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Gastric cancer (GC) is one of the leading causes of cancer death in the world (http://globocan.iarc.fr). In the Russian Federation, cancer of this localization ranks sixth among all malignant tumors in terms of incidence and second in mortality. Our study used a sample consisting of DNA samples isolated from the peripheral venous blood of patients with gastric cancer and healthy donors aged 21 to 88 years living in the Republic of Bashkortostan. The group of patients consisted of 156 people. As a control, a group of unrelated healthy donors without any gastrointestinal diseases was studied, consisting of 307 people of various ethnicities also living in the Republic of Bashkortostan. One of the promising areas is the study of mitochondrial dysfunction as a consequence of changes in energy metabolism, which are one of the signs of malignancy (Lee et al., 2014). In our study, we screened for known mutations of mtDNA molecules in patients with gastric cancer. The results of our studies show that all three loci we examined - a 4977 bp deletion located in the 8483-13459 mtDNA region, single nucleotide substitutions 15767 C>G in the CYB gene and 7080 T>C in the COI gene - most likely do not play a role as driver events in the occurrence of gastric cancer in individuals of Russian, Tatar and Bashkir ethnicity from the Republic of Bashkortostan.

Aging is a natural and inevitable process that worsens the quality of life and shortens its duration. In the process of aging, the cardiovascular system undergoes significant restructuring, diastolic dysfunction is observed, vascular stiffness increases and vasodilation decreases. α₂-ARs are widely distributed in the body and are involved in the regulation of heart and vascular functions. In pathological conditions, there is an increase in the expression of α₂-AR subtypes, a violation of their functions, and a decrease in the effectiveness of the associated signalling cascades. The study aimed to investigate the effect of the α₂-AR agonist clonidine hydrochloride at concentrations of 10^-9-10^-6 M on the inotropy, chronotropy and coronary flow of the old rats isolated heart. α₂-AR stimulation changes all the studied parameters of the old rats isolated heart. The force of left the ventricular myocardium contraction decreases at concentrations of 10^-9 and 10^-8 M, and increases at concentrations of 10^-7 and 10^-6 M. The α₂-AR agonist causes a decrease in heart rate in all studied concentrations. Stimulation of α₂-AR in lower concentrations (10^-9 - 10^-7 M) reduces coronary flow, and the maximum concentration of clonidine hydrochloride (10^-6 M) increases.

The study examined the possibility of using vesicular mRNA for diagnostic purposes using real-time PCR as a tool for analyzing the stage of development of changes in the body in response to prolonged alcohol intake. The study simulated the intermittent nature of prolonged alcohol consumption in Wistar rats, which reflects the pattern of alcohol consumption typical of individuals who abuse alcohol. Extracellular vesicles were isolated from the blood plasma of rats using differential ultracentrifugation. Their presence was confirmed by scanning electron microscopy. Total RNA extraction, cDNA synthesis, and real-time PCR were performed using commercial reagent kits.  The study revealed elevated levels of several pro-inflammatory mRNAs in extracellular vesicles isolated from blood plasma. In the group of animals with prolonged alcoholization, the levels of Tnfα mRNA were increased, and the presence of Hmgb1 mRNA was confirmed. In the conditions of the cancellation of long-term alcoholization, on the 10th day, an increased level of pro-inflammatory mRNA Tnfα and Il1β were revealed and the content of mRNA Hmgb1 was again found. The obtained data show the diagnostic value of vesicular mRNA and open the prospect for subsequent research in this direction.

