ISSN (print): 1608-4101, ISSN (online): 2687-1378 Founders: Institute of Experimental Medicine, Eco-Vector Editor-in-Cheif: G.A. Safronov, academician of RAS, Doctor of Sc., Professor Frequency / Access: 4 issues per year / Subscription Included in: White List (3rd level), Higher Attestation Commission list, RISC
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READ the details online (tap to see in details) Author’s license agreement (public offer) on the publication of an article in a scholarly journal “Medical academic journal” Eco-Vector, represented by its CEO Evgeniy Schepin and acting on the basis of the Charter (hereinafter referred to as the Publisher), on the one hand, offers an indefinite circle of persons (hereinafter referred to as the Author), and on the other hand, hereinafter jointly referred to as the Parties, to execute this agreement (hereinafter referred to as the Agreement) on the publication of scientific article (hereinafter referred to as the Article) in a scholarly journal “Medical academic journal” (further-the Journal) in accordance with the conditions stated below. I. General Provisions This Agreement, in accordance with clause 2 of Article 437 of the Civil Code of the Russian Federation, is a public offer (hereinafter referred to as the Offer) requiring full and unconditional acceptance (Acceptance), which, in accordance with Article 438 of the Civil Code of the Russian Federation, means the sending by the Author of his/her materials by way of uploading the same to the online electronic system designed to accept manuscripts for consideration, and subsequently posted in the corresponding section of the Journal’s website on the Internet information and telecommunications network (hereinafter referred to as the Internet). In accordance with the current legislation of the Russian Federation regarding the observance of copyright on electronic information resources, all materials found in a website, including submitted and published in electronic journals, may not be reproduced in whole or in part in any form (electronic or printed) without the prior written permission of the Publisher. Prior permission can be given by publishing an article in the open access with Creative Commons license. The journal requires license users to reference the original source, i.e., the publication, if the Author permits use of the public materials in the context of other documents. II. Terms used in the Agreement “Author” refers to an individual (or individuals) whose creative work has led to the creation of the manuscript of a scientific Article, or to a representative of these persons. “Manuscript” is the result of intellectual activity in the form of a scientific work containing text, graphic and numerical data, audiovisual information, program code and other elements submitted by the Author for publication in the Journal; it is also the mean “a draft of an Article submitted by the Author to be published in the Journal”. “Offer” is the current agreement (an offer to the author for the publication of an Article in the Journal). “Publication” is the process of placement of an Article in the Journal. “Article” is the manuscript that has been published in the Journal (after successful selection, editing, type-setting, copyediting, proofreading, translation). “Acceptance of the offer” refers to the full and unconditional acceptance of the offer on the terms specified in paragraph 3 of this agreement (the Author accepts offer by submitting a Manuscript to the Publisher via the online electronic submission system on the Journal’s Internet website). “Journal” is a scientific peer-reviewed periodical registered as a mass media entity in the Roskomnadzor register of the Russian Federation and ISSN-center. “Submission” is an electronic appeal of the Author to the Publisher for the publication of an Article in the Journal by uploading the manuscript and accompanying materials to the online electronic submission system on the Journal’s Internet website). “Publisher” refers to Eco-Vector, which is the Publisher of the journal. Article metadata includes the information that are intended for inclusion in International Scientific Databases and search engines, namely the following: title of the Article; information about each of the Authors (surname and first name; patronymic; place of work with the postal address indicated, contact information (e-mail)); abstract; keywords; thematic rubricator: UDC (Universal Decimal Classification) or other library and bibliographic classification and subject indexes; list of references. “Editorial board” is the creative team that prepares the journal for publication. “Parties” refers to the Author and the Publisher. “Author Guidelines” are the requirements for Articles published in the Journal, posted in the “For authors” section of the Journal’s Internet website. III. Subject of the Agreement (Offer) Under this agreement, the Author grants the Publisher, free of charge for the entire period of validity in accordance with the legislation of the Russian Federation, an exclusive license to use the Article created by the former for publication in the Journal, as well as the rights to use the article in the following ways: Reproduction of the Article or its sections or parts, as well as the metadata of the Article in any languages, in any material form, including on paper and electronic media, as a separate work in Journals and/or databases (local or in the Internet) of the Publisher and/or other persons, at the discretion of the Publisher; Distribution of the