Peer-rewieved journal "Siberian Scientific Medical Journal"
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3D modeling of the renal arterial bed: comparative analysis of visualization methods (ultrasonography, computed tomography and magnetic resonance imaging)
Modern imaging techniques provide various opportunities for assessing vascular anatomy, but their comparative effectiveness in creating accurate three-dimensional models of the renal arterial bed remains poorly understood. Material and methods. A systematic review of the scientific literature for the period 2005–2022 was conducted using the PubMed, Scopus, Web of Science and eLIBRARY.RU databases. Technical characteristics, diagnostic capabilities and limitations of ultrasonography, computed tomography and magnetic resonance imaging were analyzed. Results. Ultrasonography is an accessible screening method, but has limitations in constructing accurate 3D models. Computed tomography angiography provides the highest spatial resolution and detailing of vascular architecture, but is associated with radiation exposure and the risk of nephropathy. Magnetic resonance imaging represents an optimal balance between visualization quality and safety, especially with the use of non-contrast techniques and dynamic sequences. Conclusions. It is advisable to use a comprehensive approach using complementary visualization methods to create accurate threedimensional models of renal arterial vessels, which allows compensating for the limitations of each individual method. The introduction of modern 3D modeling technologies into clinical practice helps improve preoperative planning and increase the safety of organ-preserving kidney surgeries, which is of fundamental importance for a personalized approach in modern urology and vascular surgery.
Targeting the feminized nature of prostate cancer exploring estrogen-driven metabolic reprogramming and its therapeutic intervention: а narrative review
Prostate cancer (PCa) has long been classified as an androgen-driven malignancy; however, mounting evidence underscores the pivotal role of estrogen in its initiation, progression, and therapeutic resistance. This review establishes that PCa exhibits intrinsic estrogen dependence through intratumoral aromatization, positioning it within the spectrum of estrogen-driven malignancies. Through integrative molecular analyses, we elucidate how estrogen orchestrates metabolic reprogramming, shifting prostate tumors toward enhanced lipid oxidation and glucose uptake a hallmark of glucolipotoxicity. Mechanistically, estrogen signaling, primarily via the PI3K/AKT pathway, drives the upregulation of carnitine palmitoyltransferase 1 and glucose transporter 1, fueling a metabolic storm characterized by oxidative stress, mitochondrial dysfunction, and chronic inflammatory signaling. This metabolic adaptation enables androgenindependent survival, presenting a critical vulnerability overlooked by conventional androgen-targeted therapies. Our findings necessitate a paradigm shift in the classification and treatment of PCa, advocating for a novel therapeutic framework targeting the estrogen–metabolic axis. We propose a precision strategy integrating aromatase inhibition, estrogen receptor blockade, and metabolic stress modulation to counteract castration-resistant disease. Recognizing PCa as an estrogen-driven, metabolically adaptive malignancy transforms its clinical understanding and therapeutic approach, demanding urgent reconsideration of current oncologic paradigms.
Peculiarities of inhibitory receptor expression on effector and regulatory T cells in the context of immune checkpoint inhibitor therapy
Inhibitory receptors PD-1, TIM-3, LAG-3, etc. – “immune checkpoints” – are expressed by activated effector T cells in order to limit the intensity of the immune response. Under the conditions of chronic infectious process and tumor growth, checkpoint receptors are expressed by T lymphocytes in a state of T cell exhaustion, characterized by a decrease in its proliferative, cytotoxic and cytokine-producing activity. Restoring the functional activity of T cells underlies the mechanism of action of therapeutic monoclonal antibodies – “checkpoint inhibitors”, such as anti-PD-1/PD-L1 and antiLAG-3 used in antitumor therapy. At the same time, checkpoint receptors are expressed by multiple cell populations, including regulatory T cells (T-regs), which suppress immune response. Data on the functions of inhibitory receptors on T-reg continue to be studied. In this article, we provide the recent knowledge on T-reg populations’ expression of inhibitory checkpoint receptors and how these relate to checkpoint inhibitor therapy’s outcomes.
Epidemiological, etiopathogenetic, pathophysiological characteristics of deforming arthrosis of the hip joint and predictors of its development (literature review)
The aim of the study was to review the literature on coxarthrosis, one of the main problems of modern orthopedics. Material and methods. A search was performed for literature sources for 2018–2023 devoted to the study of the problem of osteoarthrosis of the hip joint in modern traumatological and orthopedic practice in order to outline ideas about the etiopathogenetic, epidemiological and pathophysiological characteristics and early diagnosis of the disease. The following databases were used: Pubmed, ResearchGate, eLIBRARY.RU, CyberLeninka; dissertations, dissertation abstracts, and materials from scientific forums were excluded. As a result of the search, more than 53 articles on this topic were found and analyzed. Research interest in the problem of coxarthrosis has increased significantly in the last decade, which reflects the social significance of the disease. Results. Current information on the initiation and development of hip joint osteoarthrosis is systematized. The results of studies on the epidemiological and pathogenetic characteristics of coxarthrosis are reflected, the relationship of the chemical composition of bone tissue and synovial fluid with its development is determined, the main clinical manifestations and methods of early diagnosis are described. The issue of actively expressed genes involved in the metabolic processes of connective tissue is considered. The main predictors of coxarthrosis are identified: genetic, non-genetic, bioimpedance. A problem of the population is presented: with an increase in life expectancy, loss of working capacity as a result of degenerative-dystrophic disease. Conclusions. The literature review presented modern scientific articles, reviews, meta-analyses devoted to coxarthrosis and its characteristic features. New research directions in genetics, immunology, problems of diagnostics and timely detection of this pathology were described.
