Acta Naturae最新文献

{"title":"mRNA-Based Personalized Cancer Vaccines: Opportunities, Challenges and Outcomes.","authors":"A A Ibragimova, A A Fedorov, K M Kirilenko, E L Choynzonov, E V Denisov, M R Patysheva","doi":"10.32607/actanaturae.27707","DOIUrl":"10.32607/actanaturae.27707","url":null,"abstract":"<p><p>mRNA-based cancer vaccines represent an innovative approach to cancer treatment. Cancer mRNA vaccines are structurally based on specific tumor antigens, a technique which enables the patient's immune system to become activated against cancer cells. Clinical trials of mRNA vaccines against various types of tumors, including melanoma, lung cancer, pancreatic carcinoma, breast cancer and others, are currently underway. Because of their favorable safety profile and adaptability, these therapeutics hold considerable promise in efforts to enhance cancer treatment efficacy and prolong patient life. This review outlines steps in the development of manufacturing technologies for mRNA-based therapeutics, describes the algorithm used to design personalized anti-tumor mRNA vaccines, discusses their practical implementation, and summarizes current clinical trials in cancer immunotherapy.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 4","pages":"17-37"},"PeriodicalIF":2.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12755870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888546","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 Potential of the Peptide Drug Semax and Its Derivative for Correcting Pathological Impairments in the Animal Model of Alzheimer's Disease.","authors":"A I Radchenko, E V Kuzubova, A A Apostol, V A Mitkevich, L A Andreeva, S A Limborska, Yu V Stepenko, V S Shmigerova, A V Solin, M V Korokin, M V Pokrovskii, N F Myasoedov, A A Makarov","doi":"10.32607/actanaturae.27808","DOIUrl":"10.32607/actanaturae.27808","url":null,"abstract":"<p><p>Alzheimer's disease, first described over a century ago, is currently among the most common neurodegenerative diseases whose significance is increasingly growing with the aging of populations. Throughout the entire period of its study, no remedies have been found that would be effective in treating - or at least significantly slowing - the pathological process, while being sufficiently safe. In this regard, significant attention is paid to the development and application of natural peptide drugs lacking side effects. The present study assessed the effect of the known neuroprotective peptide Semax and its derivative on the behavioral characteristics and development of amyloidosis in transgenic APPswe/PS1dE9/Blg mice acting as a model of Alzheimer's disease. The open field, novel object recognition, and Barnes maze tests demonstrated that both Semax and its derivative improved cognitive functions in mice. Histological examination showed that these peptides reduced the number of amyloid inclusions in the cortex and hippocampus of the animals' brains. These findings demonstrate the high potential of Semax and its derivatives when used to develop therapeutic and corrective strategies for Alzheimer's disease.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 4","pages":"110-120"},"PeriodicalIF":2.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12755871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888589","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":"Targeted Radionuclide Detection of Malignant Tumors Using Affibody.","authors":"O D Bragina, A A Nesynov, E Yu Sitnikova, S V Patalyak, S M Deyev","doi":"10.32607/actanaturae.27677","DOIUrl":"10.32607/actanaturae.27677","url":null,"abstract":"<p><p>This review examines the potential applications of affibody molecules in various fields of biotechnology and clinical medicine. Consideration is given to the high affinity and specificity of affibody molecules for selected molecular targets, as well as their potential for the in vivo visualization of various malignant tumors. Significant attention is paid to preclinical and clinical studies of affibody conjugates with various radioisotopes for targeted radionuclide tumor imaging, which is particularly relevant in addressing challenges encountered during the diagnosis and treatment of these patients. Clinical trials demonstrate that radiopharmaceuticals are well-tolerated and effective for the assessment of tumor process prevalence and the determination of HER2/neu status in breast cancer patients, supporting further research.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 4","pages":"4-16"},"PeriodicalIF":2.