Biomeditsinskaya khimiya最新文献

{"title":"A dual-vector phospholipid nanosystem of doxorubicin: accumulation and cytotoxic effect in breast cancer cells in vitro.","authors":"Yu A Tereshkina, F N Bedretdinov, L V Kostryukova","doi":"10.18097/PBMC20236906409","DOIUrl":"10.18097/PBMC20236906409","url":null,"abstract":"<p><p>Various chemotherapeutic agents are used to treat breast cancer (BC); one of them is the anthracycline antibiotic doxorubicin (Dox), which, in addition to its cytostatic effect, has serious side effects. In order to reduce its negative impact on healthy organs and tissues and to increase its accumulation in tumors, Dox was incorporated into phospholipid nanoparticles. The additional use of vector molecules for targeted delivery to specific targets can increase the effectiveness of Dox due to higher accumulation of the active substance in the tumor tissue. The integrin αvβ3, which plays an important role in cancer angiogenesis, and the folic acid receptor, which is responsible for cell differentiation and proliferation, have been considered in this study as targets for such vector molecules. Thus, a phospholipid composition of Dox containing two vector ligands, cRGD peptide and folic acid (NPh-Dox-cRGD-Fol(3,4)), was prepared. Study of the physical properties of the developed composition NPh-Dox-cRGD-Fol(3,4) showed that the average particle size was 39.62±4.61 nm, the ζ-potential value was 4.17±0.83 mV. Almost all Dox molecules were incorporated into phospholipid nanoparticles (99.85±0.21%). The simultaneous use of two vectors in the composition led to an increase in the Dox accumulation in MDA-MB-231 BC cells by almost 20% as compared to compositions containing each vector separately (folic acid or the cRGD peptide). Moreover, the degree of Dox internalization was 22% and 24% higher than in the case of separate use of folic acid and cRGD peptide, respectively. The cytotoxic effect on MDA-MB-231 cells was higher during incubations with the compositions containing folic acid as a single vector (NPh-Dox-Fol(3,4)) and together with the RGD peptide (NPh-Dox-cRGD-Fol(3,4)). Experiments on the Wi-38 diploid fibroblast cell line have shown a significantly lower degree of cytotoxic effect of the phospholipid composition, regardless of the presence of the vector molecules in it, as compared to free Dox. The results obtained indicate the potential of using two vectors in one phospholipid composition for targeted delivery of Dox.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048295","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 for finding new pharmacological agents among adenosine receptor agonists, antagonists, or their allosteric modulators for the treatment of cardiovascular diseases.","authors":"V N Perfilova, E A Muzyko, A S Taran, A A Shevchenko, L V Naumenko","doi":"10.18097/PBMC20236906353","DOIUrl":"10.18097/PBMC20236906353","url":null,"abstract":"<p><p>A1-adenosine receptors (A1AR) are widely distributed in the human body and mediate many different effects. They are abundantly present in the cardiovascular system, where they control angiogenesis, vascular tone, heart rate, and conduction. This makes the cardiovascular system A1AR an attractive target for the treatment of cardiovascular diseases (CVD). The review summarizes the literature data on the structure and functioning of A1AR, and analyzes their involvement in the formation of myocardial hypertrophy, ischemia-reperfusion damage, various types of heart rhythm disorders, chronic heart failure, and arterial hypertension. Special attention is paid to the role of some allosteric regulators of A1AR as potential agents for the CVD treatment.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048296","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":"Secondary metabolites of plants and their possible role in the \"age of superbugs\".","authors":"V M Nesterovich, D A Belykh, N V Gorokhovets, L K Kurbatov, A A Zamyatnin, L N Ikryannikova","doi":"10.18097/PBMC20236906371","DOIUrl":"10.18097/PBMC20236906371","url":null,"abstract":"<p><p>Bacterial infections are a serious cause of high morbidity and mortality worldwide. Over the past decades, the drug resistance of bacterial pathogens has been steadily increasing, while the rate of development of new effective antibacterial drugs remains consistently low. The plant kingdom is sometimes called a bottomless well for the search for new antimicrobial therapies. This is due to the fact that plants are easily accessible and cheap to process, while extracts and components of plant origin often demonstrate a high level of biological activity with minor side effects. The variety of compounds obtained from plant raw materials can provide a wide choice of various chemical structures for interaction with various targets inside bacterial cells, while the rapid development of modern biotechnological tools opens the way to the targeted production of bioactive components with desired properties. The objective of this review is to answer the question, whether antimicrobials of plant origin have a chance to play the role of a panacea in the fight against infectious diseases in the \"post-antibiotic era\".