-25, IL-33, TSLP, IL-12, IL-1β, IL-23). After 3 days, concentrations of proinflammatory cytokines TNF-α, IFN-γ, IL-6, IL-8, and IL-4 were determined in cell supernatants by enzyme immunoassay. Mometasone (10⁻⁸ M final concentration) effectively suppressed the secretion of proinflammatory cytokines TNF-α, IFN-γ, IL-6, and IL-8 under conditions of stimulation of IR of all types. A similar decrease in secretion, although less pronounced, occurred when stimulated cells were cultured in the presence of nortriptyline. The concentration of TNF-α in the culture medium decreased under these conditions both with stimulation of type 1, type 2, and type 17 IR. The level of IFN-γ secretion decreased only in the case of type 1 and type 17 IR as compared to MNCs with the stimulated IR, which were cultured without this inhibitor. The level of IL-6 secretion decreased only in the culture medium of cells with stimulated type 1 and type 2 IR and IL-8 secretion decreased only under conditions of stimulated type 1 IR. This study has shown that mometasone and nortriptyline are able to suppress the secretion of proinflammatory cytokines by blood cells; their effect is selective and depends on the IR type.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 4","pages":"300-307"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144990899","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":"The role of the redox signaling system (H2О2 and the thiol system) in the regulation of the functional activity of nervous tissue in health and disease.","authors":"E E Dubinina, L V Shchedrina, N A Gomzyakova","doi":"10.18097/PBMCR1588","DOIUrl":"10.18097/PBMCR1588","url":null,"abstract":"<p><p>The review highlights the role of reactive oxygen species (ROS) and the thiol system in the regulation of functional activity of neurons. Their controlling function has been analyzed in the context of processes of synaptic plasticity and functioning of neurotrophins, as well as participation in such cellular processes as proliferation, apoptosis, and cell aging. Special attention has been paid to the role of individual components of the thiol system, their interaction with H2О2 in the regulation of the redox signaling system of cells. Summarizing literature data reflecting the participation of H2О2 in the regulation of key metabolic cascades of nervous tissue and own results we have come to conclusion about the dual nature of the stress system components depending on the functional state of the organism. The manifestation of their toxic effect, first of all, depends on their concentration and chemical structure.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 4","pages":"243-255"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991114","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":"Glycyrrhizic acid: novel potential protein targets.","authors":"P V Ershov, E O Yablokov, L A Kaluzhskiy, Yu V Mezentsev, O V Gnedenko, M A Konstantinov, I Yu Toropygin, A S Ivanov","doi":"10.18097/PBMCR1595","DOIUrl":"https://doi.org/10.18097/PBMCR1595","url":null,"abstract":"<p><p>To date, a large body of data has been accumulated on the biological activity of a low-toxic natural glycoside, glycyrrhizic acid (GA), but the mechanism of its action at the molecular level has not been fully studied. Expanding knowledge about the spectrum of cellular protein targets of GA contributes to understanding new features of pharmacodynamics. The aim of the work was the experimental identification of a tissue-specific spectrum of protein molecules interacting with GA in a model system. Samples of an intact rat liver tissue lysate were incubated with GA covalently immobilized on EAH-Sepharose 4B, followed by elution of affinity-isolated protein molecules and their trypsinolysis. Using mass spectrometric analysis, 88 potential protein targets of GA were identified. According to the results of gel chromatographic separation of the rat liver lysate and semi-quantitative analysis of proteins, GA influenced Aldh6a1, Decr1, and Sod1 in fractions. Molecular docking in the Flare™ program used to model protein complexes with GA, resulted in selection of 5 proteins (Acox2, Acr1c9, Maoa, Mat1a, Nalcn), which formed complexes with GA with the most favorable ΔG and Rank score parameters. More than half (57%) of the affinity-isolated proteins are involved in the processes of basic cellular metabolism and biotransformation of endogenous and exogenous compounds. Data on the associations of potential protein targets of GA with diseases and different types of biological activity of GA have been systematized and compared.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 4","pages":"270-282"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991536","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":"Interaction of antirenalase antibodies with recombinant human renalases 1 and 2 and their C-terminal regions encoded by the alternative exones.","authors":"V I Fedchenko, A A Kaloshin, S A Kaloshina, O A Buneeva, A T Kopylov, A E Medvedev","doi":"10.18097/PBMCR1608","DOIUrl":"https://doi.org/10.18097/PBMCR1608","url":null,"abstract":"<p><p>The interaction of antirenalase antibodies with full-length recombinant human renalases RNLS1 and RNLS2, as well as fragments of these proteins encoded by alternative exons 9 and 10 and expressed as fusion proteins with dihydrofolate reductase (DHFR) in Escherichia coli cells has been investigated. In this study we used custom made polyclonal antibodies to the full-length recombinant RNLS1 (amino acid residues (aa) 1-342), created at our request, as well as commercially available monoclonal antibodies to the renalase fragment (aa - 18-342), specific for the RNLS1 isoform and its C-terminal sequence encoded by exon 9. According to Western blot analysis, the antibodies interacted not only with recombinant RNLS1 and RNLS2 preparations, but also with fusion proteins containing C-terminal sequences specific for these isoforms (DHFR-RNLS-9ex and DHFR-RNLS-10ex). The results obtained indicate that the studied antibodies, in addition to their direct targets, also \"recognized\" other protein constructs of RNLS1 and RNLS2, which were absent in the immunogen preparations used for antibody generation.