Biochemistry (Moscow)最新文献

{"title":"Thermal Inactivation of Penicillin Acylase from Escherichia coli: Rate-Limiting Step and Role of Protein Aggregation","authors":"Tatiana A. Shcherbakova,&nbsp;Nikolai V. Panin,&nbsp;Vytas K. Švedas","doi":"10.1134/S0006297926601322","DOIUrl":"10.1134/S0006297926601322","url":null,"abstract":"<p>Using kinetic and structural methods – differential scanning calorimetry, dynamic laser light scattering, turbidimetry, and mathematical modeling – a comprehensive study of the process of thermal inactivation of penicillin acylase (PA) from <i>Escherichia coli</i> was conducted. The first step of the process is denaturation of the protein globule. As denatured protein accumulates, start aggregates are formed, and after reaching a critical amount, rapid clustering of aggregates (formation of clusters) occurs, which proceeds in the kinetic regime of diffusion-limited cluster–cluster aggregation. A distinctive feature of the process of PA thermal aggregation is absence of enzyme dissociation into subunits and very prolonged accumulation of start aggregates. The rate-limiting step of the PA thermal inactivation process is denaturation of the protein globule and pronounced tendency of the denatured enzyme to aggregate makes this process irreversible. When searching for the ways to stabilize PA, primary attention should be paid not to prevention of protein aggregation but to preservation its three-dimensional structure.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 7","pages":"1265 - 1275"},"PeriodicalIF":2.1,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148628487","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":"Extrachromosomal DNA in Oncology: History of Discovery, Research Methods, and Current Perspectives","authors":"Vera S. Mukhina,&nbsp;Alexander V. Favorov","doi":"10.1134/S0006297926600778","DOIUrl":"10.1134/S0006297926600778","url":null,"abstract":"<p>Extrachromosomal DNA (ecDNA) refers to circular DNA molecules without centromeres that are often found in the nuclei of cancer cells. The presence of ecDNA is associated with the development of drug resistance and poor disease prognosis. Although ecDNA was discovered 60 years ago, technological advances of the past decade have dramatically expanded our understanding of its biological significance and revealed a far greater role in cancer development than previously recognized, thus driving a rapid increase in research interest. This review describes the milestones in the history of ecDNA research and summarizes the current state of knowledge as of 2025. It provides a comprehensive overview of the mechanisms underlying ecDNA formation, organization, and functions, describes the principal methods used for ecDNA detection and analysis, and discusses its clinical relevance, as well as future directions in ecDNA research.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 7","pages":"1073 - 1092"},"PeriodicalIF":2.1,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148628489","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":"Monitoring Early Efficacy of the Checkpoint Immunotherapy Based on Fluorescence Lifetime Imaging Microscopy of the Patient-Derived Lymphocyte Subsets","authors":"Diana V. Yuzhakova,&nbsp;Anastasia I. Kononova,&nbsp;Anna V. Izosimova,&nbsp;Margarita M. Sazhina,&nbsp;Ilya D. Shchechkin,&nbsp;Artem M. Mozherov,&nbsp;Pavel A. Bureev,&nbsp;Dmitry A. Kuzmin,&nbsp;Alena I. Gavrina,&nbsp;Irina S. Shumskaya,&nbsp;Sergey V. Gamayunov,&nbsp;Marina V. Shirmanova","doi":"10.1134/S0006297926601206","DOIUrl":"10.1134/S0006297926601206","url":null,"abstract":"<p>Despite the success of immune checkpoint inhibitor (ICI) therapy, the problem of resistance makes the search for early response biomarkers critical. This study investigates the potential of monitoring autofluorescence of the NAD(P)H coenzyme in the T-lymphocyte subsets to assess early treatment efficacy. The ability of NAD(P)H FLIM to reflect sensitivity to ICI therapy was tested on the B16F0 mouse melanoma model and validated in the pilot study of the samples from melanoma patients during treatment. The mean fluorescence lifetime of NAD(P)H, τ_m, showed the best correlation with subsequent clinical response and was identified as a sensitive marker of early lymphocyte activation following anti-PD-1 or combination therapy. In the patients who responded to treatment, an increase in τ_m was observed, associated with metabolic reprogramming toward enhanced biosynthetic and bioenergetic pathways, as confirmed by the standard molecular analysis. Thus, the proposed approach represents a promising solution for personalized monitoring of early immunotherapy efficacy.