Acta Naturae最新文献

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"title":"Visualization of Nucleic Acids in Microand Nanometer-Scale Biological Objects Using Analytical Electron Microscopy.","authors":"O S Sokolova, T S Trifonova, N I Derkacheva, A V Moiseenko","doi":"10.32607/actanaturae.27483","DOIUrl":"10.32607/actanaturae.27483","url":null,"abstract":"<p><p>Analytical electron microscopy techniques, including energy-dispersive X-ray spectroscopy (EDX) and electron energy-loss spectroscopy (EELS), are employed in materials science and biology to visualize and chemically map diverse elements. This review presents cases of successful identification of nucleic acids in cells and in DNA- and RNA-containing viruses that use the chemical element phosphorus as a marker.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 4","pages":"38-47"},"PeriodicalIF":2.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Antibacterial Activity of Yeasts from Unique Biocenoses.","authors":"O V Shulenina, E A Sukhanova, B F Yarovoy, E A Tolstyko, A L Konevega, A Paleskava","doi":"10.32607/actanaturae.27527","DOIUrl":"10.32607/actanaturae.27527","url":null,"abstract":"<p><p>The replenishment of our stock of substances that possess a therapeutic potential is an important objective in modern biomedicine. Despite the important advances achieved in chemical synthesis, the natural diversity of organisms and microorganisms remains an important source of biologically active compounds. Here, we report the results of our study of a unique collection containing more than 3,000 samples of yeasts found on the Kamchatka Peninsula, the Kuril Islands, and Sakhalin Island, Russia. Since yeast and bacteria coexist in a variety of habitats and can interact with each other, we analyzed the antibacterial activity of the collection of yeast strains towards <i>E. coli</i> cells using a fluorescent bacterial reporter. It was uncovered that the Sakhalin strains for the most part stimulate bacterial growth, while most of the strains found on the Kamchatka Peninsula possess inhibitory properties. Moreover, the samples with the most pronounced antibacterial activity, identified as members of the genus <i>Cryptococcus (Naganishia)</i>, were found in a gorge in the vicinity of Pauzhetka village on the Kamchatka Peninsula on wormwood (<i>Artemisia vulgaris</i>) and thistle (<i>Onopordum acanthium</i>). Our data indicate that the combination of a plant and its growth site is important for the emergence of yeast strains capable of secreting antibacterial compounds.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 4","pages":"95-104"},"PeriodicalIF":2.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacteriocin from the Raccoon Dog Oral Microbiota Inhibits the Growth of Pathogenic Methicillin-Resistant Staphylococcus aureus.","authors":"M N Baranova, E A Soboleva, M A Kornienko, M V Malakhova, Yu A Mokrushina, A G Gabibov, S S Terekhov, I V Smirnov","doi":"10.32607/actanaturae.27349","DOIUrl":"10.32607/actanaturae.27349","url":null,"abstract":"<p><p>The growing incidence of infections caused by antibiotic-resistant strains of pathogens is one of the key challenges of the 21^st century. The development of novel technological platforms based on single-cell analysis of antibacterial activity at the whole-microbiome level enables the transition to massive screening of antimicrobial agents with various mechanisms of action. The microbiome of wild animals remains largely underinvestigated. It can be considered a natural reservoir of biodiversity for antibiotic discovery. Here, the <i>Staphylococcus pseudintermedius</i> E18 strain was isolated from the oral microbiome of a raccoon dog (<i>Nyctereutes procyonoides</i>) using a microfluidic ultrahigh-throughput screening platform. <i>S. pseudintermedius</i> E18 efficiently inhibited the growth of pathogenic methicillin-resistant <i>Staphylococcus aureus</i> (MRSA). It was established that the main active substance of the <i>S. pseudintermedius</i> E18 strain was a bacteriocin with a molecular weight of 27 kDa. The identified bacteriocin had a high positive charge and an extremely narrow spectrum of activity. Bacteriocin <i>S. pseudintermedius</i> E18 was inactivated by elevated temperature, proteinase K, and EDTA. Further investigation on the structure of the bacteriocin produced by <i>S. pseudintermedius</i> E18 will provide a comprehensive understanding of its mechanism of action, which will open up prospects for developing novel DNA-encoded antimicrobials.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 4","pages":"105-108"},"PeriodicalIF":2.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intraventricular Administration of Exosomes from Patients with Amyotrophic Lateral Sclerosis Provokes Motor Neuron Disease in Mice.","authors":"A V Stavrovskaya, D N Voronkov, A K Pavlova, A S Olshanskiy, B V Belugin, M V Ivanova, M N Zakharova, S N Illarioshkin","doi":"10.32607/actanaturae.27499","DOIUrl":"10.32607/actanaturae.27499","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a severe disease of the central nervous system (CNS) characterized by motor neuron damage leading to death from respiratory failure. The neurodegenerative process in ALS is characterized by an accumulation of aberrant proteins (TDP-43, SOD1, etc.) in CNS cells. The trans-synaptic transmission of these proteins via exosomes may be one of the mechanisms through which the pathology progresses. The aim of this work was to study the effect of an intraventricular injection of exosomes obtained from the cerebrospinal fluid (CSF) of ALS patients on the motor activity and CNS pathomorphology of mice. The exosomes were obtained from two ALS patients and a healthy donor. Exosome suspensions at high and low concentrations were injected into the lateral brain ventricles of male BALB/c mice (<i>n</i> = 45). Motor activity and physiological parameters were evaluated twice a month; morphological examination of the spinal cord was performed 14 months after the start of the experiment. Nine months after administration of exosomes from the ALS patients, the animals started exhibiting a pathological motor phenotype; i.e., altered locomotion with paresis of hind limbs, coordination impairment, and increasing episodes of immobility. The motor symptoms accelerated after administration of a higher concentration of exosomes. The experimental group showed a significant decrease in motor neuron density in the ventral horns of the spinal cord, a significant increase in the number of microglial cells, and microglia activation. The TDP43 protein in the control animals was localized in the nuclei of motor neurons. TDP43 mislocation with its accumulation in the cytoplasm was observed in the experimental group. Thus, the triggering effect of the exosomal proteins derived from the CSF of ALS patients in the development of a motor neuron pathology in the experimental animals was established. This confirms the pathogenetic role of exosomes in neurodegenerative progression and makes it possible to identify a new target for ALS therapy.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 4","pages":"73-80"},"PeriodicalIF":2.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057774","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}