Doklady Biochemistry and Biophysics最新文献

{"title":"Starch as a Polymer-Based Medium Modifier to Analyze Enzyme Activity under Conditions Close to Intracellular Media: Butyrylcholinesterase as a Model Enzyme.","authors":"V I Lonshakova-Mukina, A A Gromova, E N Esimbekova, P Masson, V A Kratasyuk","doi":"10.1134/S160767292560143X","DOIUrl":"https://doi.org/10.1134/S160767292560143X","url":null,"abstract":"<p><p>The study demonstrates the possibility of using starch to model macromolecular crowding and intracellular medium. A kinetic approach is used to reveal specific functioning of butyrylcholinesterases from different sources in the starch medium. In the study solutions, the Michaelis constant increases, indicating a decrease in the enzyme affinity for the substrate in the presence of the polymer. In the 9% starch solution, this parameter for butyrylcholinesterase from equine serum is 4.6 times higher than in the buffer solution, while the decrease in V_max is not significant; V_max values in most solutions are close to those in buffer solution. Model compounds-glycerol and sucrose-are used to impair diffusion control of the reaction studied. Inhibition mechanisms are retained in solutions with starch concentrations, ranging from 1 to 5%, whatever the inhibitor-chlorophos or neostigmine-is used.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local RNA Structure, not Primary Sequence, Governs the Binding Specificity of PCID2 in Drosophila melanogaster.","authors":"Y A Vdovina, S G Georgieva, D V Kopytova","doi":"10.1134/S1607672926600399","DOIUrl":"https://doi.org/10.1134/S1607672926600399","url":null,"abstract":"<p><p>Nuclear export of mRNA is one of the key stages of gene expression in eukaryotes. A wide range of mRNAs is exported by the TREX-2 complex, which includes the PCID2 RNA-binding protein. Previously, we showed that PCID2 is responsible for specific recognition of transcripts, and we identified its binding site on the Drosophila ras2 gene mRNA within the 3'-non-coding region. However, the interaction was not localized for other mRNAs, which makes it impossible to identify the general patterns of PCID2 interaction with mRNA. In this work, we investigated the interaction of PCID2 with the mRNA of the kruppel gene of Drosophila melanogaster. In the EMSA experiments, we showed that PCID2 binds to two fragments of kruppel mRNA, from the 5' non-coding and coding mRNA regions. Thus, the PCID2 binding site can be located not only in the 3'-non-coding region, as in the case of the ras2 mRNA, but also in other mRNA regions. PCID2 has a lower affinity for binding sites in the kruppel mRNA than in the ras2 mRNA. Our analysis of the mRNA structure at three binding sites led to a general interaction model, in which a hairpin-type conformation emerges as the most probable structural motif at these sites.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein Kinase D1 Inhibits AMP-Activated Protein Kinase Activity in the Rat Postural Muscle during the Initial Stage of Mechanical Unloading.","authors":"N A Vilchinskaya, T M Mirzoev, B S Shenkman","doi":"10.1134/S1607672926600181","DOIUrl":"https://doi.org/10.1134/S1607672926600181","url":null,"abstract":"<p><p>It is well established that the early stage of mechanical unloading in both humans and animals is characterized by a decline in the activity of the key cellular energy sensor, AMP-activated protein kinase (AMPK). This decline triggers signaling pathways that drive myosin phenotype remodeling and muscle atrophy. However, the molecular mechanisms underlying the reduction in AMPK activity under these conditions remain poorly understood. We hypothesized that elevated activity of protein kinase D1 (PKD1) could contribute to the decline in AMPK activity during the initial stage of rat hindlimb unloading. The present study demonstrates that the suppression of upregulated PKD1 activity via a specific inhibitor (CRT0066101) during 24-hour unloading results in the restoration of AMPK activity in the rat soleus muscle. Thus, we have shown for the first time the contribution of PKD1 to the regulation of AMPK activity in the mammalian postural muscle during the initial stage of hindlimb unloading.