Biochemistry (Moscow)最新文献

{"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}

{"title":"Fo∙F1 ATP-synthase/ATPase of Paracoccus denitrificans: Mystery of Unidirectional Catalysis","authors":"Tatiana V. Zharova,&nbsp;Vera G. Grivennikova","doi":"10.1134/S000629792460399X","DOIUrl":"10.1134/S000629792460399X","url":null,"abstract":"<p>F_o∙F₁ ATP synthases/ATPases (F_o∙F₁) catalyze ATP synthesis by consuming energy of electrochemical potential of hydrogen ions (<i>pmf)</i>, or ATP hydrolysis resulting in the <i>pmf</i> formation. It is generally accepted to consider F_o∙F₁ as a reversible chemomechanical-electrical molecular machine, however: (i) the mechanism of energy-dependent ATP synthesis is based only on the data on hydrolytic activity of the enzyme, (ii) F_o∙F₁ from a number of organisms effectively synthesize, but is unable to hydrolyze ATP, which indicates non-observance of the principle of microreversibility and requires development of a new hypotheses concerning the enzyme mechanism. Since 1980, the group of A. D. Vinogradov has been developing a concept according to which the elementary catalysis stages of ATP hydrolysis and ATP synthesis do not coincide, and there are two independently operating forms of F_o∙F₁ in the coupled membranes – <i>pmf</i>-generating ATPase and <i>pmf</i>-consuming ATP synthase. F_o∙F₁ of <i>P. denitrificans</i> as a natural model of an irreversibly functioning enzyme is a convenient object for experimental verification of the hypothesis of unidirectional energy conversion. The review considers modern concepts of the molecular mechanisms of regulation of F_o∙F₁ ATP synthase/ATPase of <i>P. denitrificans</i> and development of the hypothesis of two forms of F_o∙F₁.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S86 - S104"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717040","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":"Moonlighting Proteins of Human and Some Other Eukaryotes. Evolutionary Aspects","authors":"Sergei S. Shishkin","doi":"10.1134/S0006297924602855","DOIUrl":"10.1134/S0006297924602855","url":null,"abstract":"<p>This review presents materials on formation of the concept of moonlighting proteins and general characteristics of different similar proteins. It is noted that the concept under consideration is based on the data on the existence in different organisms of individual genes, protein products of which have not one, but at least two fundamentally different functions, for example, depending on cellular or extracellular location. An important feature of these proteins is that their functions can be switched. As a result, in different cellular compartments or outside the cells, as well as under a number of other circumstances, one of the possible functions can be carried out, and under other conditions, another. It is emphasized that the significant interest in moonlighting proteins is due to the fact that information is currently accumulating about their involvement in many vital molecular processes (glycolysis, translation, transcription, replication, etc.). Alternative hypotheses on the evolutionary origin of moonlighting proteins are discussed.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S36 - S59"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717041","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":"Mitochondrial Genome Variants and Alzheimer’s Disease","authors":"Maxim S. Kozin,&nbsp;Olga G. Kulakova,&nbsp;Ivan S. Kiselev,&nbsp;Ekaterina V. Semina,&nbsp;Viktor V. Kakotkin,&nbsp;Mikhail A. Agapov,&nbsp;Olga O. Favorova","doi":"10.1134/S0006297924603174","DOIUrl":"10.1134/S0006297924603174","url":null,"abstract":"<p>Alzheimer’s disease (AD), a severe neurodegenerative disease of the central nervous system, is the most common cause of cognitive impairment in people over the age of 60. The etiology and pathogenesis of Alzheimer’s disease are still unclear despite decades of active research. Numerous studies have shown that neurodegenerative processes in AD are associated with the mitochondrial dysfunction. In this review, we briefly discuss the results of these studies and present the reported evidence that mitochondrial dysfunction in AD is associated with mitochondrial DNA (mtDNA) variations. The results of association analysis of mtDNA haplogroups and individual polymorphic variants, including those whose combinations define haplogroups, with AD are described in detail. These data clearly indicate the role of variations in the mitochondrial genome in the susceptibility to AD, although the problem of significance of individual mtDNA variants is far from being resolved.