The prevalence of chronic gastritis (CG) in the population is extremely high (50–80% among the adult population) and correlates with Helicobacter pylori (H. pylori) infection. CG is a multifactorial process influenced by both environmental and genetic factors. In gastritis (especially associated with H. pylori), immune cells (macrophages, neutrophils) actively produce matrix metalloproteinases (MMPs). MMPs degrade the basement membrane of the gastric epithelium, disruption of its integrity and deepening of damage. The aim of this study is to analyze the association of polymorphic variants of the matrix metalloproteinase genes MMP9 (rs17576, 836A>G) and MMP12 (rs652438, 1070A> G) with the risk of developing chronic gastritis in individuals living in the Republic of Bashkortostan. Material and methods. DNA samples from 154 patients with gastritis and DNA samples from 122 individuals in the control group aged 18-50 years living in the Republic of Bashkortostan were used as research material. Genotyping was performed using the real-time PCR method. Results. In males, the G allele of the rs17576 polymorphic variant of the MMP9 gene was found to be a marker of an increased risk of developing CG. Association analysis of the rs652438 polymorphic variant of the MMP12 gene with the development of CG revealed no statistically significant differences between the compared groups of patients and controls. Conclusion. The obtained data allow for a deeper study of the mechanisms and molecular basis of CG pathogenesis, as well as the identification of important molecular genetic markers of the risk of developing this disease.
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Periodic changes of intracellular mediators concentration play a key role in the functioning of both electrically excitable and non-excitable cells. In particular, fluctuations in calcium and nitric oxide in microvascular cells are important for their functioning, and changes in these mediators are associated with pathological conditions. However, the characteristics of calcium and nitric oxide fluctuation synchronization in non-excitable cells have been little studied. The main reason for this is the lack of an adequate research method. In this study, we successfully adapted the method of polyspectral analysis for the quantitative assessment of the synchronization of calcium and NO oscillations in non-excitable cells using microvascular cells as an example. The polyspectral analysis method allows us to accurately assess the proportion of cells with synchronized calcium and NO oscillations, the strength of synchronization, the direction of transmission of the synchronizing frequency from cell to cell, and which mediators are involved in the transmission of this frequency. In addition, stress factors (heating, excess glucose) alter the number of synchronized cells, the distribution of synchronized oscillations by frequency and amplitude, and the direction of transmission of the synchronizing frequency from cell to cell. We believe that the data obtained can be used in personalised medicine and other fields.
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The development of photopolymer 3D printing materials for biomedical applications requires the creation of a new class of polymer resins, that combine high strength, antibacterial activity, and low toxicity against eukaryotic cells. In this paper, a new material for 3D printing based on polymethyl methacrylate (PMMA) and tellurium nanoparticles (NPs) was developed. NPs Te were synthesized by laser ablation in water, transferred in acetone, and then included in a MMA solution. NPs concentrations Te were 0.001, 0.01, and 0.1% by volume. The introduction of Te NPs did not alter the energy required for polymerization or the mechanical properties of the finished polymer; however, it increased the degree of final polymerization as indicated by FTIR data. Additionally, it added significant bacteriostatic properties without increasing toxicity against eukaryotic cells. The mechanism of antibacterial action can be mediated through the induction of oxidative stress in bacteria (increased generation of 8-oxoGua and long-lived reactive forms of proteins in aqueous solutions). The severity of the antibacterial action is determined by the dose of the introduced NPs Te.
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Connective tissue dysplasia (CTD) is associated with complex metabolic changes, including the metabolism of amino acids. However, the currently available data are contradictory. Therefore, the aim of the present study was to investigate the levels of amino acids in the urine of children with undifferentiated (uCTD). The present research involved 524 children who were included in the control group and 1266 children with uCTD syndrome who were included in the experimental group. The levels of amino acids in urine were assessed using GC-MS Agilent GC 7820/MSD 5975. The statistical analysis was performed using SPSS program, version 22. The results of the study by means of chromatography-mass spectrometry of the amino acid composition of urine in children with undifferentiated connective tissue dysplasia syndrome living in permafrost conditions of the Republic of Sakha (Yakutia) are presented in this paper. The analysis of amino acids in urine enables to evaluate their qualitative and quantitative composition, to obtain information about the existing imbalance, which may indicate nutritional and metabolic disorders underlying a large number of diseases, including disorders associated with connective tissue.