Article or its sections or parts, as well as the metadata of the Article in any languages, on any medium as part of the Journal and/or databases of the Publisher or other persons, at the discretion of the Publisher, or as an independent work around the world whether on Open-Access terms or for a fee without remuneration to the Author; Making the Article or any of its sections or parts, as well as the Article’s metadata in any languages, publicly available in such a way that any person can access the Article from any place, including via the Internet, and at any time of their own choosing; Granting permission/s for the use of the Article or its sections or parts, as well as its metadata in any languages, to third parties with notice to the Author made by posting relevant information on the Journal’s website, without paying remuneration to the Author; Processing the Article (i.e., editing, correcting, annotating, tagging, translating to any languages, typesetting) and using the revised (translated) Article in the aforementioned ways. Other rights not directly transferred to the Publisher under this Agreement, including patent rights to any process, method etc., described by the Author in the Article, as well as trademark rights, are reserved for the Author. The territory where the rights to the Article are allowed to be used is the whole world. The validity of this Agreement commences only if the manuscript of the Article is accepted for publication in the Journal and only from the moment of sending a notification of acceptance of the Article for publication to the Author from the official e-mail of the Journal. The rights are granted by the Author to the Publisher free of charge; the publication of the Article in the Journal does not entail any financial deductions to the Author. If the Publisher decides to reject the Submission or refuse to publish the Article in the Journal (i.e., retraction of the published Article), this Agreement becomes invalid. The decision to refuse publication will be sent to the Author at the e-mail address specified in the Submission. IV. Rights and Duties of the Parties The Author guarantees that: s/he holds the copyright the exclusive rights to the materials submitted to the Publisher as part of the manuscript of the Article; the rights granted to the Publisher under this agreement have not been previously transferred and will not be transferred to third parties in the future during the duration of the Agreement; the manuscript contains all references to the cited authors and/or publications (materials) provided for under the current copyright legislation; the Author has obtained all the necessary permissions for all information and other materials s/he holds no copyright to and that are used in the manuscript of the Article; the Article manuscript contains only materials permitted to be published in the open press in accordance with the current legislative acts of the Russian Federation, and its publication and distribution will not lead to the disclosure of secret (confidential) information (including state secrets); the Author has informed co-authors about the terms of this Agreement and has received their consent to execute this Agreement under the terms provided for in the Agreement. The Author carries certain obligations under the terms of the Agreement: s/he should prepare and submit the manuscript of the Article in accordance with the Author Guidelines posted on the Journal’s website; the Author should not use an electronic copy of the Article for commercial purposes and in other journal publications without the consent of the Publisher; in the process of preparing a manuscript for publication, the Author is obligated to undertake the following: make corrections to the text of the manuscript that have been marked by the peer-reviewers and accepted by the editorial board, and/or as necessary, upon the request of the Publisher and the editorial board, finalize the manuscript of the Article; revising and proofreading the manuscript of the Article in accordance with the editorial recommendations; suggest only the minimum of corrections to the type-setted (layout) Article. The Author has the following rights and duties: Use preprint or prior-to publication versions of an unpublished Article in the form and content accepted by the Publisher for publication in the Journal. Such prior-to-publish versions can be placed as electronic files on the personal websites of the Author (co-authors) or on the protected external websites of the employers of the Author; however, the Author cannot use the unpublished version(s) for commercial sale or for systematic external distribution by a third party (i.e., post on social media). The author or co-authors must, in turn, carry out certain duties, namely: include the following warning in the prior-to-publish version: “This is prior-to-publish version of the article accepted for publication in (Journal’s name), © Eco-Vector (year)”; provide the corresponding electronic link to the Publisher’s website at https://journals.eco-vector.com/ and/or via the DOI. Copy or transfer a copy of the published Article in whole or in part to colleagues free of charge for their personal or professional use, for the promotion of academic or scientific research, or for informational purposes of the Author’s employer. Use materials from a published Article in a book written by one of the co-authors. Use figures, tables and text excerpts from the Article for his or her (or co-authors’) own training purposes, or to include them in other published works in printed or electronic format by a third party, or to submit them in electronic format on an internal computer network, or on the public website of the Author (co-authors) or his/her employer. Include the Article in educational collections for use in the classroom, either for free distribution to the Author’s (co-authors’) students or in electronic format on a local server for access by students as part of the training course, as well as for internal training programs at the institution of the Author’s employer. 