Medical peer-review journal. Publishes quarterly from 2001. Editor-in-Cheif: G.A. Safronov, MD, PhD, Professor Indexation: SCOPUS, RSCI, Google Scholar, Ulrich's Periodicals directory, Crossref, Dimensions. ISSN 1608-4101 (Print) ISSN 2687-1378 (Online)
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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. The Publisher, for its part, is obliged to: publish the Author’s article in the Journal in printed and electronic form in accordance with the terms of this Agreement; if necessary, as so decided by the Journal’s editorial board, provide the Author with the proofreading of the manuscript and make a reasonable editing; provide to the Author the unlimited access to the final electronic version of the published Article (Version of Record) through the online electronic submission system on the Journal’s Internet website; comply with the Author’s rights as provided for by the current legislation, as well as protect them and take all necessary measures to prevent copyright infringement by third parties. 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. 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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.
Epigenetic changes in post-traumatic stress disorder: possibilities and limitations of epigenetic therapy
In recent decades, the steadily increasing pressure of extreme, life-threatening stressors worldwide has significantly contributed to a rise in the prevalence of mental and behavioral disorders. One of the most severe consequences of experiencing psychotraumatic situations is the development of post-traumatic stress disorder. Current therapeutic approaches benefit only a minority of patients and are frequently accompanied by high non-response and relapse rates. In this case, the possible reasons for the lack of therapeutic effectiveness include not only genetic but also epigenetic factors, which may determine individual characteristics of the pharmacokinetics and pharmacodynamics of the drugs used. This review outlines epigenetic mechanisms that may underlie interindividual differences in treatment resistance, risk of development, and clinical severity of post-traumatic stress disorder. It summarizes the roles of DNA methylation, histone modifications, non-coding RNAs, chromatin remodeling, and the three-dimensional genome architecture in post-traumatic and stress-related disorders. Data are presented on the potential use of epigenetic modifications as biomarkers of traumatic stress and as factors responsible for the transmission to offspring of the adverse consequences of psychogenic trauma experienced by the parents. The possibilities and limitations of applying epigenetic therapy for post-traumatic stress disorder are discussed.
Copyright (c) 2025 Eco-Vector https://creativecommons.org/licenses/by-nc-nd/4.0/
Development of a chimeric hemagglutinin-based live-attenuated influenza vaccine against both lineages of influenza B virus
BACKGROUND: The development of a universal influenza vaccine remains a critical goal to enhance protection against diverse influenza virus strains. While vaccines against influenza type A viruses have benefited from the use of chimeric hemagglutinin designs, strategies for influenza type B vaccines still lag. AIM: The study aimed to investigate the efficacy of chimeric vaccine strains to induce humoral immune response targeting conserved antigenic sites of influenza type B virus. METHODS: A chimeric hemagglutinin was engineered by combining the head domain from the B/Brisbane/60/2008 virus (Victoria lineage) with the stalk domain from the B/Phuket/3073/2013 virus (Yamagata lineage). The gene encoding the chimeric hemagglutinin was incorporated into a vaccine virus based on the cold-adapted B/USSR/60/69 master donor virus to produce live-attenuated influenza vaccine. Mice were sequentially vaccinated with the conventional live-attenuated influenza vaccine and then with the recombinant live-attenuated influenza vaccine expressing the chimeric hemagglutinin. Immune responses and cross-protection against both homologous and heterologous influenza type B virus strains were assessed. RESULTS: The engineered chimeric hemagglutinin did not impair the replication or assembly of the vaccine virus. Sequential vaccination induced a robust humoral immune response and provided protection against both homologous and heterologous influenza type B virus strains in the mouse model. CONCLUSION: Live-attenuated influenza type B vaccines expressing chimeric hemagglutinin show promise in broadening protection against influenza type B virus infection. These findings support the development of a universal influenza type B vaccine using a chimeric hemagglutinin design.
