Biochemistry (Moscow)最新文献

{"title":"Memory T Cells: Investigation of Original Models with Transgenic T Cell Receptors","authors":"Dmitry B. Kazansky,&nbsp;Anastasiia A. Kalinina,&nbsp;Ludmila M. Khromykh","doi":"10.1134/S0006297924603940","DOIUrl":"10.1134/S0006297924603940","url":null,"abstract":"<p>This review summarizes the research data on original mouse models developed in the laboratory of regulatory mechanisms in immunity of the Research Institute of Carcinogenesis, N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation. Transfer of the genes of individual α- and β-chains of T cell receptors (TCRs) of memory cells has resulted in production of transgenic animal lines valuable for studying T lymphocyte homeostasis and patterns of formation of their activation profile markers. Investigation of the transgenic models revealed new features of immune selection and tumor progression. In particular, the fundamental property of some TCRs, termed “chain-centricity”, has been confirmed; it involves dominance of one of the TCR chains during recognition of the MHC (major histocompatibility complex)/peptide complex. This property makes it possible to artificially generate a significant pool of immunocompetent T cells so it could be used in adoptive immunotherapy for oncological and infectious diseases. Transfer of the dominant active TCR α-chains provides the possibility for constructing organisms with innate specific immunological resistance to certain pathogens. The results of recent studies indicate that TCR, determining the T lymphocyte relationship with its MHC microenvironment, has an instructive role in formation of its functions and phenotype. One of these functions may be production of cyclophilin A by the cortisone-resistant memory cells localized in thymus. The evidence has been accumulated that expression of TCR with a certain structure and specificity is a sufficient condition for formation of the functional potential of memory cells in a T cell, regardless of its former interaction with antigenic MHC/peptide complexes.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 2","pages":"161 - 172"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848908","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 Fibroblast-to-Myofibroblast Differentiation by Changing Cytoplasmic Actin Ratio","authors":"Yulia G. Levuschkina,&nbsp;Vera B. Dugina,&nbsp;Galina S. Shagieva,&nbsp;Sergey V. Boichuk,&nbsp;Ilya I. Eremin,&nbsp;Natalia V. Khromova,&nbsp;Pavel B. Kopnin","doi":"10.1134/S000629792460412X","DOIUrl":"10.1134/S000629792460412X","url":null,"abstract":"<p>Myofibroblasts, which play a crucial role in the tumour microenvironment, represent a promising avenue for research in the field of oncotherapy. This study investigates the potential for the induced differentiation of human fibroblasts into myofibroblasts through downregulation of the γ-cytoplasmic actin (γ-CYA) achieved by RNA interference. A decrease in the γ-CYA expression in human subcutaneous fibroblasts resulted in upregulation of myofibroblast markers, including α-smooth muscle actin (α-SMA), ED-A FN, and type III collagen. These changes were accompanied by notable alterations in cellular morphology, characterized by a significant increase in cell area and the formation of pronounced supermature focal adhesions. Downregulation of γ-CYA resulted in the compensatory increase in expression of the β-cytoplasmic actin and α-SMA, and formation of the characteristic α-SMA-positive stress fibers. In conclusion, our results demonstrate that a decrease in the γ-CYA expression leads to myofibroblastic trans-differentiation of human subcutaneous fibroblasts.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 2","pages":"289 - 298"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848883","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":"Mechanisms of Glucocorticoid Resistance in Nonclassical T Helper Populations Th17.1/Ex-Th17","authors":"Elena M. Kuklina","doi":"10.1134/S0006297924604222","DOIUrl":"10.1134/S0006297924604222","url":null,"abstract":"<p>The nonclassical population of Th1-polarized Th17 lymphocytes (Th17.1/ex-Th17) is currently in the focus of researchers’ attention. These cells possess a unique proinflammatory potential and ability to penetrate blood-tissue barriers and play a key role in the pathogenesis of many inflammatory diseases, primarily autoimmune ones. Th1-polarized Th17 lymphocytes prevail in the autoimmune lesion foci and are considered to be a promising therapeutic target in these pathologies. At the same time, recent studies have shown another distinctive feature of Th1-polarized Th17 – their selective resistance to glucocorticoids. Since glucocorticoids are the first-line drugs for the treatment of the autoimmune disease exacerbation, understanding the causes of this phenomenon is crucial for predicting patients’ response to therapy and improving the treatment effectiveness. This review analyzes the mechanisms of drug resistance of Th1-polarized Th17 cells, compares these mechanisms with those typical of nonpathogenic classical Th17 cells, and discusses the role of glucocorticoid resistance in the body’s response to glucocorticoid therapy.