Paranasal sinus and nasal cavity dimensions determined by computed tomography in relation to skull shape, sex and age
This literature review is devoted to the study of the sizes of the paranasal sinuses and nasal cavity, determined by computed tomography, depending on the shape of the skull (megacephalic, dolichocephalic, brachycephalic), gender and age. The main craniotypes – mesocephaly, dolichocephaly and brachycephaly – form the morphological features of the skull, which are directly reflected in the anatomy of the nasal cavity and sinuses. The study of the morphometric characteristics of the paranasal sinuses (maxillary sinuses, frontal, latticed, sphenoid sinuses) and the nasal cavity (length of the nasal cavity, width, height of the choana, length and width of the middle and lower nasal concha) depending on craniotype, gender and age is an important area of modern anatomy, anthropology and clinical morphology. One of the key aspects of these studies is the identification of the anatomical dimensions of the nasal cavity, the paranasal sinuses of the nose and the correlation of these parameters with each other depending on individual anthropometric characteristics. The anatomical and physiological features of the sinuses, their relationship with the morphology of the skull, as well as sex and age differences are considered. Modern investigations were analyzed to identify gaps in the study of anatomical variations of the paranasal sinuses and nasal cavity, taking into account craniotype, gender and age, which can significantly expand the understanding of their morphological variability. Visualization technologies are considered ‒ one of the most informative tools for studying the morphology of the paranasal sinuses.
Methods for predicting the risks of developing cardiovascular diseases
Forecasting the risks of developing cardiovascular diseases (CVD) is one of the priority tasks of modern preventive medicine. One of the promising areas is the use of machine learning methods and mathematical modeling, which allows considering the combined impact of diverse risk factors. Aim of the study was to summarize and analyze research data devoted to methods for predicting the risk of developing CVD. Material and methods. The information search was carried out in the PubMed, eLibrary, and CyberLeninka databases for the period from 1961 to 2025. A total of 820 sources were analyzed, of which 68 were included in the review. Results and discussion. The review provides an analysis of methods for predicting the development of chronic non-communicable diseases (CVD, prognosis of the ten-year risk of developing CVD and death from them). The development of this area in foreign and domestic medicine is shown in chronological order and the most common methods for predicting the development of circulatory system diseases are presented. The article provides argumentation for the active use of artificial intelligence methods in the field of preventive medicine, which allow processing big data and taking into account various combinations of risk factors. Conclusions. To ensure high accuracy of prognostication of CVD, it is important to consider a wide range of risk factors (ethnic, socioeconomic, cultural, behavioral, medical and biological, production process factors) that operate within the framework of a separately studied group.
The possibilities of blockchain technologies application in the healthcare sector
The article is addressed to analysis of possibilities and prospects for integration of blockchain technologies (BT) in the healthcare sector. BT, originally developed for cryptocurrencies, offers unique advantages such as decentralization, data immutability, transparency and security, which makes it especially relevant for medical sphere. Key applications include medical data management, telemedicine, pharmaceutical logistics, clinical research, and health insurance. In medical data management, BT solves the problems of data fragmentation and security by providing unified access to electronic medical records and protecting them from unauthorized access. Examples of successful projects such as Guardtime and Medicalchain demonstrate efficiency of BT application for data storage and exchange. In telemedicine, blockchain guarantees security of remote consultations, as shown in the Patientory and Robomed Network projects. In the pharmaceutical industry, these technologies help to track supply chains and combat counterfeiting, which is implemented in the Mediledger and Blockpharma platforms. The prospects for the development of BT in healthcare remain promising, especially in combination with areas such as personalized medicine and artificial intelligence. However, despite the advantages of BT, their implementation faces a number of challenges, including high cost, energy consumption, scalability difficulties, and legislative barriers. In addition, an important aspect is the need to achieve «cultural adaptation» to these technologies among medical professionals and patients. In conclusion, blockchain technologies have significant potential to transform healthcare, but their successful implementation requires addressing technical, organizational, and regulatory issues, as well as the active participation of all stakeholders.
The impact of metabolic disorders on the therapeutic efficacy and toxicity of amiodarone: mechanisms and management strategies
Amiodarone is one of the most effective and commonly prescribed class III antiarrhythmic agents. However, its pharmacokinetics may be impaired and toxicity may be aggravated by metabolic disorders. The review presents data showing that dyslipidemia, obesity, and type 2 diabetes mellitus significantly affect pharmacokinetics, pharmacodynamics and toxic profile of amiodarone. These conditions alter the drug’s binding to lipoproteins, the activity of cytochrome P450- dependent monooxygenases and tissue distribution, thereby increasing the risk of accumulation and toxic effects. Chronic heart failure further impairs drug metabolism and contributes to multisystem toxicity. The current clinical guidelines do not adequately address these critical aspects. Therefore, more rigorous monitoring of these patients and their plasma drug concentration (on individual basis) is suggested, along with a generally more cautious approach to amiodarone use. Future perspectives include prospective clinical trials on amiodarone, physiologically based pharmacokinetic modeling for personalized dosing, based on body mass index, lipid profile, and comorbidities, pharmacogenomic studies (cytochrome P450 polymorphisms), as well as biomarker discovery for drug toxicity prediction.
The effect of biologic disease-modifying antirheumatic drugs on the pathology of the hemostatic system in patients with rheumatoid arthritis
Patients with rheumatoid arthritis (RA) have an increased risk of developing atherosclerosis. A significant contribution to the progression of atherosclerotic arterial disease in patients with RA is made by activation of the hemostatic system and systemic inflammation. Biologic disease-modifying antirheumatic drugs (bDMARD) are increasingly used in patients with RA. Considering the relationship between systemic inflammation and hemostatic disorders, it is not unreasonable to assume that bDMARD may have an effect on the hemostatic system in patients with RA. The aim of the study is to demonstrate the effect of bDMARD on the hemostasis system based on the analysis of scientific research data, as well as evaluate the relationship between systemic inflammation and hypercoagulation in patients with RA. Material and methods. The search for publications was carried out in scientific databases Scopus, Web of Sciences, PubMed, the Cochrane Library, and eLibrary. The following keywords and phrases were used as search markers: rheumatoid arthritis, atherosclerosis, hemostasis, thrombosis, antirheumatic therapy, cytokines, systemic inflammation. Search depth – 2014– 2024. Results and discussion. The beneficial effect of bDMARD on reducing the prothrombogenic potential in patients with RA is associated with a decrease in systemic inflammation, modification of cytokine status, and improvement of endothelial function. There is evidence of a negative effect of bDMARD on the hemostatic system in patients with RA, which is reflected in an increased risk of venous and arterial thrombosis and the development of bleeding. Conclusions. Studying the effect of bDMARD on the blood coagulation system, as well as clarifying the pathogenetic relationships between the pathology of hemostasis and systemic inflammation in patients with RA is of significant scientific interest from the point of view of both reducing the risk of developing cardiovascular diseases, preventing thromboembolic complications, and searching for new therapeutic targets.