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The Publisher has a right to: conduct an expert evaluation of the manuscript (peer-reviewing and editorial evaluation) and invite the Author to make the necessary changes (revisions) to the manuscript; provide editing, copyediting, type-setting, proofreading, tagging, indexation and translation of the Article’s manuscript without altering the main content; in any subsequent authorized use by the Author (and/or other persons) of the Journal and/or Article (including any separate part or fragment thereof), require that a link to the Journal, Publisher, Author or other copyright holders, the title of the Article, the Journal’s volume/issue, and the year of publication be specified in the Journal; post preliminary and/or advertising information about the upcoming publication of the Article in the media and other information sources; make changes to the offer in accordance with the procedure established by the offer. The editorial board of the Journal, headed by the editor-in-chief, has the exclusive rights to select and/or reject materials sent to the Journal editorial office for publications purposes. The manuscript sent by the Author to the Journal editorial office is not subject to return. The editorial board of the Journal does not enter into correspondence about rejection of submissions. In all cases not stipulated and not provided for in this agreement, the parties are obliged to be guided by the relevant current laws of the Russian Federation. V. Acceptance of the Offer and Execution of the Agreement. Terms of the Agreement The Author accepts the Offer by submitting the manuscript on the Article to the Publisher through the electronic manuscript submission system on the Journal's Internet website. Acceptance of the offer by the author creates an Agreement in writing (Articles 438 and 1286.1 of the Civil Code of the Russian Federation) on the terms of the offer. This Agreement is valid for the duration of the exclusive rights to the Article. When transferring (alienating) the exclusive right to the Article by the Author to a third party, this Agreement does not terminate. VI. Procedure for changing and terminating the Agreement The Publisher has the right to unilaterally change the terms of this Agreement, in advance, at least 10 (ten) calendar days before the entry into force of the intended relevant changes, but with notice to the Author through the Journal’s website or by e-mail to the Author’s e-mail address specified in the Author’s Submission. The changes will take effect from the date specified in the relevant notification. If the Author rejects the changes to the terms of this Agreement, s/he has the right to notify the Publisher by sending a written notification through the online manuscripts submission system, making sure that the same is sent to the official e-mail address of the editorial office. This Agreement may be terminated prematurely, either by agreement of the parties at any time, or on other grounds provided for in this Agreement. The Author has the right to unilaterally withdraw from the execution of this Agreement by sending the Publisher a corresponding notification in writing at least 60 (sixty) calendar days in advance before the expected date of publication of the Article in the Journal. Termination of the Agreement for any reason does not release the parties from liability for any violation of the terms of the Agreement that occurred during the validity period. VII. Responsibility The parties are responsible for non-fulfillment or improper fulfillment of their obligations under the Agreement in accordance with the current relevant legislation of the Russian Federation. All information provided by the Author must be reliable. The Author is expected to provide accurate and complete the information to the Publisher. When using false information received from the Author, the Publisher is not responsible for the negative consequences caused by his actions on the basis of the false information provided. With regard to the content of the Article, the Author is solely responsible for compliance with the requirements of the laws of the Russian Federation pertaining to advertising, copyright and related rights’ protection, protection of trademarks and service marks, and the protection of consumer rights. The Publisher does not bear any responsibility under the agreement: for any actions that are a direct or indirect result of Author’s illegal actions; for any loss incurred by the Author, regardless of whether the Publisher could have foreseen the possibility of such losses or not. The Publisher is released from liability for violation of the terms of the Agreement if such violation is caused by force majeure, including actions of state authorities (including the adoption of legal acts), fire, flood, earthquake, other natural disasters, lack of electricity and/or computer network failures, strikes, civil unrest, riots, etc. VIII. Dispute resolution Disputes and disagreements will be resolved by the