Relevance. Excess methionine entering the body (with food, drugs, dietary supplements) is accompanied by toxic accumulation of homocysteine and adverse effects leading to the formation of pathology of some systems. Small amount of studies are devoted to the comparative effect of methionine isomers. Objective: to establish the features of the biological effect of methionine isomers used as a dietary supplement on biochemical and cytological parameters of the blood of experimental animals. Materials and methods. Experimental rats received a feed additive with an increased content of methionine in the form of DL-form (racemate DL-methionine, Belgium) or L-form (100% L-methionine, Fingres Biotech Inc, China) for 0.15 g / 100 g of animal weight. In control animals, the feed did not contain additives. After 25 days, blood was taken from the animals under ether anesthesia by transcardial puncture. The following was determined: homocysteine concentration (Axis-Shield PLC (UK)); cytological analysis of white and red blood was performed (System XS-500i hematological analyzer (Japan)); for qualitative assessment, blood smears were stained with the hematological dye Leukodif-200 (Lachema, Czech Republic) and viewed under a Carl Zeiss microscope (Germany) at a magnification of × 1000. The body’s allergization index and the erythrocyte loading coefficient were calculated. Statistical analysis was performed using the Shapiro-Wilk normality analysis of data distribution, one-way ANOVA analysis of variance, multiple comparisons were performed using the Tukey test. Results and discussion. Introduction of racemic mixture of DL-methionine resulted in increase of homocysteine in blood to 28.9 ± 2.65 (p = 0.05), L-form to 79.38 ± 3.91 (p = 0.05) μmol/l (in control 8.5 ± 0.6 μmol/l). In blood of animals of group 1 increase of absolute number of granulocytic forms of leukocytes (by 1.4 times, p = 0.049) was revealed, neutrophilia was noted. When introducing L-form of methionine in animals there was sharp decrease of both absolute (by 3.7 times in comparison with control group, p = 0.01) and relative number of neutrophils, appearance of hypersegmented forms of neutrophils and immature forms of eosinophils was noted. In both groups, allergic predisposition of the organism was manifested, more pronounced in animals with the introduction of the L-form of methionine, the allergization index was increased by 49.2 ± 3.61% (p = 0.01). With the introduction of the L-form, the number of platelets decreased; ESR increased; the erythrocyte loading coefficient increased by 15.7% (p = 0.043). Conclusion. Thus, the severity of hyperhomocysteinemia, the direction of the responses of white and red blood, the coefficients reflecting the allergic disposition of the body and the functional erythrocyte load with excessive administration of methionine as a dietary supplement are determined by the form of the isomer included in its composition.
Relevance. Intronic enhancers are cis-regulatory DNA elements located within introns of protein-coding or non-coding genes. Although introns were historically regarded mainly as non-coding interruptions removed during pre-mRNA splicing, contemporary functional genomics has shown that they are repositories of regulatory information. Intronic enhancers can control the expression of their host genes, neighboring genes, or even distant genes. Their activity is usually cell-type-specific and is associated with open chromatin, transcription-factor binding, enhancer-associated histone modifications such as H3K4me1 and H3K27ac, recruitment of coactivators, enhancer-promoter looping, and in many cases transcription of enhancer RNAs. Results and discussion. This article reviews the biological significance of intronic enhancers with particular attention to two areas: tissue differentiation and disease. During differentiation, intronic enhancers integrate lineage-determining transcription factors, developmental signals and determine tissue specificity. They contribute to hematopoietic, endothelial, muscle, adipocyte, neuronal, and immune-cell identity by controlling the timing, intensity, and specificity of gene expression. In disease, intronic enhancers are vulnerable sites for pathogenic single-nucleotide variants, insertions, deletions, copy-number changes, epigenetic disruption, and aberrant enhancer hijacking. Examples include GATA2 enhancer mutations in immunodeficiency and myeloid malignancy predisposition, FTO intronic variants affecting IRX3/IRX5 regulation in obesity, and oncogenic enhancer activation near TAL1 in T-cell acute lymphoblastic leukemia. Conclusion. Thus intronic enhancers should not be treated as secondary regulatory elements merely because they lie inside genes. Instead, they represent a major layer of genome regulation, connecting non-coding variation to developmental biology, complex traits, and disease mechanisms. Their study is increasingly important for precision medicine, functional interpretation of genome-wide association studies, and future enhancer-targeted therapeutic strategies.