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S146 - S163"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717013","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 Virulence of Mycobacterium abscessus and Interaction with the Host Immune System","authors":"Ekaterina V. Zakhareva,&nbsp;Billy A. Martini,&nbsp;Elena G. Salina","doi":"10.1134/S0006297924603496","DOIUrl":"10.1134/S0006297924603496","url":null,"abstract":"<p><i>Mycobacterium abscessus</i> is a non-tuberculosis fast-growing mycobacterium that has recently become a serious concern due to its rapidly increasing prevalence worldwide, mainly in individuals with a high susceptibility to pulmonary infections, for example, patients with cystic fibrosis, bronchiectasis, chronic obstructive pulmonary disease, and previous tuberculosis infection. According to present estimations, at least 20% of patients with cystic fibrosis are infected with <i>M</i>. <i>abscessus</i>. This bacterium is extremely resistant to most drugs, leading to a severe and difficult-to-treat infection. That is why <i>M. abscessus</i>, previously classified as a low-virulent opportunistic pathogen, is now reconsidered as a true pathogenic bacterium. There are no effective drugs for successful <i>M. abscessus</i> infection therapy, as well as no vaccines to prevent its spread. This review focuses on the molecular mechanisms ensuring <i>M. abscessus</i> resistance to immune response and its ability to survive in the aggressive intracellular environment of human immune cells, and describes virulence factors that can serve as potential targets for the development of innovative therapeutic approaches to combat the spread of infections caused by <i>M. abscessus</i>.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S214 - S232"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717015","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":"Factors Affecting Pathological Amyloid Protein Transformation: From Post-Translational Modifications to Chaperones","authors":"Vladimir I. Muronets,&nbsp;Sofiya S. Kudryavtseva,&nbsp;Lidia P. Kurochkina,&nbsp;Evgeniia V. Leisi,&nbsp;Yulia Yu. Stroylova,&nbsp;Elena V. Schmalhausen","doi":"10.1134/S0006297924604003","DOIUrl":"10.1134/S0006297924604003","url":null,"abstract":"<p>The review discusses the influence of various factors (e.g., post-translational modifications and chaperones) on the pathological transformation of amyloidogenic proteins involved in the onset and development of neurodegenerative diseases (Alzheimer’s and Parkinson’s diseases) and spongiform encephalopathies of various origin with special focus on the role of α-synuclein, prion protein, and, to a lesser extent, beta-amyloid peptide. The factors investigated by the authors of this review are discussed in more detail, including posttranslational modifications (glycation and S-nitrosylation), cinnamic acid derivatives and dendrimers, and chaperonins (eukaryotic, bacterial, and phage). A special section is devoted to the role of the gastrointestinal microbiota in the pathogenesis of amyloid neurodegenerative diseases, in particular, its involvement in the transformation of infectious prions and possibly other proteins capable of prion-like transmission of amyloidogenic diseases.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S164 - S192"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717009","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":"Fibroblast Activation Protein Alpha (FAPα) as a Promising Target in the Diagnostics and Treatment of Cancer and Fibrotic Diseases: Recent Approaches to Imaging and Assessment of Functional Activity","authors":"Daria A. Butuzova,&nbsp;Maria A. Kulebyakina,&nbsp;Nataliya A. Basalova,&nbsp;Anastasia Yu. Efimenko","doi":"10.1134/S000629792460279X","DOIUrl":"10.1134/S000629792460279X","url":null,"abstract":"<p>Fibroblast activation protein alpha (FAPα) is a transmembrane serine peptidase and a well-known marker of activated fibroblasts that are formed during onco- and fibrogenesis and play an important role in the progression of cancer and fibrosis. Identification of FAPα-positive cells is widely used to visualize pathological changes in the stroma in the diagnosis and treatment of cancer diseases. Recent evidence suggests that FAPα itself contributes to the development of tumors and fibrosis-associated diseases through its enzymatic activity and other mechanisms. Various methods for visualization and evaluation of FAPα enzymatic activity are being developed, which are essential for deciphering the role of FAPα in the development of stromal pathologies. Here we discuss current approaches to visualization and regulation of FAPα enzymatic activity.