</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048298","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 hyperglycemia on the activation of peritoneal macrophages of albino rats.","authors":"I A Golyako, V S Kuzmin, L R Gorbacheva","doi":"10.18097/PBMC20236906394","DOIUrl":"10.18097/PBMC20236906394","url":null,"abstract":"<p><p>Hyperglycemia is one of the main damaging factors of diabetes mellitus (DM). The severity of this disease is most clearly manifested under conditions of the inflammatory process. In this work, we have studied the activation features of rat peritoneal macrophages (MPs) under conditions of high glucose concentration in vitro. Comparison of the independent and combined effects of streptozotocin-induced DM and hyperglycemia on proliferation and accumulation of nitrites in the MPs culture medium revealed similarity of their effects. Elevated glucose levels and, to a lesser extent, DM decreased basal proliferation and NO production by MPs in vitro. The use of the protein kinase C (PKC) activator, phorbol ester (PMA), abolished the proinflammatory effect of thrombin on PMs. This suggests the involvement of PKC in the effects of the protease. At the same time, the effect of thrombin on the level of nitrites in the culture medium demonstrates a pronounced dose-dependence, which was not recognized during evaluation of proliferation. Proinflammatory activation of MPs is potentiated by hyperglycemia, one of the main pathological factors of diabetes. Despite the fact that high concentrations of glucose have a significant effect on proliferation and NO production, no statistically significant differences were found between the responses of MPs obtained from healthy animals and from animals with streptozotocin-induced DM. This ratio was observed for all parameters studied in the work, during analysis of cell proliferation and measurement of nitrites in the culture medium. Thus, the results obtained indicate the leading role of elevated glucose levels in the regulation of MPs activation, which is comparable to the effect of DM and even \"masks\" it.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048300","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":"Neuroprotective effects of isatin and afobazole in rats with rotenone-induced Parkinsonism are accompanied by increased brain levels of Triton X-100 soluble alpha-synuclein.","authors":"O A Buneeva, I G Kapitsa, V G Zgoda, A E Medvedev","doi":"10.18097/PBMC20236905290","DOIUrl":"10.18097/PBMC20236905290","url":null,"abstract":"<p><p>Effects of the endogenous neuroprotector isatin and the pharmacological drug afobazole (exhibiting neuroprotective properties) on behavioral reactions and quantitative changes in the brain proteomic profile have been investigated in rats with experimental rotenone Parkinsonism. A single dose of isatin (100 mg/kg subcutaneously on the last day of a 7-day course of rotenone administration) improved the motor activity of rats with rotenone-induced Parkinsonism in the open field test (horizontal movements) and the rotating rod test. Afobazole (10 mg/kg intraperitoneally, daily during the 7-day course of rotenone administration) reduced the manifestations of rigidity and postural instability. Proteomic analysis, performed using brain samples obtained the day after the last administration of rotenone and neuroprotectors, revealed similar quantitative changes in the brain of rats with rotenone Parkinsonism. An increase in the relative content of 65 proteins and a decrease in the relative content of 21 proteins were detected. The most pronounced changes - an almost ninety-fold increase in the alpha-synuclein content - were found in the brains of rats treated with isatin. In animals of the experimental groups treated with \"Rotenone + Isatin\", as well as \"Rotenone + Afobazole\", the increase in the relative content of this protein in the brain was almost 60 and 50 times higher than the control values. Taking into consideration the known data on the physiological role of alpha-synuclein, an increase in the content of this protein in the brain upon administration of neuroprotectors to animals with rotenone Parkinsonism may represent a compensatory reaction, at least in the early stages of this disease and the beginning of its treatment.