Molekulyarnaya Biologiya最新文献

{"title":"[Toxin-Antitoxin Systems: Formation of Genetic Networks of Human Microbiome Bacteria and Prospects for Application].","authors":"N I Akimova, M G Alekseeva, O B Bekker, V N Danilenko","doi":"10.7868/S3034555326020049","DOIUrl":"10.7868/S3034555326020049","url":null,"abstract":"<p><p>Toxin-antitoxin systems are modules consisting of genes that encode a stable toxin and a labile antitoxin. These systems are found in the genomes of most bacteria and archaea species. At present, eight types of toxin-antitoxin systems are distinguished. They perform a variety of functions in bacterial cells, the most important of which is adaptation to environmental stress. This review focuses on various types of toxin- antitoxin systems, their functions, and the mechanisms regulating interactions between the main components. These systems are described in detail for Bifidobacterium bifidum, Bifidobacterium longum, Lacticaseibacillus rhamnosus, and Mycobacterium tuberculosis. Furthermore, promising applications of toxin-antitoxin systems in biotechnology and infectious disease therapy are described.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"60 2","pages":"248-265"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Organ-Specific Changes in the Expression of Inflammatory Response and Antioxidant Defense Genes in the Late Period after Hemorrhagic Shock].","authors":"N V Andrianova, K N Lapin, A A Brezgunova, A D Bocharnikov, I B Pevzner, M I Buyan, E S Remneva, D A Kirpicheva, S N Kalabushev, I A Ryzhkov, E Y Plotnikov","doi":"10.7868/S3034555326020088","DOIUrl":"10.7868/S3034555326020088","url":null,"abstract":"<p><p>Hemorrhagic shock (HS) is a life-threatening condition that leads to multiple organ failure due to centralization of blood flow and impaired blood clotting. In this study, we investigated the acute and delayed effects of HS on the brain, kidneys, and liver of rats to identify molecular targets for therapy of the consequences of shock. Blood acid-base balance and electrocardiography (ECG) parameters were studied in rats in the acute phase of HS. Gene expression of antioxidant enzymes (Gpx1, Sod1, Cat, Nfe2l2) and inflammatory markers (Ptprc, Cxcl1, Cd86, Itgal, Il1b, Il6, Tnf, Tlr2, Cox2, Cst7, Ccl3, Il10) in brain, kidney, and liver tissues was analyzed, as well as the amount of protein markers for kidney damage (NGAL, KIM-1) in urine 24 h after HS. In addition, markers for the activation of astrocytes (Gfap) and microglia (Aif1) as well as neuronal markers (Eno2, Tubb3) in brain tissue were analyzed. Biochemical markers for liver and kidney damage and total antioxidant activity were determined in blood serum. Acute HS caused decompensated lactic acidosis, arterial hypotension and characteristic changes in the ECG. Although no pronounced inflammatory response was detected in brain, kidney and liver tissue in the late phase after acute blood loss, the brain and liver tissue were more susceptible to the adverse effects of acute blood loss than the kidneys according to a number of indicators. This points to the need to develop targeted strategies to protect organs in the postresuscitation period by targeting specific molecular targets in specific tissues.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"60 2","pages":"311-327"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[GLUT8- and AMPK-Dependent Autophagy Signaling in the Mechanism of the Neuroprotective Action of Trehalose].","authors":"A B Pupyshev, M A Tikhonova","doi":"10.7868/S3034555326020071","DOIUrl":"10.7868/S3034555326020071","url":null,"abstract":"<p><p>Trehalose disaccharide has a stable neuroprotective effect used in inhibiting experimental neurodegeneration. However, the mechanism of its action on brain neurons remains largely unclear. In hepatocytes, the main target of trehalose is the activation of mTOR-independent autophagy, which is achieved by inhibiting the glucose transporter GLUT8, leading to energy deficiency. An increase in AMP levels activates AMP-dependent kinase AMPK by phosphorylation at Thr172 and further activates autophagy regulator kinase ULK1. In neurons, the GLUT8 transporter inhibitors and other disaccharides also activate autophagy, but less effectively than trehalose. The neuroprotective effect of trehalose includes a chaperone-like effect, inhibition of the accumulation of aberrant proteins, reduction of oxidative stress, increased antioxidant protection, and suppression of neuroinflammation. Similar to the effect on hepatocytes, trehalose triggers the activation of autophagy by the short signaling pathway pAMPK-pULK1. AMPK inhibition prevents the activation of autophagy in neurons and weakens the neurotherapeutic effect of trehalose. AMPK activation is accompanied by the pleiotropic effect of suppression of biosynthetic processes and cellular metabolism related to activation of mTOR-dependent autophagy; however, no such effect has been detected for trehalose. In vivo data on the relationship among GLUT8 expression, AMPK activity, and autophagy levels in the brain are analyzed. The therapeutic advantages of the molecular effects of trehalose in comparison with the activation of mTOR-dependent autophagy and the possibilities of their combined therapeutic use are discussed.