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 4","pages":"283-287"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991552","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":"Prediction of the course of chronic obstructive pulmonary disease by blood biomarkers.","authors":"D I Murashka, A D Tahanovich, M M Kauhanka, I A Nikitina, A V Kolb, L S Bogush, E I Davidovskaya, O A Budnik","doi":"10.18097/PBMCR1579","DOIUrl":"https://doi.org/10.18097/PBMCR1579","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is one of the most common pathologies of the respiratory system; it is characterized by increasing airflow limitation. The course of COPD is unstable and is often accompanied by periods of exacerbation, when respiratory symptoms of the disease significantly increase. The frequency of COPD exacerbations is an important predictor of its course, allowing to predict the decline in lung tissue function and the outcome of the disease. Currently, the risk of future COPD exacerbations in a patient is assessed based on the history of previous exacerbations, and the improvement of his condition is evaluated on the basis of the weakening of COPD symptoms. However, the lack of objective criteria complicates unambiguous verdict on the probability of acute condition development and the effectiveness of treatment of COPD patients. Based on the analysis of literature data we propose determination of the levels of chemokines (CXCL5, CXCL8, CXCR1/2, CD44v6), HIF-1α, procalcitonin, albumin and C-reactive protein, leukocyte cells, as well as their possible combination in the peripheral blood as an informative tool for evaluation in COPD patients.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 4","pages":"256-269"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144990961","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":"Comparative analysis of the effect of hybrid vaterite microparticles with various polysaccharides on neutrophils activity.","authors":"D V Grigorieva, E V Mikhalchik, D V Mosievich, P I Mishin, N G Balabushevich, O M Panasenko, A V Sokolov, I V Gorudko","doi":"10.18097/PBMCR1561","DOIUrl":"https://doi.org/10.18097/PBMCR1561","url":null,"abstract":"<p><p>Carriers based on natural biominerals attract much attention in the context of the development of new drug delivery systems. In this study, the effects of native (CC) and hybrid vaterite microparticles with the inclusion of dextran sulfate (CCDS), chondroitin sulfate (CCCS), heparin (CCHE), fucoidan (CCFU), and pectin (CCPE) have been investigated on the viability and functional activity of neutrophils. Among the tested preparations, only CCFU exhibited a slight cytotoxic effect. Native CC stimulated actin cytoskeleton rearrangements and cell production of reactive oxygen species (ROS), which decreased in the presence of diphenyleneiodonium chloride (DPI), an inhibitor of NADPH oxidase assembly. The CC-induced NADPH oxidase activation was reduced in the presence of inhibitors of non-receptor tyrosine kinases of the Src family, phosphatidylinositol 3-kinase (PI3K), and phospholipase C (PLC). Similar to native CC, hybrid vaterite microparticles also initiated ROS production by neutrophils. After addition of CC and hybrid vaterite microparticles (except CCDS), an increase in the number of neutrophils characterized by higher values of the side scattering value was detected thus indicating a change in the morphological characteristics of the cells. Given the ability of hybrid vaterite microparticles with polysaccharides to activate neutrophil NADPH oxidase, they could be promising systems for the delivery of antibacterial and antiviral drugs.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 3","pages":"227-238"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504793","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":"Problems and prospects of metabolomic studies in the alteration of the gut microbiome.","authors":"E I Savelieva, M D Shachneva","doi":"10.18097/PBMCR1556","DOIUrl":"https://doi.org/10.18097/PBMCR1556","url":null,"abstract":"<p><p>The review summarizes existing knowledge on the relationship between certain diseases and alteration (degeneration) of the intestinal microbiome. We consider major microbial metabolites firmly recognized as signaling molecules acting in communication between the microbiome and the host organism. These include short-chain fatty acids, bile acids, amines, amino acids, and their metabolites. Special attention is paid to metabolomic studies of the microbiome in chronic kidney diseases, in particular, immunoglobulin A nephropathy. The arguments supporting a concept of the microbiome of blood, previously considered an exclusively sterile environment in healthy humans, are considered. Metagenomic methods plays a key role in characterization of both the composition and potential physiological effects of microbial communities. The advantages and limitations of metabolomic analysis of blood serum/plasma and feces have been analyzed. Since the potential of clinical studies of the mutual impact of the microbiome-metabolome is limited by genetic and external factors, preclinical studies still employ both germ-free models and models based on the effects of antibiotics. The review considers the problems and prospects of metabolomics in studying the nature and mechanisms of the mutual impact of the microbiome and metabolome.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 3","pages":"195-208"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504794","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":"The effect of fecal microbiota transplantation on levels of tryptophan metabolites in intestine and serum of gnotobiotic mice.","authors":"O P Shatova, A V Shestopalov, E Yu Zlatnik, I A Novikova, A S Goncharova, A Yu Maksimov","doi":"10.18097/PBMCR1554","DOIUrl":"https://doi.org/10.18097/PBMCR1554","url":null,"abstract":"<p><p>Gut microbiota is one of the key suppliers of tryptophan metabolites, which perform various functions in the host organism, including their role as signaling molecules. Fecal microbiota transplantation (FMT) is widely used as a method for determining the contribution of microorganisms to the content of various metabolites in the holoorganism. In this regard, the aim of our study was to investigate the effect of FMT on the level of tryptophan metabolites in feces and blood in gnotobiotic mice. It was found that both before and after FMT, indole-3-lactate, and quinolinic acid were the dominant tryptophan metabolites in the intestine. FMT increased the content of both indoles (indole-3-acetate, indole-3-acrylate, indole-3-butyrate, indole-3-lactate) and kynurenines (anthranilic and xanthurenic acids) in the intestine. In serum of mice after FMT, indole metabolites (indole-3-butyrate, indole-3-carboxaldehyde, indole-3-lactate, indole-3-propionate) predominantly increased; however, tryptamine and xanthurenic acid also demonstrated a clear increase. The use of FMT demonstrates that the intestinal microbiota is a source of not only indole derivatives of tryptophan, but also metabolites of the kynurenine pathway.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 3","pages":"209-216"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504797","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}