Breast cancer (BC) remains one of the leading causes of cancer-related mortality in women worldwide. Recent studies have explored the role of myokines, signaling proteins released during muscle contraction, in regulating tumor growth, metastasis, and the tumor microenvironment. This study investigates the correlation between myokines and breast cancer progression, focusing on the role of irisin and decorin. The study was conducted at two oncology centers in Baghdad, Iraq, from May to December 2022. A total of 88 Iraqi women, aged 20-70, were enrolled in the study across six groups: healthy controls (G1) and women with different treatment regimens (G2-G6). Blood samples were collected after fasting, and myokine concentrations were measured using ELISA. Additionally, histopathological examinations were performed on tissue biopsies to assess the presence of lobular carcinoma in situ (LCIS). The study found significant differences in myokine concentrations across the groups. Irisin levels were highest in the metastatic group (G6), while decorin levels showed significant variations across the different patient groups. Histological analysis revealed characteristic changes of LCIS, including irregular lobular structures, hyperplasia, and inflammatory cell infiltration. This study highlights the potential role of myokines, particularly irisin and decorin, as biomarkers for breast cancer progression. Elevated irisin levels in advanced stages suggest its involvement in tumor development and metastasis.

Familial hypercholesterolemia (FH) is a prevalent inherited lipid disorder marked by elevated low-density lipoprotein cholesterol (LDL-C) from early life, significantly increasing the risk of premature atherosclerotic cardiovascular disease (ASCVD). Recent advances in pharmacotherapy have transformed treatment possibilities, particularly for patients unresponsive to traditional therapies. This review synthesizes current evidence on emerging lipid-lowering agents, including PCSK9 monoclonal antibodies (e.g., evolocumab), small interfering RNA-based therapies (e.g., inclisiran), and angiopoietin-like protein 3 (ANGPTL3) inhibitors (e.g., evinacumab). Clinical trials demonstrate that these agents achieve substantial LDL-C reductions – often exceeding 40% – with favorable safety profiles, even in homozygous FH patients with null LDL receptor activity. Additionally, advances in genomic research have enabled more precise classification of pathogenic variants in genes such as APOB and ANGPTL3, improving diagnostic accuracy and guiding targeted therapy. The integration of these pharmacologic and genetic strategies represents a significant shift toward individualized management of FH. Further long-term and population-based studies are needed to validate these approaches and ensure equitable access across healthcare settings.

The aim is to determine the role of polymorphic loci of IL-1β, IL-10, TNF-α genes in families of patients with Helicobacter pylori-associated diseases. Materials and methods: Molecular genetic identification of H. pylori was carried out by PCR. Determination of cytokine gene polymorphisms (IL-1β (-31T/C), TNF-α (-308 G/A), IL-10 (-592C/A) and (+1082G/A) in 108 individuals – family members of individuals with chronic H. pylori-associated gastritis, was carried out by allele-specific PCR in real time. Results: H. pylori DNA was detected in 55.6% of patients' relatives, which is higher than the average prevalence in Russia (35.3%) and the Volga Federal District (33.0%). The distribution of gene polymorphisms of the studied cytokines in relatives of patients with and without H. pylori infection differed significantly. In H. pylori-infected family members, the T/T genotype and T allele of IL-1β (-31T/C), the C/C genotype of IL-10 (-592 C/A), and the G/G genotype of TNFα (-308 G/A) were significantly more frequently detected. No significant differences in IL-10 polymorphisms (+1082 G/A) were found in H. pylori positive and H. pylori negative individuals. Conclusions: IL 1β (-31T/C) T/T, IL 10 (-592 C/A) C/C, TNFα (-308 G/A) G/G gene polymorphisms increase the risk of H. pylori infection by more than 2 times. Carriers of such genotypes constitute a risk group for H. pylori-associated diseases, and in case of subclinical infection they are a source of infection and reinfection of relatives. Identification and treatment of infected family members is an important task in preventing the spread and recurrence of H. pylori infection.