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477628","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 prediction of main protease SARS-CoV-2 inhibition based on models of enzyme-inhibitor complexes.","authors":"Ya O Ivanova, V S Skvortsov","doi":"10.18097/PBMC20236905322","DOIUrl":"10.18097/PBMC20236905322","url":null,"abstract":"<p><p>A set of linear regression equations predicting the IC50 values for SARS-CoV-2 main protease inhibitors was analyzed. For 180 competitive inhibitors, we have simulated the molecular dynamics of enzyme-inhibitor complexes with known structures or modeled using molecular docking. In the docking procedure, the selection of final poses was restricted by similarity to known structural analogs. The values of the energy contributions obtained by means of calculation of the free energy change of the enzyme-inhibitor complex performed by two variants of the MMPBSA (MMGBSA) method and a number of physicochemical characteristics of the inhibitors were used as independent variables. During the learning process, indicator variables were used for inhibitor subsets obtained from various literature sources to compensate the existing systematic deviations from the target value. A leave one out and leave 20% out cross validation procedures were used to evaluate the prediction quality. For the total logarithmic range width of 3.71, the mean error in predicting the lg(IC50) value was 0.45 log units. The stability of the prediction depending on the variability of the complex in molecular dynamics was investigated.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477632","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":"Contribution of the gasotransmitter nitric oxide to the structural and functional organization of erythrocytes under conditions of hypoxia/reoxygenation.","authors":"N V Akulich, V V Zinchuk","doi":"10.18097/PBMC20236905315","DOIUrl":"10.18097/PBMC20236905315","url":null,"abstract":"<p><p>Hypoxia is accompanied by changes in metabolism and cell functioning. Erythrocyte hemoglobin can be involved in adaptation to hypoxia by acting as an oxygen sensor, providing a link between oxygen content and blood circulation. The mechanisms providing this function have not been completely established. The purpose of this study was to evaluate the effect of the gasotransmitter nitric oxide on the structural and functional organization of erythrocytes under conditions of hypoxia/reoxygenation. NO participated in adaptive reactions under hypoxia/reoxygenation conditions by changing hemoglobin conformation, followed by changes in hemoprotein spectral characteristics and hemoglobin affinity to oxygen together with increasing anisocytosis, volume and cell surface. The increase in intracellular NO concentrations under hypoxic conditions was provided by extracellular fluid nitrites. Molsidomine (a NO donor) induced a higher NO increase without involvement of the nitrite reductase mechanism, it caused an increase in the average erythrocyte volume, anisocytosis, and an increase in the cell surface.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477626","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":"Perspectives for the creation of a new type of vaccine preparations based on pseudovirus particles using polio vaccine as an example.","authors":"D D Zhdanov, Yu Yu Ivin, A N Shishparenok, S V Kraevskiy, S L Kanashenko, L E Agafonova, V V Shumyantseva, O V Gnedenko, A N Pinyaeva, A A Kovpak, A A Ishmukhametov, A I Archakov","doi":"10.18097/PBMC20236905253","DOIUrl":"10.18097/PBMC20236905253","url":null,"abstract":"<p><p>Traditional antiviral vaccines are currently created by inactivating the virus chemically, most often using formaldehyde or β-propiolactone. These approaches are not optimal since they negatively affect the safety of the antigenic determinants of the inactivated particles and require additional purification stages. The most promising platforms for creating vaccines are based on pseudoviruses, i.e., viruses that have completely preserved the outer shell (capsid), while losing the ability to reproduce owing to the destruction of the genome. The irradiation of