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biochemical Adaptation and Telomere Shortening in Javanese Macaques in Response to Social Isolation.","authors":"O P Chzhu, M F Timina, Y Y Bondareva, R M Kirgintsev, N S Rudenko, A V Popov","doi":"10.1134/S1607672926600363","DOIUrl":"https://doi.org/10.1134/S1607672926600363","url":null,"abstract":"<p><p>In this study, we examined changes in hormonal status, oxidative status, antioxidant defense, and peripheral blood leukocyte telomere length in male Javanese macaques (Macaca fascicularis) following transfer from group housing to individual cages as a model of social isolation. The study was performed in ten male Javanese macaques aged 11-17 years using a longitudinal design: the parameters were assessed in the same animals before transfer to individual cages and after 60 days of isolation. Malondialdehyde (MDA) concentration, superoxide dismutase (SOD) and catalase activities, cortisol, testosterone, and thyroglobulin levels, as well as absolute mean telomere length, were measured. A statistically significant decrease in telomere length (p = 0.0062), MDA concentration, and catalase activity (p < 0.01), as well as an increase in SOD activity and cortisol level (p < 0.05), was observed. Testosterone showed a decreasing trend, whereas thyroglobulin showed an increasing trend. The obtained data indicate systemic changes in the studied parameters in response to isolation. Changes in telomere length and oxidative status may reflect the involvement of mechanisms related to DNA damage and antioxidant system function. The results are consistent with the concept of stages of the general adaptation syndrome.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulin-Like Growth Factor 2 Modulates Macrophage Polarization: the Role of the IGF2-IGFBP6 Axis.","authors":"D A Averinskaya, M Yu Shkurnikov","doi":"10.1134/S160767292660034X","DOIUrl":"https://doi.org/10.1134/S160767292660034X","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is characterized by an aggressive clinical course and extremely limited targeted therapy options. One of the key drivers of immunosuppression in the tumor microenvironment is the polarization of tumor-associated macrophages (TAMs) towards the M2 phenotype. In the present study, we investigated the effect of insulin-like growth factor 2 (IGF2)-the primary ligand of the IGF1R receptor and a target of the inhibitory protein IGFBP6-on the transcriptional profile of macrophages polarized in vitro from the THP-1 cell line. We demonstrate that IGF2 exerts fundamentally different effects depending on the baseline functional state of the macrophages: in immature (M0) and M2-polarized cells, it induces the expression of pro-inflammatory genes, whereas in M1 macrophages it triggers pronounced immunosuppressive reprogramming. These findings suggest that IGFBP6, by inhibiting IGF2, may sustain an anti-tumor immune response within the TNBC microenvironment.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Low-Intensity Laser Irradiation on GAP-43 Expression in the Hippocampus of Rats.","authors":"V N Kotov, I V Kastyro, A A Tsymbal, V V Malakhovsky, E V Orlova","doi":"10.1134/S1607672926600338","DOIUrl":"https://doi.org/10.1134/S1607672926600338","url":null,"abstract":"<p><p>A study was conducted to examine the effects of visible red light phototherapy with a wavelength of 635 nm on the expression of the neuronal protein GAP-43 in the hippocampus of rats. It was shown that the use of PBMT promotes increased GAP-43 synthesis in the hippocampus, with the maximum effect developing by the 6th day of use, which may indicate a cumulative effect of this procedure.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Efficacy and Safety of Divozilimab in Patient with Systemic Sclerosis: 48-Week Results of the Randomized Double-Blind Placebo-Controlled Phase III Clinical Study LIBERIUS.","authors":"L P Ananyeva, M N Starovoytova, I Z Gaydukova, G V Lukina, E V Zonova, L V Eliseeva, G F Fatkhullina, D I Abdulganieva, D G Krechikova, T V Kropotina, O B Nesmeyanova, I B Vinogradova, E S Zhugrova, L V Ivanova, N E Nikulenkova, O R Ziganshin, T V Plaksina, M V Zlobin, Yu Yu Grabovetskaya, N F Soroka, O B Ershova, T V Povarova, O N Anoshenkova, A A Lutsky, A V Zinkina-Orikhan, Yu N Linkova, E A Fokina, A A Porozova, P S Pukhtinskaya, A V Eremeeva","doi":"10.1134/S1607672926700018","DOIUrl":"https://doi.org/10.1134/S1607672926700018","url":null,"abstract":"<p><p>of the study is to evaluate the efficacy, safety, and immunogenicity of divozilimab (DIV), anti-CD20 monoclonal antibody, in patients with systemic sclerosis (SS).</p><p><strong>Materials and methods: </strong>. Patients with SS according to ACR/EULAR (American College of Rheumatology/European Alliance of Associations for Rheumatology) 2013 criteria with modified Rodnan skin score (mRSS) ≥10 and ≤20 and forced vital capacity (FVC) ≥40% from the due took part in the study. Infusions of DIV 250 mg were administered on weeks 0 and 2, and DIV 500 mg on week 24 with the subsequent use in open mode, starting from week 48. This publication presents data obtained for 48 weeks of trial (before the DIV infusion at week 48). Primary endpoint was the change in the mRSS from baseline to week 48. The dynamic of FVC was estimated as the secondary endpoint. The safety evaluation included the frequency and profile of adverse events and adverse reactions (ARs). Immunogenicity was assessed by detection of binding and neutralizing anti-drug antibodies on weeks 2, 24, and 48.