Relevance. The review focuses on the current state of the art in the use of nano-objects in medicine and pharmacy. The relevance of this topic stems from the unique properties of nanomaterials, which exhibit various size-dependent properties in the range of 1-100 nm, where quantum phenomena come into play. The aim of this work is to outline the main strategies of modern science for the development and successful stabilization of nanoparticles intended for both the diagnosis and treatment of pathological diseases. Nanostructured heterogeneous matrices containing highly dispersed particles with sizes corresponding to the de Broglie wavelength open up promising opportunities for their use in various scientific and clinical studies. The diversity of the nature, morphology, sizes, and properties of nanoparticles used in medicine for the diagnosis and treatment of diseases of bacterial, viral, and malignant neoplasm stimulates interest in particles exhibiting quantum size effects (QZE). The QZE of nanoobjects are characterized by unique optical and magnetic properties that differ from the properties of physical structures in which particles are larger than 100 nm. Fluorophores based on quantum heterogeneous structures are actively used in medicine and biology, for example, in systems for labelling and visualizing biological data, including in the detection and control of tumor cells. Conclusion. This review describes modern approaches to the synthesis and functionalization of nanoparticles based on top-down and bottom-up principles, as well as the potential mechanisms of action of nanoparticles depending on their morphology, size, and ionic (atomic) form. The unique physicochemical properties of nanoparticles, which are due to quantum size effects, are discussed. The article describes various forms of nanoparticles, mechanisms of action, molecular targets, as well as methods of synthesis and application. These aspects are crucial for understanding the role of nanoparticles in combating infections and developing new therapeutic approaches, ensuring their continued relevance in modern science and medicine.
Relevance. Growing resistance of bacterial pathogens to antibiotics is a fundamental threat to healthcare worldwide. Many antibiotics currently used in clinical practice were developed decades ago, and their efficiency has been declining over time. Research efforts focusing on identification and optimization of new promising antibacterial compounds and new molecular targets in bacterial cells establish the foundation for developing new potent antibiotics relevant to modern day clinical needs. The bacterial RNA polymerase is a validated target for a number of natural, semisynthetic, and synthetic antibacterial compounds. This essential enzyme maintains a high potential for developing a new generation of antibiotics. Materials and methods. We prepared a complex of recombinant Escherichia coli RNA polymerase with a new small-molecule transcription inhibitor, and studied it using cryoelectron microscopy to determine the mechanism of inhibition. Results and discussion. The current work establishes the molecular basis of RNA polymerase inhibition by the compound N-(9H-fluoren-9-yl)-3-(2-methylpropyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide (compound A) that blocks transcription through binding to a previously unknown binding site. We describe interactions of the compound A with RNA polymerase and reveal its mechanism of action that involves steric restriction of template DNA binding in the enzyme active site. We demonstrate that the compound A targets only certain types of transcription complexes since its binding site is formed in part by a dissociable subunit of RNA polymerase. Conclusion. The results of the study may be used for development of conjugates of rifamycins with the compound A to obtain a new class of bacterial RNA polymerase inhibitors with a new mechanism of action.
Relevance. Single-cell sequencing technologies (scRNA-seq) provide unique opportunities for studying the heterogeneity of immune populations, enabling the analysis of expression profiles, ligand-receptor interactions, and differentiation trajectories at the single-cell level. However, the quality of cell typing significantly depends on the accuracy of data annotation. Marker ambiguity, variability in their expression depending on physiological context, limitations of automated tools such as CellTypist, Azimuth, and SingleR, and the incompleteness of databases like PanglaoDB and CellMarker, including insufficient information on the functional roles of markers, substantially hinder the identification of cell populations and require additional efforts to achieve meaningful results. Aim. To systematize markers of T- and B-cells of the adaptive immune response to facilitate scRNA-seq data annotation. Materials and Methods. An analysis of 30 scientific publications from PubMed, Scopus, and Web of Science (2008-2024) and marker data from PanglaoDB and CellMarker was conducted. Results and discussion. Key and additional T-cell (CD3D, CD3E, CD3G, CD4, CD8A, CD8B, FOXP3, GZMA, TBX21) and B-cell (CD19, MS4A1, CD27, IGHM, IGHD) markers, their roles in immune processes, including activation, cytotoxicity, and regulation, were examined. Subpopulations such as Th1 cells (T-bet, IFN-γ), follicular helper cells (CXCR5, BCL-6), and regulatory B-cells (CD24, IL-10) and their functions in health and disease were described. Conclusion. The systematization of T- and B-cell markers was developed to improve the quality of single-cell sequencing data annotation and is applicable for enhanced typing of cell functional states in health and pathological conditions, including infectious, autoimmune, and oncological diseases. This opens opportunities for a deeper understanding of immune processes and the development of immunotherapy approaches, such as CAR-T therapy. However, the limited specificity of markers and the lack of standardized annotation algorithms highlight the need for further research to refine typing methods.