Colorectal cancer (CRC) is characterized by a high mutational load and resistance to chemotherapy. Therefore, new approaches in the treatment of CRC include viral mimicry aimed at activating the expression of retroelements to stimulate the immune response against cancer. However, the role of activated retroelements in CRC carcinogenesis must be considered. Retroelements are implicated in CRC-specific chromothripsis and one of the highest percentages of retroelement insertions in CRC of any cancer type has been identified. In addition, retroelements are evolutionarily and functionally related to long noncoding RNAs, microRNAs, and circular RNAs. Therefore, a differentiated approach is needed in targeted therapy of CRC using circular RNAs as tools (as the most stable non-coding RNAs) to control the activity of retroelements. This article describes the analysis of scientific literature on the relationship in the mechanisms of CRC development of retroelements with circular RNAs, microRNAs and long non-coding RNAs. Data on the functioning of specific circular RNAs as tumor suppressors and oncogenes with their influence on microRNA and the expression of protein-coding genes are systematized. The nature of changes in the expression of transposon-derived microRNAs interacting with circRNAs and long noncoding RNAs in CRC is presented. The obtained data may form the basis for more correct epigenetic therapy of CRC with activation of only those retroelements that are not involved in CRC carcinogenesis.

Cardiovascular diseases are among the most prevalent pathologies worldwide, and myocardial infarction (MI) is a common cause of ventricular arrhythmias and sudden cardiac death. The development of MI is accompanied by profound alterations in the electrophysiological properties of cardiomyocytes, including a decrease in the amplitude and propagation velocity of the action potential. These changes lead to disturbances in excitability and impulse conduction not only in the affected region but also throughout the entire heart. Understanding the mechanisms underlying these alterations is crucial for developing novel approaches to the prevention and treatment of cardiovascular complications. The study aimed to investigate the dynamics of electrical activity changes in the right atrial myocardium at different stages of left ventricular myocardial infarction (MI) development in rats. Experimental MI was induced by ligation of the left coronary artery. We evaluated the effects of acute, subacute, and long-term consequences MI phases on the amplitude-time characteristics of action potentials in working right atrial cardiomyocytes.

This study investigated the production, purification, and vitro cytotoxic potential of L-glutaminase derived from Bacillus subtilis. Twenty-five bacterial isolates were recovered from diverse soil samples. Identification of B. subtilis was confirmed using standard biochemical assays, differential media, and the VITEK 2 automated system. Screening for L-glutaminase production identified B. subtilis isolate B7 as exhibiting the highest activity, with a crude enzyme-specific activity of 15.8 U/mg. Optimization of enzyme production parameters revealed glucose and yeast extract as optimal carbon and nitrogen sources, respectively, under controlled conditions of 40 °C and pH 6. L-glutaminase was purified using a four-step protocol: ammonium sulfate precipitation, ion exchange chromatography, gel filtration chromatography, and salt precipitation. Gel filtration chromatography resulted in the highest specific activity (754.6 U/mg), representing a 15.2-fold purification and a 21.1% yield relative to the crude extract. The in vitro cytotoxic effects of crude and purified L-glutaminase were evaluated using the MTT assay against the A549 (human lung adenocarcinoma) and WRL 68 (normal human liver) cell lines. Paclitaxel, a known chemotherapeutic agent, was a positive control for cytotoxicity against A549 cells. Treatment of A549 cells with purified L-glutaminase induced a dose-dependent reduction in cell viability, with a concentration of 400 µg/ml achieving maximal inhibition. These findings suggest that purified L-glutaminase from B. subtilis B7 demonstrates significant in vitro cytotoxic activity against A549 lung cancer cells and merits further investigation as a potential therapeutic candidate.