parties through negotiations, and in case of failure to reach an Agreement they will strive to seek resolution in accordance with the current legislation of the Russian Federation. If there are unresolved disagreements, the parties agree to resolve the disputes in court at the jurisdiction covered by the Publisher’s location in accordance with the current legislation of the Russian Federation. IX. Miscellaneous All notifications, messages, requests, etc. (with the exception of documents that must be sent as originals in accordance with the laws of the Russian Federation) are considered received by the Author if they were transmitted (sent) by the Publisher through the Journal’s website (including by publication), fax, e-mail based on the address specified in the Submission, and other communication channels. The parties recognize the legal force of notifications, messages, requests, etc., transmitted (sent) by the above methods. In the event of claims against the Publisher related to the violation of the exclusive copyright and other intellectual property rights of third parties when creating an article or in connection with the execution of this Agreement by the Author, as well as in connection with the use of the Article by the Publisher in accordance with the Agreement, the author undertakes: To immediately take measures to resolve disputes with third parties soon after receiving Publisher’s notification, and if necessary, enter into legal proceedings on the Publisher’s side and take all appropriate actions needed to exclude the Publisher from the list of defendants; To reimburse the publisher for the legal costs incurred and expenses and losses caused by the application of measures to secure the claim and execute a court decision, and the money paid to a third party for the violation of exclusive copyright and other intellectual property rights, as well as other losses incurred by the Publisher in connection with the Author’s non-compliance with the guarantees provided by them under this Agreement. X. Legal address and details of the Publisher Eco-Vector Address: 191186, St. Petersburg, Aptekarsky Pereulok, 3 letter A, room 1N TIN: 7806423692; KPP: 784101001; OGRN: 1099847039907.
Advantages and disadvantages of using silver nanoparticles in medicine. Benefits of silver nanoparticle composites with organic antibacterial substances and biocompatible polymers
The development of bacterial resistance to drugs currently used in clinical practice remains a major challenge in modern medicine. Nanoparticles are now widely applied in various industries, including medicine. Silver nanoparticles exhibit broad-spectrum antibacterial activity against both Gram-negative and Gram-positive bacteria, including multidrug-resistant strains, as well as bacteria within biofilms. Silver nanoparticles possess multiple antimicrobial targets, which makes the development of microbial resistance to them difficult. In addition, silver demonstrates other types of biological activity, including wound-healing, anti-inflammatory, and antitumor effects. However, despite the undeniable advantages of these nanomaterials, their medical application remains limited by certain adverse effects on living organisms. The wide range of biological properties and potential toxicity of silver nanoparticles are determined by their size and shape, the synthesis method, and the type of stabilizing agent used. This review provides information on approaches to modifying silver nanoparticles with antibacterial agents such as antibiotics and antimicrobial peptides, which show synergistic or additive effects against pathogenic bacteria when combined with nanoparticles. The creation of such complexes enhances antimicrobial activity and improves nanoparticle stability. Therefore, composites of silver nanoparticles with organic antibacterial agents and biocompatible polymers can be considered a promising platform for the development of new, effective antibacterial preparations with reduced undesirable properties.
Copyright (c) 2025 Eco-Vector https://creativecommons.org/licenses/by-nc-nd/4.0
Health status of military personnel after injuries sustained during combat operations
It is well established that posttraumatic stress disorder is highly prevalent among military personnel who have sustained combat-related injuries. The consequences of combat trauma for both mental and physical health can affect the long-term quality of life of veterans. Research confirms the need for psychological rehabilitation of military personnel, which should begin during combat operations and continue throughout peacetime. This review provides a current perspective on the impact of combat trauma on the physical and mental health of military personnel, as well as the main challenges associated with the reintegration of demobilized soldiers and veterans into civilian life and professions. Feelings of social isolation and difficulties in maintaining relationships are associated with a higher risk of developing posttraumatic stress disorder symptoms. Studies have shown that veterans of the armed forces with mental disorders experience fewer reintegration difficulties when supported socially and when their quality of life is higher. It may be necessary to intensify the development of additional social programs for occupational retraining and rehabilitation of military personnel. These programs should promote social resilience, develop new social skills, and expand social connections, thereby alleviating symptoms of adjustment dysphoria and improving overall quality of life.
