Crohn's disease (CD) is a chronic inflammatory bowel disorder driven by dysregulated immune responses, epithelial barrier dysfunction, and progressive tissue damage. Despite advances in biologic therapies, treatment resistance and loss of response remain common. The activating receptor NKG2D, expressed on natural killer cells and T cell subsets, recognizes stress-induced ligands (MICA, MICB, ULBP) upregulated on intestinal epithelial cells under inflammatory conditions. In CD, sustained ligand expression promotes NKG2D-dependent cytotoxicity, pro-inflammatory cytokine release (IFN-γ, IL-17), and lymphocyte trafficking into the mucosa, perpetuating a cycle of epithelial injury and chronic inflammation. Preclinical colitis models and clinical trials with anti-NKG2D monoclonal antibodies (e.g., NNC0142-0002) demonstrate reduced disease activity, improved histological outcomes, and induction of remission in moderate-to-severe CD patients. However, challenges remain, including potential impairment of immune surveillance against infections and tumors, patient heterogeneity, and pathway redundancy. Future directions include biomarker-guided patient selection, combination therapies with anti-TNF or anti-integrin agents, and next-generation biologics such as bispecific antibodies. Understanding the cellular and molecular basis of NKG2D signaling in mucosal inflammation positions this receptor as a promising, mechanistically anchored therapeutic target in Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory bowel disease with increasing global prevalence, significantly impacting patients' quality of life and healthcare costs. The introduction of monoclonal antibodies has revolutionized CD management, offering targeted therapy against specific inflammatory pathways. This review systematically analyzes the current state of monoclonal antibody therapy, including anti-TNF-α agents (infliximab, adalimumab, certolizumab pegol), anti-integrin antibodies (vedolizumab), and anti-cytokine therapies (ustekinumab, risankizumab). Despite remarkable therapeutic advances, significant limitations persist, including primary non-response (20%-40%), secondary loss of response (13%-20% annually), immunogenicity, safety concerns, and substantial economic burden. We propose evidence-based strategies to address these challenges, including therapeutic drug monitoring, combination therapy, and personalized medicine approaches. Furthermore, we identify promising novel therapeutic targets such as IL-36, IL-17C, SMAD7, TL1A, complement components, and microbiome-related factors. Targeting two or more specific targets simultaneously appears to be a promising direction of research for the development of bi- and polyspecific monoclonal antibodies capable of interfering with multiple pathological pathways in CD. The integration of advanced antibody engineering, personalized medicine, and innovative delivery systems represents the future direction for overcoming current limitations. Achieving sustained remission for all patients through safe, effective, and accessible therapeutic interventions remains the ultimate goal in CD management.

Crohn's disease (CD) is a chronic inflammatory bowel disorder driven by complex interactions between genetic susceptibility, gut microbiota, and immune dysregulation, typically associated with Th1 and Th17 responses. However, emerging evidence highlights that type 2 allergic mechanisms also significantly contribute to CD pathogenesis. This review examines the cellular and molecular basis of allergic pathways in CD, focusing on IgE-mediated hypersensitivity, mast cell and eosinophil effector functions, and Th2 cytokines (IL-4, IL-5, IL-13). Key epithelial-derived alarmins-namely IL-33, TSLP, and IL-25-are discussed as critical upstream mediators linking mucosal barrier injury to type 2 immune activation in the CD gut. Elevated serum IgE, intestinal mast cell infiltration, and tissue eosinophilia have consistently been documented in CD patients. Mechanistically, FcεRI signaling on mast cells triggers degranulation and release of histamine, proteases, and pro-inflammatory cytokines such as TNF-α and IL-6, leading to increased epithelial permeability and visceral hypersensitivity. Moreover, crosstalk between Th2 and Th1/Th17 pathways further amplifies chronic intestinal inflammation. Understanding these allergic mechanisms opens novel therapeutic avenues, including anti-IgE (omalizumab), anti-IL-4/IL-13 (dupilumab), anti-IL-33 (itepekimab), anti-TSLP (tezepelumab), and mast cell stabilizers (ketotifen). This review integrates current molecular evidence on allergic reactions in CD and highlights their clinical and therapeutic relevance. Recognizing type 2 immune signatures in subsets of CD patients may enable more personalized treatment strategies.

Crohn's disease (CD) is a chronic inflammatory bowel disease characterized by transmural inflammation that can affect any part of the gastrointestinal tract. Early and accurate diagnosis remains challenging due to the heterogeneous nature of the disease and overlapping symptoms with other gastrointestinal disorders. Current diagnostic approaches rely on a combination of clinical presentation, endoscopic findings, histological examination, and imaging studies, which can be invasive and time-consuming. The identification of reliable biomarkers could significantly improve diagnostic accuracy and reduce the need for invasive procedures. This review examines currently used biomarkers, including C-reactive protein, fecal calprotectin, and anti-Saccharomyces cerevisiae antibodies, while exploring emerging potential biomarkers such as microRNA panels, metabolomic signatures, and novel inflammatory mediators. Recent advances in genomics, proteomics, and metabolomics have revealed promising biomarker candidates that could enhance diagnostic precision and enable personalized treatment approaches. Understanding the performance characteristics and clinical utility of these biomarkers is crucial for their implementation in routine clinical practice and improved patient outcomes.