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"60 2","pages":"292-310"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Genetically Modified Pigs as Organ Donors: Challenges and Prospects].","authors":"I S Litvinova, A E Zubkova, D V Yudkin","doi":"10.7868/S3034555326020024","DOIUrl":"10.7868/S3034555326020024","url":null,"abstract":"<p><p>Organ transplantation is a treatment method for various organ failures and other severe pathologies, applied in critical cases to save a patient's life. However, there is a severe shortage of donor organs world-wide, resulting in hundreds of thousands of patients being unable to receive the organs they need in time. One possible solution to this problem is xenotransplantation-transplanting organs from animals to humans. Experiments in xenotransplantation began in the mid-1960s, with primates considered as the first potential donors. However, for a number of reasons, they proved unsuitable as a source of organs, while pigs turned out to be the best donors. The development of modern genetic engineering and genome editing methods has led to a new perspective on these animals as a source of human organs. Various genetic modifications have significantly reduced the immune response of the recipient to the graft and improved survival. To date, several successful transplants of organs and tissues from wild-type and genetically modified pigs to humans have been carried out worldwide, and a few companies are developing specialized lines of animals for xenotransplantation. In this review, we provide a detailed overview of the history of xenotransplantation worldwide, as well as all the genetic modifications introduced into the genome of pigs the organs of which have been used successfully for human transplantation, the role of these genetic modifications, and the mechanisms by which they are introduced.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"60 2","pages":"216-234"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[The Level of Methylation in the Promoter Regions of DNA Repair Genes in Chronically Exposed People].","authors":"A V Korechenkova, E A Blinova, A V Akleyev","doi":"10.7868/S3034555326020056","DOIUrl":"10.7868/S3034555326020056","url":null,"abstract":"<p><p>Nowadays, against the backdrop of a global increase in cancer incidence, the search for prognostic markers to assess individual risks is particularly relevant. Early identification of altered DNA methylation patterns may serve as a reliable indicator of malignant transformation and be used for diagnostic purposes. The objective of this study was to assess the methylation level of CpG dinucleotides in the promoter regions of DNA repair genes (AKT1, DDB2, GADD45A, XPC and XRCC3) in the blood of chronically exposed individuals who subsequently developed cancers. The study was conducted in individuals who were affected by chronic low dose-rate exposure in 1950-1960s in the Southern Urals. The main group included exposed individuals in the latent period of cancer development-104 people, the comparison group consisted of exposed individuals without cancers-188 people. The methylation level was assessed in bisulfite-converted DNA samples using methylation-specific high-resolution melting. It was established that in exposed individuals from the main group, there was a statistically significant decrease in the methylation level in the AKT1 and GADD45A gene promoter, relative to the comparison group (4.37 versus 7.23%, p < 0.001 and 10.73 versus 19.58%, p < 0.001, respectively). As for the XRCC3 gene, there was an increase in the methylation level of CpG dinucleotides in the promoter in individuals from the main group relative to the comparison group (5.38 versus 6.18%, p < 0.001). When the prognostic potential of methylation parameters of the AKT1, GADD45A, XRCC3 gene promoters was assessed for the purposes of early diagnosis of cancer development risk, it was found that when these loci were analyzed together, the AUC was 0.89 (95% CI: 0.85-0.93) at p < 0.001.