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Cardiovascular diseases and obesity are related medical and social problems. However, some obese people remain free of cardiovascular disease for long periods of time, and the concept of obesity phenotypes that differ in cardiovascular risk has been actively studied. Currently, there are no generally accepted diagnostic criteria for them, and the mechanisms underlying their formation remain unclear. The purpose of this article is to discuss the literature data on obesity phenotypes, their relationship with cardiovascular diseases and mortality, as well as the place of obesity in the domestic algorithm for diagnosing stable coronary heart disease.

Throughout history, humans have been attempting to develop the ornamental features of domestic animals in addition to their productive qualities. Many chicken breeds have developed tufts of elongated feathers that jut out from the sides and bottom of the beak, leading to the phenotype known as muffs and beard. It is an incomplete autosomal dominant phenotype determined by the Mb locus localised on chromosome GGA27. This project aimed to analyse the genetic diversity of chicken breeds using full genomic genotyping with the Chicken 60K BeadChip. A total of 53,313 Single Nucleotide Polymorphisms were analysed. DNA was obtained from breeds with the muffs and beard as a marker phenotype: Faverolles (n = 20), Ukrainian Muffed (n = 18), Orloff (n = 20), Novopavlov White (n = 20), and Novopavlov Coloured (n = 15). The Russian White (n = 20) was selected as an alternative breed without the muffs and beard phenotype. The chickens are owned by the Centre of Collective Use “Genetic Collection of Rare and Endangered Breeds of Chickens” (St. Petersburg region, Pushkin), and are also included in the Core Shared Research Facility (CSRF) and/or Large­Scale Research Facility (LSRF). Multidimensional scaling revealed that the Novopavlov White and the Novopavlov Coloured populations formed a separate group. The Ukrainian Muffed and the Orloff have also been combined into a separate group. Based on cluster analysis, with the cross­validation error and the most probable number of clusters K = 4 taken into account, the Orloff was singled out as a separate group. The Ukrainian Muffed exhibited a notable similarity with the Orloff under the same conditions. At K = 5, the populations of the Novopavlov White and the Novopavlov Coloured diverged. Only at K = 6, a distinct and separate cluster was formed by the Ukrainian Muffed. The Russian White had the greatest number of short (1–2 Mb) homozygous regions. If the HOXB8 gene is located between 3.402 and 3.404 Mb on chromosome GGA27, homozygous regions are rarely found in the chickens with the muffs and beard phenotype. Scanning the chicken genome with the Chicken 60K BeadChip provided enough information about the genetic diversity of the chicken breeds for the peculiarities of the development of the ornamental muffs and beard phenotypes in them to be understood. For example, Phoenix bantams, whose tail feathers grow throughout their lives, require greater consideration of husbandry conditions.

Today, the diagnosis and treatment of severe infectious and inflammatory diseases in newborns, e.g., congenital pneumonia (CP) and neonatal sepsis (NS), present difficult problems. Searching sensitive and specific severity markers of bacterial inflammatory process as well as early and effective treatment are crucial for the outcome and prognosis of these life-threatening diseases. The aim of our study was to assess the effects of intravenous immunoglobulin (IVIG) injections on the negatively transformed subpopulations of neutrophilic granulocytes (NG) СD64-CD16+СD32+СD11b+, СD64+CD16+СD32+СD11b+ and evaluation of their functional activity in newborns with CP and NS. We have observed 38 full-term newborn patients. Group 1 included 19 infants with CP, including 11 children who received conventional therapy and IVIG (group 1.1), and 8 children treated at conventional protocols (group 1.2). Group 2 included 19 children with NS, including 12 children who underwent conventional therapy and IVIG treatment (group 2.1), and 7 children who were subject to conventional therapy (group 2.2). The comparison group consisted of 22 healthy full-term newborns. Testing of NG population included the following parameters: counting the numbers of NG subpopulations which simultaneously expressed CD11b CD64, CD32, CD16, as well as their phenotypic patterns, with regard of the receptor expression density (MFI) using flow cytometric techniques. Moreover, we determined phagocytic and microbicidal activity of the granulocytes. We have revealed negative transformation of СD64-CD16+СD32+СD11b+ and СD64+CD16+СD32+СD11b+ subpopulations of neutrophilic granulocytes in newborns with CP and NS, The diagnostic significance of increased СD64+CD16+СD32+СD11b+NG subpopulation was more pronounced with increasing severity of bacterial infection and inflammatory process, i.e., 18.7-fold in CP, 52.3-fold in NS, along with predominant decrease in expression of appropriate membrane receptors. These phenotypic changes were associated with impaired phagocytic and killing activity of NG. The effect of IVIG on the impaired mechanisms of antibacterial immunity is associated not only with alleviation of IgG deficiency, but also with positive remodeling of negatively transformed subpopulations of СD64-CD16+СD32+СD11b+NG and СD64+CD16+СD32+СD11b+NG, improved effector functions of NG, especially in cases of CP. Thus, following IVIG treatment, a reduced number of СD64-CD16+СD32+СD11b+NG subpopulations was fully recovered in CP, while it increased 1.5 times in NS, and the content of diagnostically significant СD64+CD16+СD32+СD11b+NG subpopulation showed a significantly decrease, both in CP (2-fold) and in NS (2.6-fold). However, this index remained higher than the content of this subpopulation in healthy newborns. At the same time, we have noted the restorative or modulatory effects by changing density of trigger molecules in NG subpopulations. Limitation of the negative NG transformation in their functionally significant subpopulations in newborns with CAP and NS was accompanied by positive clinical effects, i.e., optimization of antibiotic therapy, reduced duration of treatment, and improved mortality rates.

