Biochemistry (Moscow)最新文献

{"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, Mark A. Konstantinipolsky, Sergey V. Nikolaev, Ilya O. Logvinov, Tatyana A. Antipova, 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, Niloy Kundu, Rudradip Pattanayak, 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}

{"title":"Evolution, Possibilities, and Prospects for Application of the Methods of Assessment of Pyridine Nucleotides Pool for Studying Mechanisms of Brain Plasticity in Normal and Pathological Conditions","authors":"Anna V. Zubova,&nbsp;Alexander A. Groshkov,&nbsp;Arsenii K. Berdnikov,&nbsp;Svetlana V. Novikova,&nbsp;Natalia A. Rozanova,&nbsp;Lyudmila V. Nikolaeva,&nbsp;Vladimir V. Salmin,&nbsp;Nataliya A. Kolotyeva,&nbsp;Leonid G. Khaspekov,&nbsp;Alla B. Salmina,&nbsp;Stanislav O. Yurchenko,&nbsp;Sergey N. Illarioshkin","doi":"10.1134/S0006297924604477","DOIUrl":"10.1134/S0006297924604477","url":null,"abstract":"<p>Nicotinamide adenine dinucleotide and its derivatives – NAD⁺, NADP⁺, NADH, NADPH – play an important role in cell metabolism, act as substrates or cofactors for a large number of enzymes involved in the DNA regulation of replication and repair, maintenance of calcium homeostasis in cells, biosynthetic processes, and energy production mechanisms. Changes in the ratio of oxidized and reduced forms of pyridine nucleotides accompanies development of oxidative and reductive stress that significantly contribute to the cell damage and induction of adaptive responses. Currently, a huge number of protocols aimed at quantitative or qualitative assessment of the pyridine nucleotide pool are in use, but all of them have their limitations associated with sample preparation processes, difficulties in the metabolite spectrum assessment, and complexity of data interpretation. Measuring pyridine nucleotide levels is relevant in the studies of pathophysiological regulatory mechanisms of the cell functional activity and intercellular communication. This is of particular relevance when studying the mechanisms of plasticity of the central nervous system in health and disease, since significant changes in the pools of pyridine nucleotides in cells are evident in neurodevelopmental disorders, neurodegeneration, and aging. Simple and reliable non-invasive methods for measuring levels of NAD⁺ and NADH are necessary to assess the brain cells metabolism with diagnostic and research purposes. The goal of this review is to conduct comparative analysis of the main methods for measuring the levels of oxidized and reduced pyridine nucleotides in cells and to identify key principles of their application for correct interpretation of the obtained data, including those used for studying central nervous system.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 2","pages":"231 - 246"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848913","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":"Inhibitors of Transketolase from Mycobacterium tuberculosis Targeted towards both the Diphosphate Binding Site and an Adjacent Hydrophobic Subsite","authors":"Dmitry K. Nilov,&nbsp;Irina V. Gushchina,&nbsp;Tatyana A. Shcherbakova,&nbsp;Simon M. Baldin,&nbsp;Vytas K. Švedas","doi":"10.1134/S000629792460354X","DOIUrl":"10.1134/S000629792460354X","url":null,"abstract":"<p>Transketolase from <i>Mycobacterium tuberculosis</i> (mbTK) is involved in the pentose phosphate pathway essential for bacterial survival and thus constitutes an attractive target for the antituberculosis therapy. We found a new class of active site-targeted furan sulfonate inhibitors of mbTK that are capable of binding to both the thiamine diphosphate cofactor subsite and adjacent hydrophobic subsite Ile211-Leu402-Phe464, thereby suppressing enzyme activity. The most potent compound identified by computer screening, STK106769, was found to inhibit mbTK with IC₅₀ of 7 µM and suppress the growth of <i>M. tuberculosis</i> H37Rv strain. The hydrophobic subsite Ile211-Leu402-Phe464 of mbTK is substituted by significantly more polar residues in homologous human TK, which is an important factor determining the selectivity of binding of TK inhibitors.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 2","pages":"259 - 264"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848915","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":"Direct Neural Reprogramming in situ: Existing Approaches and Their Optimization","authors":"Nikita V. Dokukin,&nbsp;Daria A. Chudakova,&nbsp;Matvey O. Shkap,&nbsp;Anna M. Kovalchuk,&nbsp;Pavel D. Kibirsky,&nbsp;Vladimir P. Baklaushev","doi":"10.1134/S000629792460426X","DOIUrl":"10.1134/S000629792460426X","url":null,"abstract":"<p>Direct <i>in situ</i> neuronal reprogramming (transdifferentiation) of glial cells (astrocytes and microglia) has attracted a significant interest as a potential approach for the treatment of a wide range of neurodegenerative diseases and damages of the central nervous system (CNS). The nervous system of higher mammals has a very limited capacity for repair. Disruption of CNS functioning due to traumatic injuries or neurodegenerative processes can significantly affect the quality of patients’ life, lead to motor and cognitive impairments, and result in disability and, in some