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"60 2","pages":"266-275"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Immunoglobulin-Like Domains Are the Key to Understanding Amyloid Aggregation].","authors":"L G Bobyleva, I M Vikhlyantsev, A G Bobylev","doi":"10.7868/S3034555326020032","DOIUrl":"10.7868/S3034555326020032","url":null,"abstract":"<p><p>Modern concepts of the mechanisms of protein aggregation with an emphasis on immunoglobulin-like domains (Ig domains) as a structural platform predisposed to the formation of aggregates with amyloid properties are presented in this review. Particular attention is paid to the muscle proteins titin and myosin-binding protein C, which form not fibrillar, but amorphous amyloid aggregates with a cross-β structure without an increase in the total content of the secondary β-structure, capable of binding thioflavin T (ThT) and Congo red. The absence of a nucleation phase during the formation of amyloid aggregates of these proteins, as well as their partial disaggregation, allows us to declare a new, previously undescribed pathway of amyloid protein aggregation. We refer to it as self-templating amorphous β-assembly (conformational conversion by a prion-like mechanism), characteristic of multidomain proteins of the sarcomeric cytoskeleton.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"60 2","pages":"235-247"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148144948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Gene and Cell Technologies for Treatment of Brain Malignancies].","authors":"I I Abdrakhmanova, K V Kitaeva, A V Gorodilova, M G Saidgaraeva, A A Rizvanov, V V Solovyeva","doi":"10.7868/S3034555326020018","DOIUrl":"10.7868/S3034555326020018","url":null,"abstract":"<p><p>Brain malignancies, such as glioblastoma, remain one of the most aggressive and difficult-to-treat cancers because of their heterogeneity, invasive growth, and resistance to conventional therapy. Significant recent progress in the treatment of these diseases has been associated with the development of gene and cell technologies, which open up new possibilities for targeted therapy, immunotherapy, and personalized approaches. The review systematically summarizes the data on current treatment strategies, including gene therapy, cell therapy, and combined approaches. Particular attention is paid to preclinical and clinical studies, as well as the prospects for overcoming major limitations, such as the blood-brain barrier, the immunosuppressive tumor microenvironment, and toxicity. Analysis of the literature demonstrates that integration of gene and cell technologies could provide a basis for developing effective treatments aimed at improving the survival of patients with central nervous system tumors.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"60 2","pages":"191-215"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Biochip for Determination of 92 Human Y-Chromosome Haplogroups by SNP Markers and Frequency Distribution of These Haplogroups in Slavic Population of European Russia].","authors":"I D Ivanovsky, S A Polyakov, M A Filippova, D O Fesenko","doi":"10.7868/S3034555326020064","DOIUrl":"10.7868/S3034555326020064","url":null,"abstract":"<p><p>A method utilizing hydrogel biological microchips was developed to genotype markers of human Y-chromosome haplogroups. With the method, 14 core haplogroups and their 78 subclades were determined, including (subclade markers are in parentheses) B-M60, C-M130 (F1906, Z18160, F6370, Y4630, Z4063, and M407), D-CTS3946, E-M5388 (P177, M5017, L539, L618, L677, Z827, M123, L29, and L791), G-P257 (F858, P15, Z6552, and L1259), H-M2920, I-U179 (M253, Z2336, Z58, M438, S2648, M436, and L596), J-M304 (PF4641, Z2363, CTS3569, CTS886, M410, PF5125, PF5130, Z7671, Z2221, and Z2417), L-M185 (Z5919, Y6288, and PH3615), N-M231 (L395, CTS10075, CTS10760, and CTS10082), O-M175 (M1422, F36, and M134), Q-M1105 (L472, L74, YP344, M7361, and L275), R-P224 (M420, S224, Z283, Z2906, CTS11962, Z91, Z686, S3357, YP237, Y33, Z93, L657, Z2124, Z2125, Z2123, Y20746, Y934, S23592, Z2122, M343, M73, CTS894, M412, M405, P312, Z2103, and M479), and T-M272. Genotyping included multiplex PCR followed by hybridization on a biochip. Haplogroup frequencies were determined in a sample of 356 males living in European Russia. The direct method can provide an alternative to indirect determination of haplogroups by Y-STR haplotype with the use of predictors. The method was developed with due regard to requirements for forensic genotyping methods and was primarily designed to obtain forensic information on the biogeographical origin of the person in question. The average amplicon length was 72 bp. The study clarified the population structure of Y haplogroups in the Slavic population of European Russia.