Acta Naturae最新文献

{"title":"The Potential Role of the Bacterial Persister Formation Gene ptsH in Hypervirulence Development in Klebsiella pneumoniae.","authors":"A V Tutel'yan, N V Vlasenko, V M Pisarev, Yu V Mikhailova, N V Sycheva, A A Tarlycheva, A A Shelenkov, D K Kondrat'eva, V G Akimkin","doi":"10.32607/actanaturae.27800","DOIUrl":"10.32607/actanaturae.27800","url":null,"abstract":"<p><p>Persistence - i.e., the ability to exist in a metabolically inactive form - allows bacteria to accumulate genetic advantages. The evolution of the pathogenic potential of Klebsiella pneumoniae has led to the emergence of strains simultaneously characterized by increased aggressiveness (virulence) and prolonged survival in the host organism. This combination of properties contributes to the emergence of \"superbugs,\" necessitating the search for specific markers that would make it possible to prevent the spread of highly adaptive clones. Hypervirulent K. pneumoniae (hvKp) strains represent a growing global health threat, since they combine high invasiveness and antibiotic resistance. An analysis of 92 K. pneumoniae clinical isolates was conducted to assess the prevalence of the key hypervirulence genes (iroB, peg-344, rmpA, rmpA2, and iucA) and investigate their association with the bacterial persister formation gene ptsH. It was found that 64.1% (59/92) of the isolates carried at least one hvKp gene, iucA being the most frequent one (62.0%). The full set of five hvKp genes was identified in only one case (1%). The strains of sequence types ST23, ST268, ST86, ST534, ST219, ST101, and ST395 accumulated virulence genes, whereas ST512 and ST14 rarely harbored hvKp genes. A key finding was the detection of a significant association between the presence of the ptsH gene (found in 50% of the strains) and the accumulation of hvKp genes: the ptsH-positive strains were statistically more likely to harbor the complete aerobactin operon (iucABCD), in combination with one or more additional hypervirulence genes, compared to the ptsH-negative strains (p < 0.05). Our findings indicate that the ptsH gene is crucial in the formation of polygenically determined hypervirulence, and that its role in controlling bacterial persistence creates evolutionary advantages under stress induced by antibiotics or immune factors, thus promoting evasion of their actions. The phosphotransferase system (PTS), to which the ptsH gene belongs, can potentially become a novel source of molecular targets for the therapy of infections caused by hypervirulent K. pneumoniae strains.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"18 2","pages":"127-134"},"PeriodicalIF":1.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13399678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148583276","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":"Genetic Predisposition to Autoimmune Diabetes Mellitus.","authors":"Y V Dvoryanchikov, I R Minniakhmetov, D N Laptev, R I Khusainova, M V Shestakova, N G Mokrysheva","doi":"10.32607/actanaturae.27704","DOIUrl":"10.32607/actanaturae.27704","url":null,"abstract":"<p><p>Type 1 diabetes mellitus (T1DM) is a multifactorial disease wherein a genetic predisposition, upon exposure to environmental factors, triggers seroconversion and subsequent beta-cell destruction. The global incidence of T1DM has risen in recent decades, underscoring the significant role environmental factors play in actuating inherent genetic risk. However, the absence of an identifiable unique triggering factor complicates the identification of risk groups. Advances in bioinformatics and epigenetic research are opening new opportunities for early diagnosis, prevention, and novel therapies for the condition. A comprehensive analysis of complex molecular pathways will make it possible to develop algorithms for the early diagnosis, disease course prediction, and therapy personalization based on a patient's genetic profile. This review systematizes current data on the genetic and epigenetic heterogeneity of autoimmune diabetes and its potential triggers. It assesses the regional and ethnic disparities in T1DM incidence globally and within the Russian Federation, and it discusses the potential of clinical-genetic models for disease prediction.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"18 2","pages":"4-19"},"PeriodicalIF":1.