Biomeditsinskaya khimiya最新文献

{"title":"Prediction of potential adverse drug reactions utilizing highly specific structural fragments.","authors":"P I Savosina, D A Filimonov, D S Druzhilovskiy","doi":"10.18097/PBMCR1634","DOIUrl":"https://doi.org/10.18097/PBMCR1634","url":null,"abstract":"<p><p>The use of in silico approaches to assess potential adverse reactions of new pharmaceutical substances reduces the risks, financial and time costs, associated with drug development. Using our previously developed method for identifying chemical motifs associated with certain types of undesirable biological activity, we have evaluated the off-target toxicity of clinically investigated pharmaceutical substances that would help to evaluate the potential risks of further research and use in clinical practice. For this purpose, we have created highly specific structural fragments for epidermal growth factor receptor and dipeptidyl peptidase 4 inhibitors, which are two molecular targets associated with a wide range of adverse reactions. A search for compounds containing these fragments was performed among 12,070 entries with information on clinical trials in the PubChem database. We have shown that five compounds entering phase I and II trials may have an unfavorable benefit-risk ratio due to the potential inhibition of at least one of the analyzed enzymes. Incorporating such analytical frameworks into early drug discovery and preclinical assessment could substantially reduce overall development costs and timelines, facilitating the introduction of safer and more cost-effective therapeutic agents.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 6","pages":"454-459"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146002942","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":"A biphasic effect of tumor necrosis factor-α on RPMI 2650 cell line in vitro.","authors":"Yu V Abalenikhina, D I Breslavets, S O Solotnova, S G Builina, A V Shchulkin, E N Yakusheva","doi":"10.18097/PBMCR1633","DOIUrl":"https://doi.org/10.18097/PBMCR1633","url":null,"abstract":"<p><p>Tumor necrosis factor-α (TNFα) is a key proinflammatory cytokine; its level increased in inflammatory diseases of the upper respiratory tract. In this study, the dose- and time-dependent effects of TNFα (1-100 ng/ml, 6-48 h) on the RPMI 2650 cell line, a model of nasal epithelium, have been investigated. Short-term exposure (6 h) caused activation of NF-κB and an increase in the levels of the intercellular contact proteins E-cadherin and ZO-1, without a significant effect on cell viability. Long-term exposure (24-48 h) led to an increase in the level of pro-IL-1β, activation of apoptosis, and a decrease in cell viability. At the same time, a decrease in the level of intercellular contact proteins was noted. Thus, short-term exposure to TNFα can exert a protective effect by increasing the density of intercellular contacts, while during prolonged exposure it triggers apoptosis and reduces the density of intercellular contacts, which can contribute to increased permeability of the cell layer.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 6","pages":"414-423"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146002917","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":"In vitro biological properties of pyridoxine and ketorolac conjugates.","authors":"M N Agafonova, O S Vasileva, E M Fafanova, D J Grishaev, M N Sarynin, M V Pugachev, Yu G Shtyrlin","doi":"10.18097/PBMCR1620","DOIUrl":"https://doi.org/10.18097/PBMCR1620","url":null,"abstract":"<p><p>Prodrugs based on pyridoxine and ketorolac (the most potent analgesic NSAIDs) exhibit analgesic activity comparable to ketorolac in vivo and significantly higher safety and prolonged action. In this study the antioxidant and protective properties, inhibitory activity against cyclooxygenase (COX) and intracellular permeability for two prodrug bipharmacophoric conjugates based on pyridoxine and ketorolac have been investigated in vitro. Their inhibitory activity towards the COX-1 and COX-2 enzymes was comparable to that of ketorolac (the IC50 values ranged from 12.0 μM to 34.7 μM). These compounds markedly protected albumin against thermal and chemical (urea and citric acid) treatments and demonstrated the cell-penetrating ability through passive diffusion.