Biochemistry (Moscow)最新文献

{"title":"Unveiling Oncogenic Power of WAVE1 in Bladder Cancer Progression","authors":"Shouxi Cui,&nbsp;Bin Liang,&nbsp;Yong Liu","doi":"10.1134/S0006297924604489","DOIUrl":"10.1134/S0006297924604489","url":null,"abstract":"<p>WAVE1 (Wiskott–Aldrich syndrome verprolin-homologous protein family member 1), a gene associated with the Wiskott–Aldrich syndrome, has been identified as an oncogene with high expression in various tumors and has been linked to metastatic conditions. Nevertheless, expression pattern of WAVE1 and its function in bladder cancer (BC) remain unknown. This study aimed to uncover the effect of WAVE1 on migration and metastasis in BC. In this study, four different human urinary BC cell lines (T24, RT4, J82, and BIU87) were examined using immunohistochemical and Western blot assays to assess the pattern of WAVE1 expression. Subsequently, the regulatory role of WAVE1 expression in migration, and EMT in the BC cell lines was investigated. WAVE1 was significantly expressed in the BC tissues <i>in vivo</i>. WAVE1 knockdown in the T24 cells inhibited cell migration, whereas WAVE1 upregulation in the RT4 cells had the opposite effect. WAVE1 was shown to trigger epithelial-mesenchymal transition (EMT) and stimulate the p38 mitogen-activated protein kinase (MAPK) signaling pathway. The findings indicate that WAVE1 enhances migration and invasion of the BC cells through EMT, which is mediated by activation of the MAPK/p38 signaling.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 4","pages":"534 - 543"},"PeriodicalIF":2.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197880","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":"Restriction–Modification Systems Specific toward GGATC, GATGC, and GATGG. Part 2. Functionality and Structure","authors":"Sergey Spirin,&nbsp;Alexander Grishin,&nbsp;Ivan Rusinov,&nbsp;Andrei Alexeevski,&nbsp;Anna Karyagina","doi":"10.1134/S0006297925600152","DOIUrl":"10.1134/S0006297925600152","url":null,"abstract":"<p>The structural and functional basics of protein functionality of restriction–modification systems recognizing GGATC/GATCC, GATGC/GCATC, and GATGG/CCATC sites have been studied using bioinformatics methods. Such systems include a single restriction endonuclease and either two separate DNA methyltransferases or a single fusion DNA methyltransferase with two catalytic domains. It is known that some of these systems methylate both adenines in the recognition sites to 6-methyladenine, but the role of each of the two DNA methyltransferases remained unknown. In this work, we proved the functionality of most known systems. Based on the analysis of structures of related DNA methyltransferases, we hypothesized which of the adenines within the recognition site is modified by each of the DNA methyltransferases and suggested a possible molecular mechanism of changes in the DNA methyltransferase specificity from GATGG to GATGC during horizontal transfer of its gene.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 4","pages":"513 - 521"},"PeriodicalIF":2.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197877","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":"R- and S-Pyruvate-Containing Polysaccharide from the Cell Wall of Rathayibacter sp. VKM Ac-2927","authors":"Maksim S. Kokoulin,&nbsp;Natalia V. Potekhina,&nbsp;Elena M. Tul’skaya,&nbsp;Yury V. Ospennikov,&nbsp;Lyudmila I. Evtushenko","doi":"10.1134/S0006297925600759","DOIUrl":"10.1134/S0006297925600759","url":null,"abstract":"<p>The structures of two cell wall glycopolymers from the strain <i>Rathayibacter</i> sp. VKM Ac-2927 (family Microbacteriaceae, class Actinomycetes), isolated from the leaves of a linden affected by leaf miner, were established using chemical and NMR spectroscopy methods. The first polymer, rhamnomannan, is a heterogeneous chain polymer composed of regularly alternating α-D-rhamnose and α-D-mannose residues linked by (1→3)- and (1→2)-glycosidic bonds and contains a minor amount of lateral β-D-xylopyranose residues (structure is presented in the text). The second polymer, acetalized with <i>R</i>- and <i>S</i>-pyruvic acid, consists of branched tetrasaccharide units, →3)-α-D-Gal<i>p</i>4,6-(<i>R-</i>Pyr)-(1→3)-β-D-Glc<i>p</i>-(1→6)-[β-D-Gal<i>p</i>3,4-(<i>S</i>-Pyr)-(1→4)]-α-D-Man<i>p</i>-(1→. Structure of this polysaccharide is new for the representatives of the genus <i>Rathayibacter</i> and prokaryotes in general. The results of present study indicate structural diversity of microbial glycopolymers and are consistent with the previously obtained data on specificity of their composition for the species of the <i>Rathayibacter</i> genus.