Role of endothelin-1 and intercellular adhesion molecules in women with miscarriage and infertility
A literature review was prepared using information databases eLIBRARY.RU, Google Scholar and PubMed for the period 1990–2025. The selection criterion was information on concentrations of endothelin-1, intercellular adhesion molecules in practically healthy women and patients with nonpregnancy and infertility. Data on the role of endothelin-1 and intercellular adhesion molecules in the mechanisms of regulation of endothelial dysfunction are presented. The necessity of development of normative limits of these molecules’ concentration in women during planning and course of pregnancy as well as identification of therapeutic targets for infertility treatment and prevention of reproductive losses is shown.
Application of artificial intelligence for cardiac imaging studies: a brief literature review
Cardiovascular diseases remain the leading cause of disability and mortality. The WHO considers them the main cause of death worldwide. In recent years, artificial intelligence and neural networks have been rapidly developing and are successfully applied in cardiology. Deep learning has become a key tool in the diagnosis of cardiovascular diseases, allowing the identification of complex patterns and relationships in data, automating the segmentation of regions of interest. Deep learning methods contribute to accurate diagnosis using echocardiography, magnetic resonance imaging (MRI), and computed tomography (CT), which can alter the natural course of the disease and reduce healthcare costs. The aim of this work is to review the application of artificial intelligence, particularly deep learning, in cardiac imaging studies (CT, cardiac MRI, echocardiography). Material and methods. The material for the review consisted of 35 articles published between 2013 and 2024. The search was carried out using the search query “deep learning AND (cardiac imaging OR CT OR cardiac MRI OR echocardiography)” in the international databases Scopus, PubMed, and Web of Science. Results. One of the main limiting factors for the application of imaging studies with subsequent neural network analysis is segmentation, which requires a clear definition of the tissue region of interest. The manual approach to segmentation has drawbacks, such as labor intensity and significant variability between researchers. To overcome these limitations, deep learning models have been developed to automate the segmentation process. It involves training various neural network architectures on image datasets, which allows for automatic segmentation with high accuracy and analysis of myocardial status. Cardiac MRI provides valuable information about the state of the myocardium, including anatomy, heart chamber volumes, the presence of fibrosis and inflammation. Automatic segmentation of individual tissues, such as fibrous tissue, allows for a more accurate assessment of the extent and severity of fibrosis, which is necessary for risk stratification and treatment planning. Conclusions. The application of deep learning in the analysis of cardiac imaging studies has enormous potential for improving the early diagnosis and management of cardiovascular diseases. Deep learning-based neural network models can be used as a screening method for the automated diagnosis of cardiovascular diseases.
Artificial intelligence in aesthetic and reconstructive surgery: Clinical applications, ethical challenges, and future trends
Artificial intelligence (AI) and machine learning (ML) are increasingly influencing aesthetic and reconstructive surgery. These technologies are transforming clinical workflows by enhancing precision, personalization, and operational efficiency across various stages of surgical care. Aim: To review the current applications, measurable benefits, and challenges of AI and ML in aesthetic and reconstructive surgery, and to explore their potential future impact on the field. Material and methods. This review synthesizes findings from recent studies, technological assessments, and clinical applications of AI and ML in surgical practice. Key areas examined include preoperative planning, imaging, robotic systems, intraoperative tools, and postoperative monitoring. Results. AI and ML have been shown to reduce surgical planning time by up to 35 % and improve breast symmetry assessment accuracy by over 90 %. Robotic systems and AI-powered automation enhance minimally invasive procedures and optimize intraoperative decisions. Furthermore, AI supports postoperative care through predictive modeling, complication monitoring, and real-time data interpretation. Despite these advances, challenges persist, including algorithmic bias, data privacy concerns, and the need for robust clinical validation. Conclusions. AI and ML are poised to significantly reshape aesthetic and reconstructive surgery. As these technologies continue to evolve, addressing ethical and regulatory challenges will be essential for their safe and effective integration into clinical practice.
Prenatal and perinatal risk factors for intellectual and speech development disorders in children: a narrative literature review and retrospective analysis results
Speech skills and intelligence level are crucial in determining a person’s success in various areas of life. Data from numerous studies on the influence of pre- and perinatal factors on children’s neurocognitive development remain contradictory, despite the fact that knowledge in this area potentially has significant practical implications. This article presents a narrative review of current literature on the impact of pre- and perinatal factors on speech and intellectual development in children, as well as the results of our own retrospective study of a sample of preschool children from the Nizhny Novgorod region of Russia. Data were obtained on the negative association of preterm birth, gestational diabetes mellitus, threatened miscarriage, cesarean section delivery, and hypertensive disorders during pregnancy with children’s speech and intellectual development. Taking these factors into account at early stages of ontogeny (preschool age) and timely correction of speech and intellectual functions may help preventing school underachievement and improving a child’s adaptation to the academic environment.
