Daria A. Butuzova, Maria A. Kulebyakina, Nataliya A. Basalova, Anastasia Yu. Efimenko
{"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, Maria A. Kulebyakina, Nataliya A. Basalova, 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}
Margarita O. Shleeva, Galina R. Demina, Arseny S. Kaprelyants
{"title":"Biochemistry of Reactivation of Dormant Mycobacteria","authors":"Margarita O. Shleeva, Galina R. Demina, 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}
Elizaveta A. Akoulina, Garina A. Bonartseva, Andrey A. Dudun, Marina Y. Kochevalina, Anton P. Bonartsev, Vera V. Voinova
{"title":"Current State of Research on the Mechanisms of Biological Activity of Alginates","authors":"Elizaveta A. Akoulina, Garina A. Bonartseva, Andrey A. Dudun, Marina Y. Kochevalina, Anton P. Bonartsev, 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., Ca<sup>2+</sup>). 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}
Nikita G. Yabbarov, Elena D. Nikolskaya, Sergei B. Bibikov, Aleksandr A. Maltsev, Margarita V. Chirkina, Mariia R. Mollaeva, Maria B. Sokol, Ekaterina Yu. Epova, Ruslan O. Aliev, Ilya N. Kurochkin
{"title":"Methods for Rapid Evaluation of Microbial Antibiotics Resistance","authors":"Nikita G. Yabbarov, Elena D. Nikolskaya, Sergei B. Bibikov, Aleksandr A. Maltsev, Margarita V. Chirkina, Mariia R. Mollaeva, Maria B. Sokol, Ekaterina Yu. Epova, Ruslan O. Aliev, Ilya N. Kurochkin","doi":"10.1134/S0006297924603678","DOIUrl":"10.1134/S0006297924603678","url":null,"abstract":"<p>Antibiotic resistance is a major challenge for public health systems worldwide. Rapid and effective identification of bacterial strains is critical for reducing the use of antibiotics and restricting the spread of antibiotic-resistant microorganisms. Various approaches have been developed in recent years for rapid bacterial identification and antibiotic susceptibility testing (AST), such as Raman spectroscopy, single cell image analysis, microfluidic techniques, mass spectrometry analysis, use of high-sensitive luminescent and fluorescent tags, impedance-based detection, and others. This review describes the methods developed for rapid bacterial identification and assessment of their antibiotic susceptibility, including general principles, specific problems, and future prospects.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S312 - S341"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717017","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":"Serine-Threonine Protein Kinases of Cyanobacteria","authors":"Anna A. Zorina, Dmitry A. Los, Oleg I. Klychnikov","doi":"10.1134/S0006297924604507","DOIUrl":"10.1134/S0006297924604507","url":null,"abstract":"<p>Protein phosphorylation is a pivotal mechanism for signal transduction, regulation of biochemical processes essential for reproduction, growth, and adaptation of organisms to changing conditions. Bacteria, which emerged more than 3.5 billion years ago, faced the need to adapt to a variety of ecological niches from the very beginning of their existence. It is not surprising that they developed a wide range of different types of kinases and target amino acid residues for phosphorylation. To date, many examples of phosphorylation of serine, threonine, tyrosine, histidine, arginine, lysine, aspartate, and cysteine have been discovered. Bacterial histidine kinases as part of two-component systems have been studied in most detail. More recently eukaryotic type serine-threonine and tyrosine kinases based on the conserved catalytic domain have been described in the genomes of many bacteria. The term “eukaryotic” is misleading, since evolutionary origin of these enzymes goes back to the last common universal ancestor – LUCA. Bioinformatics, molecular genetics, omics, and biochemical strategies combined provide new tools for researchers to establish relationship between the kinase abundance/activity and proteome changes, including studying of the kinase signaling network (kinome) within the cell. This manuscript presents several approaches to investigation of the serine-threonine protein kinases of cyanobacteria, as well as their combination, which allow to suggest new hypotheses and strategies for researchers.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S287 - S311"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717016","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}
Alexander Yu. Rudenko, Sofia S. Mariasina, Ratislav M. Ozhiganov, Petr V. Sergiev, Vladimir I. Polshakov
