Acta Naturae最新文献

{"title":"LPS-Induced Acute Lung Injury: Analysis of the Development and Suppression by the TNF-α-Targeting Aptamer.","authors":"A V Sen'kova, I A Savin, E L Chernolovskaya, A S Davydova, M I Meschaninova, A Bishani, M A Vorobyeva, M A Zenkova","doi":"10.32607/actanaturae.27393","DOIUrl":"10.32607/actanaturae.27393","url":null,"abstract":"<p><p>Acute lung injury (ALI) is a specific form of lung inflammation characterized by diffuse alveolar damage, noncardiogenic pulmonary edema, as well as a pulmonary and systemic inflammation. The pathogenesis of ALI involves a cascade inflammatory response accompanied by an increase in the local and systemic levels of proinflammatory cytokines and chemokines. The development of molecular tools targeting key components of cytokine signaling appears to be a promising approach in ALI treatment. The development of lipopolysaccharide (LPS)-induced ALI, as well as the feasibility of suppressing it by an aptamer targeting the proinflammatory cytokine TNF-α, was studied in a mouse model. The TNF-α level was shown to increase significantly and remain steadily high during the development of ALI. LPS-induced morphological signs of inflammation in the respiratory system become most pronounced 24 h after induction. Intranasal administration of TNF-α-targeting aptamers conjugated with polyethylene glycol (PEG-aptTNF-α) to mice with ALI reduced the intensity of inflammatory changes in lung tissue. Assessment of the levels of potential TNF-α target genes (<i>Usp18</i>, <i>Traf1</i>, and <i>Tnfaip3</i>) showed that their expression levels in the lungs increase during ALI development, while declining after the application of PEG-aptTNF-α. Therefore, topical use of TNF-α- targeting aptamers may be an efficient tool for treating ALI and other inflammatory lung diseases.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 2","pages":"61-71"},"PeriodicalIF":2.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071678","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":"7-Methylguanine Inhibits Colon Cancer Growth in Vivo.","authors":"K I Kirsanov, T I Fetisov, E E Antoshina, T G Gor'kova, L S Trukhanova, S I Shram, I Yu Nagaev, Yu A Zolotarev, L Abo Qoura, V S Pokrovsky, M G Yakubovskaya, V K Švedas, D K Nilov","doi":"10.32607/actanaturae.27422","DOIUrl":"10.32607/actanaturae.27422","url":null,"abstract":"<p><p>7-Methylguanine (7-MG) is a natural inhibitor of poly(ADP-ribose) polymerase 1 and tRNA-guanine transglycosylase, the enzymatic activity of which is central for the proliferation of cancer cells. Recently, a number of preclinical tests have demonstrated the safety of 7-MG and a regimen of intragastric administration was established in mice. In the present work, the pharmacological activity of 7-MG was studied in BALB/c and BALB/c nude mice with transplanted tumors. It was found that 7-MG effectively penetrates tumor tissue and suppresses colon adenocarcinoma growth in the Akatol model, as well as in a xenograft model with human HCT116 cells.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 2","pages":"50-52"},"PeriodicalIF":2.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071671","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":"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":"Modern Approaches to de novo Synthesis of Extended DNA Fragments: Assembly of a Wide Repertoire of Sequences.","authors":"T A Semashko, G Y Fisunov, E A Tsoy, D R Kharrasov, I K Chudinov, D V Evsyutina, G Y Shevelev, V M Govorun","doi":"10.32607/actanaturae.27362","DOIUrl":"10.32607/actanaturae.27362","url":null,"abstract":"<p><p>The standardization of DNA fragment assembly methods for many tasks of synthetic biology is crucial. This is necessary for synthesizing a wider repertoire of sequences, as well as for further automation and miniaturization of such reactions. In this work, we proposed conditions for the assembly of DNA fragments from chemically synthesized oligonucleotides and we identified the errors occurring in the sequence under these conditions. Additionally, we proposed conditions for further combining synthetic fragments into larger DNA fragments. We showed that the optimized conditions are suitable for the assembly of a wide range of sequences.