Acta Naturae最新文献

{"title":"An Attenuated and Highly Immunogenic Variant of the Vaccinia Virus.","authors":"S N Shchelkunov, S N Yakubitskiy, K A Titova, S A Pyankov, I S Shulgina, E V Starostina, M B Borgoyakova, D N Kisakov, L I Karpenko, G A Shchelkunova, A A Sergeev","doi":"10.32607/actanaturae.27384","DOIUrl":"10.32607/actanaturae.27384","url":null,"abstract":"<p><p>The vaccinia virus (VACV) has been used for prophylactic immunization against smallpox for many decades. However, the VACV-based vaccine had been highly reactogenic. Therefore, after the eradication of smallpox, the World Health Organization in 1980 recommended that vaccination against this infection be discontinued. As a result, there has been a rise in the occurrence of orthopoxvirus infections in humans in recent years, with the most severe being the 2022 monkeypox epidemic that reached all continents. Thus, it is crucial to address the pressing matter of developing safe and highly immunogenic vaccines for new generations to combat orthopoxvirus infections. In a previous study, we created a LAD strain by modifying the LIVP (L) VACV strain, which is used as a first-generation smallpox vaccine in Russia. This modification involved introducing mutations in the <i>A34R</i> gene to enhance extracellular virion production and deleting the <i>A35R</i> gene to counteract the antibody response to the viral infection. In this study, a strain LADA was created with an additional deletion in the DNA of the LAD strain <i>ati</i> gene. This <i>ati</i> gene directs the production of a major non-virion immunogen. The findings indicate that the LADA VACV variant exhibits lower levels of reactogenicity in BALB/c mice during intranasal infection, as compared to the original L strain. Following intradermal immunization with a 105 PFU dose, both the LAD and LADA strains were found to induce a significantly enhanced cellular immune response in mice when compared to the L strain. At the same time, the highest level of virus-specific IFN-γ producing cells for the LAD variant was detected on the 7^th day post-immunization (dpi), whereas for LADA, it was observed on 14 dpi. The LAD and LADA strains induced significantly elevated levels of VACV-specific IgG compared to the original L strain, particularly between 28 and 56 dpi. The vaccinated mice were intranasally infected with the cowpox virus at a dose of 460 LD₅₀ to assess the protective immunity at 62 dpi. The LADA virus conferred complete protection to mice, with the LAD strain providing 70% protection and the parent strain L offering protection to only 60% of the animals.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 2","pages":"82-89"},"PeriodicalIF":2.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071673","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":"Ceramides As Potential New Predictors of the Severity of Acute Coronary Syndrome in Conjunction with SARS-CoV-2 Infection.","authors":"N G Lozhkina, O I Gushchina, N V Basov, E V Gaisler, A D Rogachev, Yu S Sotnikova, Yu V Patrushev, A G Pokrovsky","doi":"10.32607/actanaturae.27400","DOIUrl":"10.32607/actanaturae.27400","url":null,"abstract":"<p><p>Acute coronary events (ACEs) associated with a SARS-CoV-2 infection can significantly differ from classic ACEs. New biomarkers, such as ceramides, may help in the diagnosis and treatment of this disease. This study included 73 ACE patients for whom the SARS-CoV-2 infection was verified. Two subgroups were formed: the favorable outcome subgroup and the fatal outcome subgroup. Plasma samples were collected from all patients at the time of admission for a metabolomic analysis. The analysis of metabolites revealed that the ceramide levels were significantly lower in the fatal outcome subgroup than in the survivor subgroup. Therefore, determining ceramide levels in patients with ACEs in conjunction with COVID-19 may help assess the prognosis of these patients and manage their risks.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 2","pages":"53-60"},"PeriodicalIF":2.