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13399666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148583279","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":"Cellular Type Is a Major Determinant of R-Loop Genomic Distribution.","authors":"K Yu Oleynikova, N A Zhigalova, A P Hutchins, A S Ruzov","doi":"10.32607/actanaturae.27833","DOIUrl":"10.32607/actanaturae.27833","url":null,"abstract":"<p><p>R-loops that contain a DNA:RNA hybrid and unpaired single-stranded DNA are important determinants of normal cell physiology and of the pathogenesis of numerous diseases. Although several different approaches to R-loop mapping in the genome have been developed, these techniques can produce conflicting results. In order to assess their robustness, a recent study by Chedin et al. compared the R-loop genomic distribution assessed using different methods in normal and cancer cell lines. Importantly, that study assumed a high degree of similarity between R-loop genomic distributions across different cellular types. Here, we compared DRIP datasets produced using the same protocol in different cell lines to show that only 26% of R-loop peaks are shared between chronic myeloid leukemia-derived HAP1 cells and human pluripotent stem cells. Meanwhile, HAP1-derived double knockout cell lines are characterized by much higher fractions of R-loop peaks that are identical both to each other (most of them) and to the R-loop peaks of their parental line (71 and 55%). We conclude that cellular type represents a major determinant of R-loop genomic distribution and, therefore, that only a systematic comparison of a large array of various cell/tissue type-derived R-loop datasets may address the inconsistencies between different R-loop mapping techniques.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"18 1","pages":"79-82"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832198","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":"Quantification of the Synergism Between HER-Targeted Drugs with Human Blood Serum and EGF.","authors":"D E Kamashev, E M Leboshchina, A V Koleboshina, I A Lavrinenko, G A Vashanov, Yu D Nechipurenko","doi":"10.32607/actanaturae.27649","DOIUrl":"10.32607/actanaturae.27649","url":null,"abstract":"<p><p>Finding the optimal combination of drugs for the effective inhibition of cancer cell growth is an extremely important task today, as the number of such drugs continues to grow. There are several approaches to determining the nature of drug interactions, allowing one to establish whether they are additive, synergis tic, or antagonistic. One such approach is described here, and it is demonstrated how to quantitatively meas ure the degree of interaction between two drugs. It is shown that human peripheral blood serum and EGF modulate the activity of HER2-targeted drugs in inhibiting the proliferation of HER2-positive BT474 and SK-BR-3 cells. We compared the effect of blood serum samples from breast cancer (BC) patients and healthy donors on the action of trastuzumab. Using the proposed method, it is possible to calculate the Combination Index (CI). For 17 serum samples from healthy donors, the mean CI was 0.396, while for 19 serum samples from patients with BC, the mean CI was 0.214. These results indicate a synergistic interaction between tras tuzumab and blood serum in both groups. We also found significant differences in CI values between healthy donors and breast cancer patients: blood serum samples from patients enhance the effect of trastuzumab to a greater extent.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"18 1","pages":"46-54"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832159","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":"Administration of rAAV Encoding Monoclonal Antibodies Protects Mice Challenged with a Lethal Dose of H3N2 Influenza Virus and Neutralizes H1 and H3 Strains.","authors":"R R Mintaev, F A Urusov, A V Soloviev, B V Belugin, D V Glazkova, G A Shipulin, E V Bogoslovskaya","doi":"10.32607/actanaturae.27774","DOIUrl":"10.32607/actanaturae.27774","url":null,"abstract":"<p><p>The influenza virus causes seasonal epidemics throughout the world. At the same time, the rapid mutation of the virus renders the use of seasonal vaccines less effective. One of the approaches sought to improve influenza prevention is the use of monoclonal antibodies that are active against a wide range of influenza virus strains. In this study, the virus-neutralizing activity of the monoclonal antibodies CR9114, MHAA4549A, MEDI8852, C585, and 1G01 against the influenza virus was assessed. To this end, recombinant vectors based on adeno-associated virus (rAAV) encoding these antibodies were used. The rAAV vectors were expressed in mice <i>in vivo</i>, and the virus-neutralizing activity of the sera against the H1N1 and H3N2 influenza virus strains was assessed. Administration of rAAV-C585, rAAV-MHAA4549A, and rAAV-1G01 conferred 100% protection to mice challenged with a lethal dose of the H3N2 influenza virus. The efficacy of rAAV-CR9114 and rAAV-MEDI8852 against this influenza virus strain was lower, at 80 and 75%, respectively.