Relevance. Head and neck squamous cell cancer (HNSCC) accounts for about 890,000 new cases of malignant neoplasms (approximately 4.5% of all diagnosed cancer cases worldwide) and 450,000 deaths per year. Even with radical antitumor treatment, more than 40-50% of patients develop relapse, 20-30% of them develop distant metastases, and the five-year survival rate in advanced cases is 25%. Patients with recurrent HNSCC have an unfavorable clinical prognosis with a median overall survival of about 12 months. A high recurrence rate indicates the possible existence of a “sourceˮ of tumor cells, which may be located near the primary tumor, namely in the peritumoral tissue, which necessitates its study. The aim of the study was to compare the structure and expression of genes in the tumor and peritumoral tissues of HNSCC. Materials and methods. Biopsy material of tumor and peritumoral (located at a distance of 2 cm from the tumor border) tissues was obtained from 35 patients with HNSCC. Biopsies were examined by histological method, then the levels of mRNA expression of EGFR, PIK3CA, PTEN, YAP, SLC26A6, ARIH2, UBE2Z, PITX1 genes were determined by real-time polymerase chain reaction in samples of tumor tissue and peritumoral region. The RNA Solo kit was used for RNA isolation, and the MMLV RT Kit (Evrogen, Russia) was used for reverse transcription. The amplification reaction with real-time detection was performed on a Real-Time DTprime amplifier (DNA Technology, Russia). Results and discussion. All tumor samples, regardless of anatomical localization, exhibited characteristic morphological features of squamous cell carcinoma. The peritumoral specimens represented visually unchanged tissue with preserved epithelial architecture. The expression of EGFR and PIK3CA genes was higher in tumor tissue samples, while PITX1 expression was higher in peritumoral tissue samples. Conclusion. Increased expression of EGFR and PIK3CA genes in tumor tissue confirms the activation of signaling pathways associated with tumor cell proliferation, survival, and disease progression. In contrast, the higher expression of the putative tumor suppressor gene PITX1 in peritumoral tissue suggests the preservation of regulatory mechanisms limiting malignant transformation outside the tumor focus.
Relevance. Understanding the fundamental mechanisms of immunothrombosis is essential for developing effective treatments and prevention of thrombotic disorders. This review aims to summarize the current knowledge on the role of programmed neutrophil death in the molecular and cellular mechanisms underlying immunothrombosis, as well as to demonstrate how dysregulation of hemostasis initiated by neutrophil death is associated with various pathological conditions. Based on a search of the electronic scientific databases Google Scholar, PubMed (MEDLINE), Scopus, and Web of Science using keywords and their combinations, with the methodological quality assessed using the AMSTAR 2 software, the role of neutrophil death in the development of immunothrombosis is presented. The review describes the types of programmed neutrophil cell death, namely apoptosis, pyroptosis, necroptosis, ferroptosis, and neutrophil extracellular traps (NETs), along with their molecular triggers and mechanisms. A modern concept of immunothrombosis pathogenesis is presented, demonstrating the involvement of hemostatic proteins, platelets, and proinflammatory cells in its pathogenesis and taking into account the complex relationship between hemostasis and inflammation. Each type of programmed neutrophil death is shown to be involved in the development of immunothrombosis. In addition, the review presents data on therapeutic strategies employing immunometabolic regulators and NET inhibitors, which potentially can attenuate immunothrombotic activity without affecting hemostasis. Such treatment approaches offer advantages for managing patients with various thrombo-inflammatory conditions. Conclusion. Overall, the data demonstrate that neutrophil apoptosis has an antithrombotic effect, whereas other types of programmed cell death promote thrombus formation and vascular events. The latter differ in that they require specific triggers: a cytokine storm for pyroptosis, the release of death-associated molecular patterns (DAMPs) for necroptosis, and oxidative stress for ferroptosis. These types of cell death are unified by their capacity to initiate NET formation, thereby providing a trigger framework for the development of severe thrombotic complications.