Redox dynamics in mononuclear cells during phagocytosis and post-exposure to UV radiation was evaluated in vitro. Mononuclear cells were isolated from rat blood using density gradient centrifugation. Phagocytosis was activated via latex beads, and redox processes were monitored at 1, 30, and 60 minutes in control samples and after UV exposure at doses of 1, 5, and 15 J/m2. Cell viability post-phagocytosis was assessed using propidium iodide staining and cytofluorimetry. Redox processes in phagocytes were evaluated by measuring fluorescence of tryptophan, Schiff bases and glycated proteins, alongside absorption spectra/florescence levels of metabolic coenzymes FAD, NAD(P) and NAD(P)H and their ratios. In controls, cell viability decreased by 15.2% after 60 minutes of phagocytosis, while tryptophan, NAD(P), and NAD(P)H levels remained stable. Concentrations of Schiff bases and glycated proteins doubled. UV radiation significantly reduced cell viability in a dose-dependent manner. At 15 J/m2, 80.99% of cells were nonviable after 60 minutes of phagocytosis. This dose also caused a 21.42-fold decrease in tryptophan fluorescence, a 3.8-fold reduction in Schiff bases/ glycated proteins, and declined metabolic coenzyme levels. Ratios of NAD(P)H/FAD and NAD(P)H/NAD(P) decreased post-UV exposure, indicating oxidative dominance and NAD(P)H deficiency. However, despite UV-induced cytotoxicity, all experimental series, regardless of the dose of UV discharge, maintained control trends: non-enzymatic glycation products (Schiff bases, glycated proteins) increased, and the NAD(P)H/FAD ratio rose due to reduced coenzyme accumulation during phagocytosis. This suggests that phagocytic redox pathways persist under UV stress, albeit at diminished intensity.

Previously, we reported that the hypomagnetic field obtained by the 100-fold deprivation of the geomagnetic field affected human cognitive processes as estimated in four different cognitive tests. The 40-minute exposure to the hypomagnetic field caused a statistically significant increase both in the task processing time and in the number of errors. The magnetic effect averaged over 40 healthy subjects was about 1.7%. In the present work, the results of a simultaneous study are described, in which the right eye of each subject was video recorded, while the subject performed the tasks. The pupil size increased in the hypomagnetic field. This effect has been calculated by processing the large data set of a few million video frames. The average magnetic effect was about 1.6% (<<0.01, ANOVA, factor of subjects - fixed). Given the heterogeneity, the effect was close to being significant (0.07, ANOVA, factor of subjects - random). The simultaneous recordings of magnetic reactions both for the different cognitive tests and for the eye pupil size were not correlated. These findings provide experimental confirmation of the random nature of the non-specific magnetic biological effects in humans.

Introduction: acute limb ischemia is characterized by a sudden and severe reduction in blood supply to the limb, posing a critical threat to its viability. The incidence of complications associated with ALI remains significantly high. Currently, there is no consensus regarding which preoperative factors influence the incidence of complications in different revascularization methods, nor to what extent they contribute to postoperative outcomes. An analysis of the key predictors of complications will facilitate the development of preventive strategies and establish criteria for selecting the most appropriate treatment approach for ALI. Materials and methods: this study analyzes the outcomes of two treatment methods for ALI classified as Rutherford class II: open surgical intervention (Group I, n = 50) and endovascular procedures (Group II, n = 50). Results and discussion: the composition and impact of preoperative risk factors differed between the two revascularization methods. In the open surgery group, patients with an inflammatory, hypovolemic, or thrombophilic etiology of ALI (11) demonstrated a higher likelihood of an unfavorable postoperative course. Additionally, advanced patient age (7.1), Rutherford ischemia class IIB (0.2), a history of CAD (6.1), DM (9.2), CKD (12.1), and RF (8.5) were identified as significant risk factors for postoperative complications. In the endovascular revascularization group, among perioperative risk factors, the following variables demonstrated significant associations with postoperative complications: CAD (4.9), CKD (12.4), DM (5.28), RF (11), and Rutherford ischemia class IIB (0.2). Conclusion: selecting an appropriate revascularization method based on an individualized risk factor profile for each patient can effectively reduce the incidence of complications in the early postoperative period.