Copyright (c) 2025 Eco-Vector https://eco-vector.com/for_authors.php#07
Therapeutic potential of exogenous mRNA encoding recombinant antibodies against viral pathogens
Antibodies produced by the human immune system in response to vaccination or pathogen exposure represent an essential—and sometimes the only—means of combating viral infections. Scientific and technological advances have led to the emergence of a new class of antiviral agents in the biopharmaceutical market: therapeutic recombinant monoclonal antibodies. However, their potential is significantly limited due to low stability and aggregation of recombinant antibodies, as well as the high cost of their production and purification. Over the past decade, the technology of transient in vivo protein expression through the delivery of exogenous mRNA encoding the protein of interest into target cells has gained widespread adoption. Exogenous mRNAs encoding recombinant antibodies can provide stable, prolonged, and safe translation of both full-length antibodies and their various truncated forms. Moreover, mRNA technologies make it possible to develop new approaches to creating protective antibodies, such as intracellular or membrane-anchored antibodies targeted to specific cell types. In 2024 alone, more than one thousand scientific papers were published on the development and use of mRNA as vaccine and therapeutic agents. This review discusses current experimental mRNA-based therapeutics encoding antibodies that exhibit protective properties against viral pathogens.
Modeling long-term consequences of poisonings caused by exposure to neurotoxicants: a review
The issue of long-term consequences of acute poisonings caused by neurotoxicants is of relevance in industrial hygiene and toxicology, as it involves not only medical and biological aspects but also social and legal considerations. This problem has received significant attention in Russia and internationally. Most studies focus primarily on the acute phase of intoxication. However, in recent years, scientific research has increasingly examined neurotoxic effects in the long-term period following exposure, as well as approaches to managing the resulting health disorders. It can be assumed that the long-term consequences of acute poisonings with neurotoxic substances are associated with the disruption of adaptive mechanisms and the initiation of a cascade of pathological reactions. These processes commonly lead to the development of psychoasthenic and psychoorganic syndromes in individuals who have experienced acute poisonings, and there is also a risk of toxic polyneuropathies. Existing studies on the mechanisms underlying the development of long-term consequences of poisonings with neurotoxic agents do not provide a definitive explanation of the pathogenesis of these disorders. Experimental modeling is one of the key methods used to study pathogenesis. The advancement of practical medicine is not possible without it. This review examines the experience in modeling the long-term consequences of intoxication caused by neurotoxicants.
Organophosphate-induced delayed neuropathy: an unresolved problem?
This work presents an analysis of recent publications devoted to delayed peripheral neuropathy caused by acute or chronic low-dose exposure to organophosphorus compounds (organophosphate-induced delayed neuropathy, OPIDN). The review discusses the clinical features of the disorder, characterized by a prolonged latent period between toxicant exposure and disease onset, and provides examples of both mass and suicidal poisonings. The morphological substrate of OPIDN includes swelling of distal segments of large axons, disruption of myelin sheath membranes, and subsequent degeneration of nerve fibers of the Wallerian type. The role of Schwann cells in axonal regeneration and the cellular and molecular mechanisms underlying axon–Schwann cell signaling are discussed. Major hypotheses regarding the noncholinergic mechanisms of OPIDN pathogenesis are presented. Special attention is given to the role of neuropathy target esterase as the principal molecular target of organophosphate action, the systemic inhibition of which, in combination with the “aging” reaction, initiates the development of OPIDN. In addition to neuropathy target esterase involvement, the potential role of other molecular targets of organophosphate action, oxidative stress, dysregulation of calcium homeostasis, and neuroinflammation is considered. Examples of experimental models of OPIDN, both in vivo and in vitro, are presented to illustrate approaches to studying its underlying mechanisms.
Immunotropic therapy: blockade of CTLA-4/B7 and PD-1/PD-L1 pathways in the treatment of cancers. Part 1: immunologic aspects
The CTLA-4/B7 and PD-1/PD-L1 signaling pathways are crucial in the development and maintenance of peripheral immune tolerance. The interaction of PD-1 and CTLA-4 receptors with their ligands triggers a cascade of reactions that suppress the activity of effector CD4+ and CD8+ T-lymphocytes. However, the role of these signaling cascades in immune responses is multifaceted. On the surface of T-cells, CTLA-4 competes with CD28 for ligands and, upon binding to members of the B7 family, inhibits signaling from the T-cell receptor (TCR). At the same time, this interaction promotes the production of anti-inflammatory cytokines IL-10 and TGF-β by regulatory T-lymphocytes (Tregs). On regulatory T-cells, CTLA-4 binding to B7 family molecules (CD80 and CD86) on the surface of antigen-presenting cells mediates CTLA-4–dependent trogocytosis, resulting in decreased expression of B7 molecules on antigen-presenting cells. This, in turn, reduces the ability of antigen-presenting cells to stimulate clonal expansion and survival of activated T-cells in lymphoid tissue. The PD-1 molecule, in contrast, is expressed on a wide range of cells, including effector CD4+ and CD8+ T-lymphocytes. It is critically important for the survival and effector function of activated antigen-specific T-lymphocytes in inflamed peripheral tissues. Moreover, the interaction between PD-1 and PD-L1 can promote the production of anti-inflammatory cytokines by regulatory T-cells. In oncologic diseases, tumor cells can exploit mechanisms of peripheral tolerance mediated by both CTLA-4 and PD-1 molecules. Therefore, blockade of these receptors represents an effective therapeutic strategy in clinical oncology for the treatment of cancers.