Relevance. Obstructive sleep apnea (OSA) is the most common medical cause of excessive daytime sleepiness and is recognised worldwide as a significant risk factor for road traffic accidents when undiagnosed or untreated. OSA presents a critical occupational health concern in the transportation industry, affecting a substantial proportion of today's transport operators, especially in the trucking sector. Aim of the study was to estimate the risk of OSA among commercial drivers in North India and investigate its association with vehicle accidents. Materials and methods. A cross-sectional study was conducted involving 153 commercial drivers aged between 24 and 65 years, each with at least 5 years of driving experience. Participants were selected through simple random sampling after giving their consent. The collected data included demographic information, driving history (total years of driving, vehicular collisions due to sleepiness, and vehicular incidents), anthropometric measurements (height, weight, and neck circumference), and health history. Sleep quality, particularly difficulty in falling asleep or maintaining restful sleep, was assessed using the Pittsburgh Sleep Quality Index (PSQI). The risk of OSA and excessive daytime sleepiness was evaluated using the STOP-BANG questionnaire and the Epworth Sleepiness Scale, respectively. Results and discussion. Among participants, 21.56% were at risk of OSA, while 28.10% exhibited poor sleep quality as per the PSQI, and 15.16% of high-risk OSA drivers experienced excessive daytime sleepiness. A significant association was observed between the high-risk OSA group and vehicle collisions (p 0.05). Conclusion. The prevalence of OSA risk is notably high among commercial drivers, who also display poor sleep quality. In a country with a population of 1.4 billion, studies on OSA among commercial drivers are limited. Currently, there are no guidelines for OSA detection in Indian commercial drivers, despite its recognised prevalence in studies from other countries and related hazards such as an increased risk of motor vehicle collisions.
Relevance. In modern biomedicine, therapeutic strategies for neurological disorders are increasingly focused on the development of multitarget therapeutic approaches. Among the promising avenues, preparations based on conditioned media stand out. In the present work, for the first time, a genome-wide transcriptomic analysis of differential gene expression was performed in primary cortical neuron cultures incubated with conditioned medium from human glial progenitor cells under conditions of induced glutamate excitotoxicity. This study allows us to infer potential molecular mechanisms underlying the observed protective effect. Materials and methods. Conditioned medium was collected from human glial progenitor cell cultures and subjected to purification and concentration by tangential ultrafiltration. Excitotoxic glutamate exposure was modeled in primary cortical neurons from newborn (P0) rats by adding sodium glutamate to a final concentration of 100 µM. Cell viability was assessed using the MTT assay. Transcriptomic libraries were sequenced on the NextSeq 1000 platform (Illumina, USA); read quality control was performed with the FastQC tool. The R package edgeR was used for differential gene expression analysis (FDR 0.05). Results and discussion. The conditioned medium was found to exert a dose-dependent neuroprotective effect: at a preparation concentration of 45 µg/mL, cell viability recovered to the level of the intact control. According to transcriptomic profiling data, the addition of conditioned medium against a background of glutamate stress was accompanied by upregulation of 173 genes and downregulation of 479 genes. The identified genes were grouped into functional categories with statistical significance. Among the most represented biological processes associated with activated genes were regeneration, cell-cell adhesion, response to oxidative stress, inhibition of apoptosis, and stimulation of the TGF-beta signaling pathway. Downregulated genes were predominantly linked to calcium transport, glutamatergic signal transmission, and regulation of neurite outgrowth and branching. The results obtained may indicate that components of the conditioned medium trigger antioxidant defense and repair cascades in neurons while simultaneously limiting excessive activation of glutamate receptors and calcium ion influx. Conclusion. The conditioned medium exhibits neuroprotective properties under conditions of glutamate-induced excitotoxicity. Presumably, this effect is based on the simultaneous induction of genes promoting survival and suppression of genes mediating glutamatergic neurotransmission. The totality of the data obtained confirms the promise of further development of therapeutic agents based on conditioned media from human glial progenitor cells for the treatment of neurological disorders.
Relevance. According to experimental data, administration of the drug cisplatin into the tumor during radiation therapy can increase its effectiveness. To date, there is no model that can predict the effectiveness of such therapy. The development of such a model is an important task for planning therapy. The goal of this work is to find analytical relationships for the survival of cells exposed to the combined effect of radiation and cisplatin in vitro. Materials and methods. Based on digitized experimental data on cell survival from a number of publicly published works, the corresponding linear-quadratic (LQ) approximation coefficients for survival were found for irradiation without the drug \( \alpha_R , \beta_R \), and for combined exposure to radiation and cisplatin \( \alpha_{RC} , \beta_{RC} \). Next, a regression analysis of the resulting set of coefficients and cell survival when exposed to cisplatin alone \( S_C \) was performed. Results and Discussion.\( \alpha_{RC} \) was found to be statistically dependent on \( \alpha_R, \beta_R \) and \( S_C \). This dependence could be described by several models, the best of which in terms of a number of indicators was \( \alpha_{RC} = \alpha_R + \alpha_R \ln S_C \), where \( \alpha = -4.27 \pm 0.57 \) is a parameter that is the same for all cell types and experimental conditions. It was found that \( \beta_{RC} \) is statistically dependent on \( \beta_R \). No signs of dependence of \( \beta_{RC} \) on \( \alpha_R \) and \( S_C \) were found. The best model for \( \beta_{RC} \) was \( \beta_{RC} = \beta_R \). These models are simple, but they allow predicting the value of cell survival under the combined effect of radiation and cisplatin \( S_{RC} \) from the values \( \alpha_R , \beta_R \) and \( S_C \) only approximately. The obtained models are collated with kinetic equations and a mechanistic interpretation is given, which is based on the hypothesis of a decrease in the rate of recovery of cells from potentially lethal lesions r , with an increase in the radiation dose and cisplatin concentration. Conclusion. The type of statistical dependence of LQ coefficients \( \alpha_{RC} \) and \( \beta_{RC} \) on \( \alpha_R , \beta_R \) and \( S_C \) has been found. In the case of high toxicity of cisplatin (low values of \( S_C \)), the combination of the above-mentioned models for \( \alpha_{RC} \) and \( \beta_{RC} \) allows to make a useful for practical application prediction of cell survival \( S_{RC} \). The results of this work will help for the future construction of more complex models of the combined effects of radiation and cisplatin, and may also have practical application in the case mentioned above.