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071674","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":"Evaluation of HER2/neu Expression in Metastatic Axillary Lymph Node Tissue of Breast Cancer Patients Using [99mTc]Tc-(HE)3-G3.","authors":"O D Bragina, L A Tashireva, D M Loos, S V Vtorushin, A A Shulga, E N Konovalova, M E Borodina, V I Chernov, V M Tolmachev, S M Deyev","doi":"10.32607/actanaturae.27448","DOIUrl":"10.32607/actanaturae.27448","url":null,"abstract":"<p><p>Anatomic visualization and molecular typing of metastatic regional lymph nodes in breast cancer patients are a serious clinical challenge in modern oncology. According to the results of previous studies, [99mTc]Tc-(HE)3-G3 has proven to be a promising diagnostic agent in differentiating the HER2/neu receptor status in primary breast tumors (<i>p</i> < 0.05, Mann-Whitney test). In this regard, the purpose of this study is to explore the possibilities of using [99mTc]Tc-(HE)3-G3 to determine the HER2/neu receptor status in the metastatic axillary lymph nodes (mALNs) of breast cancer patients. The study was conducted using clinical material from 20 breast cancer patients (T2-4N1-3M0-1) before systemic therapy (10 patients with positive and 10 patients with negative HER2/neu expression in mALNs) who underwent SPECT/CT scan 4 h after the administration of [99mTc]Tc-(HE)3-G3. Morphological and immunohistochemical studies of mALNs with assessment of the HER2/neu status were performed on all patients. We found that mALN-to-background and mALN-to-latissimus dorsi muscle ratios for [99mTc]Tc-(HE)3-G3 uptake 4 h after its administration may be used for typing of the HER2/neu status in mALNs of breast cancer patients (<i>p</i> < 0.05, Mann-Whitney test). In that case, sensitivity and specificity for the mALN-to-background ratio were identical at 80%, with the threshold value being > 12.25.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 2","pages":"22-29"},"PeriodicalIF":2.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071676","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 Effect of Calcium Ions on the Electrophysiological Properties of Single ANO6 Channels.","authors":"D O Kolesnikov, E R Grigorieva, M A Nomerovskaya, D S Reshetin, A V Shalygin, E V Kaznacheyeva","doi":"10.32607/actanaturae.27338","DOIUrl":"10.32607/actanaturae.27338","url":null,"abstract":"<p><p>Proteins belonging to the anoctamin (ANO) family form calcium-activated chloride channels (CaCCs). The most unusual member of this family, ANO6 (TMEM16F), simultaneously exhibits the functions of calcium-dependent scramblase and the ion channel. ANO6 affects the plasma membrane dynamics and phosphatidylserine transport; it is also involved in programmed cell death. The properties of ANO6 channels remain the subject of debate. In this study, we investigated the effect of variations in the intracellular and extracellular concentrations of calcium ions on the electrophysiological properties of endogenous ANO6 channels by recording single ANO6 channels. It has been demonstrated that (1) a high calcium concentration in an extracellular solution increases the activity of endogenous ANO6 channels, (2) the permeability of endogenous ANO6 channels for chloride ions is independent of the extracellular concentration of calcium ions, (3) that an increase in the intracellular calcium concentration leads to the activation of endogenous ANO6 channels with double amplitude, and (4) that the kinetics of the channel depend on the plasma membrane potential rather than the intracellular concentration of calcium ions. Our findings give grounds for proposing new mechanisms for the regulation of the ANO6 channel activity by calcium ions both at the inner and outer sides of the membrane.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 1","pages":"40-47"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140846448","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 Effect of Liposomes of Various Compositions on the Skin and Its Derivatives After II-IIIA Degree Thermal Burns.","authors":"N I Pashkevich, D V Vilyanen, A F Marcinkevich, M M Borisova-Mubarakshina, S S Osochuk","doi":"10.32607/actanaturae.27329","DOIUrl":"10.32607/actanaturae.27329","url":null,"abstract":"<p><p>This study examines the pathological processes and conditions arising from an experimental modeling of II-IIIA degree thermal burns in laboratory animals. These conditions are characterized by skin structure defects, diminished skin functions, especially the barrier function, and damage to skin derivatives like hair follicles and sebaceous glands. We compared the effect of liposomes composed of soybean lecithin of 90% phosphatidylcholine content and liposomes composed of lecithin of 26% phosphatidylcholine content on the epidermis, dermis and its capillaries, hair follicles, and the sebaceous glands of the laboratory animals 24 h after experimental modeling of II-IIIA degree thermal skin burns. We discuss the dependency of liposome effects on the skin and its derivatives on the fatty acid composition of the lecithin used, with particular focus on phosphatidylinositol, phosphatidic acids, as well as oleic and linoleic acids.