Microorganisms in modern biomedicine and biotechnology
In vaccine prophylaxis, the use of genetically modified microorganisms has become a major direction in the development of modern vaccine formulations. These approaches involve mRNA-based technologies and the genetic modification of bacteria and viruses to create live vaccines. The lecture is devoted to new trends in microbiology and their influence on the food industry, pharmacology, and vaccinology. The methodological section of the publication describes general approaches to DNA cloning, synthesis, and sequencing. Particular attention is given to strategies for bacterial genome editing. The lecture discusses current developments in genetic engineering approaches for industrial and medical purposes, as well as achievements in creating artificial microorganisms of bacterial and viral origin. Special emphasis is placed on the importance of the microbiota in maintaining human health through the correction of dysbiotic conditions by microbial therapy, including the use of health-promoting bacteria as probiotics and individualized probiotics (autoprobiotics). The potential of beneficial bacteria for treating various pathological conditions and diseases—such as irritable bowel syndrome, metabolic syndrome, and multiple sclerosis—is demonstrated. The correction of dysbiosis and microbial therapy are also significant in oncology. This lecture may be of interest to physicians and researchers not specialized in molecular genetics or microbiology but wishing to gain a general understanding of current scientific and technological trends in this rapidly developing field.
Morphological features of biodegradation and biocompatibility of combined polymeric matrices based on chitosan and hyaluronic acid
BACKGROUND: In the development of bioengineered materials used in reconstructive surgery, the tissue response to an implanted device plays a key role. Recent advances in the control of synthesis conditions have made it possible to produce materials with varying biodegradation and biocompatibility characteristics from the same polymer. AIM: This work aimed to examine the pathomorphological features of biodegradation of combined polymeric films based on chitosan and hyaluronic acid obtained under different technological conditions. METHODS: Subcutaneous implantation of 4 samples of two-component polymeric films was performed in 30 Wistar rats weighing 200–220 g. The films were produced from chitosan solutions with molecular weights of 500 and 900 kDa and hyaluronic acid with a molecular weight of 1300 kDa, followed by heat treatment (100 °C for 5 min). The type of biodegradation and biocompatibility was assessed on day 60 by histological analysis. RESULTS: During the postimplantation period, there were no signs of acute toxicity, septic or allergic inflammation, or severe tissue deformation during scarring. Biodegradation of the chitosan–hyaluronic acid polyelectrolyte complex was found to proceed through a stage of simultaneous swelling and self-disintegration of the matrix. In response, reactive aseptic inflammation developed without the formation of multinucleated giant foreign body cells. Biocompatibility was manifested in two types of connective tissue growth: replacement throughout the entire thickness of the degrading matrix or formation of a peri-implant capsule clearly delineating the implanted material. It was demonstrated that increasing the molecular weight of chitosan and applying heat treatment to the film prolonged the biodegradation time of the entire two-component polysaccharide matrix. CONCLUSION: The study demonstrated that modifying technological parameters allows the production of polymer films with an altered biodegradation pattern. The molecular weight of the polymer and the selected technological conditions for producing films based on the chitosan–hyaluronic acid polyelectrolyte complex act as regulators of the biodegradation rate of the polymer matrix in recipient tissues. This enables adaptation to specific clinical applications in tissue and organ reconstruction, where acceleration or deceleration of connective tissue development is required to promote restoration of native structure.