viruses with electron beam is the optimal way to create pseudoviral particles. In this review, with the example of the poliovirus, the main algorithms that can be applied to characterize pseudoviral particles functionally and structurally in the process of creating a vaccine preparation are presented. These algorithms are, namely, the analysis of the degree of genome destruction and coimmunogenicity. The structure of the poliovirus and methods of its inactivation are considered. Methods for assessing residual infectivity and immunogenicity are proposed for the functional characterization of pseudoviruses. Genome integrity analysis approaches, atomic force and electron microscopy, surface plasmon resonance, and bioelectrochemical methods are crucial to structural characterization of the pseudovirus particles.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477629","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":"Serum miR-181a and miR-25 in patients with malignant and benign breast diseases.","authors":"M L Perepechaeva, A A Studenikina, A Yu Grishanova, A N Glushkov, E G Polenok, P V Bajramov, A I Autenshlyus","doi":"10.18097/PBMC20236905307","DOIUrl":"10.18097/PBMC20236905307","url":null,"abstract":"<p><p>Breast tumor diseases include a wide range of pathologies that require different approaches to their treatment. MicroRNA (miR) levels, reflecting regulation of the gene expression involved in tumorigenesis, can be diagnostic and prognostic markers of breast diseases. The levels of circulating miR-181a and miR-25 were measured in patients with benign breast diseases (BBD), patients with invasive carcinoma of a nonspecific type (ICNT) and also in conditionally healthy women. Expression of both miRs was higher in patients of both groups as compared to controls; at the same time, the content of serum miR-181a and miR-25 was higher in BBD patients than in ICNT patients. The detected changes may be of interest in the context of precancerous changes in BBD. It seems possible to use them in the future as markers of the pathological process as a part of a large diagnostic panel.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477630","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 flavonoids fisetin, apigenin, kaempferol, naringenin, naringin regulate respiratory activity and membrane potential of rat liver mitochondria and inhibit oxidative processes in erythrocytes.","authors":"A I Savko, T V Ilyich, A G Veiko, T A Kovalenia, E A Lapshina, I B Zavodnik","doi":"10.18097/PBMC20236905281","DOIUrl":"10.18097/PBMC20236905281","url":null,"abstract":"<p><p>Flavonoids, secondary plant metabolites, represent the most abundant heterogeneous group of phytochemicals. The aim of this study to compare antioxidant activity and regulatory properties of several representatives of different classes of flavonoids, fisetin, apigenin, kaempferol, naringenin, naringin, using liver mitochondria and erythrocytes as research objects. In the concentration range of 2.5-25 μM fisetin, apigenin, kaempferol, naringenin, and naringin dose-dependently prevented oxidative damage of erythrocytes induced by 700 μM tert-butyl hydroperoxide: accumulation of lipid peroxidation (LPO) products and oxidation of glutathione GSH. The IC50 values corresponding to the flavonoid concentration inhibiting the LPO process in erythrocyte membranes by 50%, were 3.9±0.8 μM in the case of fisetin, 6.5±1.6 μM in the case of kaempferol, 8.1±2.1 μM in the case of apigenin, 37.8±4.4 μM in the case of naringenin, and 64.7±8.6 μM in the case of naringin. The antioxidant effect of flavonoids was significantly higher in the membrane structures compared to the cytoplasm of cells. All flavonoids studied (10-50 μM) effectively inhibited the respiratory activity of isolated rat liver mitochondria and, with the exception of kaempferol, stimulated Ca²⁺-induced dissipation of the mitochondrial membrane potential. Cyclosporine A and ruthenium red inhibited flavonoid-stimulated Ca²⁺-dependent membrane depolarization, thus indicating that the mitochondrial calcium uniporter and the mitochondrial permeability transition pore opening were involved in the flavonoid effects. Flavonoids, as the redox-active compounds with antioxidant properties, are able to regulate mitochondrial potential and respiratory activity, and prevent mitochondrial oxidative stress. They can be considered as effective pharmacological agents or nutraceuticals.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477631","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}