Acta NaturaePub Date : 2025-01-01DOI: 10.32607/actanaturae.27529
F M Izhaeva, A I Tukhvatulin, A S Dzharullaeva, I V Dolzhikova, O V Zubkova, D V Shcheblyakov, N L Lubenets, E A Smolyarchuk, T G Zubkova, A S Erokhova, I M Cherenkova, K M Bukhtin, O Popova, N M Tukhvatulina, B S Naroditsky, D Y Logunov, A L Gintsburg
{"title":"The Parameters of Long-Term Humoral Immunity Induced by a Single Injection of the Sputnik Light Vaccine Among Noninfected Volunteers and Those Infected with SARS-CoV-2.","authors":"F M Izhaeva, A I Tukhvatulin, A S Dzharullaeva, I V Dolzhikova, O V Zubkova, D V Shcheblyakov, N L Lubenets, E A Smolyarchuk, T G Zubkova, A S Erokhova, I M Cherenkova, K M Bukhtin, O Popova, N M Tukhvatulina, B S Naroditsky, D Y Logunov, A L Gintsburg","doi":"10.32607/actanaturae.27529","DOIUrl":"https://doi.org/10.32607/actanaturae.27529","url":null,"abstract":"<p><p>Although the immunogenicity of clinically approved COVID-19 vaccines remains under intensive investigation, little is still known about the parameters of long-term immune responses. In this paper, we present for the first time the parameters of humoral immunity studied in the phase 1-2 open-label clinical trial of the Sputnik Light vaccine, with a special focus on late follow-up time points (90 and 180 days). For the most accurate assessment of the parameters of humoral post-vaccination immunity (titer and avidity index of antigen-specific antibodies against the RBD domain of SARS-CoV-2), we conducted an additional analysis that allowed us to triage volunteers with immunity formed only in response to vaccination, as well as those with hybrid immunity (infected with SARS-CoV-2 before and after vaccination). The findings indicate that single-shot vaccination with the Sputnik Light vaccine induces a durable (seroconversion 73% on day 180) and mature humoral immunity. Natural immunization as a result of the SARS-CoV-2 infection leads to significant changes in the studied parameters of post-vaccination immunity.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 1","pages":"52-63"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960400","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}
Acta NaturaePub Date : 2025-01-01DOI: 10.32607/actanaturae.27549
S V Kupriyanov, K M Kirilenko, D N Starkov
{"title":"Immunoregulatory Enzymes.","authors":"S V Kupriyanov, K M Kirilenko, D N Starkov","doi":"10.32607/actanaturae.27549","DOIUrl":"https://doi.org/10.32607/actanaturae.27549","url":null,"abstract":"<p><p>Immunoregulatory enzymes, which function both as biological catalysts and regulatory elements, play a crucial role in controlling immune responses. Dysfunction of these proteins can contribute to various pathological conditions, such as the suppression of antitumor immunity or impairment of anti-infectious immune responses. This review discusses the most extensively studied immunoregulatory enzymes, including indoleamine 2,3-dioxygenase 1, arginase 1, inducible nitric oxide synthase, glyceraldehyde-3-phosphate dehydrogenase, and ectonucleoside triphosphate diphosphohydrolase 1. Their classification is provided, along with an analysis of the distinctive characteristics inherent to this group of enzymes. Additionally, new directions for the medical application of immunoregulatory enzymes are explored.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 1","pages":"11-19"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958861","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}
Acta NaturaePub Date : 2025-01-01DOI: 10.32607/actanaturae.27457
Zhipeng Zhang, Yanqin Ma, Yan He, Dong Wang, Huaien Song, Kun Yue, Xiaomei Zhang
{"title":"Inhibition of HBV Replication by a Fully Humanized Neutralizing Antibody In Vivo and In Vitro.","authors":"Zhipeng Zhang, Yanqin Ma, Yan He, Dong Wang, Huaien Song, Kun Yue, Xiaomei Zhang","doi":"10.32607/actanaturae.27457","DOIUrl":"https://doi.org/10.32607/actanaturae.27457","url":null,"abstract":"<p><p>Neutralizing antibodies are capable of specifically binding to the HBsAg virus, thereby preventing HBV infection and subsequently reducing viral antigen load in both the liver and systemic circulation. This has significant implications for restoring the postnatal immune function. By utilizing the phage antibody library technology, we successfully screened a fully humanized neutralizing antibody targeting the hepatitis B surface antigen. The antiviral activity was assessed in primary human hepatocytes (PHHs) by determining the EC<sub>50</sub> values for HBeAg and HBsAg biomarkers in HBV types B, C, and D; no cytotoxicity was observed within the tested concentration range. Furthermore, HT-102 exhibited no ADCC effect but displayed a weak CDC effect along with a dose-dependent response. We established an AAV/HBV mouse model and observed significant dose-dependent reduction in HBsAg and HBV DNA levels for both the medium-dose and highdose groups. The immunohistochemical staining data showed dose-dependent reduction in HBsAg expression in the liver, with high-dose group exhibiting minimal positive expression. Finally, a mild immune response was induced, while reducing the burden of antigen-antibody complexes circulating within the system. Consequently, strain on the patient's immune system was alleviated by effectively slowing down CD8<sup>+</sup>T lymphocyte depletion, and functional cure was ultimately achieved as intended.