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 6","pages":"432-440"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146002986","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":"Factors of variability in the composition of mixed saliva (a review).","authors":"E A Sarf, L V Bel Skaya","doi":"10.18097/PBMCR1574","DOIUrl":"10.18097/PBMCR1574","url":null,"abstract":"<p><p>The study of saliva composition attracts much attention and the number of publications in this area is constantly growing. However, the impact individual factors on saliva composition still needs better understanding. The limited use of saliva as a biological fluid for clinical laboratory diagnostics is determined by the lack of standardized preanalytical methods and the absence of reference values for biochemical parameters that take into account a number of factors affecting saliva composition and properties. In this review we have analyzed some factors influencing saliva composition. The impact of these factors on saliva composition is associated with dysfunction of the salivary glands, changes in salivation rate, salivary viscosity, dry mouth, pH balance, and electrolyte composition, leading to impaired homeostasis of the oral cavity.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 5","pages":"319-332"},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145480533","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":"Functional activity features of lactoferrin-fucoidan complexes in model systems in vitro.","authors":"D V Mosievich, N G Balabushevich, P I Mishin, I M Le-Deygen, L Y Filatova, O M Panasenko, M A Murina, T V Vakhrusheva, N A Barinov, O V Pobeguts, M A Galyamina, I V Gorudko, D V Grigorieva, K F Pashkevich, A V Sokolov, E V Mikhalchik","doi":"10.18097/PBMCR1613","DOIUrl":"10.18097/PBMCR1613","url":null,"abstract":"<p><p>Fucoidan, an anionic polysaccharide from brown algae, demonstrates anticoagulant, antioxidant, anti-inflammatory, antitumor, and antiviral activities. It can form polyelectrolyte complexes with various proteins, including the therapeutically important protein lactoferrin. The aim of this study was to investigate the physicochemical and functional properties of a fucoidan-lactoferrin complex formed by mixing their solutions at physiological pH. The complex, detected using atomic force microscopy, had a negative charge and a hydrodynamic diameter of 382 nm. Interaction with lactoferrin changed the IR spectrum of fucoidan in the absorption band in the range of 1220-1260 cm-1, corresponding to vibrations of the sulfate group. It increased the total antioxidant activity of biopolymers in the Fenton reaction and reduced the anticoagulant activity of fucoidan, assessed by determining the activated partial thromboplastin time. Fucoidan reduced luciferase activity in a luciferin-luciferase model system, and complex formation with lactoferrin attenuated the inhibitory capacity of fucoidan. These results demonstrate the possibility of targeted influence on the functional activity of biopolymers during complex formation and prospects for using fucoidan and lactoferrin as a complex in the development of new drugs and drug delivery systems.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 5","pages":"333-341"},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145480629","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":"Identification of proteins with variable levels of post-translational modifications in human temporal lobe epilepsy.","authors":"Yu V Miroshnichenko, A V Rybina, V S Skvortsov","doi":"10.18097/PBMCR1612","DOIUrl":"10.18097/PBMCR1612","url":null,"abstract":"<p><p>Comparative mass spectrometry analysis of hippocampal tissue samples from patients with sclerotic and non-sclerotic temporal lobe epilepsy and nonepileptic patients was undertaken to identify differences in the levels of protein post-translational modifications (PTMs). The original proteomic data obtained by Mathoux et al. [DOI: 10.1172/jci.insight.188612] and deposited in the PRIDE repository (PXD064519) were used in this work. Our reanalysis of the comparative proteomic data identified 53 proteins with PTMs (phosphorylation, methylation, acetylation, and citrullination) that exhibited significant changes in the levels of individual modified peptides. According to the published original data, all 53 proteins are involved in processes associated with neurological diseases in general and epileptogenesis in particular. The analysis identified PTMs of proteins that could play an important role in the pathogenesis of neurological diseases.