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Noroviruses are the leading cause of outbreaks of nonbacterial gastroenteritis and the second most common cause of all viral intestinal infections. An effective norovirus vaccine is expected to help reduce the incidence of intestinal infections, but intensive efforts to develop such a vaccine have so far been unsuccessful. Failures in vaccine development may be due to the high heterogeneity of noroviruses and/or the hypothetical low protective efficacy of the immune response to the most common virus variants, such as GII.4 Sydney 2012. The subject of the study was potential vaccine components – virus-like particles (VLPs), formed from VP1 of norovirus GII.4 Sydney 2012 (VP1N) and VLPs from a fragment of this protein containing the shell domain and hinge region (SN). We investigated the effect of VLPs on the ability of human dendritic cells (DCs) to recruit T cells into the immune response in vitro. VLP-treated DCs were cultured with pure CD4⁺ T cells, and then T cell maturity and cytokine production were assessed. It has been shown that VP1N-treated DCs, but not SN-treated DCs, have an increased ability to shift the ratio of T cell from naïve T cells to more mature central memory T cells and stimulate IL-17 production. Intracellular cytokine assay revealed no differences in T-helper type 1 (Th1), Th17 and Th1/17 levels between mixed cultures with VP1N-treated DCs and control DCs. Apparently, the increase in IL-17 production occurs due to an increase in the activity of mature Th17, and not the maturation of new producer cells.

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. Heart failure (HF), a major pathology of the myocardium, is characterized by impaired cardiac function that leads to an abnormal enlargement of the heart, known as hypertrophy. In the study of the molecular mechanisms of HF pathogenesis, animal models play a crucial role. To characterize induced HF in animal models, biochemical approaches, such as quantifying the concentration of biomarkers in blood serum, are extremely important. Here we report a new immunochemical test system based on the measurement of the concentration of the B-type natriuretic peptide, protein biomarker of HF and hypertrophy, that can be utilized for characterization of HF development in rats and serve as a tool for further BNP concentration analysis.

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder in which neuroinflammation plays a major role in its pathogenesis, alongside the formation of amyloid plaques and neurofibrillary tangles. Necroptosis, a recently discovered regulated form of cell death mediated by the kinases RIPK1 and RIPK3, is considered one of the mechanisms contributing to neuroinflammation and neuronal death in AD. In this study, we evaluated the effect of chronic necroptosis inhibition using Necrostatin-1, a RIPK1 blocker, on the progression of neurodegeneration in aged 5xFAD mice, a model of the familial form of AD. Over a 12-week treatment period, the animals’ neurological status was assessed, followed by evaluation of long-term memory using the Morris water maze test, histological analysis of the prefrontal cortex and hippocampus, and RT-PCR analysis of the expression of key genes associated with necroptosis and inflammation. Chronic administration of Nec-1 significantly slowed the progression of neurological deficits in both male and female 5xFAD mice. Inhibition of necroptosis prevented the loss of normal neurons, reduced the number of hyperchromic cells, and decreased the severity of pericellular and perivascular edema in the examined brain regions. However, in the Morris water maze test, learning and memory improved only partially in males, but not in female 5xFAD mice. This may be attributed to the increased expression of the anti-inflammatory cytokine IL-10 in the cortex and hippocampus of males. The results obtained indicate that inhibition of necroptosis by Necrostatin-1 represents a promising therapeutic approach for correcting neurological impairments and mitigating morphological brain alterations in Alzheimer’s disease.

Primary lactose non-persistence (LNP, hypolactasia) represents an autosomal-recessive condition, which is mainly attributed to the presence of the ancestral C-allele in the MCM6 -13910C>T (rs4988235) variant regulating the expression of the lactase (LCT) gene in individuals of European ancestry. Since the studies linking lactose intolerance C-allele and caloric accumulation, as well as gastrointestinal symptoms remain ambiguous to date, we decided to examine for a possible relation between the rs4988235 lactose intolerance allele and certain health parameters (body mass index, waist circumference, breastfeeding duration, and existing gastrointestinal tract diseases) in individuals (N = 2912) from four regions of the Volga-Ural region (VUR), i.e., Sverdlovsk Oblast, Republic of Bashkortostan, Chelaybinsk Oblast, and Udmurt Republic. In addition, we sought to clarify the genotype and allele frequencies of the MCM6 rs4988235 in the large sample from the VUR based on territorial and ethnic specificity. While examining a relation between several health conditions and the MCM6 variant, we determined a link between the rs4988235 CC genotype and prolonged breastfeeding duration (more than 1 year) in the total sample (OR = 1.63, 95%CI 2.32–5.88, p = 0.005) and in Russians (OR = 1.75, 95%CI 2.85–4.16, p = 0.024), which became more significant in individuals with a full-term period of gestation (more than 36 weeks) (OR = 1.67, 95%CI 1.13–2.45, p = 0.009) and was positively associated with higher birth weight (β = 3.11, p = 1.8x10^-3). Findings obtained point to a compensatory effect of prolonged breastfeeding on diminishing manifestation of genetically predisposed primary hypolactasia.