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 4","pages":"493 - 501"},"PeriodicalIF":2.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197936","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":"Novel CRISPR/Cas9-Based Approaches for Quantitative Study of DSB Repair Mechanics","authors":"Alexander V. Smirnov,&nbsp;Anastasia M. Yunusova","doi":"10.1134/S0006297924601813","DOIUrl":"10.1134/S0006297924601813","url":null,"abstract":"<p>This review examines modern approaches to studying double-strand break (DSB) DNA repair in mammalian cells, employing the CRISPR/Cas9 system. Due to its flexibility and efficacy, the Cas9 nuclease is used in numerous genetic reporters. We discuss various fluorescence-based genetic reporters used to monitor the repair process. In addition, among the innovative Cas9-based methods, special attention is given to the techniques that examine both single and multiple DSBs, including approaches such as DSB-TRIP and ddXR. These methods open new possibilities for investigating structural rearrangements or analyzing random genomic sites. Additionally, the review considers how DSBs induced by Cas9 differ from those made by other nucleases and how these peculiarities could impact DNA repair mechanisms. Understanding these differences is crucial for planning experiments aimed at studying DSB repair.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 4","pages":"437 - 456"},"PeriodicalIF":2.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197875","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":"Suppression of Il5 and Il13 Gene Expression by Synthetic siRNA Molecules Reduces Nasal Hyperreactivity and Inflammation in a Murine Model of Allergic Rhinitis","authors":"Mariya M. Kaganova,&nbsp;Igor P. Shilovskiy,&nbsp;Valeriya I. Kovchina,&nbsp;Ekaterina D. Timotievich,&nbsp;Tatiana E. Rusak,&nbsp;Alexander A. Nikolskii,&nbsp;Kirill V. Yumashev,&nbsp;George B. Pasikhov,&nbsp;Kamilla V. Vinogradova,&nbsp;Danila A. Gurskii,&nbsp;Maya V. Popova,&nbsp;Vera E. Brylina,&nbsp;Musa R. Khaitov","doi":"10.1134/S0006297924602946","DOIUrl":"10.1134/S0006297924602946","url":null,"abstract":"<p>Th2 cytokines (IL-4, IL-5, and IL-13) play an important role in the development of allergies, including allergic rhinitis (AR). IL-13 promotes mucus hyperproduction in the airway and IL-5 recruits eosinophils to the nasal mucosa, leading to increased inflammation and tissue damage. Drugs based on monoclonal antibodies that block the activity of these cytokines are being developed for the treatment of allergic diseases. However, studies of drugs that target IL-13 alone (such as Tralokinumab and Lebrikizumab) were not successful. Given that IL-5 and IL-13 have different roles in AR, simultaneous inhibition of both cytokines may be a promising approach. New methods of regulating gene activity, such as RNA interference (RNAi), offer new perspectives for the development of drugs. This study describes a complex consisting of siRNA that inhibit the activity of <i>Il5</i> and <i>Il13</i> genes and a currier peptide LTP (cationic dendrimeric peptide). The effects of this complex on the allergic inflammation in the murine AR model was studied. Suppression of <i>Il5</i> expression decreased nasal hyperreactivity and reduced the number of goblet cells in the respiratory epithelium of AR-induced mice. Inhibiting the <i>Il13</i> gene had a more beneficial effect than suppression <i>Il5</i> alone, further contributing to reducing the number of cells infiltration the nasal cavity. When both <i>Il5</i> and <i>Il13</i> were suppressed simultaneously, the result was similar that of <i>Il13</i> inhibition alone. Likely, IL-13 plays a more significant role in the development of allergic rhinitis than IL-5. As a result, the possibility of using RNAi for anti-cytokine therapy for AR has been demonstrated. However, dual inactivation of IL-5 and IL-13 by siRNA does not provide any advantages over inactivating IL-13 alone in the current mouse model of AR. However, the lack of success of anti-IL-13 therapy in clinical practice indicates the promise of an approach based on the dual blocking of IL-5 and IL-13.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 4","pages":"476 - 492"},"PeriodicalIF":2.