Relevance. A key element of human adaptation to the complex of extremе ecological factors is intensification of the energy metabolism. Mobilization of energy resources may lead to modification of the biological membranes and, as a consequence, to change their functional activity. Evaluation of the persistent imbalance degree on the level of phospholipid fractions may contribute to early diagnosis of the maladaptive states. Aim: an analysis of the levels of phosphatidylserine (PS), phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM) in the peripheral blood of the population in the Arctic and subarctic region of Russia, as well as the Southern Caucasus inhabitants. Materials and Methods. From 2010 to 2018, 687 people of both sexes aged 22 to 60 years were examined. The participants were divided into the following groups: 1) natives of the Russian Arctic region (AR); 2) residents of the subarctic region of Russia (SR); 3) residents of the South Caucasus (JUR). The level of the phospholipids was assessed using the thin-layer chromatography method. The results are presented in percentage terms. Results and Discussion. The residents of the AR revealed lower PS and higher PE levels compared to those of SR and JUR natives. At the same time, the AR individuals in the phospholipid spectrum reveal a relative decrease in the share of PC. Unlike the AR natives, the low PS content in the SR residents’ peripheral blood did not affect the overall pool of the phospholipids, which is within similar variation limits regarding the natives of the JUR. The SM medians in the compared groups had no statistically significant differences. Conclusion. The complex of adaptive alterations in the human body under Arctic conditions is associated with mobilization of mechanisms aimed at increasing physical fluidity of the biological membranes, which may indicate a significant increase in their permeability and intensification of receptor and enzymatic activity in cells.
The aim of this study was to investigate the features of heart rate variability during postural changes in women, depending on the excitability of parasympathetic centers and of the menstrual cycle phase. Material and Methods. 47 female students from Ivanovo State Medical University participated in the study. The average age of participants was 19.2±0.16 years. The study took place during the follicular and luteal phases of menstrual cycle, lasting an average of 29.3 ± 0.4 days. The features of parasymphathetic center excitability were assessed using the K30:15 ratio during the transition to an upright position. The electrocardiogram was recorded for 5 minutes using a computer electrocardiographic system Poly-spectrum (NeuroSoft, Ivanovo, Russia) both in the horizontal position and during active orthostasis, passive orthostasis and passive antiorthostasis. Results and Discussion. Based on the analysis of the dynamics of HRV indicators, it was found that the transition from a supine position to an upright body position was accompanied by a decrease in the influence of the vagus nerve on the heart. With active orthostasis, this does not depend on the excitability of the parasympathetic system and the phase of the menstrual cycle. While with passive orthostasis and reduced excitability of the parasympathetic centers, this is manifested in both phases of the cycle, and with normal excitability - only in the follicular phase. Antiorthostasis initiates an increase in parasympathetic activity in women with normal excitability only in the follicular phase, whereas in women with reduced excitability, there is a decrease in the influence of the vagus nerve in both phases of the cycle. Conclusion. The nature of circulatory system responses to changes in body position in women depend not only on type of posture but also on excitatory characteristics of parasympathetic nerves and menstrual cycle phases.