Variant anatomy of three-dimensional models of the brachial plexus in augmented and virtual reality
Modern surgical principles for repairing damaged nerves in brachial plexus injuries require individual and high-quality surgical planning based on the anatomy of a particular patient, as well as precise navigation during surgery. The aim of the study is to identify the correspondence of the variants of the brachial plexus structure on drugs and three– dimensional models for their use in augmented and virtual reality. Material and methods. 44 three-dimensional digital and polymer models of the right brachial plexuses were created from 22 corpses of men and women aged 39–89 years. The accuracy of the reconstruction was verified by determining the structural variant of the brachial plexus in the preparations and three-dimensional models. Results and discussion. The created three-dimensional digital and polymer models accurately reflect the structural variants of brachial plexus preparations, but not equally in the presence or absence of epineurium. At the epineural level, 7 variants of the structure of preparations and three–dimensional models of the brachial plexus were identified, and 4 at the perineural level. The identified variants differ in the number of spinal nerves and the structural features of the divisions of the middle and lower trunks. All three-dimensional digital models of the brachial plexus have been converted to the STL format and projected onto the surface of the human body using augmented reality and virtual reality to different depths of the digital twin. Conclusions. The created database of 44 three-dimensional digital and polymer models of 7 variants of the brachial plexus structure at the epineural and 4 at the perineural levels, projecting them onto a specific patient or a digital twin, allows performing operations in augmented and virtual reality conditions.
Interrelationships between gut microbiome and serum medium mass molecules in menopausal women
During menopause, the composition of the gut microbiota undergoes changes. At the same time, age-related deficiency of sex hormones occurs, which is considered the basis for the development of metabolic disorders, including oxidative and carbonyl stress, and this may be one of the reasons for the change in the medium mass molecules (MMM) content. Aim of the study was to establish the relationship between the MMM level and representatives of the gut microbiota in menopausal women. Material and methods. The study involved 98 women who met the following criteria: age from 45 to 69 years, amenorrhea or menstrual irregularities, anti-Müllerian hormone level less than 1.2 ng/ml. Exclusion criteria: exacerbation of chronic and presence of infectious diseases, diabetes mellitus, taking antibacterial drugs during the last three months. A quantitative assessment of the state of the gut microflora was performed using the test system Kolonoflor-16 (premium) by PCR. The MMM content was assessed in blood serum by a spectrophotometry at 238, 254, 260 and 280 nm with subsequent calculation of distribution ratio. Results. The presence of a linear relationship between the MMM content and the gut microbiome composition was revealed: an increase in the total bacterial mass, as well as the content of Bacteroides spp., Roseburia inulinivorans in fecal samples, positively correlates with the MMM level determined at all wavelengths. Bacterial indicators are also associated with distribution ratio 238/260 and 238/280. Conclusions. In menopausal women, the MMM level is interconnected with the volume of gut microbiota and the content of its individual representatives, however, changes in these indicators cannot be unambiguously interpreted as pathological, since this can be part of natural physiological processes.
Application of factor analysis in assessing the effectiveness of wound treatment
Despite the development of surgery, the problem of wound treatment remains relevant today. The effectiveness of therapy is usually assessed by a number of parameters, and the effect of the drug may not be the same in relation to each of them. Therefore, in this regard, it is necessary to apply statistical analysis methods that allow us to reduce the dimensionality of the studied indicators and to identify those that correlate with each other and play a key role in assessing the effectiveness of treatment. The aim of the study was to evaluate the effectiveness of wound treatment based on factor analysis in experiment. Material and methods. The course of the wound process was studied using the following parameters on the model of aseptic, infected and purulent-necrotic wounds in Wistar rats: local temperature, wound area, wound size reduction rate, content of creatinine, urea, alanine and aspartate aminotransferase activity, hydroxyproline level in wound tissues, wound morphometric parameters and contamination level. The efficacy of the proposed wound dressings was assessed using factor analysis, namely principal component analysis. The resulting principal components were standardized and subsequently categorized into quartiles. Results and discussion. It was found that the significance of the first factor was 1.9–4.2 times greater than the other factors, which made it the most significant in the subsequent ranking of the normalized variables. Thus, animals in the groups where the treatment was carried out with chitosan-collagen complexes with silver or with lidocaine and dioxidine (respectively in relation to the aseptic and infected wound) always fell into the group with excellent and good treatment results according to the first factor, and the animals receiving chitosan-collagen complexes with silver and chymotrypsin – in 70–100 %. Conclusions. The use of factor analysis allowed us to reduce the dimensionality of the parameters under study, identify the most important of them and group indicators according to the strength of their correlation. At different stages of the wound healing process, different parameters were combined into factors, which should also be considered when identifying significant markers at different stages of the wound healing process.
Potentiation of the restorative effect of semaglutide on metabolic and hormonal parameters in rats with diet-induced type 2 diabetes mellitus with intranasally administered insulin
Semaglutide, a glucagon-like peptide-1 receptor agonist, is widely used for the treatment of type 2 diabetes mellitus (DM2), but it is not effective in some patients, which requires the development of approaches to enhance its therapeutic effect. The combined use of semaglutide with other drugs is promising, including intranasally administered insulin (IAI), which improves certain metabolic and hormonal parameters in DM2 through central mechanisms. Aim of the study was to investigate the effects of combined and separate administration of semaglutide and IAI to male rats with DM2 on the body weight and fat mass, metabolic and hormonal parameters, including thyroid hormone levels. Material and methods. DM2 was induced by a high-fat diet (15 weeks) and streptozotocin injection (15 mg/kg). Semaglutide (50 μg/kg/day, subcutaneously) and IAI (0.5 and 2.0 IU daily per rat) were administered separately and together for 4 weeks. Hormonal levels were measured using ELISA, glucose tolerance and glucose-stimulated insulin and leptin content were assessed by a glucose tolerance test. Results. The combined use of semaglutide and IAI normalized the body weight and adipose tissue and restored the glucose homeostasis, insulin sensitivity, and lipid metabolism. The combination of semaglutide and IAI was superior to semaglutide monotherapy in terms of fat loss, normalization of glucose and glycated hemoglobin levels in the blood, and weakening of insulin resistance. Semaglutide restored the thyroid hormones concentration decreased at DM2. In the group treated with semaglutide and 2.0 IU IAI, the increase in free triiodothyronine level and the free triiodothyronine/free thyroxine ratio was more pronounced than with semaglutide monotherapy, indicating potentiation of the latter’s effect on the thyroid axis in the presence of IAI. Conclusions. A model of DM2 in rats has shown that combination therapy with semaglutide and IAI is superior to semaglutide monotherapy in terms of its ability to restore a number of metabolic and hormonal parameters, and this effect depends on the dose of IAI.