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S135 - S145"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717012","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":"Biochemistry of Reactivation of Dormant Mycobacteria","authors":"Margarita O. Shleeva,&nbsp;Galina R. Demina,&nbsp;Arseny S. Kaprelyants","doi":"10.1134/S0006297924603757","DOIUrl":"10.1134/S0006297924603757","url":null,"abstract":"<p>An important aspect of medical microbiology is identification of the causes and mechanisms of reactivation (resuscitation) of dormant non-sporulating bacteria. In particular, dormant <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) can cause latent tuberculosis (TB), which could be reactivated in the human organism to the active form of the disease. Analysis of experimental data suggested that reactivation of mycobacteria and reversion of the growth processes include several stages. The initial stage is associated with breakdown of the storage substances like trehalose upon the action of trehalase and with peptidoglycan hydrolysis. Demethylation of tetramethyl porphyrins accumulated in hydrophobic sites (membranes) of the dormant cell also occur in this stage. Metabolic reactivation, starting with cAMP synthesis and subsequent activation of metabolic reactions and biosynthetic processes take place at the stage two as has been shown in the omics studies. Mechanisms of cell reactivation by exogenous free fatty acids via activation of adenylate cyclase and cAMP production have been also suggested. Onset of the cell division is a key benchmark of the third and final stage. Hydrolysis of peptidoglycan as a result of enzymatic action of peptidoglycan hydrolases of the Rpf family is an important process in reactivation of the dormant mycobacteria. Two possible mechanisms for participation of Rpf proteins in reactivation of the dormant bacteria are discussed. On the one hand, muropeptides could be formed as products of peptidoglycan hydrolysis, which could interact with appropriate receptors in bacterial cells transducing activating signal via the PknB phosphotransferase. On the other hand, Rpf protein could presumably change structure of the cell wall, making it more permeable to nutrients and substrates. Both hypotheses were examined in this review. Upon reactivation, independent enzymatic reactions resume their functioning from the beginning of reactivation. Such activation of the entire metabolism occurs rather stochastically, which concludes in combining all biochemical processes in one. This review presents current knowledge regarding biochemical mechanisms of the dormant mycobacteria reactivation, which is important for both fundamental and medical microbiology.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S193 - S213"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717011","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":"Current State of Research on the Mechanisms of Biological Activity of Alginates","authors":"Elizaveta A. Akoulina,&nbsp;Garina A. Bonartseva,&nbsp;Andrey A. Dudun,&nbsp;Marina Y. Kochevalina,&nbsp;Anton P. Bonartsev,&nbsp;Vera V. Voinova","doi":"10.1134/S0006297924604519","DOIUrl":"10.1134/S0006297924604519","url":null,"abstract":"<p>Alginates are anionic unbranched plant and bacterial polysaccharides composed of mannuronic and guluronic acid residues. Alginates can form hydrogels under mild conditions in the presence of divalent cations (e.g., Ca²⁺). Because of their capacity to form gels, high biocompatibility, and relatively low cost, these polysaccharides are employed in pharmaceutical industry, medicine, food industry, cosmetology, and agriculture. Alginate oligomers produced by enzymatic cleavage of high-molecular-weight algal alginates are used as medicinal agents and dietary supplements. The global market for alginate-based products exceeds $1 billion. Alginates and their oligomers have attracted a special interest in biomedical sciences due to manifestation of various types of therapeutic activity. Across more than 50-year history of studies of alginates, over 60% scientific articles in this field have been published in the last 5 years. Unfortunately, the works dedicated to the mechanisms of biological activity of alginates and their oligosaccharides are still very scarce. This review analyzes the current state of research on the mechanisms (mainly biochemical) underlying biological and therapeutic activities of alginates (antioxidant, antibacterial, anti-inflammatory, antitumor, neuroprotective, antihypertensive, regenerative, and prebiotic). A comprehensive understanding of these mechanisms will not only improve the efficiency of alginate application in medicine and other traditional fields (cosmetology, food industry), but might also reveal their potential in new areas such as tissue engineering, nanobiotechnology, and bioelectronics.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S263 - S286"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717014","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}