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"60 2","pages":"276-291"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[microRNA in the Realization of Molecular Mechanisms of Lymphocyte Development and Their Malignant Transformation].","authors":"Yu A Veryaskina, S E Titov, I B Kovynev, S S Fyodorova, Ya Yu Shebunyaeva, O V Antonenko, T I Pospelova, I F Zhimulev","doi":"10.7868/S3034555326020109","DOIUrl":"10.7868/S3034555326020109","url":null,"abstract":"<p><p>The immune system consists of a diverse range of cell types, each performing its specific function. T-lymphocytes, B-lymphocytes, and NK (natural killer) cells provide protection against infections and tumors and participate in the regulation of immune responses. Disorders in the development and function of lymphocytes can lead to various immunodeficiencies, autoimmune diseases, and oncological conditions. The functional and morphological diversity of the B- and T-cell immune system in health and disease is maintained by dynamic genetic and epigenetic changes, including those mediated by small regulatory molecules-microRNAs (miRNAs). This review presents current data on the role of miRNAs in the development of B- and T-cells, their activation, and malignant transformation. Aberrant expression of miRNAs plays a key pathogenic role in the development and maintenance of lymphomas, characterizing them as promising diagnostic and prognostic markers.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"60 2","pages":"345-362"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Glial Progenitor Cell Therapy Improves Mitochondrial Function in the Hippocampus of 5xFAD Mice, but Does Not Restore the Multiscale Structure of Behavioral Stress Response].","authors":"A I Andreev, M E Neganova, Yu R Aleksandrova, D I Salikhova, E V Belousova, M O Shedenkova, A K Sudina, Ya M Maksimov, E A Orlova, M A Lapshina, V S Popov, E A Ahremenko, D V Goldshtein, A A Ustyugov, V O Nebogatikov","doi":"10.7868/S3034555326020096","DOIUrl":"10.7868/S3034555326020096","url":null,"abstract":"<p><p>Cell therapy is increasingly used to treat a variety of medical conditions, including cancer, immune system disorders, and neurodegeneration. Stem cells secrete growth factors, signaling molecules, and extracellular vesicles, that can be used to treat neurological diseases and promote neuronal regeneration. Transgenic 5xFAD mice, which are a model for Alzheimer's disease (AD), were used in this study. The mice were 7 months old and received retro-orbital injections of glial progenitor cells (GPCs) once a week for 4 months. At 11 months, their behavior was analyzed using a multichannel actigraphy system. Brain tissues from the cortex, hippocampus, and midbrain were collected for postmortem analysis of mitochondrial respiratory chain enzyme activity. The results showed that the GPCs injection significantly improved the response of the hippocampal p2 mitochondrial fraction in 5xFAD mice to succinate, reaching a level observed in control animals. A similar trend was also observed for the cytochrome c oxidase complex. The oxygen consumption rate of mitochondria did not differ from that of clinically healthy mice after ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride administration. A similar decrease in the efficiency of the electron transport chain was detected in the midbrain of 5xFAD mice, but no recovery was observed after GPCs treatment. Behavioral differences between non-transgenic and transgenic groups were observed in a multiparameter analysis using the actigraphy system. The behavior of transgenic mice in the treated and untreated groups was similar, while the behavior of non-transgenic mice varied. Additional analysis of locomotor activity and transient events in particular revealed that the activity of the GPCs-treated 5xFAD mice was differed fundamentally compared to other groups. Specifically, GPCs-treated mice exhibited greater number of transitions between intermediate activity states. In contrast, untreated mice showed transitions between extreme activity states, such as from low to high activity or vice versa. These findings suggest that changes in behavior and activity of the AD mice may be associated not only with hippocampal dysfunction, but also with disruptions in midbrain structures.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"60 2","pages":"328-344"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148144984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}