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197879","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":"Peripheral Immune-Inflammatory Parameters in Parkinson’s Disease. Dependence on the Stage of Progression","authors":"Galina V. Idova,&nbsp;Svetlana Ya. Zhanaeva,&nbsp;Elizaveta L. Alperina,&nbsp;Sergei S. Dzemidovich,&nbsp;Margarita M. Gevorgyan,&nbsp;Kseniya I. Kulikova,&nbsp;Lyubomir I. Aftanas","doi":"10.1134/S0006297925600334","DOIUrl":"10.1134/S0006297925600334","url":null,"abstract":"<p>According to the modern concepts, neuroinflammation and peripheral immune dysfunction play key roles in the onset and progression of Parkinson’s disease (PD), one of the most common and severe neurodegenerative diseases. However, changes in the cellular and molecular immune parameters during the development of PD are still poorly understood. This work is devoted to analysis of the immune cell populations (monocytes, T- and B-cells and their subtypes), expression of Toll-like receptors (TLR), and spontaneous and mitogen-induced production of pro- and anti-inflammatory cytokines in the peripheral blood of the patients at different stages of idiopathic PD and healthy individuals. It was shown that the stage II of PD is characterized by the decrease in amount of the CD3⁺ T-cells, increase in the TLR2 expression on CD4⁺CD25⁺ Tregs, as well as increase in the spontaneous production of proinflammatory cytokines IFNγ and IL-17A. The stage III of PD is associated with the decrease in production of mitogen-induced IFNγ. Relative number of the CD19⁺CD25⁺ Breg cells in the patients with PD increased regardless of the disease stage. Thus, the obtained results indicate differences in the cellular and molecular immune parameters in the patients with PD and in the healthy individuals, which are dependent on the stage of the disease. These data are important for understanding molecular basis of PD development and prognosis of its course, and may be useful in identifying biomarkers of the disease severity and developing new treatment approaches depending on the stage of the disease.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 3","pages":"364 - 373"},"PeriodicalIF":2.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919186","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":"Development of Immunochemical Systems for Detection of Human Skeletal Troponin I Isoforms","authors":"Agnessa P. Bogomolova,&nbsp;Ivan A. Katrukha,&nbsp;Alexey M. Emelin,&nbsp;Artur I. Zabolotsky,&nbsp;Anastasia V. Bereznikova,&nbsp;Olga S. Lebedeva,&nbsp;Roman V. Deev,&nbsp;Alexey G. Katrukha","doi":"10.1134/S0006297924601928","DOIUrl":"10.1134/S0006297924601928","url":null,"abstract":"<p>Troponin I (TnI), together with troponin T (TnT) and troponin C (TnC), forms the troponin complex, a thin filament protein of the striated muscle that plays a key role in regulation of muscle contraction. In humans, TnI is represented by three isoforms: cardiac, which is synthesized only in myocardium, and fast and slow skeletal, which are synthesized in fast- and slow-twitch muscle fibers, respectively. Skeletal TnI isoforms could be used as biomarkers of skeletal muscle damage of various etiologies, including mechanical trauma, myopathies, muscle atrophy (sarcopenia), and rhabdomyolysis. Unlike classical markers of muscle damage, such as creatine kinase or myoglobin, which are also present in other tissues, skeletal TnIs are specific for skeletal muscle. In this study, we developed a panel of monoclonal antibodies for immunochemical detection of skeletal TnI isoforms using Western blotting (sensitivity: 0.01-1 ng per lane), immunohistochemical assays, and fluorescence immunoassays. Some of the designed fluorescence immunoassays enable quantification of fast skeletal (limit of detection [LOD] = 0.07 ng/mL) and slow skeletal (LOD = 0.1 ng/mL) TnI isoforms or both isoforms (LOD = 0.1 ng/ml). Others allow differential detection of binary (with TnC) or ternary (with TnT and TnC) complexes, revealing composition of troponin forms in the human blood.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 3","pages":"349 - 363"},"PeriodicalIF":2.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1134/S0006297924601928.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Ionizing Radiation Exposure Improves Behavioral Symptoms and Modulates Brain Innate Immune System Activity in the Tau P301S Mice Line","authors":"Viktor S. Kokhan,&nbsp;Ruslan A. Ageldinov,&nbsp;Petr K. Anokhin,&nbsp;Inna Yu. Shamakina","doi":"10.1134/S0006297924604453","DOIUrl":"10.1134/S0006297924604453","url":null,"abstract":"<p>Tauopathy is a group of neurodegenerative diseases associated with abnormal phosphorylation and aggregation of microtubule-associated tau protein. There are currently no disease-modifying therapies for the treatment of tauopathies, however, substantial evidence has shown that there is a major role of neuroinflammation in the disease progression. According to the literature, ionizing radiation (IR) may serve as an effective tool for managing neuroinflammation. In this study, we investigated effects of the combined IR (γ-rays and carbon-12 nuclei) on locomotor abilities and microglial activation markers in the brain of Tau P301S mice, a transgenic model for tauopathy. Irradiation resulted in the improvement of behavioral symptoms in mice: increased endurance and locomotor activity in the early symptomatic and terminal stages of the disease, respectively. At the same time, irradiation led to increase in the levels of both pro-inflammatory and anti-inflammatory cytokines in the cerebellum and, to a lesser extent, in the hippocampus of the irradiated animals. The obtained data indicate a significant modulatory effect of IR on the innate immune system, highlighting high potential of radiotherapy as a new strategy for neurodegenerative disease treatment.