Relevance. Acute respiratory distress syndrome (ARDS) is a severe, life-threatening form of acute lung injury with a high mortality rate. In severe cases, pathological changes extend to the systemic level and manifest as cytokine storm syndrome. The lack of effective treatment options underscores the importance of exploring therapeutic approaches, including cell therapy. Interest in this treatment option increased during the SARS-CoV-2 pandemic, as evidenced by the numerous clinical trials registered for the use of cell preparations to treat ARDS. The aim of the study: Thus, this review summarizes preclinical and clinical studies on using highly differentiated cells, including immune system cells, to treat ARDS. To this end, we will describe key points in the pathogenesis of ARDS, including etiologic subtypes and stages, as well as the key cells involved and the results of their use in ARDS therapy. This review highlights the potential of using alveolar cells type 1 and type 2, as well as epithelial cells, for rapid lung regeneration after ARDS. Currently, there are no data describing the use of neutrophils, which trigger primary pathological changes in the lungs, for ARDS treatment. The use of macrophages, which play a key role in ARDS pathogenesis, is limited by their ability to quickly repolarize. Natural killer cells (NK cells), regulatory T cells (Tregs), and invariant natural killer T (iNKT cells) have shown high efficacy in treating ARDS in preclinical and clinical studies. Conclusion. Thus, using NK cells, Tregs, and iNKT cells for ARDS cell therapy seems promising. However, the lack of standardized protocols for preparing and administering cell therapies, as well as small sample sizes, indicate the need for additional studies.
Relevance. Obtaining reliable data on the levels of cardiovascular morbidity and mortality among patients with rheumatoid arthritis remains important. These aspects of patient management are very important; they determine further therapeutic tactics and are aimed at reducing the risks of complications. Target - to analyze cardiovascular pathology in the structure of comorbidity and mortality of patients with RA in the cohort of patients of the Center for Responsible Rheumatology ″Induction″ LLC in the period 2015-2022. Materials and Methods. A sample of 1020 patients with a reliable diagnosis of RA, established according to the classification criteria (ACR/EULAR, 2010), who were treated at the LLC Center for Responsible Rheumatology ″Induction″, was made. The average age was 55.3 ± 1.8 years, women predominated (88.8%). Comorbid status was assessed on the basis of lifetime consultations and analysis of medical documentation of the examined patients according to a developed chart, including a specified cardiovascular disease, as well as the fact of death. A systematic review of scientific works (2019-2024) on rheumatoid arthritis in the aspect of cardiovascular pathology was carried out. Results and Discussion. The incidence of cardiovascular pathologies in patients with RA, according to numerous studies (2019-2024), varies widely. Hypertension, coronary artery disease, heart failure, cardiac rhythm and conduction disorders, and atherosclerotic cardiovascular diseases occupy the leading place in prevalence. Patients with RA in the study cohort were characterized by a complex comorbidity structure. Cardiovascular pathology is the most common (42.29%). Respiratory diseases (23.07%), COVID-19 (11.53%), and Blastomatosis (7.69%) follow it. Acute pancreatitis complicated by pancreatic necrosis, bronchial asthma, lymphocytic leukemia, hypothyroidism, autoimmune thyroiditis, diabetes mellitus were recorded in no more than 3.85% of the cohort. Cardiovascular disorders included ischemic heart disease (30.76%) and hypertension (11.53%). The three main causes of death in patients with RA included cardiovascular, respiratory diseases, and sepsis. The leading position was occupied by cardiovascular events (47.83%), predominantly acute myocardial infarction (30.43%). Conclusion. An analysis of new data on the place of cardiovascular diseases in the structure of comorbidity and mortality of patients in the Stavropol Territory of the LLC “Center for Responsible Rheumatology ″Induction″ cohort with an established diagnosis of RA was carried out. The information obtained is useful for a better understanding of the clinical portrait of RA patients with cardiovascular pathology, and can be taken into account by rheumatologists to optimize management tactics for RA and the risk of cardiovascular events.
Relevance. Angiotensin converting enzyme 2 (ACE 2) is recognised as a significant regulator of cardiovascular and pulmonary homeostasis owing to its involvement in the renin-angiotensin system (RAAS). This extensive review addresses ACE 2’s conventional role in converting Angiotensin II (Ang II) to the Angiotensin-(1-7) to its broader implications in cardiovascular illness, pulmonary pathology, metabolic diseases, and cancers. Conclusion. Recent research has shed light on ACE2’s significance beyond its enzymatic capabilities, specifically as a cellular receptor of various pathogens. Furthermore, recent evidence shows that ACE2 is involved in inflammation, glucose metabolism, and gut microbiome modulation. The tissue distribution patterns, regulatory mechanisms, and therapeutic possibilities show its dual role as a protective factor in and a possible entryway for the viral infections. Understanding these multiple processes in health and disease state serves to be essential in establishing tailored treatments for the diseases. This review outlines the existing understanding of ACE 2 and emphasizes areas for further research, notably its potential as a therapeutic target. Furthermore, we have discussed the challenges and future directions in ACE2-based therapeutics.