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12755867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888563","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 Production, SpeciesSpecific Activity at the TRPA1 Channel, and Significance of the N-Terminal Residue of ProTx-I Toxin from Thrixopelma Pruriens Tarantula Venom.","authors":"M A Shulepko, M Zhang, E A Zhivov, D S Kulbatskii, A S Paramonov, Yu Che, A V Kuznetsov, A V Popov, M P Kirpichnikov, Z O Shenkarev, E N Lyukmanova","doi":"10.32607/actanaturae.27590","DOIUrl":"10.32607/actanaturae.27590","url":null,"abstract":"<p><p>The ProTx-I toxin from Thrixopelma pruriens tarantula venom inhibits voltage-gated sodium (NaV), potassium, and calcium channels, as well as the chemosensitive TRPA1 ion channel, affecting the activating processes of these channels. Due to its action at the NaV1.7, NaV1.8, and TRPA1 channels involved in pain perception and propagation, ProTx-I may be used as a model for the development of next-generation analgesics. ProTx-I consists of 35 amino acid residues, with three disulfide bonds forming an inhibitor cystine knot (ICK) motif, which challenges its heterologous production. An efficient ProTx-I production system is necessary to study, at the molecular level, the mechanism by which the toxin acts. In this study, we tested several approaches for bacterial production of disulfide-containing toxins. Cytoplasmic expression of ProTx-I fused with either thioredoxin or glutathione-S-transferase failed to yield a correctly folded toxin. However, the natively folded ProTx-I was successfully obtained by \"direct\" expression in the form of cytoplasmic inclusion bodies, followed by renaturation, as well as by secretion into the periplasmic space via fusion with maltose-binding protein. The activity of the recombinant ProTx-I was studied by electrophysiology in X. laevis oocytes expressing rat and human TRPA1 channels. The toxin proved to be more active on the rat channel than on the human channel (IC₅₀ = 250 ± 85 and 840 ± 190 nM, respectively). The presence of an additional N-terminal methionine residue in the toxin obtained through \"direct\" expression significantly attenuated its activity.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 4","pages":"121-129"},"PeriodicalIF":2.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12755868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888641","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 Design, Synthesis, and Evaluation of the Biological Activity of Hydroxamic Derivatives of Sorafenib.","authors":"A A Kleymenova, I A Abramov, Ya V Tkachev, P S Galeeva, V A Kleymenova, N F Zakirova, S N Kochetkov, M V Kozlov","doi":"10.32607/actanaturae.27566","DOIUrl":"10.32607/actanaturae.27566","url":null,"abstract":"<p><p>Sorafenib is a multiple tyrosine kinase inhibitor that is used in the treatment of liver and renal cancers. We synthesized the hydroxamic derivatives of sorafenib bearing the pharmacophore elements of zinc-dependent histone deacetylase inhibitors. We uncovered that suppression of cancer cell proliferation by the synthesized hybrid inhibitors critically depends on the structure of the \"deacetylase\" element.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 3","pages":"56-66"},"PeriodicalIF":1.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342592","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":"Cabbage Peptide miPEP156a Enhances the Level of Accumulation of Its mRNA in Transgenic Moss Physcomitrium patens.","authors":"T N Erokhina, E V Ryabukhina, I S Lyapina, D Y Ryazantsev, S K Zavriev, S Y Morozov","doi":"10.32607/actanaturae.27668","DOIUrl":"10.32607/actanaturae.27668","url":null,"abstract":"<p><p>MicroRNAs are endogenous, small non-coding RNAs that regulate gene expression at the post-transcriptional level by cleaving target mRNAs. Mature microRNAs are products of the processing of their primary transcripts (pri-miRNAs). Now, it has been discovered that the products of the translation of some plant pri-miRNAs are peptide molecules (miPEP). These peptides have the capacity to physically interact with their open reading frames (ORFs) in the transcribed pri-miRNAs and, thus, positively regulate the accumulation of these RNAs and the corresponding mature microRNAs. Most conserved microRNAs play an important role in plants development and their response to stress. In this work, we obtained transgenic <i>Physcomitrium patens</i> moss plants containing <i>Brassica oleracea</i> miPEP156a ORF in the genome under the control of a strong 35S cauliflower mosaic virus promoter and analyzed the effect of the exogenous peptide on the transcription of this ORF in the protonemata of two transgenic moss lines. It turned out that the chemically synthesized peptide miPEP156a increases the accumulation of its own mRNA during moss culture growth, as was previously shown in studies by foreign researchers and in our own work for a number of peptides in monocotyledonous and dicotyledonous plants. These findings confirm that pri-miRNA regions that are located outside the coding region of the peptide are not required for transcriptional activation. Moreover, we have also succeeded in showing that the presence of a specific promoter of the microRNA gene does not affect the phenomenon of transcription activation; this phenomenon <i>per se</i> is not species-specific and is observed in transgenic plants, regardless of the origin of the miPEP.