Differentiation of macrophages in the presence of anaphylatoxin C3a: effect on efferocytosis
BACKGROUND: Macrophages are unique professional phagocytes involved in both innate and adaptive immune responses. This is made possible by their functional plasticity—the ability to acquire different phenotypes. Switching between subtypes during interactions with other immune system components is referred to as polarization. Anaphylatoxin C3a has been shown to influence macrophage polarization. Depending on the polarization state, macrophages exhibit different phagocytic activities. Given the contradictory evidence regarding C3a’s effects on macrophages, determining its impact on phagocytosis in general and on efferocytosis in particular is of special interest. AIM: The work aimed to investigate the effect of anaphylatoxin C3a on efferocytosis by M0 and M2 macrophages. METHODS: The experiments were conducted using human peripheral blood mononuclear cells. Macrophages were differentiated in the presence of C3a, and M2 polarization was induced with interleukin-4. Efferocytosis was assessed using confocal microscopy, whereas phagocytosis was evaluated via flow cytometry. Real-time reverse transcription polymerase chain reaction was used to measure expression of the efferocytosis receptor genes mertk, axl, and tyro3. RESULTS: M2 macrophages demonstrated greater efferocytic capacity compared to M0 macrophages. Anaphylatoxin C3a did not affect the phagocytosis of dead Escherichia coli bacteria but inhibited the phagocytosis of apoptotic cells in both unpolarized M0 and alternatively activated M2 macrophages. It was also shown that C3a reduces the expression of the Tyro3 receptor gene in both M0 and M2 macrophages. CONCLUSION: Anaphylatoxin C3a exerts a suppressive effect on efferocytosis, likely through modulation of apoptotic cell recognition processes.
Exosomes facilitate mRNA and siRNA delivery using cationic liposomes 2X3-DOPE to rat heart mesenchymal cells in vitro
BACKGROUND: The delivery of nucleic acids to mesenchymal stem cells, which are used as model objects in in vitro experiments or as therapeutic agents in regenerative medicine and oncology, is an actively developing area of research. Existing non-viral delivery systems either have low effectiveness or highly toxic to mesenchymal stem cells. Therefore, the development of new carriers has become an urgent priority. AIM: To demonstrate the feasibility of delivering model messenger RNA and small interfering RNA to rat heart mesenchymal stem cells (MSCs) in vitro using original cationic liposomes 2X3-DOPE (1:3 molar ratio) and to evaluate the influence of exosomes incorporated into hybrid nanoparticles with 2X3-DOPE on the efficiency of RNA delivery. METHODS: Exosomes were isolated using a standard ultracentrifugation technique followed by characterization of the obtained vesicles through Western blotting, transmission electron microscopy, atomic force microscopy, and hydrodynamic diameter measurement using dynamic light scattering. Small interfering RNA was chemically synthesized; whereas messenger RNA was obtained by in vitro transcription. Complexes of liposomes or hybrid nanoparticles with RNA were prepared by mixing; the properties of the resulting particles were assessed using dynamic light scattering and atomic force microscopy. To evaluate the efficiency of RNA delivery to rat heart mesenchymal stem cells derived from both healthy and ischemic myocardium, we used fluorescence microscopy, laser scanning confocal microscopy, and flow cytometry. RESULTS: Complexes of cationic liposomes 2X3-DOPE (1:3 molar ratio) with messenger RNA and 2X3-DOPE modified with DSPE-PEG2000 (0.62 mol%) complexed with small interfering RNA were successfully prepared and characterized. It was demonstrated that 2X3-DOPE is ineffective for messenger RNA delivery to rat cardiac mesenchymal stem cells; whereas hybrid nanoparticles incorporating exosomes based on these liposomes exhibited up to 40% transfection efficiency. In addition, 2X3-DOPE modified with DSPE-PEG2000 (0.62 mol%) was effective for small interfering RNA delivery to rat cardiac mesenchymal stem cells, achieving up to 90% transfection efficiency; whereas the use of hybrid nanoparticles based on this formulation resulted in 100% transfected cells with more than a twofold increase in small interfering RNA in the cells as indicated by the average fluorescence intensity. CONCLUSION: Cationic liposomes 2X3-DOPE (1:3 molar ratio) modified with DSPE-PEG2000 (0.62 mol%) are promising vehicles for small interfering RNA delivery to mesenchymal stem cells, both independently and in combination with exosomes. Exosomes integrated in hybrid nanoparticles based on 2X3-DOPE improve the transfection efficiency of both messenger RNA and small interfering RNA in rat cardiac mesenchymal stem cells in vitro.
