Biomeditsinskaia Khimiia[JOURNAL]
Sun
200 papers
Identification of proteins with variable levels of post-translational modifications in human temporal lobe epilepsy.
Miroshnichenko YV, Rybina AV, Skvortsov VS
Biomed Khim · 2025 Nov · PMID 41211733 · Publisher ↗
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...
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.
The preconditioning effect of a structural analogue of apelin-12 in a rat model of acute myocardial infarction.
Veselova OM, Serebryakova LI, Studneva IM … +4 more , Azmuko AA, Avdeev AV, Sidorova MV, Pisarenko OI
Biomed Khim · 2025 Nov · PMID 41211732 · Publisher ↗
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 apel...
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.
Functional activity features of lactoferrin-fucoidan complexes in model systems in vitro.
Mosievich DV, Balabushevich NG, Mishin PI … +13 more , Le-Deygen IM, Filatova LY, Panasenko OM, Murina MA, Vakhrusheva TV, Barinov NA, Pobeguts OV, Galyamina MA, Gorudko IV, Grigorieva DV, Pashkevich KF, Sokolov AV, Mikhalchik EV
Biomed Khim · 2025 Nov · PMID 41211731 · Publisher ↗
Fucoidan, an anionic polysaccharide from brown algae, demonstrates anticoagulant, antioxidant, anti-inflammatory, antitumor, and antiviral activities. It can form polyelectrolyte complexes with various proteins, includin...
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.
Factors of variability in the composition of mixed saliva (a review).
Sarf EA, Bel Skaya LV
Biomed Khim · 2025 Nov · PMID 41211730 · Publisher ↗
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. Th...
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.
Bioinformatic identification of proteins with varying levels of post-translational modifications in a model of atherogenesis in mice.
Miroshnichenko YV, Rybina AV, Skvortsov VS
Biomed Khim · 2025 Sep · PMID 40904183 · Publisher ↗
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 (PT...
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.
The inhibitory effect of mometasone and nortriptyline on the production of proinflammatory cytokines by blood mononuclear cells of patients with allergic rhinitis under conditions of stimulated immune response.
Mironova TV, Tahanovich AD, Kadushkin AG … +3 more , Makarevich VV, Shilovskiy IP, Khaitov MR
Biomed Khim · 2025 Sep · PMID 40904182 · Publisher ↗
Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa; it develops when the immune system reacts to an allergen. Side effects of topical glucocorticosteroids (GCS) used for AR treatment, the develo...
Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa; it develops when the immune system reacts to an allergen. Side effects of topical glucocorticosteroids (GCS) used for AR treatment, the development of steroid resistance in patients and the continuing increase in morbidity explain the clear need to search for new approaches for AR treatment. The tricyclic antidepressant nortriptyline has demonstrated anti-inflammatory properties in a number of experimental studies, as well as its ability to complement the action of corticosteroids. The aim of this study was to compare the effects of nortriptyline and the synthetic GCS mometasone on the culture of mononuclear cells (MNC) of AR patients. Blood MNCs from six AR patients were cultured in the presence of nortriptyline or mometasone, and then type 1, type 2, or type 17 immune response (IR) were stimulated by adding recombinant activator proteins (IL-2, IL-25, IL-33, TSLP, IL-12, IL-1β, IL-23). After 3 days, concentrations of proinflammatory cytokines TNF-α, IFN-γ, IL-6, IL-8, and IL-4 were determined in cell supernatants by enzyme immunoassay. Mometasone (10⁻⁸ M final concentration) effectively suppressed the secretion of proinflammatory cytokines TNF-α, IFN-γ, IL-6, and IL-8 under conditions of stimulation of IR of all types. A similar decrease in secretion, although less pronounced, occurred when stimulated cells were cultured in the presence of nortriptyline. The concentration of TNF-α in the culture medium decreased under these conditions both with stimulation of type 1, type 2, and type 17 IR. The level of IFN-γ secretion decreased only in the case of type 1 and type 17 IR as compared to MNCs with the stimulated IR, which were cultured without this inhibitor. The level of IL-6 secretion decreased only in the culture medium of cells with stimulated type 1 and type 2 IR and IL-8 secretion decreased only under conditions of stimulated type 1 IR. This study has shown that mometasone and nortriptyline are able to suppress the secretion of proinflammatory cytokines by blood cells; their effect is selective and depends on the IR type.