Relevance. Uveal melanoma is a rare form of cancer that originates in the eye, most frequently arises in the choroid (90%). BAP1 is a tumor suppressor gene, mutations in this gene were found in 40-84% of primary UM. Given many investigators have proven the association of mutations in the BAP1 gene with UM. Aim: our study aims to figure out UM associated polymorphisms by sequencing DNA in exon 10, exon 11, exon 15, exon 16, and exon 17 as well as to assess the role of BRCA1 mutations in risk of UM development. Materials and Methods. A total of 95 individuals recruited in the study, out of them 42 as a patient group, 23 as a risk group, and 30 as a control group. The target regions of BAP1 gene amplified by PCR were sequenced by Sanger method and BRCA1 was genotyped by real-time PCR using commercially produced kits. Results and Discussion. This study did not demonstrate presence of any polymorphisms in the sequenced regions of the BAP1 gene or the genotyped specific BRCA1 sites that are correlated with an increased risk of uveal melanoma development. Our findings do not deny the published strong association between BAP1 inactivating mutations and the UM disease. This study’s findings instead propose that within this targeted population, the molecular mechanisms for BAP1 loss-function may include aberrations other than changes in the examined exons. Conclusion. Consequently, we recommend future research that includes sequencing the entire BAP1 gene in larger sized samples and studying of other candidate genes.
Relevance. Autotransplantation of fat is used in plastic, reconstructive and aesthetic surgery. Currently, there are no studies aimed at studying the proliferative activity of autotransplants of fat after its various preoperative treatment. Aims. To evaluate Ki-67 expression in fat autografts as a marker of proliferation at distant time points in rats. Materials and Methods. Ki-67 protein expression was examined in adipocytes after fat autografting in rats after 30, 90 and 180 days. Three types of fat autografts were used: solid graft (group 3), scalpel-shredded graft (group 4) and homogenised fat in Luer Lock syringe (group 5). Group 1 consisted of intact animals and group 2 consisted of animals injected once in the withers with 0.9 % sodium chloride solution. Results and Discussion. The findings of the study indicated that, 30 days following the surgical procedure, the number of Ki-67-positive cells in the fat graft of group 3 was considerably higher than in the SCF of the recipient site of groups 3 and 5 (p 0.001). The same marker was found to be significantly higher in the 4th group when compared to the control group of the autotransplantation of fat in the 3rd and 5th groups (p 0.001), and to the 3rd group (p 0.05). On the 90th day following surgery, the number of Ki-67-positive cells in the solid graft of group 3 was significantly higher than in the subcutaneous fat of the recipient site of the same group and group 5 (p 0.001), as well as group 4 (p 0.01). In group 4, the number of Ki-67-positive cells in subcutaneous fat at the injection site of fat autografts was significantly higher than in subcutaneous fat in group 3 (p 0.001) and group 5 (p 0.01). In the group of homogenised fat, this indicator was found to be statistically higher than in subcutaneous fat in the area of the autotransplantation site of the solid graft in group 3 (p 0.05). Conclusion. The transplantation of a solid graft after a period of three months has been shown to stimulate the formation of subcutaneous fatty tissue at the site of its insertion. Furthermore, high activity of Ki-67 protein expression by cells in the fat graft itself has been observed. Moreover, at the time of autotransplantation of small-sized fat grafts (1×2×1 mm) and homogenised fat after 30 and 90 days, sprouting of connective-tissue strands containing Ki-67-positive cells and blood vessels was observed.
Relevance. The Far Eastern Federal District is a territory of advanced development, requiring a large number of specialists. Healthcare work is one of the most complex and demanding jobs, with high psychological stress, requiring attentiveness, endurance, and a high work ethic. Medical education has its own specifics; even in their first years, at least 80 % of students face a range of challenges: stress, sleep deprivation, fatigue, and other factors, which have negative consequences for learning, behavior, and communication, and impact their health. Building a motivational system is one of the most important steps in studying at medical universities. A highly motivated student will be engaged in the learning process, and therefore will study voluntarily and actively master the curriculum. Therefore, studying the motivation of medical students at medical schools is relevant. The aim of this study was to conduct a comparative analysis of the interaction between motivation to learn and the health status of medical students at medical universities in the Far East. Materials and Methods. Within the framework of the educational, scientific and industrial cluster «Far Eastern» on the basis of cooperation agreements, within the framework of social partnership of educational organizations of higher education and interaction of universities of the Far Eastern region, the following universities participated in the study: Far Eastern State Medical University (FESM), Amur State Medical Academy (ASMA), North-Eastern Federal University named after M.K. Ammosov (NEFU), Far Eastern Federal University (FEFU), Pacific State Medical University (TSMU). The health status of 2,676 first- to fifth-year students aged 17-24 was studied. The study utilized health group data obtained as a result of medical examinations and preventive checkups, the academic motivation scales (AMS) questionnaire, and self-assessment using a developed individual questionnaire. Students from Tver State Medical University, Far Eastern Federal University, and Far Eastern State Medical University completed the survey in the university classroom using printed questionnaires, while students from North-Eastern Federal University and Altai State Medical Academy participated in the survey using Google forms online. The Statistica 12.0 software package and the analytical functions of Microsoft Office Excel were used for mathematical and statistical processing. Results and Discussion. The conducted comparative characteristics of motivation for learning of students in medical specialties in medical universities of the Far East revealed a high intrinsic motivation for learning from 3.4 to 4.9. The highest values in assessing the motivation to achieve were among students of NEFU - 4.07, in TSMU and ASMA this criterion was 4.0. A relationship between the level of external and internal motivation with the health status of students was revealed. Students with health group 3 showed significant (group 3B p = 0.55) cognitive motivation, strong, almost absolute (p = 0.9) - external motivation and high motivation for achievement. Introjected motivation was weak (from p = 0.2 to p = 0.344) and did not depend on the health group. Conclusion. The relationship between extrinsic and intrinsic motivation for learning and health status among medical students at medical universities was identified and studied.