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 1","pages":"97-105"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957938","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}
Acta NaturaePub Date : 2025-01-01DOI: 10.32607/actanaturae.27555
S V Zubova, Ya V Radzyukevich, N I Kosyakova, I R Prokhorenko
{"title":"Rhodobacter capsulatus PG Lipopolysaccharide As a Potential Blocker of Toll-like Receptor 2 and 4 Activation.","authors":"S V Zubova, Ya V Radzyukevich, N I Kosyakova, I R Prokhorenko","doi":"10.32607/actanaturae.27555","DOIUrl":"https://doi.org/10.32607/actanaturae.27555","url":null,"abstract":"<p><p>TLR2 and TLR4 play a key role in the development of an inflammation in response to a bacterial infection. We studied the effect of <i>Rhodobacter capsulatus</i> PG lipopolysaccharide (LPS) on proinflammatory cytokine synthesis activation by the TLR2 and TLR4 agonists <i>E. coli</i> LPS, <i>Streptococcus pyogenes</i> lipoteichoic acid (LTA), and Pam3CSK4 (a synthetic bacterial lipopeptide) in human whole blood cells. <i>Rhodobacter capsulatus</i> PG LPS was shown to exhibit antagonistic properties against the studied TLR4 and TLR2 agonists, blocking the synthesis of the cytokines TNF-α, IL-6, and IL-8. Possible mechanisms behind the suppressing effect of <i>Rhodobacter capsulatus</i> PG LPS are proposed. <i>Rhodobacter capsulatus</i> PG LPS can serve as a prototype for drugs against both gram-negative and gram-positive bacteria.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 1","pages":"106-109"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954880","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}
Acta NaturaePub Date : 2025-01-01DOI: 10.32607/actanaturae.27528
A V Nedoluzhko, F S Sharko, S M Rastorguev
{"title":"Intergeneric Introgression Enhances the Adaptive Potential of Nine-Spined Stickleback (Pungitius pungitius).","authors":"A V Nedoluzhko, F S Sharko, S M Rastorguev","doi":"10.32607/actanaturae.27528","DOIUrl":"https://doi.org/10.32607/actanaturae.27528","url":null,"abstract":"<p><p>Over the past decades, number of evidences has accumulated that demonstrates the importance of genomic introgression between relatively distant eukaryote species, including the introgression of teleost fish species; the three-spined stickleback (<i>Gasterosteus aculeatus</i>) and the nine-spined stickleback (<i>Pungitius pungitius</i>). The whole-genome datasets of both teleost species give reasons for suggesting that the marine population of nine-spined stickleback increases its adaptive potential to the marine environment through introgression with the anadromous three-spined stickleback. These findings demand a reinterpreting of the mechanisms of evolution towards a process in which organisms acquire new traits not only through longterm accumulation and selection of spontaneous mutations, but also via introgression from other species and ecological forms.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 1","pages":"110-113"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959201","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}
Acta NaturaePub Date : 2025-01-01DOI: 10.32607/actanaturae.27497
A G Emelyanova, M A Zolotovskaia, E V Poddubskaya, A A Modestov, V S Prassolov, D V Kuzmin, A A Buzdin
{"title":"Activation of the ERK1/2 Molecular Pathways and Its Relation to the Pathogenicity of Human Malignant Tumors.","authors":"A G Emelyanova, M A Zolotovskaia, E V Poddubskaya, A A Modestov, V S Prassolov, D V Kuzmin, A A Buzdin","doi":"10.32607/actanaturae.27497","DOIUrl":"https://doi.org/10.32607/actanaturae.27497","url":null,"abstract":"<p><p>Mitogen-activated protein kinases, ERK1/2 (MAPK3/1), play a key role in the regulation of cell growth, differentiation, and apoptosis. We have previously presented evidence proving that activation of the ERK1/2 axis in cancer cells following the administration of therapeutics leads to the overexpression of growth factor receptors and drug resistance. Recently, we have proposed a new bioinformatic technique that enables direct