Platelet functional activity in patients with immune thrombocytopenia.
Bodrova VV, Khaspekova SG, Shustova ON … +2 more , Tsvetaeva NV, Mazurov AV
Biomed Khim · 2025 Sep · PMID 40904181 · Publisher ↗
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 d...
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.
Interaction of antirenalase antibodies with recombinant human renalases 1 and 2 and their C-terminal regions encoded by the alternative exones.
Fedchenko VI, Kaloshin AA, Kaloshina SA … +3 more , Buneeva OA, Kopylov AT, Medvedev AE
Biomed Khim · 2025 Sep · PMID 40904180 · Publisher ↗
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...
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.
Glycyrrhizic acid: novel potential protein targets.
Ershov PV, Yablokov EO, Kaluzhskiy LA … +5 more , Mezentsev YV, Gnedenko OV, Konstantinov MA, Toropygin IY, Ivanov AS
Biomed Khim · 2025 Sep · PMID 40904179 · Publisher ↗
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. E...
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.
Prediction of the course of chronic obstructive pulmonary disease by blood biomarkers.
Murashka DI, Tahanovich AD, Kauhanka MM … +5 more , Nikitina IA, Kolb AV, Bogush LS, Davidovskaya EI, Budnik OA
Biomed Khim · 2025 Sep · PMID 40904178 · Publisher ↗
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...
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.
The role of the redox signaling system (H2О2 and the thiol system) in the regulation of the functional activity of nervous tissue in health and disease.
Dubinina EE, Shchedrina LV, Gomzyakova NA
Biomed Khim · 2025 Sep · PMID 40904177 · Publisher ↗
The review highlights the role of reactive oxygen species (ROS) and the thiol system in the regulation of functional activity of neurons. Their controlling function has been analyzed in the context of processes of synapt...
The review highlights the role of reactive oxygen species (ROS) and the thiol system in the regulation of functional activity of neurons. Their controlling function has been analyzed in the context of processes of synaptic plasticity and functioning of neurotrophins, as well as participation in such cellular processes as proliferation, apoptosis, and cell aging. Special attention has been paid to the role of individual components of the thiol system, their interaction with H2О2 in the regulation of the redox signaling system of cells. Summarizing literature data reflecting the participation of H2О2 in the regulation of key metabolic cascades of nervous tissue and own results we have come to conclusion about the dual nature of the stress system components depending on the functional state of the organism. The manifestation of their toxic effect, first of all, depends on their concentration and chemical structure.
Comparative analysis of the effect of hybrid vaterite microparticles with various polysaccharides on neutrophils activity.
Grigorieva DV, Mikhalchik EV, Mosievich DV … +5 more , Mishin PI, Balabushevich NG, Panasenko OM, Sokolov AV, Gorudko IV
Biomed Khim · 2025 Jun · PMID 40570074 · Publisher ↗
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...
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.
The delayed effect of the neuroprotector fabomotizole on the brain proteome in rats with the rotenone model of parkinsonism.
Buneeva OA, Kapitsa IG, Zavyalova MG … +3 more , Kaloshina SA, Zgoda VG, Medvedev AE
Biomed Khim · 2025 Jun · PMID 40570073 · Publisher ↗
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...
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.
The effect of fecal microbiota transplantation on levels of tryptophan metabolites in intestine and serum of gnotobiotic mice.
Shatova OP, Shestopalov AV, Zlatnik EY … +3 more , Novikova IA, Goncharova AS, Maksimov AY
Biomed Khim · 2025 Jun · PMID 40570072 · Publisher ↗
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 us...
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.
Problems and prospects of metabolomic studies in the alteration of the gut microbiome.
Savelieva EI, Shachneva MD
Biomed Khim · 2025 Jun · PMID 40570071 · Publisher ↗
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 mol...