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 2","pages":"188 - 199"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848910","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":"Techniques for Selective Labeling of Molecules and Subcellular Structures for Cryo-Electron Tomography","authors":"Evgeny P. Kazakov,&nbsp;Igor I. Kireev,&nbsp;Sergei A. Golyshev","doi":"10.1134/S0006297924604015","DOIUrl":"10.1134/S0006297924604015","url":null,"abstract":"<p>Electron microscopy (EM) is one of the most efficient methods for studying the fine structure of cells with a resolution thousands of times higher than that of visible light microscopy. The most advanced implementation of electron microscopy in biology is EM tomography of samples stabilized by freezing without water crystallization (cryoET). By circumventing the drawbacks of chemical fixation and dehydration, this technique allows investigating cellular structures in three dimensions at the molecular level, down to resolving individual proteins and their subdomains. However, the problem of efficient identification and localization of objects of interest has not yet been solved, thus limiting the range of targets to easily recognizable or abundant subcellular components. Labeling techniques provide the only way for locating the subject of investigation in microscopic images. CryoET imposes conflicting demands on the labeling system, including the need to introduce into a living cell the particles composed of substances foreign to the cellular chemistry that have to bind to the molecule of interest without disrupting its vital functions and physiology of the cell. This review examines both established and prospective methods for selective labeling of proteins and subcellular structures aimed to enable their localization in cryoET images.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 2","pages":"173 - 187"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848909","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":"Differential Expression of hsa-miR-134, hsa-miR-155, hsa-miR-122 as Biomarkers of Epileptogenesis in Patients with Acute Cerebral Injury","authors":"Anastasia A. Vasilieva,&nbsp;Elena E. Timechko,&nbsp;Anastasia I. Paramonova,&nbsp;Alexey M. Yakimov,&nbsp;Kristina D. Lysova,&nbsp;Marina I.Severina,&nbsp;Diana V. Dmitrenko","doi":"10.1134/S0006297924603538","DOIUrl":"10.1134/S0006297924603538","url":null,"abstract":"<p>It is difficult to predict the process of occurrence of an epileptogenic focus in patients who have suffered acute cerebral damage. The aim of our study is to investigate and describe the possibility of using microRNAs as biomarkers of epileptogenesis. Objective of our work was to evaluate expression of hsa-miR-134-5p, hsa-miR-155-5p, and has-miR-122-5p in different groups of patients. Quantitative comparison of relative concentrations of the studied microRNAs in the blood plasma of three groups of patients was carried out: Group I – patients with temporal lobe epilepsy; Group II – patients with potential epileptogenic injuries; Group III – control group. The study showed increased expression of hsa-miR-134-5p in patients with temporal lobe epilepsy, which confirms the published data on its involvement in the mechanisms of epileptogenesis. Hsa-miR-155-5p was overexpressed in the Group II in comparison with other groups, the data indicate involvement in the mechanisms of inflammation, which could indirectly affect occurrence of epilepsy. Hsa-miR-122-5p was overexpressed in two study groups, but the levels were higher in the group of patients with acute cerebral injuries. The obtained results allow us to propose has-miR-122-5p as a potential biomarker of epileptogenesis.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 2","pages":"247 - 258"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848914","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":"Erratum to: Low-Molecular Neurotrophin-3 Mimetics with Different Patterns of Postreceptor Signaling Activation Attenuate Differentially Morphine Withdrawal in Rats","authors":"Larisa G. Kolik,&nbsp;Mark A. Konstantinipolsky,&nbsp;Sergey V. Nikolaev,&nbsp;Ilya O. Logvinov,&nbsp;Tatyana A. Antipova,&nbsp;Tatiana A. Gudasheva","doi":"10.1134/S0006297925020014","DOIUrl":"10.1134/S0006297925020014","url":null,"abstract":"","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 2","pages":"299 - 299"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848954","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":"Erratum to: Denaturation Properties and Folding Transition States of Leghemoglobin and Other Heme Proteins","authors":"Pijush Basak,&nbsp;Niloy Kundu,&nbsp;Rudradip Pattanayak,&nbsp;Maitree Bhattacharyya","doi":"10.1134/S0006297925020026","DOIUrl":"10.1134/S0006297925020026","url":null,"abstract":"","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 2","pages":"300 - 301"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848991","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":"Tumor Spheroids, Tumor Organoids, Tumor Explants, and Tumoroids: What Are the Differences between Them?","authors":"Mikhail Durymanov","doi":"10.1134/S0006297924604234","DOIUrl":"10.1134/S0006297924604234","url":null,"abstract":"<p>Three-dimensional (3D) cell cultures that mimic tumor microenvironment have become an essential tool in cancer research and drug response analysis, significantly enhancing our understanding of tumor biology and advancing personalized medicine. Currently, the most widely mentioned 3D multicellular culture models include spheroids, organoids, tumor explants, and tumoroids. These 3D structures, exploited for various applications, are generated from cancer and non-cancer cells of different origin using multiple techniques. However, despite extensive research and numerous studies, consistent definitions of these 3D culture models are not clearly established. The manuscript provides a comprehensive overview of these models, detailing brief history of their research, unique biological characteristics, advantages, limitations, and specific applications.