construction of interactome network-based molecular pathways for gene products of interest, as well as quantitation of their activation levels using high-throughput gene expression data. In this study, we, for the first time, algorithmically constructed ERK1/2 molecular pathways and investigated how their activation levels (PALs) affect survival and responsiveness to targeted drugs at the pan-cancer level based on transcriptomic data. We examined a total of 11 287 human tumor profiles from 31 types of cancer, drawn from 53 of our previously published and other literature datasets, looking at patient survival and clinical response to 29 chemo- and targeted therapy regimens. We found that activation of the ERK1/2 pathways has different prognostic significance depending on cancer type. In glioblastoma, sarcoma, lung, kidney, bladder, gastric, colon, and several other cancer types, ERK pathway activation was associated with worse survival. In contrast, the same phenomenon was associated with a better chance of survival in HER2+, luminal A and luminal B breast cancer, and uterine corpus cancer. These trends were consistent with treatment response analysis. At the same time, we found significantly worse associations with the expression levels of individual <i>MAPK1</i> and <i>MAPK3</i> genes: hence, ERK1/2 pathway activation levels can be considered putative biomarkers for predicting clinical outcomes and selecting new personalized treatment strategies, such as the use of MAPK inhibitors.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 1","pages":"36-51"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960384","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}
Acta NaturaePub Date : 2025-01-01DOI: 10.32607/actanaturae.27355
S O Pipiya, A O Ivanova, Yu A Mokrushina, I E Eliseev, A G Gabibov, I V Smirnov, S S Terekhov
{"title":"Heterologous Production of Antimicrobial Peptides in Yeast Allows for Massive Assessment of the Activity of DNA-Encoded Antimicrobials In Situ.","authors":"S O Pipiya, A O Ivanova, Yu A Mokrushina, I E Eliseev, A G Gabibov, I V Smirnov, S S Terekhov","doi":"10.32607/actanaturae.27355","DOIUrl":"https://doi.org/10.32607/actanaturae.27355","url":null,"abstract":"<p><p>Antibiotic resistance threatens global healthcare. In clinical practice, conventional antibiotics are becoming gradually less effective. Moreover, the introduction of new antimicrobial agents into clinical practice leads to the emergence of resistant pathogenic strains within just a few years. Hence, the development of platforms for massive creation and screening of new antimicrobial agents is of particular importance. Massive parallel screening will greatly reduce the time required to identify the most promising drug candidates. Meanwhile, DNA-encoded antimicrobial agents offer unique opportunities for the high-throughput development of new antibiotics. Here, the yeast <i>Pichia pastoris</i> was engineered to produce a panel of antimicrobial peptides (AMPs), followed by high-throughput screening of AMP producers that inhibit bacterial growth <i>in situ</i>. Yeast clones producing thanatin and protegrin-1 exhibited the highest level of antimicrobial activity among the panel of AMPs under investigation. The production level of recombinant thanatin was significantly higher than that of protegrin-1, which correlates with its low toxicity. The designed technique of massive assessment of the activity of DNA-encoded antimicrobial agents enables the identification of drug candidates with an increased therapeutic index. Further development of methods for a rational design of artificial diversity in AMPs, followed by deep functional profiling of antimicrobial activity, will yield new AMPs with improved therapeutic characteristics.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 1","pages":"71-77"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958857","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}
Acta NaturaePub Date : 2024-10-01DOI: 10.32607/actanaturae.27348
A I Kalganova, I E Eliseev, I V Smirnov, S S Terekhov