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 1","pages":"67-76"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848255","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":"A Method for the Production of Recombinant VSVs with Confirmation of Biological Activity.","authors":"V D Moroz, N B Gasanov, A D Egorov, A S Malogolovkin, M O Nagornykh, E N Subcheva, E S Kolosova, A Yu Fizikova, R A Ivanov, A V Karabelsky","doi":"10.32607/actanaturae.27314","DOIUrl":"10.32607/actanaturae.27314","url":null,"abstract":"<p><p>The design of new effective cancer treatment methods is a promising and important research field in translational medicine. Oncolytic viruses can induce immunogenic cell death by activating the body's immune system to recognize tumor cells. This work presents the results for optimizing the production of recombinant vesicular stomatitis viruses (rVSVs). To ensure the assembly of viral particles, we developed the HEK293TN-T7 cell line, which stably expresses DNA-dependent RNA polymerase 7 for viral genome transcription, and obtained helper plasmids encoding viral genes under the control of the CAG promoter. The oncolytic activity of the purified virus preparation was assessed in a murine model of B16F10Red melanoma cells expressing a red fluorescent protein. The presented method makes it possible to obtain purified viral preparations with a high titer and oncolytic activity. The amplification of viral particles in a HEK293 suspension culture allows for rapid scalability. Therefore, the developed approach can be used to obtain other recombinant VSV-based oncolytic viruses for tumor immunotherapy.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 1","pages":"59-66"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852359","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":"Post-transcriptional Regulation of Gene Expression via Unproductive Splicing.","authors":"L G Zavileyskiy, D D Pervouchine","doi":"10.32607/actanaturae.27337","DOIUrl":"10.32607/actanaturae.27337","url":null,"abstract":"<p><p>Unproductive splicing is a mechanism of post-transcriptional gene expression control in which premature stop codons are inserted into protein-coding transcripts as a result of regulated alternative splicing, leading to their degradation via the nonsense-mediated decay pathway. This mechanism is especially characteristic of RNA-binding proteins, which regulate each other's expression levels and those of other genes in multiple auto- and cross-regulatory loops. Deregulation of unproductive splicing is a cause of serious human diseases, including cancers, and is increasingly being considered as a prominent therapeutic target. This review discusses the types of unproductive splicing events, the mechanisms of auto- and cross-regulation, nonsense-mediated decay escape, and problems in identifying unproductive splice isoforms. It also provides examples of deregulation of unproductive splicing in human diseases and discusses therapeutic strategies for its correction using antisense oligonucleotides and small molecules.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 1","pages":"4-13"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848337","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":"Ultrastructural 3D Microscopy for Biomedicine: Principles, Applications, and Perspectives.","authors":"K E Mochalov, D S Korzhov, A V Altunina, O I Agapova, V A Oleinikov","doi":"10.32607/actanaturae.27323","DOIUrl":"10.32607/actanaturae.27323","url":null,"abstract":"<p><p>Modern biomedical research often requires a three-dimensional microscopic analysis of the ultrastructure of biological objects and materials. Conceptual technical and methodological solutions for three-dimensional structure reconstruction are needed to improve the conventional optical, electron, and probe microscopy methods, which to begin with allow one to obtain two-dimensional images and data. This review discusses the principles and potential applications of such techniques as serial section transmission electron microscopy; techniques based on scanning electron microscopy (SEM) (array tomography, focused ion beam SEM, and serial block-face SEM). 