BACKGROUND:Cells of different human organs and tissues contain different numbers of mitochondria. In these organelles, there are different copies of the mitochondrial genome, which is characteristic of a certain organ or tissue. OBJECTIVE:The aim of the investigation was to analyze the results of scientific works dedicated to the analysis of heteroplasmy levels of mitochondrial genome mutations in a number of organs and tissues. METHODS:Based on literature data, the level of heteroplasmy of mitochondrial genome mutations was analyzed in organs such as the liver, lungs, muscles, small intestine, large intestine, spleen, kidney, brain, heart, and hair. In addition, this parameter was studied in such tissues as leukocytes, buccal epithelium, and epithelial cells from urine. RESULTS:Significant differences in the mutational burden of the mitochondrial genome were found in various samples of organs and tissues. The highest heteroplasmy level for mtDNA mutations was in muscles; it was lower in buccal epithelium; and in human blood cells, the heteroplasmy level of mitochondrial mutations turned out to be significantly lower compared to other tissues. During the comparison of samples of patients with different diseases and healthy people, significant differences were found in the heteroplasmy level between some organs and tissues. CONCLUSION:The heteroplasmy level of mitochondrial genome mutations can significantly differ in the organs and tissues of individuals. In addition, in a number of literature sources, it is noted that there is a dependence on the mutational burden of the mitochondrial genome from the type of disease, sex, and age of a person.

Based on nutrigenomics approaches, the mechanisms of action of glucan on the accumulation and efflux of cholesterol from macrophages derived from the THP-1 cell line were studied. At the first stage, it was established that glucan does not have the ability to inhibit the accumulation of Cholesterol in the macrophages caused by the action of modified low-density lipoproteins (mLDL) on them. However, glucan accelerates the efflux of Cholesterol from the macrophages loaded with it, and this effect is commensurate with the action of verapamil and alpinetin. At the second stage of the work, transcriptomic analysis made it possible to detect differentially expressed genes by observing the effect of glucan on both accumulation and efflux of Cholesterol from the macrophages. In mLDL-induced Cholesterol accumulation, the presence of glucan in the cell model did not change the overall pattern of gene expression, at the same time, monitoring Cholesterol efflux revealed the ability of glucan to increase (LDLR, INSIG1, SCARB1, STARD3, ABCA1) or decrease (FADS1, SR-BI, DSC1) the expression of a set of genes different from the key Cholesterol accumulation genes. Evaluation of the biological activity of genes, associated with accumulation Cholesterol, indicates their role in immune and inflammatory processes, while genes with other functions, including genes known as regulators of Cholesterol metabolism, are involved to a greater extent in & Scy;holesterol efflux under the action of glucan. A conclusion was made that in relation to the pathology of atherosclerosis, it is necessary to consider glucan not so much as a prophylactic, but as a therapeutic agent.

Background and Aims: Tandem telomere repeats serve to maintain the stability of the nuclear genome. Telomere shortening is associated with factors such as unfavorable environmental factors and various diseases; i.e. with states characterized by the intensification of oxidative stress. The aim of this work was to study the association of telomere repeat length variants with coronary heart disease with old myocardial infarction (CHD with old MI). Methods: We analyzed relative telomeric repeat length (RTRL) variants in 150 DNA samples from samples of patients with CHD with old MI and 150 apparently healthy study participants by real-time PCR method on a BIO-RADCFX 96 Real-Time System amplifier. The results are presented as a percentage of the calibrator. DNA isolated from HeLa cell line was used as a calibrator. It should be noted that the RTRL variants have designations, depending on their relative length in percent to the calibrator. Results: According to the obtained results, the mean value of RTRL was significantly lower in patients with coronary heart disease with old myocardial infarction (by 25.0%), compared to apparently healthy study participants. Correlation analysis revealed an association of CHD with old MI with 5 RTRL variants: RTRL-46, RTRL-49, RTRL-51, RTRL-53 and RTRL-56. At the same time, 6 RTRL variants have a protective effect in CHD with old MI: RTRL-63, RTRL-65, RTRL-68, RTRL-70, RTRL-71 and RTRL-73. Conclusions: Five variants of RTRL are associated with CHD with old MI. This study was supported by Russian Science Foundation (Grant # 20-15-00364).

Polysaccharides (PSs) of plant origin have a variety of biological activities, including antiatherosclerotic, but their use in atherosclerosis therapy is hindered by insufficient knowledge based on the cellular and molecular mechanisms of action. In this review, the influence of several natural PSs on the function of macrophages, viral activity and macrophage cholesterol metabolism has been discussed, considering the tight interplay between these aspects in the pathogenesis of atherosclerosis. The anti-atherosclerotic activities of natural PSs related to other mechanisms have also been explored. Directions for further research of the antiatherosclerotic effects of natural PSs have been outlined, the most promising of which can be nutrigenomic studies.

