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Vol 25, No 3 (2025)
- Year: 2025
- Articles: 12
- URL: https://journals.rcsi.science/MAJ/issue/view/25895
- DOI: https://doi.org/10.17816/MAJ.253
Analytical reviews
Advantages and disadvantages of using silver nanoparticles in medicine. Benefits of silver nanoparticle composites with organic antibacterial substances and biocompatible polymers
Abstract
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.
5-21
Health status of military personnel after injuries sustained during combat operations
Abstract
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.
22-30
Therapeutic potential of exogenous mRNA encoding recombinant antibodies against viral pathogens
Abstract
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.
31-46
Modeling long-term consequences of poisonings caused by exposure to neurotoxicants: a review
Abstract
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.
47-55
Organophosphate-induced delayed neuropathy: an unresolved problem?
Abstract
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.
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Immunotropic therapy: blockade of CTLA-4/B7 and PD-1/PD-L1 pathways in the treatment of cancers. Part 1: immunologic aspects
Abstract
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.
69-77
Lecture
Microorganisms in modern biomedicine and biotechnology
Abstract
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.
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Original study articles
Morphological features of biodegradation and biocompatibility of combined polymeric matrices based on chitosan and hyaluronic acid
Abstract
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.
88-95
Synergistic effect of exogenous P53 and sodium butyrate on tumor cell survival
Abstract
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.
96-107
Histological features of the human anorectal lining at certain stages of embryonic development
Abstract
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.
108-114
DNA fragmentation and hydroxymethylation in ejaculated spermatozoa in normozoospermia and pathozoospermia
Abstract
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.
115-124
Characteristics of early–stage fibrosis model in chronic alcoholic liver disease in rats
Abstract
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.
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