The dual-action monophenolic antioxidant TS-13 accelerates hair coat restoration in a mouse model of chemotherapy-induced alopecia
Chemotherapy remains a mainstay in the treatment of malignant neoplasms, and the search for strategies to overcome or mitigate its side effects, including hair loss (CIA, chemotherapy-induced alopecia), remains extremely important. Despite the proven role of oxidative stress in the pathogenesis of CIA, the number of studies on the potential use of antioxidants for its prevention and treatment is limited. The aim of the study was to investigate the effect of the monophenol sodium 3-(3′-tert-butyl-4′-hydroxyphenyl) propylthiosulfonate (TS-13), which possesses direct and indirect antioxidant activity, on hair regrowth in mice modeling CIA. Material and methods. The study was performed on 30 outbred mice of both sexes, divided into 4 groups. Group 1 animals served as controls (n = 7). Mice in Group 2 received TS-13 in drinking water at a dose of 100 mg/kg body weight starting 14 days before depilation and throughout the experiment (Group “TS-13”, n = 7). CIA was modeled in mice of Group 3 (Group “CIA”, n = 8) and Group 4 (Group “CIA + TS-13”, n = 8). Animals in Group 4 received TS-13 in drinking water throughout the entire experiment. The backs of all animals were shaved, and the treated areas were depilated. On day 9, mice in Groups 3 and 4 received an intraperitoneal injection of cyclophosphamide solution (120 mg/kg body weight). Subsequently, the backs were photographed every other day, and the obtained images were analyzed. On day 51, the animals were euthanized, organs (liver, heart, left kidney, spleen) were extracted and weighed. Results and discussion. No significant differences in body weight dynamics were observed between the groups during the experiment; only a tendency towards weight loss was detected in males receiving cyclophosphamide on day 17 (p = 0.0662). In mice of the control group and those receiving TS-13 in drinking water, intensive hair growth began on days 11–13 of the experiment, with complete hair regrowth occurring by days 13–15. In animals of the CIA group, the phase of pronounced hair growth was significantly delayed, starting on day 25 and reaching complete regrowth only by day 40. Administration of TS-13 to mice with CIA (Group 4) accelerated the process, although not to the level of the intact control (Group 1, p = 0.015) or the positive control (Group 2, p = 0.002). Rapid hair growth began on day 17, and complete hair regrowth occurred on day 31; the difference compared to Group 3 was statistically significant (p = 0.004). Conclusions. TS-13 administration accelerates hair regrowth in mice with CIA model, although it does not completely abolish cyclophosphamide’s ability to induce hair loss. We consider the latter a positive outcome, indicating that the substance does not negate the key therapeutic effect of antitumor agents – their antiproliferative action.
Changes in the intestinal microbiota of female Wistar rats with chemically induced breast cancer
Breast cancer (BC) is the leading cancer in terms of incidence and is among the five most lethal malignant tumors in the world and in Russia. The number of studies revealing the relationship between microbiota and the occurrence and/or progression of BC, as well as other oncological diseases, is increasing. Intestinal microbiota is considered as a potential diagnostic and prognostic oncobiomarker. The aim of the study was to conduct a metagenomic analysis of the intestinal microbiota composition using 16S rRNA gene sequencing in female Wistar rats with chemically induced BC and subsequent chemotherapy, surgery, and a combination of these treatment methods. Material and methods. The studies were performed on mature female Wistar rats. At the beginning of the experiment, the age of female Wistar rats was 3 months, and the weight of the animals was 250–300 g. For the study, 5 groups were formed: intact rats (n = 6); rats with BC without treatment (n = 7); rats with BC that received chemotherapy alone (n = 8); rats with BC that received only surgical removal of the tumor (n = 10); rats with BC that received surgical removal of the tumor and chemotherapy (n = 9). Fecal samples from the studied groups of rats were collected for subsequent metagenomic analysis by 16S rRNA gene sequencing, which was performed using the MiSeq System (Illumina, USA) with the MiSeq Reagent Kit v2 (500-cycles) with 2×250 bp double-ended reads. Results and discussion. The most of the isolated bacteria in the experimental groups belonged to the Firmicutes and Bacteroidetes types, typical representatives of the gastrointestinal tract microbiota of Wistar rats. In the group with ВС without treatment, dysbiosis was observed in the intestinal microflora due to an increase in the level of Bacteroidetes and the number of bacteria such as Actinobacteria. After chemotherapy, a decrease in the level of Firmicutes with an increase in the number of Bacteroidetes and Proteobacteria was found, after surgical treatment an increase in Verrucomicrobia was revealed, due to the effect of Verrucomicrobia on the reparation of the surgical wound. With chemically induced ВС, as well as with different treatment methods, a decrease in the Firmicutes /(Firmicutes + Bacteroidetes) ratio was found in the intestines of rats compared to the intact animals. Further studies in breast cancer patients are needed to understand whether this ratio can be used as an additional diagnostic biomarker for ВС.