Background: The present review article considers some chronic diseases of vascular and metabolic genesis, the causes of which may be mitochondrial dysfunction. Very often, in the long course of the disease, complications may occur, leading to myocardial infarction or ischemic stroke and, as a result, death. In particular, a large percentage of human deaths nowadays belongs to cardiovascular diseases, such as coronary heart disease (CHD), arterial hypertension, cardiomyopathies, and type 2 diabetes mellitus. Objective: The aim of the present review was the analysis of literature sources, devoted to an investigation of a link of mitochondrial DNA mutations with chronic diseases of vascular and metabolic genesis. Results: The analysis of literature indicates the association of the mitochondrial genome mutations with coronary heart disease, type 2 diabetes mellitus, hypertension, and various types of cardiomyopathies. Conclusion: The detected mutations can be used to analyze the predisposition to chronic diseases of vascular and metabolic genesis. They can also be used to create molecular-cell models necessary to evaluate the effectiveness of drugs developed for the treatment of these pathologies. MtDNA mutations associated with the absence of diseases of vascular and metabolic genesis could be potential candidates for gene therapy of the said diseases.

The main problem of the Russian market of specialized food products (SFP) is the lack of reliably confirmed data on their efficacy. Most likely, due to the duration and high cost of clinical trials, this situation will continue in the foreseeable future. However, it seems that the current state of science makes it possible to propose new approaches to confirming the SFP effectiveness, including at the level of individual consumption.

A comparative genotoxicity of marine and freshwater fish as indicators of the ecological hazard of the aquatic environment of the Barents Sea basin was analyzed. We used the Ames Salmonella/microsomes test to study mutagenicity of various tissues and liver fat of polar cod, sea bass, common whitefish and river bass with subsequent chromatography-mass spectrometry analysis of liver fat samples for the content of genotoxicants (organic pollutants). No significant excess of mutagenic activity was found in all fish samples except polar cod liver fat and sea bass liver fat. Promutagenic action caused gene mutations of both frameshifting and base pair substitution. Analysis of fat samples using the method of chromatography-mass spectrometry confirmed the presence of persistent organic pollutants in marine fish fat. The findings indicate that at present the ecology of the Barents Sea basin rivers is in more favorable conditions than the ecology of this sea.

Background and Aims: Cytoplasmatic hybrids (cybrids) are widely used in scientific researches as a cell model for investigating different human diseases. The aim of the present study was creation of cybrid lines with mtDNA mutation m.14846G>A. In our preliminary studies, it was found that, after reaching the threshold level of heteroplasmy, mutation m.14846G>A had a protective effect in atherosclerosis (17.5%).

The article presents the scientific basis for designing the optimal composition of specialized food products applying nutrigenetic and nutrigenomics tools. The effect of functional ingredients on the levels of the target genes expression associated mainly with immunity and adaptation of the organism to physical activity was studied. Caffeine, vitamin D and beta-glucan were applied; their target genes were identified in experiments based on the scientific literature analysis. It was established that the efficiency of vitamin D and caffeine depends on the genotype of the consumer, determined by genetic testing to specify alleles. The individual reaction of consumers to beta-glucan indicates the absence of polymorphism in the target gene. It does not require a personal approach to its consumption. An algorithm of new specialized food products development by including functional ingredients in their composition with the efficiency confirmed by nutrigenomics was developed.

Background and Aims: The aim of the study was to identify heteroplasmic mutations mtDNA associated with atherosclerotic plaques in carotid arteries (AP CA) by the NGS (next-generation sequencing) method.

Background and Aims: Myocardial infarction is one of clinical manifestations of coronary heart disease. In some cases, the cause of myocardial infarction may be atherosclerotic plaques which occurred in the human aorta. The association of mtDNA mutations with atherosclerotic lesions in human arteries was previously detected by our research group. The aim of the study was to detect mutations mtDNA associated with myocardial infarction.

Chronic stress is a combination of nonspecific adaptive reactions of the body to the influence of various adverse stress factors which disrupt its homeostasis, and it is also a corresponding state of the organism's nervous system (or the body in general). We hypothesized that chronic stress may be one of the causes occurence of several molecular and cellular types of stress. We analyzed literary sources and considered most of these types of stress in our review article. We examined genes and mutations of nuclear and mitochondrial genomes and also molecular variants which lead to various types of stress. The end result of chronic stress can be metabolic disturbance in humans and animals, leading to accumulation of reactive oxygen species (ROS), oxidative stress, energy deficiency in cells (due to a decrease in ATP synthesis) and mitochondrial dysfunction. These changes can last for the lifetime and lead to severe pathologies, including neurodegenerative diseases and atherosclerosis. The analysis of literature allowed us to conclude that under the influence of chronic stress, metabolism in the human body can be disrupted, mutations of the mitochondrial and nuclear genome and dysfunction of cells and their compartments can occur. As a result of these processes, oxidative, genotoxic, and cellular stress can occur. Therefore, chronic stress can be one of the causes forthe occurrence and development of neurodegenerative diseases and atherosclerosis. In particular, chronic stress can play a large role in the occurrence and development of oxidative, genotoxic, and cellular types of stress.