Synergistic effect of exogenous P53 and sodium butyrate on tumor cell survival
BACKGROUND: The P53 protein is a transcription factor that regulates the expression of genes involved in numerous cellular processes, including cell cycle arrest, apoptosis, cell proliferation, and DNA repair. Its role as a multifunctional tumor suppressor makes P53 an attractive and promising target for cancer therapy. AIM: This work aimed to analyze the combined effect of transfection with a plasmid encoding the p53 gene (a genetic approach), the histone deacetylase inhibitor sodium butyrate (epigenetic regulation), and co-cultivation with exosomes secreted by cells expressing wild-type P53 (modeling intercellular communication) on the survival of various human tumor cell lines. METHODS: The study was conducted using four transplantable cell lines: HeLa (epithelioid cervical carcinoma) and HT-1080 (fibrosarcoma) cells harboring the wild-type p53 gene, as well as K562 (chronic myelogenous leukemia) and Gl-V (primary glioma cell culture) cells deficient in p53 (P53–/–). Cell transfection was performed using a P53-GFP plasmid constructed in the Laboratory of Cell Biology, National Research Center “Kurchatov Institute.” This plasmid encodes the P53 protein fused to green fluorescent protein (GFP) at its N-terminus. Successful transfection was confirmed by detecting P53-GFP expression using confocal microscopy. The level of P53 protein in the cells was determined by Western blotting. To quantitatively assess proliferation and cell cycle parameters under conditions of histone deacetylase inhibition, sodium butyrate (NaBu) was added to the culture medium at a final concentration of 2.5 mM. The analysis was performed using an automated cell counter, flow cytometry, or colony formation assays. Exosomes were isolated from the collected conditioned medium by ultracentrifugation. RESULTS: When only one of the above approaches was applied, the outcome largely depended on the P53 status of the analyzed tumor cells. The combination of epigenetic modulation through inhibition of histone deacetylase activity with genetic regulation or exposure to exosomes derived from wild-type P53–expressing cells produced a pronounced synergistic effect and several-fold increase in the efficiency of tumor cell growth suppression compared with monotherapy. CONCLUSION: It appears that a strategy combining genetic methods, epigenetic modulation, and intercellular communication mechanisms that affect different components of the P53 regulatory network may substantially enhance the efficacy of P53-targeted anticancer therapy.
Histological features of the human anorectal lining at certain stages of embryonic development
BACKGROUND: Contemporary studies on the histological structure of the rectum mainly focus on the characteristics of its layers in adults under normal and pathological conditions and are largely devoted to anatomical and morphogenetic processes. However, there is a lack of information regarding the histological features of the epithelial lining of the anorectum during the first half of human embryogenesis. Meanwhile, according to observations by clinicians and pathologists, anatomical regions where genetically and morphologically distinct epithelia are in direct contact are often prone to malignant transformation. Therefore, a detailed study of their embryonic development is necessary to identify possible histogenetic prerequisites for such disorder. AIM: This work aimed to characterize the histological features of the epithelial lining of the human anorectum at specific stages of embryonic development. METHODS: We used histological specimens of human embryos at 7–8 and 17–18 weeks of gestation obtained from the archive of the Department of Histology with a Course in Embryology, Kirov Military Medical Academy. The sections were stained with hematoxylin and eosin, amidoblack 10B, by the Shabadash method, and by the Feulgen reaction. Karyometric analysis of epithelial cells of the anorectal canal was performed. RESULTS: For the first time, the characteristics of the stratified epithelium of the anal invagination in a 7–8–week human embryo are presented. Histological features of the lining of the intermediate portion of the human anorectum at 17–18 weeks of embryonic development were identified for the first time: in the region of anal sinus formation, clearly demarcated areas corresponding to three morphologically distinct epithelial types were observed. Between the stratified nonkeratinized squamous epithelium of ectodermal origin and the simple columnar epithelium of endodermal origin, a previously undescribed bilayered, pseudostratified, urothelium-like epithelium was identified. We suggest that this epithelium represents a site of an evolutionarily developed mechanism responsible for the division of the anorectal canal into three segments (proctodeum, urodeum, and coprodeum) in animals and serves as a provisional structure. CONCLUSION: The findings may contribute to understanding the mechanisms underlying the development of anorectal malformations, to identifying additional criteria for the microscopic diagnosis of reactive changes in the anorectal region, and may also further refine the concept of critical periods of embryogenesis.