Bacteria of the species Streptococcus pneumoniae, dominant in the etiological structure of community-acquired pneumonia in children, are represent a serious problem in the field of human infectious pathology. Detailed molecular and genetic characteristics of eleven S. pneumoniae strains isolated from sputum samples of children with community-acquired pneumonia were obtained using whole genome sequencing and bioinformatic analysis. Based on the analysis of the nucleotide sequences of seven housekeeping genes (aroE, gdh, gki, recP, spi, xpt, ddl), it was found that S. pneumoniae strains included in the study belong to six sequence types: ST1367, ST819, ST1262, ST180, ST15069, ST66. Using SeroBA algorithm S. pneumoniae strains were assigned to five serotypes:11C, 22F, 15C, 9N, 3. Genome annotation using ResFinder and CARD databases allowed us to identify determinants of resistance to macrolides (ermB, RImA), fluoroquinolones (patA, patB, pmrA), lincosamides (RImA), aminoglycosides (aph(3')-Ia) and tetracyclines (tetM and tet32). A high frequency of detection of pathogenicity genes encoding choline-binding proteins, fibronectin-binding proteins, pneumolysin, autolysin, hyaluronidase, neuraminidase, capsule proteins, zinc metalloproteinase in the genome of S. pneumoniae strains was noted.  Phylogenetic analysis of the nucleotide sequences of the genome of Nishny Novgorod strains and strains deposited in GenBank/NCBI showed a high level of genetic variability of pneumococci circulating both in Russia and abroad.

Vitex negundo is a medicinal plant renowned for its wide spectrum of therapeutic properties, including significant anticancer activity. This study explores the inhibitory effects of V. negundo methanolic extract and essential oil on α-amylase purified from the serum of Iraqi lung cancer patients, as well as their cytotoxic effects on the A549 human lung cancer cell line. α-Amylase, an enzyme involved in carbohydrate metabolism, exhibits altered activity under cancerous conditions, making it a potential therapeutic target. The enzyme was purified through a multi-step procedure comprising ammonium sulfate precipitation, dialysis, ion-exchange chromatography, and gel filtration chromatography. This process resulted in an increase in specific activity from 0.94 to 17.0 U/mg protein. Both extracts of V. negundo were assessed for their capacity to inhibit α-amylase activity and reduce the viability of lung cancer cells. The methanolic extract demonstrated a more pronounced inhibitory effect on α-amylase (88.4% at 10 µg/mL) compared to the essential oil (77.0% at 10 µg/mL). Moreover, MTT assay results indicated concentration -dependent cytotoxicity against A549 cells, with IC₅₀ values of 68.79 µg/mL for the methanolic extract and 81.14 µg/mL for the essential oil. These findings underscore the potential of V. negundo—particularly its methanolic extract—as a promising natural anticancer agent, capable of targeting cancer-related metabolic pathways and suppressing tumor cell viability. The results warrant further investigation into the development of V. negundo-based therapeutics for lung cancer treatment.

Chronic lymphocytic leukaemia (CLL) is distinguished from other lymphoid tumours due to the fact that its biology and clinical symptoms are very different from those of other lymphoid cancers. In the past ten years, there has been significant progress made in the understanding of the pathogenesis of the disease. In the field of cancer research, there have been numerous significant areas that have been investigated. The mechanisms of genetic vulnerability, the role of immunogenetic factors in the development of disease, genomic changes, epigenetic subtypes, epigenomic reprogramming of tumour cells, the control of interactions between tumour cells and their environment, and the dynamics of clonal evolution from monoclonal B cell lymphocytosis to diffuse large B-cell lymphoma are some of the topics that are investigated. As a result of the accumulation of information, new targeted drugs and management strategies have been developed, which has resulted in the opening of new therapy avenues. The purpose of this review is to examine the patterns of DNA methylation, immunological markers, and molecular and immunological characteristics that are present in patients who have chronic lymphocytic leukaemia.

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.