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Acute limb ischemia (ALI) is characterized by a sudden reduction in arterial blood flow and may result in gangrene, systemic complications, and death. Urgent revascularization can be limb- and life-saving; however, it is associated with a risk of early postoperative complications. Both perioperative and intraoperative risk factors contribute to these outcomes and are influenced by the selected method of revascularization. The aim of this study was to assess the impact of intraoperative risk factors on postoperative outcomes according to the chosen treatment modality for acute limb ischemia, namely open or endovascular revascularization. Patients with Rutherford class II ALI from a single population were divided into two groups comparable in clinical and demographic characteristics: Group I – open surgical treatment (n = 50) and Group II – endovascular revascularization (n = 50). The influence of identified intraoperative risk factors on the development of complications differed between the two revascularization approaches. An operative time exceeding 85 minutes in the open surgery group (2.73) and exceeding 92 minutes in the endovascular group (1.52) was associated with an increased risk of adverse postoperative outcomes. The urgent nature of the procedure was also an independent predictor of adverse events in both groups, with ORs of 12.11 and 9.13 for Groups I and II, respectively. Outcomes of ALI treatment and the early postoperative course in the overall population depend on the selection of the revascularization method in accordance with each patient’s individual perioperative risk profile. Comparison of endovascular and open approaches demonstrated differences in outcomes favoring endovascular revascularization only in a specific subgroup of patients with a less severe functional class of limb ischemia.
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Acute limb ischemia (ALI) during the acute phase of coronavirus infection - an urgent complication, associated with a high rate of adverse events. Antithrombotic therapy remains the cornerstone of prevention and treatment of thrombotic complications in patients with COVID-19. The aim of study was to evaluate the effectiveness of combined outpatient antiplatelet and anticoagulant therapy compared with antiplatelet monotherapy during the 12-month postoperative period after arterial revascularization in the acute phase of coronavirus infection. Materials and Methods: The study included 257 patients. Group I (control; n = 100) comprised patients without a history of COVID-19, while Group II (study; n = 157) included patients with laboratory-confirmed acute coronavirus infection. Patients in Group I received an antiplatelet agent (aspirin 100 mg once daily). Patients in Group II were prescribed outpatient combination therapy after revascularization: an antiplatelet agent (aspirin 100 mg once daily) and an anticoagulant (rivaroxaban 10 mg once daily for 30–45 days, followed by 2.5 mg twice daily). The results demonstrated a significant reduction in the rates of limb amputation and recurrence of ALI among Group II patients with a history of COVID-19 who received combination therapy with rivaroxaban and aspirin, consistent with findings from the COMPASS study. SF-36 scores improved significantly, approaching the quality-of-life levels observed in patients without a history of COVID-19. Conclusion: The findings support the feasibility of routine use of combined antiplatelet and anticoagulant therapy in the outpatient setting for up to one year after revascularization for ALI in the context of the COVID-19 pandemic.
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The Role of Retroelements in the Formation of CNV in the Human Genome in the Development of Diseases
Copy number variations (CNVs) are involved in eukaryotic genomes evolution. CNVs also the causes of multifactorial and monogenic diseases. Retroelements can be causes of CNVs emergence and evolution. Retroelements occupy 42.5% of the human genome and are located mainly in intergenic, intronic and regulatory regions. The mechanisms of CNVs formation are due to non-allelic homologous recombination between retroelements due to their distribution across all chromosomes and the presence of homologous sequences. Role of recombinations between retroelements as causes of neurofibromatosis type 1, Cowden syndrome, Peutz-Jeghers syndrome, Langer-Gideon syndrome, Fanconi anemia, amelogenesis imperfecta, and spastic paraplegia type 4 and other monogenic diseases is described. Mechanisms of CNVs formation using retroelements suggest the role for retroelements as causes of trinucleotide repeat expansion diseases. The influence of LINE1 in Huntington's chorea caused by CAG expansion is described. In fragile X syndrome, CGG expansion occurs in the FMR1 gene, which homologue in Drosophila is involved in retroelements inhibition. In humans, CGG-binding protein influence on Alu and LINE1 described. Role for Alu in GAA expansion identified in Friedreich's ataxia. These relationships suggest the possible retroelements role in triplet code development during the origin of life. At the human population level, the underlying mechanisms of evolution through the influence of retroelements are the cause of numerous diseases. However, in the wild, the same mechanisms serve as substrates for the natural selection of more adaptive traits and eukaryotes evolution.