Markers of halogenating stress and netosis in patients with type 2 diabetes mellitus
BACKGROUND: Leukocyte myeloperoxidase catalyzes the formation of reactive halogen species, which oxidize and chlorinate biomolecules, thereby contributing to the development of halogenating stress. Myeloperoxidase is a key enzyme in neutrophil extracellular traps (NETs) during NETosis. There is reason to believe that under hyperglycemic conditions in patients with type 2 diabetes mellitus, halogenating stress and NETosis develop, which contribute to disease progression and complications. AIM: The work aimed to assess the levels of blood markers of halogenating stress (myeloperoxidase, chlorinated albumin) and NETosis (neutrophil extracellular traps) in patients with type 2 diabetes mellitus. METHODS: The study included patients with a previously established diagnosis of type 2 diabetes mellitus. Myeloperoxidase and chlorinated albumin in plasma were measured by enzyme-linked immunosorbent assay. The number of neutrophil extracellular traps was determined using light microscopy on standardized whole-blood smears stained according to Romanowsky. RESULTS: In patients with type 2 diabetes mellitus, blood levels of myeloperoxidase and chlorinated albumin were significantly higher than in the group of healthy volunteers, indicating the development of halogenating stress. At the same time, in the blood of patients with type 2 diabetes mellitus, a significant increase in the concentration of neutrophil extracellular traps was recorded compared to the control group of healthy volunteers, both in the absence of the activator—phorbol 12-myristate 13-acetate—and after its addition to the blood, indicating activation of NETosis in type 2 diabetes mellitus. CONCLUSION: The findings support the hypothesis that halogenating stress, caused by an excessive increase in blood myeloperoxidase concentration/activity, accompanies the development of type 2 diabetes mellitus and contributes to its progression and complications.
Characteristics of the functional state of peripheral blood neutrophils in patients with luminal breast cancer
BACKGROUND: Neutrophils are essential in tumor growth, and their functional state can serve as a prognostic biomarker. However, the functional characteristics of peripheral blood neutrophils, such as chemotaxis and predisposition to NETosis, in female patients with luminal breast cancer have not been sufficiently explored. Studying these parameters may provide new insights into the mechanisms of disease progression and response to therapy. AIM: This work aimed to analyze the chemotactic activity of neutrophils and predisposition to NETosis in blood samples of female patients with locally advanced luminal breast cancer undergoing treatment (neoadjuvant chemotherapy) at the Loginov Moscow Clinical Scientific Center. METHODS: The study was conducted on blood samples from six patients with stage 3 luminal B, HER2-negative breast cancer before and 2 months after the start of antitumor therapy. Blood samples from healthy adult volunteers were used as controls. The work was performed using fluorescence microscopy methods for neutrophil chemotaxis with the growth of blood clots and the number of extracellular DNA traps of neutrophils by reaction with Hoechst 33342 and antibodies against myeloperoxidase and neutrophil elastase in smears of blood plasma rich in leukocytes. RESULTS: Before the start of neoadjuvant therapy, the level of NETosis is significantly increased (30% ± 14% versus 4.6% ± 3.4% in healthy donors), whereas most female patients undergoing therapy experience its reduction (17% ± 17%). The speed of neutrophil movement is increased in some female patients (0.17 ± 0.06 versus 0.113 ± 0.009 μm/s in healthy donors) and goes down during therapy (0.10 ± 0.03 μm/s). At the same time, the number of neutrophils associated with blood clots decreases during therapy (25 ± 18 versus 61 ± 23) even in patients with neutrophilia. CONCLUSION: It has been demonstrated for the first time that in female patients with luminal B, HER2-negative breast cancer, the neutrophil chemotaxis speed deviates from the standard; at the same time, their adhesion is reduced, and peripheral blood neutrophils are significantly more predisposed to NETosis than in healthy donors.
Effect of kisspeptin-10 on sexual activity in male rats after exposure to restraint stress
BACKGROUND: Sexual dysfunctions are of high social significance, and their steady growth necessitates the search for new pharmacological targets for correction. Mental stress is a trigger of decreased sexual activity. Previously, the effect of predator presentation stress on sexual motivation of male rats was established, which manifested itself in a decrease in exploratory activity toward female rats in estrus. The neuropeptide kisspeptin regulates the hypothalamic-pituitary-gonadal system and is involved in the modulation of sexual behavior. AIM: This works aimed to assess the effect of kisspeptin-10 introduced centrally and peripherally on sexual behavior of rats after restraint stress. METHODS: Male Wistar rats were exposed to restraint stress. To assess sexual behavior, a male rat was placed in a cage with a female rat in estrus. The latency time to approach the female and the number of mounts per female within 3 minutes were recorded. RESULTS: The latency time for approaching female rats in stressed animals increased by 1.3 times (p < 0.01) compared to intact controls. After intranasal introduction of kisspeptin-10, the latency time decreased by 1.4 times compared to the control group (p < 0.05) and by 1.8 times compared to the stressed group without drug introduction (p < 0.001). After a single intraperitoneal introduction of kisspeptin-10, the latency time decreased by 2 times compared to the control group (p < 0.01) and by 2.6 times compared to the stressed group without drug introduction (p < 0.001). After a course of intranasal introduction of kisspeptin-10, the latency time decreased by 2.4 times compared to the control group (p < 0.01) and by 3 times compared to the stressed group without drug introduction (p < 0.001). After a course of intraperitoneal introduction of kisspeptin-10, the latency time decreased by 2 times (p < 0.05) compared to the control group and by 2.4 times compared to the stressed group without drug introduction (p < 0.01). After a single intraperitoneal introduction of kisspeptin-10, the number of mounts per female increased by 3.3 times compared to the control group (p < 0.001) and by 3 times compared to the stressed group without drug introduction (p < 0.01). After a course of intraperitoneal introduction of kisspeptin-10, the number of mounts per female increased by 3.7 times compared to the control group (p < 0.001) and by 3.3 times compared to the stressed group without drug introduction (p < 0.01). CONCLUSION: Kisspeptin-10 enhances sexual activity in male rats after restraint stress. Intranasal and intraperitoneal drug introduction triggers a reduced latency time of approaching a female rat. After intraperitoneal introduction, the number of mounts per female increases.