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 5","pages":"351-363"},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145480617","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":"Vitaphospholip® (water-soluble phosphatidylcholine) in the treatment of combined hyperlipidemia: a randomized, placebo-controlled clinical trial.","authors":"V V Kukharchuk, E A Ponomarenko, A V Lisitsa, Yu A Romashova, T O Pleshakova, E B Yarovaya, V A Kutsenko, M K Guseva, O M Ipatova, E A Karpova, M Yu Zubareva, A M Pyatigorsky, S V Ivanov, V V Beregovykh, D A Kudlai, S S Markin, A I Archakov","doi":"10.18097/PBMCR1619","DOIUrl":"10.18097/PBMCR1619","url":null,"abstract":"<p><p>Vitaphospholip®, a water-soluble form of phosphatidylcholine, has been evaluated in a clinical trial aimed at reducing non-HDL-cholesterol (non-HDL-C) and triglyceride (TG) levels in patients with combined hyperlipidemia. The randomized, double-blind, placebo-controlled study included 100 patients. Vitaphospholip® or placebo was administered orally 500 mg twice a day for 12 weeks.Treatment with Vitaphospholip® resulted in a 13.2% decrease in non-HDL-C compared to 4.3% in the placebo group (p = 0.001). The absolute decrease of non-HDL-C was 0.6 mmol/l compared to -0.2 mmol/l in the placebo group (p = 0.001). The target non-HDL-C level of less than 3.4 mmol/L was achieved in 15 of 39 patients (38.5%) in the Vitaphospholip® group versus 2 of 41 patients (4.9%) in the placebo group (p = 0.000). The absolute decrease of TG in the group of patients treated with Vitaphospholip® was -0.7 mmol/l versus -0.1 mmol/L in the placebo group (p = 0.001). During therapy with Vitaphospholip®, a significant decrease in the levels of apolipoprotein B, total cholesterol, and very low-density lipoprotein cholesterol was observed. No changes in liver or kidney function, vital signs, or ECG were registered. No serious adverse events were identified. Thus, Vitaphospholip® significantly reduced the levels of non-HDL-C, TG, and atherogenic lipoprotein in patients with combined hyperlipidemia and moderate cardiovascular risk.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 5","pages":"364-374"},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145480703","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 preconditioning effect of a structural analogue of apelin-12 in a rat model of acute myocardial infarction.","authors":"O M Veselova, L I Serebryakova, I M Studneva, A A Azmuko, A V Avdeev, M V Sidorova, O I Pisarenko","doi":"10.18097/PBMCR1622","DOIUrl":"10.18097/PBMCR1622","url":null,"abstract":"<p><p>The use of pharmacological agents to trigger preconditioning mechanisms may improve the prevention and treatment of coronary heart disease. The aim of this study was to evaluate the ability of a structural analog of apelin-12 ((NαMe)Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Nle-Pro-Phe-OH, metilin) to reproduce the effect of ischemic preconditioning (IP) of rat hearts in vivo. Control rats were exposed to 40-min occlusion of the left descending coronary artery (LDCA) followed by 60-min restoration of coronary blood flow (reperfusion). IP was modeled by three cycles of 5-min occlusion/5-min reperfusion of the LDCA before prolonged regional myocardial ischemia and reperfusion. Metilin (5 mg/kg) was administered to rats intravenously by bolus injection 30 min before LDCA occlusion. IP or metilin had a significant impact on the studied parameters. The size of necrotic damage to the left ventricle, expressed as the percentage ratio of myocardial infarction/myocardial area at risk (MI/AAR, %), at the end of reperfusion was 26.9±2.0% and 29.3±2.6%, respectively, compared with 43.8±1.2% in the control (p < 0.01). The activity of creatine kinase-MB (CK-MB) in blood plasma decreased to 1026.1±93.9 IU/ml and 1195.2±142.0 IU/ml, respectively, compared with 1986.3±193.7 IU/ml in the control (p < 0.02). Administration of metilin, as well as IP, increased the reduced content of ATP, total adenine nucleotide pool (ΣAN) and phosphocreatine (PCr) in the AAR at the end of reperfusion compared to the control (p < 0.05-0.01). In the metilin group, the content of total creatine (ΣCr) in AAR was higher than in the control (p < 0.05). Intravenous administration of 5 mg/kg 5-hydroxydecanoate (5HD), an inhibitor of mitochondrial ATP-dependent K+ channels (mitoKATP), abolished the preconditioning effect of metilin, and increased the MI/AAR, %, and plasma CK-MB activity to values that insignificantly differed from the control (39.4±2.8% and 2258.2±179.1 IU/ml, respectively). Simultaneously, 5HD significantly reduced the ATP and ΣAN levels in AAR compared to those in the metilin group and the ATP, ΣAN, and PCr levels compared to the IP group. The results indicate that pharmacological preconditioning by metilin reduced cardiac ischemia/reperfusion injury via the involvement of mitoKATP in the mechanism of metilin action.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 5","pages":"342-350"},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145480648","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":"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}