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 3","pages":"44-48"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342455","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 Humoral and Cellular Immune Response to the Administration of OrthopoxVac Vaccine to Volunteers.","authors":"S N Shchelkunov, E Yu Prudnikova, A A Shestakova, S N Yakubitskiy, S A Pyankov, A E Nesterov, S V Usova, M P Bogryantseva, E A Nechaeva, T V Tregubchak, A P Agafonov","doi":"10.32607/actanaturae.27654","DOIUrl":"10.32607/actanaturae.27654","url":null,"abstract":"<p><p>OrthopoxVac, a fourth-generation smallpox vaccine, was the first of its kind registered worldwide in 2022, and it has been shown to be both safe and to induce only a mild reaction. A six-month clinical study confirmed its immunogenicity as compared to the first-generation live smallpox vaccine. Our study aimed to determine the levels of specific humoral and T-cell immune responses in volunteers following intradermal OrthopoxVac vaccine administration either in a single dose of 107 PoFU or in two doses of 106 PoFU, at 1.5, 3, and 5 years after initial vaccination. Following the immunization of volunteers with the OrthopoxVac vaccine at a dosage of 107 PoFU, the T-helper response remained at a relatively high level for three years, before it significantly dropped. Administration of the same vaccine twice at a dose of 106 PoFU resulted in a considerable decrease in the level of T-helpers, after 1.5 years. Additionally, some patients exhibited a reduction in viral neutralizing antibody (VNA) titers after 1.5 years of OrthopoxVac vaccine administration. When OrthopoxVac was administered at a dosage of 107 PoFU, no substantial differences were noted between groups at the 1.5-, 3-, and 5-year marks. In contrast, in the groups receiving two doses of 106 PoFU, VNA titers showed a significant reduction after 1.5 years. These findings indicate that a single intradermal dose of 107 PoFU of the OrthopoxVac vaccine elicits a significant and lasting immune response involving both antibodies and T-cells for a minimum of three years.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 3","pages":"104-118"},"PeriodicalIF":1.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342566","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":"PepString Server As a Tool to Search for Short Amino Acid Subsequences: Identification of Potential Amyloid-Beta Targets.","authors":"S A Kozin, A A Anashkina, D G Matsuga, B S Suvaan, V G Tumanyan, V A Mitkevich, A A Makarov","doi":"10.32607/actanaturae.27630","DOIUrl":"10.32607/actanaturae.27630","url":null,"abstract":"<p><p>This paper presents a new bioinformatics tool to meet the needs of researchers in the search for short (≥ 3) amino acid subsequences in protein sequences annotated in public databases (UniprotKB, SwissProt) and illustrates its efficacy with the example of a search for the EVHH tetrapeptide in the human proteome, which is a molecular determinant of amyloid beta and is involved in interactions that are crucial in Alzheimer's disease pathogenesis. The topicality of developing such a tool is, on the one hand, supported by experimental data on the role of short tetrapeptide motifs in the architecture of intermolecular interfaces. On the other hand, there are currently no software products for efficient search for short (≥3) amino acid sequences in public databases, which drastically limits researchers' ability to identify proteins with exact matches of short subsequences. This tool (PepString server, http://pepstring.eimb.ru/) allows one to use intuitive queries to retrieve information about all the proteins that contain sequences of interest, as well as their combinations.