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 3","pages":"400 - 412"},"PeriodicalIF":2.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919183","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 Issue on Dualistic Role of Neutrophils in Carcinogenesis and Their Possible Use for Treatment of Malignant Neoplasms","authors":"Anna N. Gabashvili,&nbsp;Anastasiia A. Vasiukova,&nbsp;Aleksandra S. Rakitina,&nbsp;Anastasiia S. Garanina","doi":"10.1134/S000629792460368X","DOIUrl":"10.1134/S000629792460368X","url":null,"abstract":"<p>Neutrophils are phagocytic leukocytes of the myeloid series, which are the most common myeloid cells in human blood, normally accounting from 65 to 80% of all circulating leukocytes. Over the years of investigation of these cells, more and more evidence has emerged indicating functional plasticity of neutrophils and their ambiguous role in the tumor development. Similarly to the M1/M2 classification of macrophages, the N1/N2 paradigm could be applied to neutrophils, where N1-neutrophils exhibit tumor-suppressive properties, and N2-neutrophils contribute to tumor development and immune suppression. An important natural feature of neutrophils is their mobility and ability to overcome physical barriers, thus these cells, as well as their vesicles and membranes, could be used to deliver therapeutic drugs to tumor cells. In addition, neutrophils themselves could be activated and mobilized to fight the tumor. This review describes current state of research on the role of neutrophils in carcinogenesis, as well as possible approaches of using these cells and their derivatives as systems for targeted delivery of therapeutic drugs for treatment of malignant neoplasms.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 3","pages":"303 - 320"},"PeriodicalIF":2.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919260","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":"Mavacamten Inhibits the Effect of the N-Terminal Fragment of Cardiac Myosin-Binding Protein C with the L352P Mutation on the Actin–Myosin Interaction at Low Calcium Concentrations","authors":"Anastasia M. Kochurova,&nbsp;Evgenia A. Beldiia,&nbsp;Julia Y. Antonets,&nbsp;Victoria V. Nefedova,&nbsp;Natalia S. Ryabkova,&nbsp;Ivan A. Katrukha,&nbsp;Sergey Y. Bershitsky,&nbsp;Alexander M. Matyushenko,&nbsp;Galina V. Kopylova,&nbsp;Daniil V. Shchepkin","doi":"10.1134/S0006297924604131","DOIUrl":"10.1134/S0006297924604131","url":null,"abstract":"<p>Hypertrophic cardiomyopathy (HCM)-associated mutations in sarcomeric proteins lead to the disruption of the actin–myosin interaction and its calcium regulation and cause myocardial hypercontractility. About half of such mutations are found in the <i>MYBPC3</i> gene encoding cardiac myosin-binding protein C (cMyBP-C). A new approach to normalize cardiac contractile function in HCM is the use of β-cardiac myosin function inhibitors, one of which is mavacamten. We studied the effect of mavacamten on the calcium regulation of the actin–myosin interaction using isolated cardiac contractile proteins in the <i>in vitro</i> motility assay. The L352P mutation did not affect the maximum sliding velocity of regulated thin filaments on myosin in the <i>in vitro</i> motility assay and the calcium sensitivity of the velocity but led to the underinhibition of the actin–myosin interaction at low calcium concentrations. Mavacamten decreased the maximum sliding velocity of thin filaments in the presence of the WT and L352P C0-C2 fragments, and abolished their movement in the presence of the L352P C0-C2 fragment at low calcium concentrations. Slowing down the kinetics of cross-bridges and inhibition of actin–myosin interaction at low calcium concentrations by mavacamten may reduce the hypercontractility in HCM and the degree of myocardial hypertrophy.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 3","pages":"389 - 399"},"PeriodicalIF":2.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919184","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}