cases, death. Restoration of lost neurons <i>in</i> <i>situ</i> via direct reprogramming of glial cells without the intermediate stage of pluripotency seems to be the most attractive approach from the viewpoint of translational biomedicine. The ability of astroglia to actively proliferate in response to the damage of neural tissue supports the idea that these neuron-like cells, which are already present at the lesion site, are good candidates for transdifferentiation into neurons, considering that the possibility of direct neuronal reprogramming of astrocytes both <i>in</i> <i>vitro</i> and <i>in</i> <i>vivo</i> have demonstrated in many independent studies. Overexpression of proneuronal transcription factors, e.g., neurogenic differentiation factors 1-4 (NeuroD1-4), Neurogenin 2 (NeuroG2), Ascl1 (Achaete-Scute homolog 1), and Dlx2 (distal-less homeobox 2), including pioneer transcription factors that recognize target sequences in the compacted chromatin and activate transcription of silent genes, has already been proven as a potential therapeutic strategy. Other strategies, such as microRNA-mediated suppression of activity of PTB and REST transcription factors and application of small molecules or various biomaterials, are also utilized in neuronal reprogramming. However, the efficiency of direct <i>in</i> <i>situ</i> reprogramming is limited by a number of factors, including cell specificity of transgene delivery systems and promoters, brain regions in which transdifferentiation occurs, factors affecting cell metabolism, microenvironment, etc. Reprogramming <i>in</i> <i>situ</i>, which takes place in the presence of a large number of different cell types, requires monitoring and precise phenotypic characterization of subpopulations of cells undergoing transdifferentiation in order to confirm the reprogramming of the astroglia into neurons and subsequent integration of these neurons into the CNS. Here, we discussed the most efficient strategies of neuronal reprogramming and technologies used to visualize the transdifferentiation process, with special focus on the obstacles to efficient neuronal conversion, as well as approaches to overcome them.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 2","pages":"214 - 230"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848912","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":"Polymeric Drug Delivery Systems in Biomedicine","authors":"Ivan A. Gulyaev,&nbsp;Maria B. Sokol,&nbsp;Mariia R. Mollaeva,&nbsp;Maksim A. Klimenko,&nbsp;Nikita G. Yabbarov,&nbsp;Margarita V. Chirkina,&nbsp;Elena D. Nikolskaya","doi":"10.1134/S0006297924603976","DOIUrl":"10.1134/S0006297924603976","url":null,"abstract":"<p>Our review examines the key aspects of using polymeric carriers in biomedicine. The section “Polymers for Biomedicine” provides an overview of different types of polymers, their structural features and properties that determine their use as drug delivery vehicles. The section “Polymeric Carriers” characterizes the role of polymeric delivery systems in modern medicine. The main forms of polymeric carriers are described, as well as their key advantages for drug delivery. The section “Preclinical and Clinical Trials of Polymeric Drug Carriers” reviews the examples of clinical and preclinical studies of polymeric forms used for antitumor therapy, therapy for bacterial and infectious diseases. The final section “Targeted Drug Delivery Systems” is devoted to the discussion of approaches, as well as ligands that provide targeted drug delivery using polymeric carriers. We have paid special attention to modern approaches for increasing the efficacy of antibacterial therapy using vector molecules.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S233 - S262"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717010","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":"“Aging Clocks” Based on Cell-Free DNA","authors":"Aleksandr V. Sergeev,&nbsp;Olga V. Kisil,&nbsp;Andrey A. Eremin,&nbsp;Aleksandr S. Petrov,&nbsp;Maria E. Zvereva","doi":"10.1134/S0006297924604076","DOIUrl":"10.1134/S0006297924604076","url":null,"abstract":"<p>Aging is associated with systemic changes in the physiological and molecular parameters of the body. These changes are referred to as biomarkers of aging. Statistical models that link changes in individual biomarkers to biological age are called aging clocks. These tools facilitate a comprehensive evaluation of bodily health and permit the quantitative determination of the rate of aging. A particularly promising area for the development of aging clocks is the analysis of cell-free DNA (cfDNA), which is present in the blood and contains numerous potential biomarkers. This review explores in detail the fragmentomics, topology, and epigenetic landscape of cfDNA as possible biomarkers of aging. The review further underscores the potential of leveraging single-molecule sequencing of cfDNA in conjunction with long-read technologies to simultaneously profile multiple biomarkers, a strategy that could lead to the development of more precise aging clocks.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S342 - S355"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717018","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}