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"18 1","pages":"64-71"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832186","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":"Novel Nicotinic Acetylcholine Receptor Inhibitors Derived from Oleoylcholine Analogs.","authors":"M V Vladykina, I S Kokaeva, I E Kasheverov, N M Gretskaya, G N Zinchenko, V I Tsetlin, Yu N Utkin, V V Bezuglov, I V Shelukhina","doi":"10.32607/actanaturae.27696","DOIUrl":"10.32607/actanaturae.27696","url":null,"abstract":"<p><p>Fatty acid-acylated cholines, a recently identified class of endogenous compounds, have been de tected in both human and animal organisms. Our prior work established that oleoylcholine (Ol-Chol), and other acylcholines, at micromolar levels, modulate the cholinergic system and are suitable as cationic lipids for introducing nucleic acids into human and animal cells. The present research examines the interaction with the nicotinic acetylcholine receptors (nAChR) of two ionic forms of Ol-Chol and two synthesized cat ionic lipids, each featuring a quaternary ammonium moiety and two oleic acid chains. A radioligand bind ing assay revealed that the affinity of acylcholines and synthetic cationic lipids for the muscle-type nAChR surpasses that for the human neuronal α7 nAChR by a factor of 2-5.5. Oleoylcholine iodide demonstrated a two-fold higher efficacy of mesylate in binding to the orthosteric site of muscle and α7 nAChR. In a func tional calcium imaging assay, both compounds exhibited superior inhibition of α7 nAChR by several orders of magnitude, suggesting potential interaction with allosteric binding sites. Compared to oleoylcholine, syn thetic cationic lipids demonstrated markedly reduced efficacy in binding to α7 nAChRs and, in contrast to oleoylcholine, induced a substantial cytotoxic impact on SH-SY5Y neuroblastoma cells, a phenomenon unaf fected by specific nAChR ligands. As a result, the nAChR-inhibitory properties are attributed to the quater nary ammonium group present in all studied compounds. However, the modification of the lipophilic moiety with two oleic acid residues curbs these properties but enhances cytotoxic activity through an alternative mechanism independent of nAChR.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"18 1","pages":"36-45"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832207","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":"Reduced Expression of Immune Response Genes in Neural Cells with Mutations in the PARK2 Gene in Parkinson's Disease.","authors":"V B Fedoseyeva, E V Novosadova, V V Nenasheva, L V Novosadova, I A Grivennikov, V Z Tarantul","doi":"10.32607/actanaturae.27664","DOIUrl":"10.32607/actanaturae.27664","url":null,"abstract":"<p><p>Parkinson's disease (PD) is one of the most common chronic neurodegenerative diseases. PD is characterized by the dysfunction of multiple body functions caused by changes in the expression of a large number of genes. Current evidence suggests that changes in the innate immunity and neuroinflammation may play an important role in the pathogenesis of the disease. However, the exact mechanism through which immune dysfunction develops in the context of PD pathogenesis remains unclear. In this study, with the use of transcriptome sequencing (RNA-seq), followed by quantitative PCR, we managed to detect a differential expression of the genes involved in the immune activity in neural progenitors (NPs) and glial cells derived from induced pluripotent stem cells from healthy donors (HDs) and PD patients carrying mutations in the <i>PARK2</i> gene. Expression of many of the genes involved in a number of innate immune signaling pathways (in particular, in the canonical NFκB, non-canonical NFκB, the TNFα/NFκB, IL6/STAT3, IL2/STAT5 pathways, as well as the IFNγ and IFNα response) in cells from PD patients was found to be reduced compared to that in the cells from healthy donors. A mechanism for regulating these signaling pathways in the neural precursors of PD patients carrying mutations in the <i>PARK2</i> gene is proposed.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"18 1","pages":"104-113"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831459","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 Microbiomic Metaproteome of the Taiga Tick Ixodes persulcatus from the Tyumen Region.","authors":"A S Kozlova, A V Zgoda, N A Petushkova, N A Bolochenkov, V G Zgoda, M A Salnitska, D V Kazakov, A V Lisitsa","doi":"10.32607/actanaturae.27741","DOIUrl":"10.32607/actanaturae.27741","url":null,"abstract":"<p><p> Metagenomic studies have revealed the taxonomic composition of the taiga tick (Ixodes persulca tus) microbiome, whereas metaproteomic data has provided information on the biochemically active fraction of the microbial community residing in the tick. The aim of this study was to characterize the biological pro cesses taking place within the microbiome of the taiga tick I. persulcatus using a metaproteomic approach. To expand