P V Ershov, E O Yablokov, L A Kaluzhskiy, Yu V Mezentsev, O V Gnedenko, M A Konstantinov, I Yu Toropygin, A S Ivanov
{"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}
V I Fedchenko, A A Kaloshin, S A Kaloshina, O A Buneeva, A T Kopylov, A E Medvedev
{"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}
D I Murashka, A D Tahanovich, M M Kauhanka, I A Nikitina, A V Kolb, L S Bogush, E I Davidovskaya, O A Budnik
{"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}
D V Grigorieva, E V Mikhalchik, D V Mosievich, P I Mishin, N G Balabushevich, O M Panasenko, A V Sokolov, I V Gorudko
{"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}
O P Shatova, A V Shestopalov, E Yu Zlatnik, I A Novikova, A S Goncharova, A Yu Maksimov
{"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}
O A Buneeva, I G Kapitsa, M G Zavyalova, S A Kaloshina, V G Zgoda, A E Medvedev
{"title":"The delayed effect of the neuroprotector fabomotizole on the brain proteome in rats with the rotenone model of parkinsonism.","authors":"O A Buneeva, I G Kapitsa, M G Zavyalova, S A Kaloshina, V G Zgoda, A E Medvedev","doi":"10.18097/PBMCR1586","DOIUrl":"https://doi.org/10.18097/PBMCR1586","url":null,"abstract":"<p><p>Fabomotizole is an original anxiolytic agent developed at the Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies that acts on a number of important receptor systems of the brain. In a model of Parkinson's disease induced in rats by a course of rotenone administration, fabomotizole attenuated manifestations of behavioral impairments and influenced the profile and relative content of brain proteins. Five days after the last administration of rotenone, the fabomotizole effect on the behavioral reactions of rats persisted. According to the proteomic study, the profile of brain proteins and changes in their relative content differed significantly from the results obtained immediately after the last administration of rotenone, as well as rotenone in combination with fabomotizole. Changes in the relative content of almost all proteins detected immediately after the last administration of rotenone or rotenone with fabomotizole were not detectable five days later. However, at this time point, there were changes in the relative content of other proteins associated with neurodegeneration in Parkinson's and Alzheimer's diseases. Such dynamics suggests a wave-like change in the content of pathogenetically important brain proteins involved in the mechanisms of neurodegeneration and neuroprotection.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 3","pages":"217-226"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504796","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":"Selection of optimal protein sets as serological tumor marker signatures.","authors":"S N Naryzhny, O K Legina","doi":"10.18097/PBMCR1552","DOIUrl":"https://doi.org/10.18097/PBMCR1552","url":null,"abstract":"<p><p>Currently, various potential tumor markers have been proposed for clinical practice. Although some of them are successfully used in diagnostics, and treatment, none of them fully meets the needs of oncology. Therefore, the search for new markers continues. In this context much attention is paid to multiomics technologies such as genomics, transcriptomics, and metabolomics. However, since tumor biomarkers are mainly proteins, proteomics plays a central role in the search of tumor markers. Blood is the most popular source of information about a patient's health and therefore the search is focused on plasma/serum proteins In order to increase the sensitivity and specificity of the analysis, a very promising approach is to assess the levels of certain sets of relevant proteins rather than individual proteins and this review is devoted to analysis of this problem.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 3","pages":"163-194"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504795","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}
M I Airapetov, S O Eresko, A A Shchukina, N M Matveev, M A Andreev, E R Bychkov, A A Lebedev, P D Shabanov
{"title":"The study of the azithromycin effect on gene expression of the toll-like receptor system in the brain nucleus accumbens of rats during ethanol withdrawal and search for possible molecular targets by an in silico method.","authors":"M I Airapetov, S O Eresko, A A Shchukina, N M Matveev, M A Andreev, E R Bychkov, A A Lebedev, P D Shabanov","doi":"10.18097/PBMCR1523","DOIUrl":"https://doi.org/10.18097/PBMCR1523","url":null,"abstract":"<p><p>The brain's nucleus accumbens (NAc) is a key link in the internal reinforcement system, which mediates manifestations of various components of addiction, including ethanol. The neuroinflammatory theory of alcoholism development suggests that changes in the molecular mechanisms of the innate immune system may be involved in the development of this pathology. The aim of our study was to investigate the effect of azithromycin (AZM) on expression of toll-like receptor system genes in the NAc during experimental alcoholization of rats. The objectives of the study also included an in silico search for possible molecular targets for AZM that could be associated with the toll-like receptor system. AZM corrected the changes observed in the expression of toll-like receptor system genes under conditions of alcohol withdrawal after long-term ethanol exposure in the NAc of the brain. The in silico analysis revealed the most probable proteins which could be involved in the interaction with AZM. Based on results of these predictions a number of assumptions about possible ways of implementing the observed pharmacological effect of AZM in the experiment have been made.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 2","pages":"95-102"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965631","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":"Slow-binding inhibitors of enzymes: kinetic characteristics and pharmacological interest.","authors":"Z M Shaihutdinova, T N Pashirova, P Masson","doi":"10.18097/PBMCR1536","DOIUrl":"https://doi.org/10.18097/PBMCR1536","url":null,"abstract":"<p><p>Currently, the search for new slow-binding inhibitors of enzymes (SBI) and their identification primary in vitro studies still attracts much attention in the context of their potential role as putative pharmacological agents for the treatment of various diseases. In contrast to their classical reversible analogues, SBI exhibit a slow enzyme binding kinetics, where the equilibrium steady-state is reached not in microseconds, but after longer time intervals. Such compounds could be promising drugs, because regardless of their pharmacokinetics in the bloodstream, they have such advantages as high affinity for the target enzyme, long residence time on the target, and therefore, prolonged action. These pharmacological properties ensure optimized dosage of drugs required to achieve high activity with less side effects. In this review we have considered mechanisms of SBI interaction with enzyme targets, the principles of their recognition at the level of in vitro studies and analysis of binding and kinetic parameters.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 2","pages":"81-94"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969636","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}