Biomeditsinskaya khimiya最新文献

{"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}

{"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}

{"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}

{"title":"Interaction of kidney proteins of normal and hypertensive rats with fragments of renalase peptide RP220.","authors":"O A Buneeva, V I Fedchenko, S A Kaloshina, M G Zavyalova, V G Zgoda, A E Medvedev","doi":"10.18097/PBMCR1567","DOIUrl":"https://doi.org/10.18097/PBMCR1567","url":null,"abstract":"<p><p>Renalase (RNLS) is a protein involved in the regulation of blood pressure; it has various functions inside and outside cells. The twenty-membered peptide RP220, corresponding to the amino acid sequence of human RNLS 220-239, reproduces a number of effects of extracellular RNLS and can bind to many intracellular proteins in the kidney. The RP220 sequence contains several cleavage sites for extracellular proteases, which could potentially produce RP224-232 and RP233-239 peptides. The aim of this work was to perform proteomic profiling of kidney tissue from normotensive Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) derived from WKY, using potential proteolytic fragments (RP224-232 and RP233-239) of the RP220 peptide as affinity ligands, and to compare these proteomic profiles with the profiles obtained using the parent RP220 peptide. The obtained results indicate that the relative content of proteins bound to the RNLS peptides in SHR, compared to that in WKY rats, changes most significantly in the case of the RP224-232 peptide. Almost all of these proteins, with a few exceptions, are associated with cardiovascular pathology, many with hypertension. The results of our work indicate that proteolytic processing of RP220 does not lead to the inactivation of this peptide, but to a change in its ligand/regulatory properties, as well as the repertoire of potential protein partners and, consequently, protein-protein interactions that may have possible pharmacological application.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 2","pages":"103-115"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974697","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":"Peptide toxins targeting ion channels as cytoprotective agents in ischemia-reperfusion injury of epithelial cells.","authors":"E V Iurova, E V Rastorgueva, E A Beloborodov, D E Sugak, E S Pogodina, A N Fomin, Y V Saenko","doi":"10.18097/PBMCR1553","DOIUrl":"https://doi.org/10.18097/PBMCR1553","url":null,"abstract":"<p><p>Ischemia-reperfusion injury (IRI) is a complex process accompanying cessation of blood supply to an organ or tissue followed by subsequent restoration of blood circulation. The IRI is especially prominent in surgery and organ transplantation. One of the strategies for reducing organ and tissue damage during transplantation is regulation of intracellular ion concentrations. Maintenance of ion concentrations in the cell during damage development can be controlled by influencing voltage-dependent ion channels with certain types of compounds. We propose the peptide toxins tropic to calcium (omega-hexatoxin-Hv1a) and sodium (mu-agatoxin-Aa1a) voltage-dependent ion channels as potential agents reducing IRI. The toxins were obtained using solid-phase peptide synthesis. The IRI modeling for evaluation of the action of toxins was carried out on a culture of epithelial cells CHO-K1 during their incubation under conditions of hypoxia and nutrient deprivation followed by subsequent replenishment of the nutrient medium. The level of cell death, concentrations of calcium, sodium, potassium ions, and pH were recorded using a multimodal plate reader and fluorescent dyes. Experiments have shown that regardless of different mechanisms of action, both toxins reduced the development of CHO-K1 cell death by changing ion concentrations and maintaining the pH level.