the range of identifiable proteins, we used two trypsin concentrations in sample preparation for mass spectrometric analysis. The metaproteomes of unfed female and male ticks were analyzed, which ena bled identification of protein products encoded by 2,100 genes from microorganisms belonging to 203 bacteri al and fungal species. Increased abundance of proteins associated with Ascomycota fungi, particularly abun dant in females, were detected. Proteins from the pathogenic Rickettsia and Borrelia species were identified. These findings enable a transition from a taxonomic metagenomic description to a functional analysis of the microbial consortium role in the physiology of the vector tick, particularly given the identified microbiota differences related to the tick sex.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"18 1","pages":"55-63"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831759","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":"Tumor Necrosis Factor Inhibitors.","authors":"T V Tregubchak, S N Shchelkunov","doi":"10.32607/actanaturae.27697","DOIUrl":"10.32607/actanaturae.27697","url":null,"abstract":"<p><p>Immune-mediated inflammatory diseases affect a substantial proportion of the global population, and tumor necrosis factor (TNF) plays a central role in their pathogenesis. The most common diseases in clude rheumatoid arthritis (RA), Crohn's disease, psoriasis, multiple sclerosis, and septic shock. All of these conditions are characterized by excessive production of TNF, which activates downstream signaling pathways contributing to disease development and progression. To improve the quality of life in patients with TNF overproduction, anti-TNF agents such as TNF receptors and monoclonal antibodies are used. However, the availability of these therapies is limited. Therefore, the development of novel, more affordable TNF inhibi tors with comparable efficacy and improved safety remains a pressing issue. This review summarizes recent advances in the development of promising TNF inhibitors, including those derived from orthopoxvirus im munomodulatory proteins.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"18 1","pages":"4-23"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832138","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":"Identifying microRNA Expression Alterations in Erythrocytes, Lymphocytes, and Monocytes During Severe COVID-19.","authors":"A A Artamonov, Yu V Nikitin, A A Velmiskina, S V Mosenko, V S Shimansky, A Yu Asinovskaya, S V Apalko, N N Sushentseva, A M Ivanov, S G Scherbak, K A Kondratov","doi":"10.32607/actanaturae.27610","DOIUrl":"10.32607/actanaturae.27610","url":null,"abstract":"<p><p>A significant portion of the fatal outcomes during COVID-19 have been traced mainly to cytokine storm, the uncontrolled hyperactivation of the immune system. During a SARS-CoV-2 infection, the blood plasma levels of microRNAs (miRNAs), a class of short regulatory RNAs, get significantly changed. However, it still remains unknown how the levels and characteristics of these molecules are altered in various blood cells during severe COVID-19. The aim of this research was to compare the microRNA levels in erythro cytes, monocytes, and lymphocytes in normal blood cells and those in patients with severe COVID-19-induced by cytokine storm. Erythrocytes and monocytes (five healthy donors and five patients with severe COVID-19) and lymphocytes (four healthy donors and four patients with severe COVID-19) were obtained by fluores cence-activated cell sorting. RNA was isolated from the obtained cells, and next-generation short RNA se quencing was performed. Both the known miRNAs and the novel miRNAs whose expression had changed in severe COVID-19 were analyzed and identified. In the erythrocytes, seven miRNAs had changed expres sions (five downregulated; two upregulated); all 13 miRNAs were upregulated in lymphocytes; in monocytes, 11 miRNAs were downregulated and three miRNAs were upregulated. An analysis of the novel miRNAs showed that three, previously unknown miRNAs, were downregulated in lymphocytes and one was upregu lated. In monocytes and erythrocytes, no novel, differentially expressed miRNAs were detected. Additionally, we analyzed the signaling pathways altered by miRNAs by performing a miRNA enrichment analysis (MIEAA) using the Gene Ontology miRNA target database (miRTarBase). We observed that in lymphocytes, four pathways were significantly (Q-value < 0.05) enriched and 339 were depleted; in monocytes, 118 path ways were enriched and six were depleted. No significantly altered signaling pathways were detected in erythrocytes.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"18 1","pages":"24-35"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832241","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}