Biomeditsinskaya khimiya最新文献

{"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":"69 5","pages":"290-299"},"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":"69 5","pages":"322-327"},"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":"69 5","pages":"315-321"},"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":"69 5","pages":"253-280"},"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":"69 5","pages":"307-314"},"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":"69 5","pages":"281-289"},"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}

{"title":"Interleukin-1β and TNF-α are elevated in the amygdala of adult rats prenatally exposed to ethanol.","authors":"V S Kokhan, P K Anokhin, T V Proskuryakova, V A Shokhonova, R A Ageldinov, I Yu Shamakina","doi":"10.18097/PBMC20236905300","DOIUrl":"10.18097/PBMC20236905300","url":null,"abstract":"<p><p>Affective disorders, including anxiety and depression, developed in adult offspring of the mothers who consumed alcohol during pregnancy could be associated with an imbalance in neuroimmune factors in the amygdala (corpus amygdaloideum) resulted in impaired emotional stimulus processing. The aim of this study was to compare the content of cytokines TNF-α, IL-1α, IL-1β, IL-10, and IL-17 in the amygdala of adult female rats exposed to alcohol in utero and control rats. Cytokine levels were evaluated using a multiplex immunoassay system; mRNA expression was investigated using a real-time reverse transcription-polymerase chain reaction (RT-qPCR) assay. Prenatal alcohol exposure led to the increase in the content of TNF-α and IL-1β without significant changes in the mRNA expression level. Our data suggest that ethanol exposure to the fetus during pregnancy can result in long-term alterations in the content of the key neuroinflammatory factors in the amygdala, which in turn can be a risk factor for affective disorders in the adulthood.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"69 5","pages":"300-306"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477627","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":"Prolonged alcohol consumption influences microRNA expression in the nucleus accumbens of the rat brain.","authors":"M I Airapetov,&nbsp;S O Eresko,&nbsp;S A Shamaeva,&nbsp;N M Matveev,&nbsp;E R Bychkov,&nbsp;A A Lebedev,&nbsp;P D Shabanov","doi":"10.18097/PBMC20236904235","DOIUrl":"https://doi.org/10.18097/PBMC20236904235","url":null,"abstract":"<p><p>The microRNA (miR) species analyzed in this study are involved in molecular mechanisms of TLR4 and TLR7 signaling, mediating the development of neuroinflammation and neurodegeneration. We have investigated the expression levels of miR-let7b, miR-96, miR-182, miR-155, and the mRNA content of HMGB1, TLR3, TLR4 in the nucleus accumbens (NAc) of the brain of rats exposed to long-term alcoholization. The long-term alcoholization caused a decrease in miR-let7b, miR-96, miR-182, and TLR7 mRNA levels; this was accompanied by an increase in miR-155, TLR4, and Hmgb1 mRNA levels in the NAc of rat brain. TLR7 is functionally linked to miR-let7b. The data of a simultaneous decrease in miR-let7b and TLR7 mRNA are of interest for further studies; they may indicate on the lack of functionally significant links between Hmgb1 and the miR-let7b-TLR7 system in NAc. The existing evidence of a functional relationship between TLR4 with miR-155 and miR-182 and our observations on their expression changes during chronic alcoholization are very interesting and require further investigation. The suggestion about the development of neuroinflammatory process in NAc under prolonged alcohol exposure are relevant for studying the level of TLR gene expression in NAc, as well as the expression of miR species, which may have a functional relationship with the TLR system.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"69 4","pages":"235-239"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10296076","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":"Alpha-2 macroglobulin activity in SARS-CoV-2 induced infection and in the post-COVID-19 period.","authors":"O E Akbasheva,&nbsp;D K Mitrofanova,&nbsp;L V Spirina,&nbsp;Yu G Samoilova,&nbsp;M V Matveeva,&nbsp;D V Podchinenova,&nbsp;O A Oleynik","doi":"10.18097/PBMC20236904240","DOIUrl":"https://doi.org/10.18097/PBMC20236904240","url":null,"abstract":"<p><p>The universal proteinase inhibitor α2-macroglobulin (α₂-MG) exhibiting antiviral and immunomodulatory activities, is considered as an important participant in the infectious process. The activity of α₂-MG in the new coronavirus infection and post-covid syndrome (long COVID) has not been studied yet. We examined 85 patients diagnosed with community-acquired bilateral polysegmental pneumonia developed under conditions of a new coronavirus infection SARS-CoV-2. For assessment of the post-COVID period, 60 patients were examined 5.0±3.6 months after the coronavirus infection. Among these patients, 40 people had complications, manifested in the form of neurological, cardiological, gastroenterological, dermatological, bronchopulmonary symptoms. The control group included 30 conditionally healthy individuals with a negative PCR result for SARS-CoV-2 RNA and lack of antibodies to the SARS-CoV-2 virus. The α₂-MG activity in serum samples of patients with coronavirus infection dramatically decreased, up to 2.5% of the physiological level. This was accompanied by an increase in the activity of the α₁-proteinase inhibitor, elastase- and trypsin-like proteinases by 2.0-, 4.4- and 2.6-fold respectively as compared with these parameters in conditionally healthy individuals of the control. In the post-COVID period, despite the trend towards normalization of the activity of inhibitors, the activity of elastase-like and especially trypsin-like proteinases in serum remained elevated. In overweight individuals, the increase in the activity of trypsin-like proteinases was most pronounced and correlated with an increase in the antibody titer to the SARS-CoV-2 virus. In the post-COVID period, the α₂-MG activity not only normalized, but also exceeded the control level, especially in patients with dermatological and neurological symptoms. In patients with neurological symptoms or with dermatological symptoms, the α₂-MG activity was 1.3 times and 2.1 times higher than in asymptomatic persons. Low α₂-MG activity in the post-COVID period persisted in overweight individuals. The results obtained can be used to monitor the course of the post-COVID period and identify risk groups for complications.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"69 4","pages":"240-247"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10307734","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 rifampicin on expression of the toll-like receptor system genes in the forebrain cortex of rats prenatally exposed to alcohol.","authors":"M I Airapetov,&nbsp;S O Eresko,&nbsp;P D Ignatova,&nbsp;D A Skabelkin,&nbsp;A A Mikhailova,&nbsp;D A Ganshina,&nbsp;A A Lebedev,&nbsp;E R Bychkov,&nbsp;P D Shabanov","doi":"10.18097/PBMC20236904228","DOIUrl":"https://doi.org/10.18097/PBMC20236904228","url":null,"abstract":"<p><p>Ethanol causes long-term changes in the toll-like receptor (TLR) system, promoting activation of neuroinflammation pathways. Alcohol use during pregnancy causes neuroinflammatory processes in the fetus; this can lead to the development of symptoms of fetal alcohol spectrum disorder (FASD). Our study has shown that prenatal alcohol exposure (PAE) induced long-term changes in the TLR system genes (Tlr3, Tlr4, Ticam, Hmgb1, cytokine genes) in the forebrain cortex of rat pups. Administration of rifampicin (Rif), which can reduce the level of pro-inflammatory mediators in various pathological conditions of the nervous system, normalized the altered expression level of the studied TLR system genes. This suggests that Rif can prevent the development of persistent neuroinflammatory events in the forebrain cortex of rat pups caused by dysregulation in the TLR system.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"69 4","pages":"228-234"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10589658","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}