3D analysis techniques based on modern super-resolution optical microscopy methods are described (stochastic optical reconstruction microscopy and stimulated emission depletion microscopy), as well as ultrastructural 3D microscopy methods based on scanning probe microscopy and the feasibility of combining them with optical techniques. A comparative analysis of the advantages and shortcomings of the discussed approaches is performed.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 1","pages":"14-29"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140850265","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":"Studying Signaling Pathway Activation in TRAIL-Resistant Macrophage-Like Acute Myeloid Leukemia Cells.","authors":"Y V Lomovskaya, K S Krasnov, M I Kobyakova, A A Kolotova, A M Ermakov, A S Senotov, I S Fadeeva, E I Fetisova, A I Lomovsky, A I Zvyagina, V S Akatov, R S Fadeev","doi":"10.32607/actanaturae.27317","DOIUrl":"10.32607/actanaturae.27317","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is a malignant neoplasm characterized by extremely low curability and survival. The inflammatory microenvironment and maturation (differentiation) of AML cells induced by it contribute to the evasion of these cells from effectors of antitumor immunity. One of the key molecular effectors of immune surveillance, the cytokine TRAIL, is considered a promising platform for developing selective anticancer drugs. Previously, under <i>in vitro</i> conditions of the inflammatory microenvironment (a three-dimensional high-density culture of THP-1 AML cells), we demonstrated the emergence of differentiated macrophage-like THP-1ad clones resistant to TRAIL-induced death. In the present study, constitutive activation of proinflammatory signaling pathways, associated transcription factors, and increased expression of the anti-apoptotic <i>BIRC3</i> gene were observed in TRAIL-resistant macrophage-like THP-1ad AML cells. For the first time, a bioinformatic analysis of the transcriptome revealed the main regulator, the <i>IL1B</i> gene, which triggers proinflammatory activation and induces resistance to TRAIL in THP-1ad macrophage-like cells.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 1","pages":"48-58"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140846363","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":"Dimeric Bis-Benzimidazole-Pyrroles DB2Py(n) - AT-Site-Specific Ligands: Synthesis, Physicochemical Analysis, and Biological Activity.","authors":"O Y Susova, S S Karshieva, A A Kostyukov, N I Moiseeva, E A Zaytseva, K V Kalabina, E Zusinaite, K Gildemann, N M Smirnov, A F Arutyunyan, A L Zhuze","doi":"10.32607/actanaturae.27327","DOIUrl":"10.32607/actanaturae.27327","url":null,"abstract":"<p><p>Its broad spectrum of biological activity makes benzimidazole a fundamental pharmacophore in pharmaceutics. The paper describes newly synthesized AT-specific fluorescent bis-benzimidazole molecules DB2Py(n) that contain a pyrrolcarboxamide fragment of the antibiotic drug netropsin. Physico-chemical methods using absorption, fluorescence, and circular dichroism spectra have shown the ability of bis-benzimidazole- pyrroles to form complexes with DNA. The new DB2Py(n) series have turned out to be more toxic to human tumor lines and less vulnerable to non-tumor cell lines. Bis-benzimidazole-pyrroles penetrated the cell nucleus, affected the cell-cycle synthesis (S) phase, and inhibited eukaryotic topoisomerase I in a cellfree model at low concentrations. A real-time tumor cell proliferation test confirmed the molecule's enhanced toxic properties upon dimerization. Preliminary cytotoxicity data for the bis-benzimidazole-pyrroles tested in a cell model with a MDR phenotype showed that monomeric compounds can overcome MDR, while dimerization weakens this ability to its intermediate values as compared to doxorubicin. In this respect, the newly synthesized cytotoxic structures seem promising for further, in-depth study of their properties and action mechanism in relation to human tumor cells, as well as for designing new AT-specific ligands.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 1","pages":"86-100"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847081","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}