Relevance. Globally, there are now 32.53 million hernia cases, up from about 23.92 million during the previous 3 decades. Many authors lack statistical knowledge, which could jeopardize healthcare. The aim was to use artificial intelligence as a statistical technique to assess the potential effects of AdhesixTM self-gripping mesh implants, HertraTM mesh implants, and LintexTM glue-fixed mesh implants on the outcomes of inguinal hernia patients who underwent open inguinal hernia repair in Lichtenstein. Materials and Methods. We performed 120 Liechtenstein-compliant inguinal hernia repair procedures on three evenly split patient groups (n = 40) using AdhesixTM, HertraTM, and LintexTM mesh implants. The parameters for comparison were the time-frame of the procedure, hospital-stays, challenges afterwards surgery, and issues that arose during the brief follow-up. Results and Discussion. Patients of the first group were hospitalized for shorter periods of time than those in the second and third groups (group A-4.9 bed /day, group B-4.9.5 bed /day, and group C-4.95 bed /day), with no statistically significant differences. Patients in the first group experience a significantly shorter procedure time, followed by those in the second and third groups (27.8 min, 31.4 min, and 38.9 min respectively). Unlike the third group, which included 3 patients with postoperative discomfort and 1 with postoperative seroma formation, the first and second groups’ postoperative hospitalization stays were free of complications. In contrast to the third group’s 2 patients who experienced mesh migration and hernia recurrence, the first and second groups’ patients experienced no complications during the short-term follow-up. Conclusion. Compared to LintexTM mesh implants, the operative times using AdhesixTM and HertraTM are significantly shorter with no post-operative complications or hernia recurrence.
Relevance. Primary chronic osteomyelitis (PCO) is a rare condition that poses diagnostic challenges, primarily affecting children between the ages of 5 and 17. It can occur in various bones, including the mandible in the maxillofacial region. The complexity of distinguishing PCO from infections, tumors, metabolic disorders, and other inflammatory conditions has led to misdiagnoses, resulting in inappropriate treatment strategies and recurrent episodes. Currently, there is no standardized treatment protocol for PCO, with most therapies starting with non-steroidal anti-inflammatory drugs (NSAIDs) to manage symptoms. The purpose of this case report is to find a new treatment approach by using monoclonal antibodies such as Denosumab in the treatment protocol. Monoclonal antibodies like Denosumab have shown promising results by targeting the RANKL-RANK interaction, inhibiting osteoclast activity, and reducing inflammatory bone resorption. Materials and Methods: In the Department of Maxillofacial Surgery of the Russian Children’s Clinical Hospital - a branch of the Federal State Autonomous Educational Institution of Higher Education Russian National Research Medical University named after. N.I. Pirogov of the Ministry of Health of the Russian Federation of Moscow from 2015 to 2023, 45 children underwent inpatient treatment for primary chronic osteomyelitis (PCO). Of these, 17 children received combination therapy, which included decortication with removal of all granulomatous tissue and administration of the drug Denosumab, and that is after receiving negative culture results which conforms the diagnose of PCO. From these 17 patients, a 9-year-old girl with a persistently relapsing course was selected for this article. Results: The treatment methods employed in this clinical case successfully increased the density of the affected area. However, if small cystic components were retained and the sanitation of the granulated tissues was incomplete, a relapse occurred, necessitating repeated surgical treatment. Conclusion: By using this approach, we found that the intervals between collapses have been prolonged; leaving no doubt that the addition of Denosumab to the treatment protocol has played a significant role in achieving this optimal result by maintaining remission stability, even after the symptoms disappeared.