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 3","pages":"67-76"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342472","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 Generation and Characterization of a Mouse Embryonic Stem Cell Line with Psmb9 Immunoproteasome Gene Knockout.","authors":"D V Kriger, U I Podenkova, A A Kuzmin, N D Aksenov, A V Kropacheva, A S Zinovyeva, A V Selenina, A N Tomilin, A S Tsimokha","doi":"10.32607/actanaturae.27583","DOIUrl":"10.32607/actanaturae.27583","url":null,"abstract":"<p><p>Immunoproteasomes, a unique type of proteasome complex, play a critical role in antigen presentation and cellular homeostasis. Unlike the constitutive 20S proteasome, the catalytic subunits β1, β2, and β5 in the immunoproteasome are replaced by inducible isoforms: β1i (LMP2), β2i (MECL-1), and β5i (LMP7). The expression of the genes encoding these subunits (Psmb9, Psmb10, and Psmb8) is activated by cytokines, primarily interferon-γ (IFNγ). Although it has been demonstrated more and more convincingly that immunoproteasomes are expressed in embryonic stem cells (ESCs), their involvement in maintaining pluripotency, promoting self-renewal, and regulating differentiation processes remains unexplored. This study implemented CRISPR/Cas9 technology to generate a <i>Psmb9</i> gene knockout (Psmb9KO) mouse ESC line. The resulting cells exhibited a normal karyotype and morphology, maintained normal proliferation rates, and retained the capacity to form teratomas containing derivatives of all three germ layers. However, the differentiation induced by retinoic acid (RA) and IFNγ caused an accumulation of Mecl-1 precursors in Psmb9KO cells, suggesting modifications in immunoproteasome assembly. Furthermore, an increase in the caspase-like activity of immunoproteasomes was detected, suggesting the integration of a constitutive β1-subunit into the complex in place of Lmp2. The findings underscore the adaptability of the ubiquitin-proteasome system in maintaining cellular proteostasis by compensatory mechanisms that counteract the lack of Lmp2. The Psmb9KO line can serve as a valuable model for examining the function of immunoproteasomes in proteostasis regulation during early mammalian embryogenesis differentiation.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 3","pages":"77-87"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342571","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 Impact of the Intracellular Domains of Chimeric Antigenic Receptors on the Properties of CAR T-cells.","authors":"D V Volkov, V M Stepanova, I A Yaroshevich, A G Gabibov, Y P Rubtsov","doi":"10.32607/actanaturae.27728","DOIUrl":"10.32607/actanaturae.27728","url":null,"abstract":"<p><p>The advent of the T-cell engineering technology using chimeric antigen receptors (CARs) has revolutionized the treatment of hematologic malignancies and reoriented the direction of research in the field of immune cell engineering and immunotherapy. Regrettably, the effectiveness of CAR T-cell therapy in specific instances of hematologic malignancies and solid tumors is limited by a number of factors. These include (1) an excessive or insufficient CAR T-cell response, possibly a result of both resistance within the tumor cells or the microenvironment and the suboptimal structural and functional organization of the chimeric receptor; (2) a less-than-optimal functional phenotype of the final CAR T-cell product, which is a direct consequence of the manufacturing and expansion processes used to produce CAR T-cells; and (3) the lack of an adequate CAR T-cell control system post-administration to the patient. Consequently, current research efforts focus on optimizing the CAR structure, improving production technologies, and further developing CAR T-cell modifications. Optimizing the CAR structure to enhance the function of modified cells is a primary strategy in improving the efficacy of CAR T-cell therapy. Since the emergence of the first CAR T-cells, five generations of CARs have been developed, employing both novel combinations of signaling and structural domains within a single molecule and new systems of multiple chimeric molecules presented simultaneously on the T-cell surface. A well thought-out combination of CAR components should ensure high receptor sensitivity to the antigen, the formation of a stable immune synapse (IS), effective costimulation, and productive CAR T-cell activation. Integrating cutting-edge technologies - specifically machine learning that helps predict the structure and properties of a three-dimensional biopolymer, combined with high-throughput sequencing and omics approaches - offers new possibilities for the targeted modification of the CAR structure. Of crucial importance is the selection of specific modifications and combinations of costimulatory and signaling domains to enhance CAR T-cell cytotoxicity, proliferation, and persistence. This review provides insights into recent advancements in CAR optimization, with particular emphasis on modifications designed to enhance the therapeutic functionality of CAR T-cells.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 3","pages":"4-17"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342628","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}