{"title":"Enzymatic Reactions of S-Adenosyl-L-Methionine: Synthesis and Applications","authors":"Alexander Yu. Rudenko, Sofia S. Mariasina, Ratislav M. Ozhiganov, Petr V. Sergiev, Vladimir I. Polshakov","doi":"10.1134/S0006297924604210","DOIUrl":"10.1134/S0006297924604210","url":null,"abstract":"<p><i>S</i>-adenosyl-<i>L</i>-methionine (SAM, AdoMet) is a ubiquitous biomolecule present in all living organisms, playing a central role in a wide array of biochemical reactions and intracellular regulatory pathways. It is the second most common participant in enzymatic reactions in living systems, following adenosine triphosphate (ATP). This review provides a comprehensive analysis of enzymatic reactions involving SAM, whether as a product, a reactant (cosubstrate), or as a non-consumable enzyme cofactor. The discussion encompasses various methods for SAM synthesis, including biotechnological, chemical, and enzymatic approaches. Particular emphasis is placed on the biochemical reactions where SAM functions as a cosubstrate, notably in trans-alkylation reactions, where it acts as a key methyl group donor. Beyond methylation, SAM also serves as a precursor for the synthesis of other molecular building blocks, which are explored in a dedicated section. The review also addresses the role of SAM as a non-consumable cofactor in enzymatic processes, highlighting its function as a prosthetic group for certain protein enzymes and its ability to form complexes with ribozymes. In addition, bioorthogonal systems involving SAM analogues are discussed. These systems employ engineered enzyme–cofactor pairs designed to enable highly selective interactions between target SAM analogues and specific enzymes, facilitating precise reactions even in the presence of other SAM-dependent enzymes. The concluding section explores practical applications of SAM analogues, including their use as selective inhibitors in clinical medicine and as components of reporter systems.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S105 - S134"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717042","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}
Ivan S. Kiselev, Natalia M. Baulina, Olga O. Favorova
{"title":"Epigenetic Clock: DNA Methylation as a Marker of Biological Age and Age-Associated Diseases","authors":"Ivan S. Kiselev, Natalia M. Baulina, Olga O. Favorova","doi":"10.1134/S0006297924602843","DOIUrl":"10.1134/S0006297924602843","url":null,"abstract":"<p>Age is one of the key criteria of human health used in practical medicine to predict the risk of common chronic diseases. However, biological age, which reflects the state of an individual organism, functional capabilities, social well-being, and risk of premature death from various causes, often does not coincide with chronological age. To determine biological age of a particular individuals and the rate of their aging, specific panels of DNA methylation markers called “epigenetic clock” (EC) were proposed. This review summarizes the data about the main types of ECs developed to date and their key characteristics. We described the results of works studying individual aging rates in common age-associated diseases and outlined main directions, development of which could expand application of ECs in fundamental and practical medicine. There is no doubt that revealing complex mechanisms underlying interaction between the rate of epigenetic aging and the risk of age-associated diseases could play a key role for prediction and early diagnosis, as well as for the development of preventive measures that could delay onset of the disease.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S356 - S372"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717019","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":"Immune Response and Production of Abzymes in Patients with Autoimmune and Neurodegenerative Diseases","authors":"Georgy A. Nevinsky","doi":"10.1134/S0006297924604167","DOIUrl":"10.1134/S0006297924604167","url":null,"abstract":"<p>The mechanisms of development of autoimmune, neurological, and viral diseases and the possibilities of immune response to various antigens in these pathologies still pose many questions. Human immune system is theoretically capable of synthesizing about a million antibodies with very different properties against the same antigen. It remains unclear how many antibodies and with what properties can form in healthy people and patients with autoimmune diseases (AIDs). The capabilities of traditional approaches, such as enzyme immunoassay or affinity chromatography of Abs on specific sorbents, in answering these questions and analyzing the diversity of antibodies formed against external and internal antigens, as well as their role in the pathogenesis of various diseases, are very limited. Analysis of monoclonal antibodies in the blood of patients with systemic lupus erythematosus (SLE) using phage display revealed that the number of autoantibodies against DNA and myelin basic protein (MBP) can exceed 3-4 thousand, and approximately 30-40% of them are abzymes capable of hydrolyzing DNA and MBP. However, this approach does not allow to investigate the variety of properties of such antibodies, in particular their catalytic activity. Abzymes can play either positive or negative role in the development of various diseases. For example, in HIV-infected patients, abzymes