DNA fragmentation and hydroxymethylation in ejaculated spermatozoa in normozoospermia and pathozoospermia
BACKGROUND: The search for new criteria for semen quality based on the evaluation of the structural and functional state of the sperm genome remains a relevant task in reproductive medicine. AIM: This work aimed to assess DNA integrity and the content of 5-hydroxymethylcytosine (5hmC) in the same ejaculated spermatozoa obtained from patients with normozoospermia and pathozoospermia. METHODS: The study included semen samples from 63 patients with normozoospermia (n = 33) and pathozoospermia (n = 30). Microscopic slides were prepared from the samples, on which fragmented DNA was first detected using the TUNEL assay, followed by digital image acquisition. Subsequently, 5hmC was detected by indirect immunofluorescence, and digital images of the same microscopic fields were acquired again. In total, 126,000 spermatozoa were analyzed (2000 per sample). RESULTS: A substantial proportion of spermatozoa (72.8%–94.2%) in all samples showed no DNA integrity violations and exhibited a low (background) level of 5hmC. The proportions of spermatozoa exhibiting DNA fragmentation, increased hydroxymethylation, or both characteristics simultaneously were 0.05%–13.8%, 0.15%–11.5%, and 0.99%–13.38%, respectively. The proportion of spermatozoa with DNA fragmentation and/or DNA hyperhydroxymethylation did not differ between patients with normozoospermia and those with pathozoospermia. DNA fragmentation and DNA hyperhydroxymethylation in ejaculated spermatozoa were found to be interdependent, and their coexistence in gametes was nonrandom. CONCLUSION: The nonrandom coexistence of DNA fragmentation and DNA hyperhydroxymethylation in spermatozoa, along with the interdependence of these features, indicates a common trigger, most likely oxidative stress. However, the presence of additional factors leading to DNA damage or altered hydroxymethylation levels may explain the less than complete overlap of these features in spermatozoa. The assessment of DNA fragmentation and hydroxymethylation levels in spermatozoa appears to be a promising approach for evaluating semen quality and identifying potential causes of idiopathic infertility.
Characteristics of early–stage fibrosis model in chronic alcoholic liver disease in rats
BACKGROUND: The early stage of liver fibrosis of alcoholic or drug-induced origin in humans is difficult to diagnose because it is often asymptomatic. Developing experimental models of the early stages of liver fibrosis that closely reproduce clinical characteristics and allow for the evaluation of candidate hepatoprotective agents for the prevention and treatment of fibrosis is an important task in hepatology. AIM: This work aimed to develop a model of the early stage of liver fibrosis with evaluation of typical pathomorphological and biochemical indicators of chronic alcoholic liver disease in rats. METHODS: The study was conducted on 20 white outbred male rats weighing 270–315 g, which were divided into 2 groups: experimental and control (n = 10 per group). Alcohol-induced liver injury was modeled by intragastric administration of 40% ethanol at 5 g/kg for the first 14 days and 3.75 g/kg for the subsequent 14 days. Throughout the experiment, general condition, body weight, and mortality were monitored. At the end of ethanol administration, animals were euthanized; blood was collected for biochemical analysis, and liver tissue was collected to determine S-adenosylmethionine concentration and perform histological examination. The severity of fibrosis was assessed using the METAVIR score, and the liver mass coefficient was determined. RESULTS: The induced alcoholic liver disease was characterized by mortality and neurological disturbances, including increased aggressiveness and slowed body weight gain compared with controls. Mortality in the experimental group (2 rats) occurred on day 13 after the start of ethanol administration. Biochemical analysis demonstrated increased aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase activity, as well as a decrease in the R-factor and reduced synthesis of S-adenosylmethionine in the liver. Liver dysfunction was accompanied by a reduction in the liver mass coefficient, nucleomegaly and steatosis, and moderate hepatofibrosis (stage F2 according to METAVIR), due to collagen fiber proliferation around bile ducts in portal tracts and the initiation of porto-portal septa formation. CONCLUSION: The model successfully reproduced characteristic features of alcoholic liver disease and can be recommended for studying the pathogenesis and early stages of liver cirrhosis, as well as for the screening and evaluation of candidate hepatoprotective and antifibrotic agents.