Effect of phytocomplex consisting of rice husk, green tea and sea buckthorn on bone tissue in osteoporosis model in rats
Osteoporosis develops due to an imbalance between the processes of bone tissue formation and destruction. The aim of the study was to investigate the effect of a phytocomplex with a combined composition of a mixture of rice husk, green tea and sea buckthorn cake on bone tissue in a model of osteoporosis in rats. Material and methods. Liquid chromatography and mass-spectrometry were used to determine the content of active compounds (katechins and flavonoids) of phytocomplex with rice husk, green tea and sea buckthorn. The study was conducted on female Wistar rats (n = 32) at the age of 3 months. Osteoporosis was induced by ovariectomy. Phytocomplex, reference drug or a saline solution was administered to the animals for 4 weeks. Bone density was studied using computed tomography of the femur. Histological evaluation of bone tissue was performed by Van Gieson staining. Results and discussion. It was discovered that the phytocomplex contains L-epicatechin, kempferol and isoramnetin. Animals undergoing ovariectomy develop osteoporosis as demonstrated by computed tomography. After administration of the phytocomplex and the reference drug to animals with simulated osteoporosis, bone density was significantly higher compared to the saline injection group (989 and 1018 HU, respectively). In animals receiving the phytocomplex, less intense coloration of collagen fibers than in the control, but areas with newly synthesized collagen fibers appeared around the Haversian canals and in the outer areas of bone trabeculae. Conclusions. When administered orally for 4 weeks, the phytocomplex with a combined composition of a mixture of rice husk, green tea and sea buckthorn cake leads to an increase in bone density and promotes the formation of collagen fibers in bone tissue in osteoporosis in rats. This phytocomplex can be considered promising for maintaining bone tissue in osteoporosis.
The state of the endothelium and the level of neuron-specific markers of nerve tissue damage in rats with chronic malathion intoxication and methods of correction
The state of the vascular endothelium, the severity of neurodegenerative processes, their relationship, as well as possible correction methods for chronic malathion intoxication have not been practically studied. The aim of the work was to study the dynamics of the morphological and functional state of the endothelium, the level of markers of brain tissue damage in rats with chronic malathion intoxication, to evaluate the effectiveness of low-intensity laser radiation (LILR), a complex compound of 5-oxy-6-methyluracil with succinic acid (OMU-SA), and L-arginine preparation as correction agents. Material and methods. The experiments were conducted on male rats in which chronic intoxication was simulated by intragastric administration of malathion at a dose of 0.05 LD50 daily for 90 days. The levels of nitric oxide (NO), endothelin-1, nitrotyrosine, circulating desquamated endothelial cells (CDEC), neuron-specific enolase (NSE), and protein S-100 in blood serum on days 30, 60, 90, and 120 of the experiment were studied. Results and discussion. Against the background of chronic intoxication with malathion, rats develop signs of endothelial dysfunction, which are manifested in the form of a progressive increase in the level of CDEC, endothelin-1, nitrotyrosine and a decrease in NO concentration, neurodegenerative processes also develop and the permeability of the blood-brain barrier increases: NSE and protein S-100 levels on day 90 they increase by 1.65 and 2.09 times, respectively. A relationship has been found between the degree of endothelial dysfunction and the severity of neurodegenerative processes in the brain, which has a time dependence; morphological and functional changes in the endothelium precede neurodegenerative changes. LILR, OMU-SA, and the L-arginine preparation correct endothelial dysfunction to the greatest extent when they are used together, as a result of which the content of NSE and protein S-100 in the blood serum is reduced both on day 90 of chronic intoxication malathion and on day 120 in the post-intoxication period, which indicates a decrease in the manifestations of an inflammatory reaction in the brain substance. Conclusions. Chronic intoxication with malathion is accompanied by endothelial dysfunction and neurodegeneration, the severity of which is reduced by the combined use of LILI, OMU- SA and L-arginine.
Cytokine regulation in practically healthy women and patients with miscarriage living in the European North and the Arctic regions of the Russian Federation .
Immunological factors, manifested in the form of systemic and local changes in the immune status, occupy a central place in the etiology of reproductive losses. Cytokins, having primary local effects, with an increase in their concentration in the systemic bloodstream, acquire systemic effects. The purpose of the work is to study the influence of increased and reduced concentrations of cytokines on the immune status of women in the European North and Arctic. Material and methods. 229 women of reproductive age 20–40 years were examined, of which 209 are practically healthy and 20 patients with miscarriage in the early stages of 5–7 weeks. The immunological parameters of venous blood have been studied depending on the concentration of cytokines IL-6, IL-1β, IFN-γ and IL-10 in the blood. Results. In the practically healthy women of the European North and the Arctic, the increased concentrations of IL-1β (in 29.21 and 59.46 % cases, respectively) are associated with a decrease in the level of mature T-lymphocytes, T-character, and T-cytotoxic lymphocytes, activated T-lymphocytes with a transferrin receptor, to IL-2, molecules of the main complex of the main complex histocompatibility of class II and swords with apoptosis against the background of increasing levels of circulating immune complexes. The increase in the concentration of the IFN-γ (by 1.11 and 67.42 % cases, respectively) is interconnected with the suppression of proliferation and apoptosis processes, and the increase in IL-6 level (in 2.22 and 15.73 % cases) ‒ with the activation of cellular-mediated cytotoxicity and adhesive ability of the cell. Increase in concentration of the natural inhibitor of the IL-10 immune reaction (22.52 and 12.34 % cases, respectively) is associated with the decrease in number of leukocytes, of differentiated, activated lymphocytes and cells, swept for death. In women with miscarriage in the early stages in large numbers (85%) decrease in blood IL-10 concentration was recorded, negatively affecting the ability of the fetus during pregnancy due to increased cytotoxicity, activity of NK-lymphocytes, as well as cells programmed to death, and increased reagin production against the background of raised concentration of circulating immune complexes. Conclusions. Increase of cytokine concentration in the practically healthy women of the European North and Arctic is accompanied by a decrease in the number of all circulating T lymphocytes, mature, T helper, cytotoxic lymphocytes, T lymphocytes with a transferrin receptor, with IL- receptor 2, bearing molecules of the main complex of histocompatibility of class II, and a inhibition in the processes of the proliferation and apoptosis against the background of an increase in the circulating immune complexes concentration, as well as an increase in cellular cytotoxicity and adhesive ability of cells. In women with miscarriage in the early stages there is a deficiency of IL-10, which negatively affects the ability to bear the fetus during pregnancy.