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 7","pages":"1276 - 1286"},"PeriodicalIF":2.1,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148628429","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":"Dysfunction of Primary Cilium in Huntington’s Disease: How Mutant Huntingtin Disrupts This Cellular Signaling Hub","authors":"Aleksandra S. Churkina,&nbsp;Anton S. Shakhov,&nbsp;Irina B. Alieva","doi":"10.1134/S0006297926601590","DOIUrl":"10.1134/S0006297926601590","url":null,"abstract":"<p>Primary cilia are solitary, antenna-like organelles that project from the surface of most vertebrate cells. They consist of a microtubule-based axoneme extending from a modified centriole (basal body) and enclosed by a lipid bilayer membrane. For several decades after their discovery, the functions of primary cilia had remained speculative; they were even considered vestigial structures. Currently, primary cilium is recognized as essential sensory and signaling structure involved in both chemo- and mechanosensation. Its anchoring at the centrosome surrounded by a radially organized network of microtubules and ability to detect extracellular signals through the axoneme protruding beyond the cell surface and enveloped by a receptor-rich membrane, make primary cilium a unique signaling hub of the cell. The functional activity of primary cilia is critical for numerous biological processes, including embryonic development and cellular differentiation, whereas defects in ciliogenesis result in severe somatic disorders. Prominent neurological abnormalities observed in several ciliopathies have prompted investigations into the structure and function of primary cilia in other brain disorders. It has become evident that defects of neuronal primary cilia are characteristic of several monogenic neurological diseases that have not traditionally been classified as ciliopathies. A growing body of evidence indicates that many severe neurodegenerative disorders, particularly polyglutamine diseases such as Huntington’s disease, are associated with specific alterations and dysfunction of primary cilia. In this review, we summarize current knowledge on the detrimental effects of disease-causing mutant proteins on the function of primary cilium, with particular emphasis on the disruption of PCM1 (pericentriolar material 1) trafficking by mutant huntingtin, leading to ciliary elongation and alterations in signaling pathways. We further discuss the consequences of mutant protein-induced dysfunction of this cellular antenna and analyze associated signaling pathways that may represent promising therapeutic targets. Finally, we describe potential approaches for investigating dysfunction of the neuronal signaling hub with primary cilium as an antenna.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 7","pages":"1137 - 1156"},"PeriodicalIF":2.1,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148628490","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":"Remodeling of Colorectal Cancer Extracellular Matrix after Radiotherapy","authors":"Sahil V. Amikishiev,&nbsp;Darya O. Kuzmina,&nbsp;Arseniy E. Yuzhalin","doi":"10.1134/S0006297926600328","DOIUrl":"10.1134/S0006297926600328","url":null,"abstract":"<p>Colorectal cancer (CRC) is a common and aggressive malignancy with poor prognosis. The efficacy of radiotherapy is often limited by the development of radioresistance, which can be attributed to various factors, including the extracellular matrix (ECM). The effect of radiotherapy on the ECM proteome remains poorly understood. We investigated changes in the proteome composition of CRC tumors after radiation therapy. Quantitative LC-MS/MS analysis of the purified ECM fraction was performed, that was supplemented by transcriptomic analysis of clinical samples obtained from patients after neoadjuvant radiochemotherapy. Radiotherapy markedly increased the number of identified ECM proteins, with the number of identified matrisome proteins rising from 45 to 87. In the irradiation group, 12 proteins showed significant upregulation (FDR-adjusted <i>p</i> &lt; 0.01), with fibrillin-1 (Fbn1) showing the greatest increase (632-fold). Structural ECM components, in particular glycoproteins, constituted the majority of proteins with significantly increased abundance. Transcriptomic analysis confirmed the upregulation of key ECM proteins in clinical samples and their positive correlation with the gene signatures of cancer-associated fibroblasts. We conclude that radiotherapy causes significant remodeling of the CRC ECM with predominant upregulation of structural components, indicating the induction of a fibrotic response. The identified proteins may serve as new biomarkers of the response to radiation and potential targets for overcoming radioresistance in CRC.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 7","pages":"1216 - 1229"},"PeriodicalIF":2.1,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148628486","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":"Glycosylase Base Editors: New Tools for Genome Editing","authors":"Liliya M. Kulishova,&nbsp;Dmitry O. Zharkov","doi":"10.1134/S0006297926601073","DOIUrl":"10.1134/S0006297926601073","url":null,"abstract":"<p>Genome editing using the CRISPR/Cas9 system has become a staple of modern genome manipulation. In its original form, editing involved introducing double-strand breaks into DNA, which can cause genomic instability. The appearance of the first base editors in 2016 expanded the range of editing technologies and enabled single-nucleotide changes to be introduced into the genome through deamination of nucleobases, bypassing the double-strand break stage. Further development of base editors involves the incorporation of additional modules, DNA glycosylases, that can remove modified or even normal nucleobases and create non-instructive apurinic/apyrimidinic sites in DNA, significantly expanding the range of available single-nucleotide substitutions. This review examines the operating principles of the glycosylase base editors, the main limitations of these genome manipulation tools, and promising areas for the development of this technology.