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 2","pages":"116-126"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956976","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 P2X3 receptor blocker AF-353 (Ro-4) reduces bioenergetic index of a primary mixed culture of hippocampal neurons.","authors":"A S Zelentsova, M Yu Skorkina, A V Deykin","doi":"10.18097/PBMCR1531","DOIUrl":"https://doi.org/10.18097/PBMCR1531","url":null,"abstract":"<p><p>In clinical studies, the purinergic receptor P2X3 is considered as a molecular target for pain correction in spinal sensory neurons by highly selective antagonists based on diaminopyrimidine derivatives. In the CNS, P2X3 receptors are involved in synaptic plasticity underlying memory and learning. Currently, potent and selective allosteric modulators of P2X3 and P2X2/3 receptors have been recognized among diaminopyrimidine derivatives. These include 5-(5-iodo-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine (Ro-4 or AF-353), gefapixant, which have a good pharmacokinetic profile and are less active with respect to a wide range of kinases, receptors, and ion channels. Although the therapeutic value of P2X3 receptor blockade in CNS neurons has not been studied, however, certain evidence exists in the literature that this receptor could represent a new target in the search for antiepileptic drugs, as well as drugs that reduce anxiety and stress. The aim of the work was to study the effect of the P2X3 receptor antagonist AF-353 (Ro-4) on the neuronal bioenergetic health index (BHI) in a primary mixed hippocampal culture. The P2X3 receptor blockade in embryonic and postnatal mouse hippocampal neuron cultures increased non-mitochondrial respiration by 27.5% and 15.8%, respectively, proton loss by 31.0% and 61.4%, and decreased basal respiration by 89% and 39% compared to the control. The neuronal BHI decrease in the postnatal culture was 68% compared to the control. The obtained results indicate the effect of AF-353 on mitochondrial respiration of a primary mixed culture of hippocampal neurons; this reveals the potential of the P2X3 receptor as a pharmacological target in hypoxic conditions of the brain.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 2","pages":"137-145"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962222","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 addition of two targeted vectors, cRGD peptide and folic acid, with the same linker length on the properties of the doxorubicin phospholipid composition: a study of properties in vitro.","authors":"L V Kostryukova, Yu A Tereshkina, F N Bedretdinov, A M Gisina","doi":"10.18097/PBMCR1538","DOIUrl":"10.18097/PBMCR1538","url":null,"abstract":"<p><p>Serious side effects of the chemotherapeutic drug doxorubicin prompt researchers to develop systems for its targeted delivery to cells. In this work, we continued the study on the effect of using two vectors in a phospholipid delivery system of doxorubicin (Dox) for targeted therapy of breast cancer. We have obtained a composition NPh-Dox-cRGD-Fol(2.0) with the same linker length for both targeting ligands, cRGD and folic acid (PEG 2000). The resulting composition NPh-Dox-cRGD-Fol(2.0) with a particle size less than 50 nm and with 99% Dox incorporated into nanoparticles in an experiment on drug release at different pH values (5.0 and 7.4) showed a faster release and a high level of Dox compared to the phospholipid nanoform and a composition containing only the cRGD peptide. In vitro experiments on MDA-MB-231 breast cancer cells expressing the folate receptor and integrin αvβ3 demonstrated an increase in the total accumulation and internalization of Dox upon incubation with the dual-vector composition compared to the control samples. On the MCF-7 breast cancer cell line (expressing only the folate receptor), a similar effect was observed upon incubation with the single-vector composition containing folic acid (NPh-Dox-Fol(2.0)). In experiments with normal Wi-38 cell line, the internalization and total accumulation of the drug were comparable for both the free substance and the vector compositions. After 24 h-incubation of MDA-MB-231 cells with Dox-containing (10 μg/ml DOX) samples, the lowest percentage of living cells was observed for the studied dual-vector composition NPh-Dox-cRGD-Fol(2.0). On MCF-7 cells, the cytotoxic effect was manifested equally for the studied samples. The study of the cell death pathway on MDA-MB-231 cells showed the predominance of the apoptotic pathway (late apoptosis), while in the case of MCF-7 the necrosis pathway predominated. The cell cycle study performed using MDA-MB-231 cells (folate receptor (+) and integrin αvβ3 (+)) revealed an increase in the percentage of cells in the G0/G1 phase was noted thus indicating apoptotic cell death during incubation with NPh-Dox-cRGD-Fol(2.0). No differences were found between the samples in experiments performed on MCF-7 cells (folate receptor (+) and integrin αvβ3 (-)).</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 1","pages":"37-50"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565895","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}