Time in ranges and glucose variability in patients with type 2 diabetes on different regimens of insulin therapy
Insulin is used in the treatment of a significant proportion of patients with type 2 diabetes (T2D), while many patients do not achieve glycemic control targets. Aim of the study was to assess the achievability of target parameters of time in ranges and glucose variability (GV) in hospitalized patients with T2D during insulin therapy adjustment under the control of continuous glucose monitoring (CGM) and to determine factors influencing these parameters. Material and methods. A retrospective comparative single-center study was conducted in real world settings. Patients were divided into 3 groups: 1) basal insulin (BI) therapy; 2) pre-mixed insulin (PMI) therapy; 3) basal-bolus insulin therapy (BBIT) in the mode of multiple daily injections. Time in the target range (TIR), time in the range above and below the target (TAR L-1, TAR L-2, TBR-L1, TBR L-2), coefficient of variability (CV), mean amplitude of glucose excursions (MAGE), lability index (LI), and mean absolute glucose rate of change (MAG) were derived from CGM recordings. Results. The study recruited 371 patients (167 were on BI, 40 on PMI, and 164 on BBIT). The mean glucose level, TIR, TBR, and TAR L-1 did not differ between three groups. TAR L-2 values and GV indices (CV, MAGE, LI) were higher in patients on BBIT than in those on BI. Patients on PMI did not show significant differences from other groups. In multivariate regression analysis, C-peptide level turned out to be an independent predictor of CV, MAGE, and LI; body mass index was associated with MAG and LI. Conclusions. Correction of insulin therapy under the CGM control allows achieving target glucose values in most patients with T2D. Patients on BBIT have higher GV than those on BI at similar TIR. The GV parameters in patients with T2D on insulin therapy are inversely associated with endogenous insulin secretion (C-peptide level).
Idiopathic infertility in men of different ethnic groups: 8-hydroxy-2`-deoxyguanosine as a marker of oxidative stress
Oxidative stress is a proven factor in male infertility. Recently, there is increasing evidence that 8-hydroxy-2'- deoxyguanosine (8-OHdG) is considered an accurate and sensitive biomarker of oxidative DNA damage. Studies that revealed ethnospecificity of the course of lipoperoxidation processes suggest differences in oxidation of not only lipids but also DNA in men of different ethnogroups. Aim of the study was to evaluate free-radical lipid oxidation intensity and 8-OHdG level as a possible marker of oxidative stress in men of different ethnic groups in idiopathic infertility. Material and methods. The study involved 672 men with idiopathic infertility, representatives of Russian (n = 225) and Buryat (n = 447) ethnic groups. Two control groups of practically healthy men of the corresponding ethnic groups with realized reproductive function were formed. Lipid and DNA free-radical oxidation product content was determined using spectrophotometric, fluorimetric and enzyme immunoassay methods. Results. It is confirmed that oxidative DNA damage may be important in the etiology of male infertility. In men with idiopathic infertility of the Caucasian ethnic group, a significantly higher level of 8-OHdG in serum was found compared to fertile men, indicating the presence of changes at the cellular DNA level. There were no such changes in the Mongoloids, which indicates a difference in the intensity of metabolic processes among representatives of different ethnic groups.
Comparative analysis of microbial biomarkers in healthy individuals, treatment-naive patients, and those on disease-modifying therapy for multiple sclerosis
The gut microbiota represents a complex regulatory ecosystem that influences metabolism, immune responses, and neurovegetative functions. Alterations in its composition may contribute to chronic inflammation and the activation of autoimmune processes, suggesting a potential role of intestinal dysbiosis in the pathogenesis of multiple sclerosis (MS). Aim of the study was to investigate the microbial and endotoxin profiles in healthy individuals and patients with relapsing-remitting MS (RRMS), both treatment-naive and receiving disease-modifying therapies (DMTs). Material and methods. The study included 42 participants divided into three independent groups: healthy controls, untreated RRMS patients (RRMS-Naive), and RRMS patients receiving DMTs (RRMS-DMT). To assess the levels of 57 microbial markers (49 bacterial, 4 fungal, 3 viral) and endotoxin, gas chromatography-mass spectrometry (GC-MS) of microbial markers was used. Results. Patients receiving DMTs showed reduced levels of endotoxin and several bacterial markers compared to both the control and untreated groups. The most significant differences were observed between the RRMS-DMT and RRMS-Naive groups. Statistically significant differences were identified in markers such as Clostridium propionicum, Bacteroides fragilis, Prevotella spp., Streptococcus spp., Clostridium hystolyticum, among others. Conclusions. The findings indicate an association between the clinical status of RRMS patients and the levels of microbial and endotoxin markers. GC-MS profiling of microbial markers may serve as an additional tool for evaluating systemic inflammation and therapeutic response.
Expression of genes associated with hemostasis disorders in patients with very high cardiovascular risk
Individuals at very high cardiovascular (CV) risk are a heterogeneous group, including patients with favorable and unfavorable outcomes, which prompt the search for new predictors associated with adverse CV disease outcomes. Especial attention is paid to studying the effect of expression of candidate genes encoding proteins that activate the hemostasis system in these pathological conditions. Material and methods. Of the 100 study participants, 61 patients were selected for clinical and molecular analysis, including gene expression assessment, and were divided into 2 groups: the main group, patients with very high CV risk (n = 43), and the comparison group, individuals without a history of CV disease (n = 18). In those examined using the PCR method, an assessment was made of the relative expression level of SERPINE1, FGB, ITGA2 and ITGB3 genes associated with impaired hemostasis in patients with CV pathology. Results. In patients with very high CV risk, the relative expression level of the SERPINE1 and ITGB3 genes is higher than in the comparison group. The ITGB3 gene mRNA content is significantly higher in patients with reduced left ventricular ejection fraction (LVEF) and multivessel coronary artery disease, the SERPINE1 gene mRNA – in patients 60 years of age and younger, with reduced LVEF, two-vessel coronary artery disease and right coronary artery stenting. Conclusions. A significant increase in the relative expression level of ITGB3 and SERPINE1 genes was found compared to the background actin isoform used as a load control (ACTB) in patients with very high CV risk, including those with recurrent CV events. The expression level of these genes and the rate of its achievement in the group of patients with multifocal coronary artery disease and reduced LVEF, apparently, can be considered as a universal marker of the severity of CV diseases in patients with very high CV risk.