against viral polymerase and integrase cleave these proteins, thus slowing down the development of immunodeficiency syndrome. Other antibodies play a negative role in the pathogenesis of viral, neurological, and autoimmune diseases. Thus, antibodies capable of hydrolyzing DNA and histones can penetrate through the cellular and nuclear membranes, stimulate cell apoptosis, and, as a result, trigger autoimmune processes in many pathologies. Antibodies against MBP cleave this protein in the membranes of cells in nerve tissues, leading to the development of multiple sclerosis (MS). In this case, abzymes against individual histones were able to hydrolyze each of these histones, as well as MBP, while Abs against MBP hydrolyzed MBP and all five histones. It has also been established that the substrate specificity of abzymes in the hydrolysis of histones and MBP varied greatly depending on the stage of MS or SLE development. Here, we used this example to analyze in detail the role that abzymes against various antigens play in their expanded involvement in the pathogenesis of some AIDs. The review also describes the impact of defects in the bone marrow stem cell differentiation characteristic of AIDs in the formation of B lymphocytes producing harmful abzymes and summarizes for the first time the data on the exceptional diversity of autoantibodies and abzymes, their unusual biological functions, and involvement in the pathogenesis of autoimmune pathologies.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S373 - S400"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717021","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 Big, Mysterious World of Plant 14-3-3 Proteins","authors":"Ilya A. Sedlov, Nikolai N. Sluchanko","doi":"10.1134/S0006297924603319","DOIUrl":"10.1134/S0006297924603319","url":null,"abstract":"<p>14-3-3 is a family of small regulatory proteins found exclusively in eukaryotic organisms. They selectively bind to phosphorylated molecules of partner proteins and regulate their functions. 14-3-3 proteins were first characterized in the mammalian brain approximately 60 years ago and then found in plants, 30 years later. The multifunctionality of 14-3-3 proteins is exemplified by their involvement in coordination of protein kinase cascades in animal brain and regulation of flowering, growth, metabolism, and immunity in plants. Despite extensive studies of this diverse and complex world of plant 14-3-3 proteins, our understanding of functions of these enigmatic molecules is fragmentary and unsystematic. The results of studies are often contradictory and many questions remain unanswered, including biochemical properties of 14-3-3 isoforms, structure of protein–protein complexes, and direct mechanisms by which 14-3-3 proteins influence the functions of their partners in plants. Although many plant genes coding for 14-3-3 proteins have been identified, the isoforms for <i>in vivo</i> and <i>in vitro</i> studies are often selected at random. This rather limited approach is partly due to an exceptionally large number and variety of 14-3-3 homologs in plants and erroneous <i>a</i> <i>priori</i> assumptions on the equivalence of certain isoforms. The accumulated results provide an extensive but rather fragmentary picture, which poses serious challenges for making global generalizations. This review is aimed to demonstrate the diversity and scope of studies of the functions of plant 14-3-3 proteins, as well as to identify areas that require further systematic investigation and close scientific attention.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S1 - S35"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717038","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}
Viktoriya V. Kolesnikova, Oleg S. Nikonov, Phat Tien Do, Ekaterina Yu. Nikonova
{"title":"The Proteins Diversity of the eIF4E Family in the eIF4F Complex","authors":"Viktoriya V. Kolesnikova, Oleg S. Nikonov, Phat Tien Do, Ekaterina Yu. Nikonova","doi":"10.1134/S0006297924603721","DOIUrl":"10.1134/S0006297924603721","url":null,"abstract":"<p>In eukaryotes, translation initiation occurs by the cap-dependent mechanism. Each translated mRNA must be pre-bound by the translation initiation factor eIF4E. All isoforms of this factor are combined into one family. The review considers natural diversity of the eIF4E isoforms in different organisms, provides structural information about them, and describes their functional role in the processes, such as oncogenesis, participation in the translation of certain mRNAs under stress, and selective use of the individual isoforms by viruses. In addition, this review briefly describes the mechanism of cap-dependent translation initiation and possible ways to regulate the eIF4E function.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S60 - S85"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717039","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}