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.
Selection of optimal protein sets as serological tumor marker signatures.
Naryzhny SN, Legina OK
Biomed Khim · 2025 Jun · PMID 40570070 · Publisher ↗
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, t...
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.
Changes in cell motility proteins profile in HaCaT keratinocytes response to UVA exposure.
Kisrieva IS, Samenkova NF, Bolochenkov NA … +6 more , Rusanov AL, Romashin DD, Solovyeva NA, Karuzina II, Lisitsa AV, Petushkova NA
Biomed Khim · 2025 Mar · PMID 40326021 · Publisher ↗
A comparative analysis of HaCaT keratinocyte proteins has been performed after cell exposure to subtoxic doses (5 J/cm² and 25 J/cm²) of ultraviolet A (UVA) radiation. 930 proteins were identified by two or more unique p...
A comparative analysis of HaCaT keratinocyte proteins has been performed after cell exposure to subtoxic doses (5 J/cm² and 25 J/cm²) of ultraviolet A (UVA) radiation. 930 proteins were identified by two or more unique peptides. More than half of all identified proteins (54.5%) demonstrated at least 2-fold increase in their relative content after HaCaT keratinocyte irradiation with a cumulative dose of 5 J/cm², while a decrease in the relative content was found only for 4 proteins. Irradiation of keratinocytes with a cumulative dose of 25 J/cm² resulted in a decrease in the proportion of up-regulated proteins (43.0%) and an increase in the number of down-regulated proteins (84). Among the proteins with increased relative content in HaCaT keratinocytes the most proteins were associated with "cell motility" (GO: 0048870), as well as regulation of cell shape and size, cell morphogenesis, and skin remodeling.
The P2X3 receptor blocker AF-353 (Ro-4) reduces bioenergetic index of a primary mixed culture of hippocampal neurons.
Zelentsova AS, Skorkina MY, Deykin AV
Biomed Khim · 2025 Mar · PMID 40326020 · Publisher ↗
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...
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.
The m6A methylation system limits hepatitis B virus replication.
Kachanov AV, Brezgin SA, Ponomareva NI … +4 more , Lukashev AN, Chulanov VP, Kostyushev DS, Kostyusheva AP
Biomed Khim · 2025 Mar · PMID 40326019 · Publisher ↗
N6-methyladenosine (m6A) is a common RNA modification, which plays a critical role in RNA fate and regulating such aspects as splicing, stability, nuclear export, and translation efficiency. The introduction, removal, an...
N6-methyladenosine (m6A) is a common RNA modification, which plays a critical role in RNA fate and regulating such aspects as splicing, stability, nuclear export, and translation efficiency. The introduction, removal, and recognition of m6A modifications in RNA are regulated by a number of factors, known as writer, eraser, and reader proteins. It is known that the m6A modification can play an important role in the life cycle of viruses, including hepatitis B virus. The m6A methylation system has a significant impact on the hepatitis B viral cycle (HBV), particularly, on stability of mRNA transcripts, encapsidation efficiency, and reverse transcription of HBV pgRNA. In this study, we assessed the effect of knockout and activation of expression of several factors of the m6A methylation system on the HBV viral cycle, including pregenomic RNA (pgRNA) and circular covalently closed DNA (cccDNA). The study was carried out using the StCas9 nuclease system for knockout and the dCas9-p300 system for activation of gene expression. The levels of pgRNA and cccDNA were estimated by real-time PCR. The data obtained show the restriction of the viral cycle at the basal level by the factors METTL3, METTL14, METTL16, FTO, JMJD6, and hnRNPA2B1, as well as suppression of the viral cycle with overexpression of all of the above factors, except for hnRNPA2B1.
Peptide toxins targeting ion channels as cytoprotective agents in ischemia-reperfusion injury of epithelial cells.
Iurova EV, Rastorgueva EV, Beloborodov EA … +4 more , Sugak DE, Pogodina ES, Fomin AN, Saenko YV
Biomed Khim · 2025 Mar · PMID 40326018 · Publisher ↗
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...
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.
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