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 2","pages":"200 - 213"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848911","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":"JNK Signaling Pathway Activity Alterations in the Rat Hippocampus: Effect of Age, Alzheimer’s Disease-Like Pathology Development, and the JNK Inhibitor IQ-1S","authors":"Natalia A. Muraleva,&nbsp;Anna A. Zhdankina,&nbsp;Andrey I. Khlebnikov,&nbsp;Nataliya G. Kolosova","doi":"10.1134/S0006297924603903","DOIUrl":"10.1134/S0006297924603903","url":null,"abstract":"<p>Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder and the leading cause of senile dementia. The key risk factor for a more common (&gt;95% of cases) sporadic form of AD is age. So far, there are no effective methods for AD prevention or treatment. A growing body of evidence indicates that the development of AD and other neurodegenerative diseases is associated with the activation of mitogen-activated protein kinase (MAPK) pathways, and JNK signaling pathway is considered as a potential target for the prevention and treatment of AD. However, the information on alterations in its activity in ontogenesis, which are evaluated by changes in the phosphorylation of its components, is extremely limited. The aim of this study was to compare age-related changes in the activity of JNK signaling pathway in the hippocampus of Wistar rats and senescence-accelerated OXYS rats (which spontaneously develop the key symptoms of AD-like pathology) and to evaluate the effect of the selective JNK3 inhibitor IQ-1S (11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt). The ability of IQ-1S to suppress accelerated brain aging in OXYS rat has been proven previously, but the effect of this inhibitor on the JNK activity has not been studied. Here, we showed that with age, the activity of the JNK signaling pathway increased in the hippocampus of rats of both strains. At the same time, the manifestation and active progression of AD-like pathology in OXYS rats was accompanied by the increase in the phosphorylation level of the key kinase of this signaling pathway, JNK3, and its target proteins compared to Wistar rats, which allowed us to suggest JNK3 as a potential target for interventions aimed at preventing neurodegenerative processes. This suggestion was supported by the fact that the neuroprotective effect of the selective JNK3 inhibitor IQ-1S and its ability to suppress the development of neurodegenerative processes in OXYS rats were associated with a decrease in the phosphorylation levels of JNK3, c-Jun, APP, and Tau in the hippocampus.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 2","pages":"265 - 275"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848881","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":"Molecular Biomarkers of Neurodegeneration in Amyotrophic Lateral Sclerosis","authors":"Denis V. Shevchuk,&nbsp;Amir I. Tukhvatulin,&nbsp;Alina S. Dzharullaeva,&nbsp;Irina A. Berdalina,&nbsp;Maria N. Zakharova","doi":"10.1134/S0006297924604039","DOIUrl":"10.1134/S0006297924604039","url":null,"abstract":"<p>Amyotrophic lateral sclerosis (ALS) is the most prevalent motor neuron disease. However, definitive diagnosis could be delayed by up to 12 months due to the lack of specific and sensitive biomarkers for ALS. In our study, conducted for the first time on a large cohort of ALS patients (<i>n</i> = 100) within the Russian population, we assessed key biomarkers of neurodegenerative pathology, including β-amyloids (Aβ40 and Aβ42) and tau proteins (Tau-total and Tau-p181), as well as other pathogenetically relevant, promising biomarkers such as FGF-21, Kallikrein-6 (KLK-6), NCAM-1, Neurogranin (NRGN), TDP-43, Apolipoprotein E4, Clusterin (Apo J), Complement Factor H, Fetuin-A, α2-Macroglobulin, Apo AI, Apo CIII, Apo E, Complement C3, GDNF, sRAGE, and S100B protein. Significant differences between the ALS patients and the control group were observed for Aβ40 (<i>p</i> = 0.044), Aβ42 (<i>p</i> &lt; 0.001), FGF-21 (<i>p</i> &lt; 0.001), Tau-total (<i>p</i> = 0.001), Tau-p181 (<i>p</i> = 0.014), Clusterin (<i>p</i> &lt; 0.001), Complement C3 (<i>p</i> = 0.001), and S100B (<i>p</i> = 0.024). A significant direct correlation was found between the ALSFRS-R score and concentrations of Aβ40 and Aβ42. Changes in the complement system (Complement C3 and Complement Factor H) were identified, highlighting critical role of neuroinflammatory processes in ALS pathogenesis. Additionally, increased levels of FGF-21 were observed in the patients with the bulbar onset of ALS. Significant increase in the concentration of the chaperone protein clusterin in the patients with rapid disease progression suggests its potential as a prognostic biomarker for motor neuron disease. Furthermore, its role in maintaining proteostasis could provide novel therapeutic targets.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 2","pages":"276 - 288"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848882","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}