This paper presents the possibilities of using the Unity engine to create the research software for cognitive neuroscience using the brain-to-brain synchrony paradigm. Neurofeedback software for neuroscience research in the brain-to-brain synchrony paradigm is represented by software that allows to implement three research protocols based on the EEG signals recording: the “eyes-to-picture” in the double glasses HTC VIVE PRO protocol, the “eyes-to-eyes”/“ face-to-face” protocol and the “eyes-to-screens” protocol. The presented brain-to-brain synchrony software solution for the implementation of different protocols is a digital platform allowing to perform hyperscanning of electrical activity of the cerebral cortex simultaneously in several persons and thus study the functions of higher neural networks of socially determined areas of the cerebral cortex.

Aim: the effect of cryopreservation and molecular hydrogen (Н2) on the sperm quality characteristics, metabolic, oxidative and antioxidant indices of spermatozoa. Sperm diluted with BioXcell diluent, sperm after cryopreservation and sperm after cryopreservation with Н2 were studied as comparison groups. Qualitative indices of spermatozoa, intensity of free-radical processes, activity of antioxidant enzymes and ATP concentration were measured in all groups. Lipoperoxidation was found to be reduced, and antioxidant activity was increased in sperm after cryopreservation with Н2. It was shown that the content of diene, triene conjugates, malonicdialdehyde decreased in spermatozoa and the activity of superoxidedismutase and catalase increased in sperm after cryopreservation with Н2. Reduction of oxidative processes under the action of Н2 was accompanied by an increase in the concentration of ATP in spermatozoa. After thawing, a significant preservation of spermatozoa motility was recorded under H2 action compared to the group without H2. Thus, H2 is effective in its ability to quench reactive oxygen species and thereby protect spermatozoa from the effects of oxidative stress during cryoconservation. These properties of H2 protect spermatozoa at low temperatures and determine the preservation of high functional activity of spermatozoa after thawing.

Hexavalent chromium Cr (VI) causes reactive stress and inflammation in the heart; hence this study examines how oxidative stress from Cr (VI) affects the circulatory system and the inflammatory and oxidative processes that generate it. Fifty mice were split into five groups. One group was a control, while four received oral Cr (VI) (5 mg, 10 mg, 20 mg, and 50 mg) daily for 30 days. At the conclusion of the study, blood concentrations of ATP, troponin I, and CK-MB were assessed for cardiac injury. To assess oxidative stress, glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and catalase (CAT) were examined. Inflammatory biomarkers, including tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), were identified in a composite of cardiac tissue. Significant cardiac injury and reactive stress were evidenced by the substantial increases in CK-MB, troponin I, and MDA levels in relation to dosage. Antioxidant markers like CAT, SOD, and GSH went down a lot, which means the body's antioxidant defenses were not as strong as they used to be. Increased TNF-α and IL-1β levels, particularly with larger Cr (VI) doses, indicated an inflammatory response. Research demonstrates that Cr (VI) causes oxidative stress and inflammation in the heart, which worsens with greater doses. This study shows how important it's to find more safety drugs that can protect the heart from the damage that Cr (VI) does.

Background: acute myeloid leukemia (AML) is characterized as an aggressive blood cancer with rapid growth of immature leukemic cells. It appears that each subtype of AML displays a distinct miRNA profile. miRNAs play a role in regulating gene expression that is implicated in AML pathogenesis. This study was designed to assess the level of miRNA-155 gene expression in relation to chemotherapy resistance in various AML patient groups, with the hope of developing a novel marker for targeted therapy and early diagnosis and prognosis of cancer stem cells in AML patient. Methods: 120 AML cases were studied. Based on chemotherapy stage, 40 patients were assigned to each group (newly diagnosed, under treatment, and relapsed). Baghdad Teaching Hospital (Iraq) provided the cases and samples from February 2022 to April 2023. This study also included 40 healthy controls. The qRT-PCR method, which uses the ΔCt-value and fold change (2-ΔΔCt), was used to count the genes after they were standardized to the level of a housekeeping gene (U6). Results: in this study, significantly elevated levels of miRNA-155 were observed in AML patients compared to controls, with a higher fold change detected in the newly diagnosed group. Conclusions: upregulation of miRNA-155 is suggested to be linked to AML development and is strongly associated with the progression of leukemic stem cells. These results might serve as accurate predictors of AML and potential therapeutic targets for the elimination of LSCs.