Molecular mechanisms involved in analgesic effects of 1-deamino-8-D-arginine-vasopressin under thermal exposure and electrocutaneous stimulation in rats
BACKGROUND: The analgesic properties of arginine vasopressin and its synthetic analogue, 1-deamino-8-D-arginine vasopressin, are known. However, it is difficult to use neuropeptides in clinical practice due to the possible development of side effects. The study of the molecular mechanisms and effects of 1-deamino-8-D-arginine-vasopressin in the management of various types of pain will allow us to identify new therapeutic targets and determine the conditions for the safe use of the peptide. AIM: The study aimed to evaluate the effect of intranasal 1-deamino-8-D-arginine-vasopressin administration on pain sensitivity, the content of monoamines and BDNF in the parietal cortex and spinal cord in thermal and electrocutaneous stimulation in rats. METHODS: 1-deamino-8-D-arginine-vasopressin was administered intranasally in a thermal pain model at 0.002 µg/day (0.01 µg/course) and 2 µg/day (10 µg/course); 0.02 µg/day (0.1 µg/course) and 2 µg/day (10 µg/course) for electrocutaneous stimulation. Serum corticosterone and brain-derived neurotrophic factor levels in the parietal cortex and spinal cord were determined using enzyme-linked immunosorbent assay. The levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT), and their metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), in the brain were determined using high-performance liquid chromatography. RESULT: 1-deamino-8-D-arginine vasopressin reduced pain sensitivity regardless of the type of pain and doses administered. The involvement of monoamines and brain-derived neurotrophic factor in the analgesic effects depended on the type of exposure and dose of the drug. NE and brain-derived neurotrophic factor at the supraspinal and spinal levels, 5-HT at the spinal cord level have been implicated in analgesia in the thermal pain model. During electrocutaneous stimulation, DA and 5-HT contributed to analgesia at the supraspinal level; 5-HT, DA and NE at the spinal level. 1-deamino-8-D-arginine-vasopressin did not affect the blood corticosterone in rats with different types of pain. CONCLUSION: The peptide caused reduced pain sensitivity under various influences. However, this effect in different conditions was due to different neurochemical mechanisms; in thermal pain, it was associated with the modulatory effect of the peptide on monoamine and BDNF levels in the brain or only monoamines in electrocutaneous stimulation.