</p><p><strong>Results: </strong>: The patients (151) were randomized into two groups: DIV (n = 76) and placebo (n = 75). The most were female; the median duration of the disease was about 3-4 years. The initial value of the mRSS was 14 and 13 points in DIV and Placebo groups, respectively. The change of mRSS from baseline to week 48 was -5.8 ± 1.1 points in DIV group and -2.7 ± 1.0 points in placebo group (adjusted mean difference (AMD) with 95% confidence interval -3.1 (-4.5; -1.7); p < 0.0001). The lung function was stable in patients treated with DIV. A comparable safety profile of DIV and placebo was demonstrated. The most frequent ARs were infusion reactions and a decrease in the number of lymphocytes. There were no severe and serious ARs in DIV group. All infusion reactions were mild and moderate. 5.3% (4/76) patients in DIV group had binding antibodies without neutralizing activity.</p><p><strong>Conclusions: </strong>: Divozilimab has demonstrated a significant decrease in severity of skin fibrosis, a positive effect on the respiratory function, and a favorable safety profile, which allows it to be considered as a promising therapeutic option for SS.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of Cytogenetic Effects in Human Peripheral Blood Lymphocytes After Exposure to Low and Medium Doses of a Pencil Scanning Proton Beam with Different Linear Energy Transfer.","authors":"V E Balakin, O M Rozanova, T A Belyakova, E N Smirnova, N S Strelnikova","doi":"10.1134/S1607672926600090","DOIUrl":"https://doi.org/10.1134/S1607672926600090","url":null,"abstract":"<p><p>The effect of a pencil scanning proton beam in two regions of the Bragg curve with different linear energy transfer (LET) relative to X-ray radiation on the induction of micronuclei (MN) in cytochalasin-blocked binucleate lymphocytes (CBBLs) during in vitro irradiation of human peripheral blood at doses ranging from 0 to 2.0 Gy was studied. A nonlinear dose-response relationship was observed in the dose range of 0 to 1.0 Gy. The frequency of MN in CBBLs during proton irradiation was 2 times lower than during X-rays and did not depend on the LET value. In the dose range above 1 Gy, the dose dependences were linear, the value of the relative biological effectiveness depended on LET and was equal to 0.76 before the Bragg peak, and 1.16 at the peak.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Kinetics of Intrinsic Luminescence of Bacterial Luciferase during Catalysis Indicates Flavin Binding and Enzyme Recovery.","authors":"A E Lisitsa, D V Gulnov, I V Shakhmatov, E A Kirichenko, L P Burakova, V A Kratasyuk, E V Nemtseva","doi":"10.1134/S1607672926600132","DOIUrl":"https://doi.org/10.1134/S1607672926600132","url":null,"abstract":"<p><p>The study proposes an experimental approach to determining the rates of individual stages of a reaction catalyzed by bacterial luciferase, based on the tryptophan fluorescence of the protein and the stopped-flow technique. The relationship between the fluorescence intensity of tryptophan residues in luciferase and the presence of substrates and reaction products in the active site of the enzyme is substantiated. The non-steady-state kinetics of bioluminescence in the reaction of two bacterial luciferases with aliphatic aldehydes of different chain lengths, as well as the kinetics of enzyme fluorescence intensity during the reaction, were analyzed. The obtained results confirmed the relationship between the rate of the two kinetic stages of enzyme luminescence and the processes of flavin substrate binding and enzyme activity recovery after the catalytic act.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design of Nucleoside Prodrugs for the Inhibition of Tick-Borne Encephalitis Virus Reproduction.","authors":"A A Zenchenko, M K Kaleda, V I Uvarova, E V Khvatov, D I Osolodkin, V E Oslovsky","doi":"10.1134/S1607672926600156","DOIUrl":"https://doi.org/10.1134/S1607672926600156","url":null,"abstract":"<p><p>The design of prodrugs for nucleoside antiviral agents is the primary approach to achieving target profiles not only in terms of safety but also efficacy. We have proposed a new chemotype of inhibitors of tick-borne encephalitis virus (TBEV) reproduction among N⁶-substituted adenosine derivatives, characterized by the presence of a hydrophobic aromatic substituent at the N⁶ position of adenine and benzoic acid residues attached via ester bonds to the ribofuranose scaffold. The compounds inhibited TBEV reproduction at micromolar concentrations only in their benzoylated form, while exhibiting no detectable cytotoxicity regardless of the substitution on the ribofuranose moiety. Our study demonstrates that modifying nucleoside analogs with hydrophobic groups can yield compounds with improved antiviral activity, and the identified compounds may subsequently serve as prototypes for the development of new antiviral drugs against epidemiologically significant pathogenic RNA viruses affecting humans.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}