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 7","pages":"1093 - 1113"},"PeriodicalIF":2.1,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148628482","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":"Secreted Cyclophilin A Induces M1 and M2 Macrophage Polarization in the THP-1 Model in vitro","authors":"Anastasiia A. Kalinina,&nbsp;Marina V. Kubekina,&nbsp;Maria A. Zamkova,&nbsp;Nadezhda A. Persiyantseva,&nbsp;Alexandra V. Bruter,&nbsp;Dmitry B. Kazansky,&nbsp;Ludmila M. Khromykh","doi":"10.1134/S0006297926600432","DOIUrl":"10.1134/S0006297926600432","url":null,"abstract":"<p>Fate of monocytes that migrate into tissues is determined by various mediators at the site of inflammation. The microenvironment governs monocyte differentiation and polarization into macrophages, which acquire different surface markers and opposite functions. Secreted cyclophilin A (CypA) is a pro-inflammatory factor and a component of the monocyte humoral microenvironment. In these studies, effects of recombinant human CypA (rhCypA) on differentiation of human monocytic cells were evaluated in the THP-1 <i>in vitro</i> model. RhCypA induced polarization of M1 macrophages in the early stages of THP-1 ontogenesis without additional stimuli, whereas it promoted M2 polarization only in the cells differentiated to M0 monocytes and in the presence of IL-4 and IL-13. Under conditions of M2 induction, rhCypA significantly upregulated expression of the genes of characteristic M2 markers CD163 and IL-10 in the THP-1 cells, and decreased the level of p38 MAP kinase activation, suggesting diminished pro-inflammatory activity of the generated cells. The RhCypA-induced M1 and M2 macrophages inhibited proliferation of activated CD4+ T cells via direct cell-cell contact. These findings suggested that secreted CypA could induce generation of suppressor M2 macrophages and/or myeloid-derived suppressor cells at the site of inflammation during infection or cancer progression. This new immunoregulatory effect of rhCypA could be of particular clinical relevance for the development of strategies for controlling chronic inflammation and reprogramming the tumor microenvironment.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 7","pages":"1230 - 1240"},"PeriodicalIF":2.1,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1134/S0006297926600432.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148628483","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":"Chemically Induced Dimerization Systems: From FKBP/FRB Engineering to Expanded Biological Applications","authors":"Hui Yuan,&nbsp;Shuo Lin,&nbsp;Ziyi Lin,&nbsp;Shuangpeng Li,&nbsp;Xia Zuo,&nbsp;Haihua Yin,&nbsp;Ruilin Cheng,&nbsp;Yuqian Tang,&nbsp;Zihao Luo,&nbsp;Min Chen,&nbsp;Qingjian Zou","doi":"10.1134/S0006297926600705","DOIUrl":"10.1134/S0006297926600705","url":null,"abstract":"<p>The FKBP-based chemically induced dimerization (CID) technology is a fundamental tool for spatiotemporal precise modulation of protein functions in living cells, widely used in gene editing, protein function regulation, disease therapy, and drug development. However, its widespread application is limited by the inherent drawbacks including issues with immunosuppressive activity, stability, reversibility, and <i>in vivo</i> delivery. Recent years have seen remarkable progress in addressing these challenges: orthogonalization strategies eliminate immunosuppressive effects, fast-dissociating ligands and optogenetic systems enable reversible regulation, and protein engineering optimizes the FKBP/FRB domains to enhance stability and reduce immunogenicity. Moreover, integration with novel delivery technologies broadens its application scope greatly. This review summarizes the key optimization strategies and innovative applications of this technology in the cutting-edge biological research, aiming to reference the development of next-generation chemogenetic tools with higher precision, better safety, and greater application potential.