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Cryopreservation significantly impacts sperm integrity, reducing their fertility potential. These processes are largely dependent on increased oxidative stress. Low-level laser irradiation (LLLI) can increase energy delivery to cells and reduce reactive oxygen species (ROS). Our goal was to analyze the effects of LLLI on metabolic, oxidative and antioxidant parameters in cryopreserved bovine spermatozoa and the possible mechanisms of its action. We analyzed 50 samples of bull semen, dividing them into two groups: a control group without laser irradiation and a group exposed to laser irradiation. We also analyzed the effects of LLLI in combination with the adenylatecyclase stimulator - forskolin, the Ca2+ channel blocker - verapamil and the protein kinase C inhibitor - staurosporine. Irradiation was performed in petri dishes of 30 mm containing 3 ml of sperm at a wavelength of 650 nm. Cryopreservation was found to increase lipid peroxidation and decrease metabolism which was accompanied by a decrease in sperm motility and viability of sperm. ATP concentrations was increased while sperm motility and MDA concentrations were decreased during cryopreservation with LLLI. The effects of LLLI varied depending on the added substances. A combination of LLLI and forskolin demonstrated increased motility and metabolic activity compared to LLLI alone. The effects of LLLI were significantly weakened by staurosporine. The Ca2+ channel blocker - verapamil partially inhibited the effects of LLLI. Thus, lipid peroxidation was reduced and ATP concentration and sperm motility were increased during cryopreservation under LLLI. These properties of LLLI are associated with cell signaling pathways.
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Gamma-wave stimulation represents one of the most promising non-pharmacological approaches for enhancing cognitive function, which declines with aging and in neurodegenerative diseases. The aim of the present study was to identify optimal protocols for maximizing the effectiveness of gamma-wave stimulation. We investigated the effects of various combinations of physical and cognitive loads during visual gamma-wave stimulation at a frequency of 40 Hz using light of different wavelengths on the amplitude of gamma rhythms in the human brain. The effects were evaluated both at the level of individual EEG leads and across global brain electrical activity. The strongest response to visual gamma stimulation was observed in the occipital region. This effect exhibited a cumulative component, reflected by an increase in baseline activity at the stimulation frequency. The cumulative effect was most pronounced in the occipital and temporal regions. The magnitude of the gamma-stimulation response depended on the wavelength of the light stimulus and increased in the order of white, pink, and red. The most robust effect was observed with red-light stimulation combined with physical exercise. The influence of cognitive load was more prominent in the frontal and parietal regions of the brain.
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Oral immunoglobulin preparations are a promising therapeutic approach for inflammatory bowel diseases. During enteral administration, antibodies inevitably encounter low pH conditions in the stomach, which can alter their conformation and functions. Understanding how acidic exposure influences the activity of therapeutic immunoglobulins is essential for improving their stability and clinical efficacy. In this study, a human plasma-derived immunoglobulin preparation containing IgG, IgA, and IgM was exposed to mildly and strongly acidic buffers. The treated samples were analyzed using dynamic light scattering to assess structural stability, enzyme-linked immuno-sorbent assay and Western blotting to evaluate antigen-binding specificity, and flow cytometry and confocal microscopy to study neutrophil functions. Acidic treatment did not induce aggregation or major structural destabilization but caused marked functional changes. Exposure to low pH in-creased the polyreactivity of IgG and IgA toward bacterial and viral antigens, while IgM lost its binding specificity. Acid-modified immunoglobulins enhanced bacterial recognition by neutrophils without affecting phagocytosis or oxidative activity but promoted the release of extracellular DNA structures, a hallmark of neutrophil activation. These findings indicate that short-term acidic expo-sure modifies antibody specificity and immune function without compromising structural integrity. Such effects may be relevant for optimizing therapeutic formulations and understanding antibody behavior in acidic mucosal environments.
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