Infertility is a major public health problem worldwide and its prevalence is as high as 17, 5% depending on the population studied The research is aimed to study the possibility of using miR-20a, miR-135a, miR-34b, miR-449v, miR-449c as markers of male infertility and to evaluate the dependence of the effectiveness of ART programs on the level of expression of exosomal microRNAs. The experimental group included patients entering the program of ART (assisted reproductive technologies) with the diagnosis of idiopathic male infertility (n = 30), the control group included couples with female infertility of tubal origin (n = 19). The isolation of exosomal microRNA from ejaculate was performed using the exoRNeasy Midi regent kit. The miRCURY LNA miRNA SYBR® Green PCR System was used to evaluate the expression of the following exosomal microRNAs: miR-20a, miR-135a, miR-34b, miR-449c, miR-449c and control miR-16. The expression of exosomal miR-449c and miR-135a was significantly different in the experimental group (p = 0.03 and p = 0.04, respectively). There was also a tendency to decrease the expression for such microRNAs as: miR-20a, miR-34b and miR-449c. Moreover, the expression level of miR-34b, miR-449c, and miR-449c and miR-135a has a direct correlation with the effectiveness of ART programs (p < 0.05 for miR-135a). The strength of correlation relationship of the above relationships using Cheddock scale was moderate. MicroRNA molecules selected for the study not only demonstrated their potential ability to be used as a diagnostic marker of male infertility, but also showed the ability to reflect the efficiency of fertilization and embryo formation processes.

The present study was carried out to evaluate different estrus synchronization protocols in mice and follow up the proportion of delivery and gender of litters. Five protocols were tested with total number of 48 adult females that divided equally into six groups including control. Total number of 24 adult males were divided equally and introduced for mating for four days. Hormonal synchronization including intraperitoneal administration of single or double dose of 0.5 µg Cloprostenol (Prostaglandin F(PGF)) and 3 µg of Progesterone (P4), with or without 5 IU of equine Chorionic Gonadotropin (eCG) in five protocols. Results showed that estrus and mating rate increase significantly after administration of PGF (P<0.05). However, low delivery rate was evident in all groups. There were no differences in the average number and the proportion of gender of litters within groups. In conclusion, synchronization of estrus in mice was not fully achieved using the current protocols. However, administration of prostaglandin increases mating rate, but the pregnancy success might fundamentally depend on other factors such as managemental.

Cognitive impairments are among the most common types of neurological disorders that require the creation of reliable diagnostic and correction tools. Along with the development of effective drugs, in recent years a line of research has been actively developing, in which various methods of non-invasive brain stimulation with feedback from the current physiological parameters of a person, and primarily from the rhythmic components of the electroencephalogram (EEG), are successfully used to diagnose and correct cognitive impairments. The purpose of the presented work is to analyze recent publications, consider the achievements of this line of research and highlight the most promising directions for its further development. Studies using transcranial magnetic and electrical stimulation, as well as sensory types of stimulation - acoustic, photic and audiovisual stimulations, in which non-invasive stimulation is carried out on the basis of feedback signals from the patient's own bioelectrical processes, are considered. The advantages of EEG-guided light-music stimulation, developed by the authors for the correction of various cognitive disorders, are demonstrated.

Previous studies have demonstrated that administration of clobetasol at a concentration of 0.25 mg/kg stimulates the synthesis of neurotrophic growth factors, likely triggering the phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways, resulting in increased levels of structural and axonal proteins necessary for the functional recovery of damaged somatic nerves. However, it has been shown that using higher concentrations of the drug (0.5 and 1.0 mg/kg) leads to a reduction in both structural and axonal proteins in both segments of the nerve conduit and exerts an inhibitory effect on the expression of neurotrophic factors responsible for cytoskeletal remodeling and axonal growth regulation.