The role of neoadjuvant chemotherapy in the treatment of locally advanced colon cancer in comorbid patients
Colon cancer is one of the most common cancers in the world. In most patients, a locally advanced process is detected, which requires careful selection of optimal management tactics. In this connection, neoadjuvant chemotherapy (NACHT) is being actively introduced into clinical practice. Aim of the study was to evaluate the effectiveness of NACHT in comorbid patients with locally advanced colon cancer. Material and methods. The study was prospective and randomized, it included 254 patients with locally advanced colon cancer (cT4N0M0, cT1-4N1-2M0). Various comorbidities were detected in 96.5 % of patients. The final analysis included 53 patients from the NACHT + ACHT group and 98 patients receiving only ACHT. Statistical data processing was performed using RStudio software (version 2024.12.1+563) in the R programming language. Results. Disease progression was significantly more frequent in patients receiving NACHT + ACHT compared to patients in the ACHT group: 35.3 and 19.6 %, respectively (p = 0.036). In addition, patients receiving NACHT + ACHT progressed faster than patients receiving ACHT only: the median time without progression was 10.0 and 12.0 months, respectively (p = 0.033). The 3-year relapse-free survival rate was lower in the NACHT + ACHT group than in patients who underwent surgery followed by ACHT at the first stage – 40 and 76 %, respectively (р = 0,000). Cox regression analysis showed that the use of NACHT at the first stage of treatment in comorbid patients with locally advanced colon cancer increases the risk of progression by 3.912 times, regardless of the stage of the disease (hazard ratio = 3.912; 95 % confidence interval 1.859–8.232; p < 0.001). Conclusions. For comorbid patients with locally advanced colon cancer, it is most advisable to perform surgery at the first stage of treatment without prior NACHT, which is associated with a higher risk of disease progression regardless of the stage. The obtained results may be related to the increased time to surgery due to the administration of NACHT, which creates a potential temporal "window" for the maintenance of the tumor process.
Clinical and functional disorders and limitations of life activity of people with disabilities due to malignant neoplasms of the colon as the basic basis of rehabilitation measures
Malignant neoplasms of the colon are one of the most common oncological diseases in the world, characterized by a high incidence of morbidity and mortality. This disease has a significant impact on the quality of life, often leading to disability. In this regard, the study of the clinical and functional characteristics of people with disabilities due to malignant neoplasms of the colon is of particular importance. The effectiveness of their rehabilitation and improving quality of life depends on the compliance of the technologies used, the severity of persistent clinical and functional disorders of the body and the dynamics of their changes, leading to varying severity of disability. Material and methods. A selective retrospective study (319 units) was conducted, which was formed in the form of Excel spreadsheets using the following methods: data extraction. The χ2 test was used to compare two independent groups, and the relationship between variables was examined using Spearman’s rank test. The critical significance level for the null statistical hypothesis (p) was set to 0.05. Results and discussion. In people with disabilities, due to malignant neoplasms of the colon, disorders of the functions of the blood, the immune and digestive systems were mainly noted. The greatest share in the structure of disability was made up of restrictions on the ability to work, self-service and movement of the II–III degree. A relationship has been established between the degree of malignancy of the tumor and the severity of disorders of body function, as well as between impaired body function and disability. Conclusions. Expert rehabilitation diagnostics of people with disabilities due to malignant neoplasms of the colon contributes to the development of patient-oriented programs that take into account the principles of the International Classification of Functioning, Disability and Health, which makes it possible to cover the medical, social, psychological and functional aspects of the patient’s condition. The implementation of such programs will enhance the effectiveness of rehabilitation and improve long-term outcomes. Medical, social and expert rehabilitation diagnostics will allow predicting the volume of examinations, the course of the disease and optimizing medical, social and rehabilitation care.
Prevalence of modifiable cardiovascular risk factors among industrial workers
Diseases of the circulatory system remain the leading cause of death among the working-age population of the Russian Federation, which determines the relevance of identifying risk factors for their development in different professional cohorts in order to develop targeted preventive measures. Aim of the study was to investigate the prevalence of modifiable cardiovascular risk factors among workers in the production of polyacrylonitrile (PAN) fibers for the subsequent development of targeted preventive measures. Material and methods. Based on generally accepted sociological, hygienic, clinical-laboratory and epidemiological methods, the prevalence of industrial, behavioral and metabolic factors of cardiovascular risk among workers (137 people) in the production of PAN fibers was studied. Results and discussions. Factors of labor conditions of workers of PAN fiber production that contribute to the development of circulatory system diseases (CSD) are industrial noise (classes 3.1–3.2), the severity of the work process (classes 3.1–3.3), emotional stress. A high prevalence of behavioral factors of cardiovascular risk has been established: insufficient physical activity (74.8 %), unhealthy diet (67.6 %), smoking (46.7 %), alcohol consumption (81.7 %), arterial hypertension (54.7 %), exceeding the Russian average population level. Metabolic dysfunctions are represented by general (41.6 %) and abdominal (52.5 %) obesity, excess fat mass (81.2 %), insulin resistance (64.2 %) and are combined with hyperglycemia (34.3 %), elevated levels of non-high-density lipoprotein cholesterol (80.2 %), triglycerides (36.7 %) and atherogenic coefficient (30.6 %). High and very high risk of fatal outcomes according to the SCORE scale was revealed in 36.9 % of the examined workers over 40 years old; moderate risk dominated in women (77.4 %), high and very high (52.8 %) in men. CSD occupied the second rank place (16.04 %) in the structure of chronic morbidity after diseases of the musculoskeletal system and connective tissue (24.3 %). Conclusions. Based on the results of the study, integrative measures for the prevention of CSD have been developed, including the improvement of working conditions, early detection and correction of modifiable risk factors, motivation for a healthy lifestyle and health-preserving behavior, and medical and preventive measures.
RAS Academician Mark Borisovich Stark is 95 years old