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 1","pages":"77-85"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911258","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":"ELABELA-APJ Axis Enhances Mesenchymal Stem Cell Proliferation and Migration via the METTL3/PI3K/AKT Pathway.","authors":"D Xu, J Fu, X Liu, Y Hong, X Chen, S Li, J Hou, K Zhang, C Zhou, C Zeng, G Zheng, H Wu, T Wang","doi":"10.32607/actanaturae.17863","DOIUrl":"10.32607/actanaturae.17863","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) possess a strong therapeutic potential in regenerative medicine. ELABELA (ELA) is a 32 amino acid peptide that binds to the apelin peptide jejunum receptor (APJ) to regulate cell proliferation and migration. The aim of this study was to investigate the function of ELA vis-a-vis the MSC proliferation and migration, and further explore the underlying mechanism. We demonstrated that the exogenous supplement of ELA boosts the proliferation and migration ability of MSCs, alongside improved <i>in vitro</i> cell viability. These capabilities were rendered moot upon APJ knockdown. In addition, ELA (5-20 μM) was shown to upregulate the expression of METTL3 in a concentrationdependent pattern, a capacity which was suppressed by APJ reduction, whereas the downregulation of METTL3 expression blocked the beneficial effects induced by ELA. ELA was also observed to upregulate the phosphorylation level of AKT. This ELA-induced activation of the PI3K/AKT pathway, however, is inhibited with knockdown of METTL3. Our data indicate that ELA could act as a promoter of MSC proliferation and migration <i>in vitro</i> through the APJ receptor, something which might be attributed to the activation of the METTL3/PI3K/AKT signaling pathway. Therefore, ELA is a candidate for optimizing MSC-based cell therapy, while METTL3 is a potential target for its promoting action on MSCs.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 1","pages":"111-118"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140846606","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":"Streptomyces phaeochromogenes BV-204, K-1115A Anthraquinone-Producing Strain: A New Protein Biosynthesis Inhibitor.","authors":"A R Belik, Yu V Zakalyukina, V A Alferova, Y A Buyuklyan, I A Osterman, M V Biryukov","doi":"10.32607/actanaturae.27315","DOIUrl":"10.32607/actanaturae.27315","url":null,"abstract":"<p><p>In the search for new antibiotics, it is a common occurrence that already known molecules are \"rediscovered\" while new promising ones remain unnoticed. A possible solution to this problem may be the so-called \"target-oriented\" search, using special reporter microorganisms that combine increased antibiotic sensitivity with the ability to identify a molecule's damaging effect. The use of such test organisms makes it possible to discover new promising properties even in known metabolites. In this study, we used a high-throughput screening method based on the pDualrep2 dual reporter system, which combines high sensitivity through the use of modified strains of test organisms and makes it possible to easily and accurately identify the interaction mechanisms of a substance and a bacterial cell at the initial stages of screening. This reporter system is unknown in Russia and is significantly superior to its global analogues. In the system, translation inhibition induces the expression of the fluorescent protein Katushka2s, while DNA damage is induced by TurboRFP. Using pDualrep2, we have isolated and described BV-204, an <i>S. phaeochromogenes</i> strain producing K-1115A, the biologically active substance that we have previously described. In our study, K-1115A for the first time has demonstrated antibiotic activity and an ability to inhibit bacterial translation, which was confirmed <i>in vitro</i> in a cell-free translation system for FLuc mRNA. K-1115A's antibacterial activity was tested and confirmed for <i>S. aureus</i> (MRSA) and <i>B. subtilis</i>, its cytotoxicity measured against that for the HEK293 cell line. Its therapeutic index amounted to 2 and 8, respectively. The obtained results open up prospects for further study of K-1115A; so, this can be regarded as the basis for the production of semi-synthetic derivatives with improved therapeutic properties to be manufactured in dosage forms.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 1","pages":"30-39"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140849664","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}