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 7","pages":"1051 - 1072"},"PeriodicalIF":2.1,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148628484","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 Levels of Neurotrophic Factors in the Rat Hippocampus in the Acute Period after Middle Cerebral Artery Occlusion Are Associated with the Hypothalamic–Pituitary–Adrenal Axis Activation","authors":"Mikhail V. Onufriev,&nbsp;Yulia V. Moiseeva,&nbsp;Margarita R. Novikova,&nbsp;Pavel A. Kostryukov,&nbsp;Natalia V. Gulyaeva","doi":"10.1134/S0006297925604162","DOIUrl":"10.1134/S0006297925604162","url":null,"abstract":"<p>Ischemic stroke is one of the most prevalent neurological disorders, with primary injury typically localized to the neocortex. However, secondary damage often extends to anatomically distant regions, particularly the hippocampus. One of the early neuroendocrine responses to cerebral ischemia is activation of the hypothalamic–pituitary–adrenal (HPA) axis. Increased release of corticosterone (CORT) by the adrenal glands into the bloodstream leads to its accumulation in the hippocampus. We hypothesize that this process may contribute to the hippocampal damage and underlie delayed cognitive and affective impairments following stroke. To test this, we investigated the levels of neurotrophic factors reflecting the neuroprotective potential of the hippocampus using two established middle cerebral artery occlusion (MCAO) models that differ in their effects on CORT production: the Koizumi et al. (1986) model (MCAO1) and the Longa et al. (1989) model (MCAO2). Although both models produced comparable neurological deficits, mortality rates, and infarct volumes, they differed markedly in endocrine and hippocampal responses. Significant increases in circulating CORT and its accumulation in both ipsilateral and contralateral hippocampus were observed only in MCAO1. Moreover, correlations between the CORT levels (in the blood and hippocampus) and both rat body weight and neurological deficit were stronger in MCAO1 than in MCAO2. In both acute models, brain-derived neurotrophic factor (BDNF) levels were elevated in the ipsilateral hippocampus, whereas the content of glial cell line-derived neurotrophic factor (GDNF) remained unchanged. In contrast, ciliary neurotrophic factor (CNTF) increased in the ipsilateral hippocampus only in MCAO2. These findings suggest that differential activation of the HPA axis and consequent variations in corticosteroid signaling in the hippocampus selectively modulate the neurotrophic response during the acute phase following MCAO.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 7","pages":"1187 - 1199"},"PeriodicalIF":2.1,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1134/S0006297925604162.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148628480","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":"Aptamer Sensors for Inflammaging Biomarkers: Principles of Molecular Recognition, Analytical Platforms, and Unaddressed Targets","authors":"Nataliya O. Kudryashova,&nbsp;Igor V. Dobrokhotov,&nbsp;Elizaveta S. Ershova,&nbsp;Alexey A. Moskalev","doi":"10.1134/S0006297926601127","DOIUrl":"10.1134/S0006297926601127","url":null,"abstract":"<p>Inflammaging, a chronic, low-grade systemic inflammatory state that develops with advancing age, is one of the key drivers of age-associated pathology and promotes the emergence of the senescence-associated secretory phenotype (SASP). Timely quantitative monitoring of pro-inflammatory and SASP-associated biomarkers therefore demands highly sensitive analytical platforms capable of reliable performance in complex biological matrices. Aptamer-based biosensors (aptasensors), which employ short single-stranded oligonucleotides offering high affinity and specificity for molecular recognition, have emerged as promising alternatives and complements to conventional antibody-based assays. This review provides a comprehensive overview of aptasensor platforms developed for biomarkers of age-associated inflammation and identifies molecular targets of relevance to aging biology that remain unexplored. Following PRISMA guidelines, a systematic literature search of the PubMed database was conducted for studies published between 2020 and 2026. A total of 221 original studies met the inclusion criteria and were qualitatively analyzed, encompassing 47 biomarkers and seven classes of analytical platforms. The analysis revealed a pronounced research bias: 73% of published studies focused on just five well-established biomarkers – VEGF, CRP, IL-6, IFN-γ, and TNF-α – leaving many biomarkers with recognized relevance to aging without any aptasensor-based detection strategy. The review also discusses the molecular mechanisms underlying aptamer–target recognition, recent advances in SELEX technologies, and chemical modifications, including 2′-F nucleotides, locked nucleic acids (LNAs), SOMAmers, and spiegelmers, that enhance aptamer stability and affinity. Finally, we discuss the principal obstacles limiting clinical translation of aptamer technologies and propose priorities for future research, including multiplex ratiometric aptasensors for SASP cytokine profiling, aptamer-based extracellular vesicle capture as a route to intracellular biomarkers, and novel strategies for generating aptamers against currently inaccessible molecular targets.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 7","pages":"1114 - 1136"},"PeriodicalIF":2.1,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148628688","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}