Changes in the spectrum of extracellular vesicles produced by THP-1 cells during polarization toward M1 or M2 macrophages
BACKGROUND: Macrophages are capable of secreting extracellular vesicles that exert a wide range of biological effects, including modulation of the immune response under pathological conditions. AIM: The work aimed to compare the qualitative and quantitative composition of extracellular vesicles produced by THP-1 cells depending on the concentration and duration of activation with phorbol 12-myristate 13-acetate and the direction of polarization toward M1 or M2 macrophages. METHODS: THP-1 cells were activated with different concentrations of phorbol 12-myristate 13-acetate (100 and 10 ng/mL). Polarization toward M1 macrophages was induced using IFN-γ and LPS, and toward M2 using IL-4 and IL-13. Cells and their extracellular vesicles were immunophenotyped for CD80, CD64, HLA-DR, CD206, CD209, and CD163. Relative gene expression levels of IL-1β, IL-6, IL-8, IL-12p40, TNFα, CXCL10, CD163, CD206, CCL22, IL-10, FN, and GAPDH were assessed. The size and concentration of extracellular vesicles were measured by nanoparticle tracking analysis. The protein composition of extracellular vesicles was additionally assessed for the presence of tetraspanin receptors (CD9, CD63, CD82, and CD81) and flotillin-1. RESULTS: Activation of cells with high doses of phorbol 12-myristate 13-acetate followed by polarization toward M1, compared to M2, led to increased expression of CD80, CD209, and CD163. Regardless of the applied activation–polarization protocol, THP-1 cells were distributed into distinct, compact clusters according to the results of discriminant analysis of gene expression levels. Activation was accompanied by a more than 10-fold increase in extracellular vesicle production. High-dose phorbol 12-myristate 13-acetate activation followed by M1 polarization resulted in secretion of the highest number of extracellular vesicles (188×108 [185×108; 202.5×108] particles/mL), of larger size (134 ± 6.1 nm), and expressing CD63 and CD82. However, their flotillin-1 content was reduced. CONCLUSION: Thus, high-dose phorbol 12-myristate 13-acetate activation of THP-1 cells is more effective for subsequent polarization. Depending on the applied polarization protocol, cells produce extracellular vesicles differing in both quantity and composition.
Comparative analysis of key pathogenic factors of inflammatory bowel disease in in vitro and in vivo models
BACKGROUND: Inflammatory bowel diseases are characterized by inflammation of the intestinal mucosa and increased intestinal barrier permeability. When studying the biological effects of drugs, it is important that experimental models adequately reproduce the key pathogenic factors of the disease. AIM: The work aimed to compare the parameters of intestinal epithelial barrier permeability and inflammatory response in inflammatory bowel disease models: Caco-2 cells stimulated with lipopolysaccharides and mice with a knockout of the mucin 2 gene (Muc2–/–). METHODS: In the in vitro model of inflammatory bowel disease, Caco-2 cells were cultured in the presence of lipopolysaccharide at concentrations ranging from 0.1 to 100.0 μg/mL, and its effects on transepithelial electrical resistance, monolayer permeability, expression of the tight junction genes ZO-1 and Claudin-1 and the pro-inflammatory cytokines IL-8 and TNF-α, as well as IL-8 secretion, were evaluated. In the in vivo model of inflammatory bowel disease, mice with a knockout of the mucin 2 gene (Muc2–/–) were used. Intestinal permeability was determined by plasma fluorescein isothiocyanate-dextran concentration after intragastric administration. Histological analysis of colon samples was performed, with evaluation of TNF-α, IL-1β, and IL-10 gene expression and IL-1β and IL-10 protein levels. RESULTS: In in vitro experiments on Caco-2 cells, lipopolysaccharide at a concentration of 10 μg/mL reduced transepithelial electrical resistance by 57% and increased monolayer permeability to fluorescein isothiocyanate-dextran by 38%. At the same time, it increased IL-8 and TNF-α expression 2.8- and 2.3-fold, decreased ZO-1 and Claudin-1 expression by 54% and 53%, and increased IL-8 secretion 27-fold compared with the control. In vivo, intestinal permeability in Muc2–/– mice was 5.8-fold higher; IL-1β and TNF-α expression was 9.9- and 6.8-fold higher; IL-10 expression in Muc2–/– mice was 71% lower; IL-1β content in the colon was 94% higher, and IL-10 content was 44% lower compared with healthy mice. CONCLUSION: The studied in vitro and in vivo models of inflammatory bowel disease exhibit similar trends in intestinal permeability and inflammatory response parameters. These models adequately reproduce the relevant pathogenic factors and complement each other.
The previously unknown facts of the biography of Maria K. Petrova, a student and colleague of academician I.P. Pavlov, are presented. Archival research and analysis of previously inaccessible materials allowed to restore her biography hidden from the public by shedding light on the development of her personality and scientific perspective. Maria spent her early childhood far from St. Petersburg, in a small military garrison in the Caucasus. However, she graduated from high school in the capital of the Russian Empire. The discovered data both shed light on her childhood and youth and provide background information on her parents, spouse, brothers and sisters. This information allows us to reinterpret her decision to get a higher education and practice medicine and reveals the roots of her loyalty to Ivan Pavlov. The article describes Maria Petrova’s character traits, which allowed her to become an outstanding researcher rather than just a mother of a family. Her decision to get a medical degree could not but affect her relationship with her husband, Grigory S. Petrov, from whom she later divorced. Undoubtedly, the new findings will be an impetus for historians of science.