{"title":"Platforms for the Search for New Antimicrobial Agents Using In Vivo C. elegans Models.","authors":"A I Kalganova, I E Eliseev, I V Smirnov, S S Terekhov","doi":"10.32607/actanaturae.27348","DOIUrl":"10.32607/actanaturae.27348","url":null,"abstract":"<p><p>Despite the achievements brought about by high-throughput screening technologies, there is still a lack of effective platforms to be used to search for new antimicrobial drugs. The antimicrobial activity of compounds continues, for the most part, to be assessed mainly using <i>in vitro</i> pathogen cultures, a situation which does not make easy a detailed investigation of the molecular mechanisms underlying host-pathogen interactions. <i>In vivo</i> testing of promising compounds using chordate models is labor-intensive and expensive and, therefore, is used in preclinical studies of selected drug candidates but not in primary screening. This approach does not facilitate the selection of compounds with low organ toxicity and is not suitable for the identification of therapeutic compounds that affect virulence factors. The use of microscopic nematode <i>C. elegans</i> to model human infections is a promising approach that enables one to investigate the host-pathogen interaction and identify anti-infective compounds with new mechanisms of action.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 4","pages":"15-26"},"PeriodicalIF":2.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057817","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}
Acta NaturaePub Date : 2024-10-01DOI: 10.32607/actanaturae.27501
K A Vorona, V D Moroz, N B Gasanov, A V Karabelsky
{"title":"Recombinant VSVs: A Promising Tool for Virotherapy.","authors":"K A Vorona, V D Moroz, N B Gasanov, A V Karabelsky","doi":"10.32607/actanaturae.27501","DOIUrl":"10.32607/actanaturae.27501","url":null,"abstract":"<p><p>Cancer is one of the leading causes of death worldwide. Traditional cancer treatments include surgery, radiotherapy, and chemotherapy, as well as combinations of these treatments. Despite significant advances in these fields, the search for innovative ways to treat malignant tumors, including the application of oncolytic viruses, remains relevant. One such virus is the vesicular stomatitis virus (VSV), which possess a number of useful oncolytic properties. However, VSV-based drugs are still in their infancy and are yet to be approved for clinical use. This review discusses the mechanisms of oncogenesis, the antiviral response of tumor and normal cells, and markers of tumor cell resistance to VSV virotherapy. In addition, it examines methods for producing and arming recombinant VSV and provides examples of clinical trials. The data presented will allow better assessment of the prospects of using VSV as an oncolytic.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 4","pages":"4-14"},"PeriodicalIF":2.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057819","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}
Acta NaturaePub Date : 2024-10-01DOI: 10.32607/actanaturae.27510
M N Gordeev, A S Zinovyeva, E E Petrenko, E V Lomert, N D Aksenov, A N Tomilin, E I Bakhmet
{"title":"Embryonic Stem Cell Differentiation to Definitive Endoderm As a Model of Heterogeneity Onset During Germ Layer Specification.","authors":"M N Gordeev, A S Zinovyeva, E E Petrenko, E V Lomert, N D Aksenov, A N Tomilin, E I Bakhmet","doi":"10.32607/actanaturae.27510","DOIUrl":"10.32607/actanaturae.27510","url":null,"abstract":"<p><p>Embryonic stem cells (ESCs) hold great promise for regenerative medicine thanks to their ability to self-renew and differentiate into somatic cells and the germline. ESCs correspond to pluripotent epiblast - the tissue from which the following three germ layers originate during embryonic gastrulation: the ectoderm, mesoderm, and endoderm. Importantly, ESCs can be induced to differentiate toward various cell types by varying culture conditions, which can be exploited for <i>in vitro</i> modeling of developmental processes such as gastrulation. The classical model of gastrulation postulates that mesoderm and endoderm specification is made possible through the FGF-, BMP-, Wnt-, and Nodal-signaling gradients. Hence, it can be expected that one of these signals should direct ESC differentiation towards specific germ layers. However, ESC specification appears to be more complicated, and the same signal can be interpreted differently depending on the readout. In this research, using chemically defined culture conditions, homogeneous naïve ESCs as a starting cell population, and the <i>Foxa2</i> gene-driven EGFP reporter tool, we established a robust model of definitive endoderm (DE) specification. This <i>in vitro</i> model features formative pluripotency as an intermediate state acquired by the epiblast <i>in vivo</i> shortly after implantation. Despite the initially homogeneous state of the cells in the model and high Activin concentration during endodermal specification, there remains a cell subpopulation that does not reach the endodermal state. This simple model developed by us can be used to study the origins of cellular heterogeneity during germ layer specification.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 4","pages":"62-72"},"PeriodicalIF":2.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057773","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}