Background. The processes occurring in plants and their seeds under stress, as well as the defense mechanisms used by plants under stress, are poorly understood, which makes it impossible to use them to increase yields. Purpose. Review and analysis of scientific publications, devoted to the phenomenon of stress memory acquired by plants as a result of physical stressors on their seeds and possible applications of this phenomenon in plant growing and crop breeding. Materials and methods. A selection and systematic review of scientific articles on the research topic for the period 2016-2023 was performed. The study consisted of the following steps: research literature search, evaluation and selection, data synthesis and analysis. Results. The use of hormetic effects of physical agents to stimulate seed germination of crops is effective. Responses to abiotic stresses could be 'trained' by priming so that the plant becomes better able to cope with later stress. Evidence of short-term and transgenerational memory formation following plant priming has been obtained. An epigenetic mechanism for the formation of long-term stress memory in plants as a result of a physical eustressor has been identified. The eustressor induces specific epigenetic marks associated with environmental adaptation, forming a new stress-resistant plant phenotype. Physical eustressors have the potential to impart stress tolerance to crops to enhance phenotypic characteristics to prevent yield losses. Conclusion. Seed treatment with physical stressors builds plant tolerance and memory to abiotic stresses, but scientific evidence on this issue is incomplete and sketchy. The understanding and application of stress memory for breeding purposes is currently limited, but it has great potential for the development of new crop varieties.

Background: Differences in the embryonic development of the colonic mucosa determine the physiological embryonic-anatomical asymmetry of its structure and can manifest themselves via different molecular phenotypes (expression profiles) of the colon segments. These molecular characteristics are hypothesized to determine differences in the carcinogenesis mechanisms and influence the prognosis of right- or left-sided colorectal cancer (CRC). Studies of the tumors molecular phenotypes depending on their localization may be of interest for assessment of the prognosis and choice of treatment for CRC. Aim: To perform comparative analysis of molecular phenotypes of the normal colonic mucosa and adenocarcinoma CRC tissues depending on the natural embryonic anatomic asymmetry of the colon. Materials and methods: We performed a retrospective study of molecular phenotypes (mRNA expression of 61 genes) from different embryonic-anatomical parts of healthy colon and CRC. The normal group included 254 samples of mucosa from three different parts of the colon from 74 healthy donors who had no cancer and no organic abnormalities of the colon, including 90 samples from the right colon, 116 from the left colon, and 48 from the rectum. The CRC group consisted of 154 samples of localized stage T1–4N0–2M0 adenocarcinoma from 154 patients who had not received neoadjuvant radio- and chemotherapy, including 40 samples from the right colon, 54 from the left colon, and 60 from the rectum. The relative mRNA abundance of 61 genes was assessed by reverse-transcriptase polymerase chain reaction. In both groups, the resulting expression phenotypes were compared between the anatomical parts of the colon. Statistical management of the data included the discriminant analysis with stepwise inclusion of variables. Results: Based on the assessment of the mRNA level of the studied genes, a discriminant model was built that allows for classification of the normal group samples according to their anatomic origin in the colon with an accuracy of 95.8%. The most significant (p 0.05) for classification are the following 19 genes: CCND1, SCUBE2, TERT, BAG1, NDRG, IL1b, IL2Ra, IL7, ESR1, TGFb, IGF1, MMP9, MMP11, PAPPA, CD45, CD69, TLR2, TLR4, LIFR. The discriminant model built for the CRC group included 27 genes and made it possible to differentiate samples from three parts of colon with an accuracy of 75.2%. A statistically significant (p 0.05) contribution to the samples differentiation by the discriminant model was made by the COX-2, BIRC5, LIFR, TPA, IL1b, MMP11, MMP7, and P16INK4A genes. When combining samples from the two groups into one model in accordance with their embryonic-anatomical origin, there was a clear separation of tumor tissue samples and healthy colonic mucosa in the discriminant function space. Conclusion: The analysis of CRC gene expression profiles using the discriminant model showed that genetic changes in the colonic mucosa in CRC flatten the molecular phenotypic boundaries of the embryonic-anatomical parts. These changes are specific to CRC, forming a particular “pathological” molecular phenotype.

In recent decades, the prevalence of osteoarthritis (OA), one of the most disabling diseases, has increased worldwide, which imposes a significant burden on society. At the international multidisciplinary meeting, experts of various specialties (rheumatology, neurology, endocrinology, geriatrics, rehabilitation, traumatology and orthopedics) from Russia, Uzbekistan, and Kazakhstan discussed the importance of an individualized approach to the treatment of patients with OA, taking into account comorbidities, identified the most important and common clinical phenotypes of the disease, discussed known symptom- and structure-modifying effects of a combination of glucosamine and chondroitin sulfate, and new data on additional (pleiotropic) effects of these drugs that may have a positive impact on the course of comorbid diseases and conditions. The resolution of the Expert Council summarizes the results of the discussion and focuses on issues that are important for the further development of therapeutic approaches and recommendations for the management of such patients.

Natural killer (NK) cells represent one of the innate lymphoid cell subsets, which are often studied in the context of antitumor and antiviral immunity, as well as due to their localization in the zone of the mother-fetus contact (in the uterus), therefore underlying their extensive investigation in developing pregnancy. At the same time, their role in antibacterial immune response has been poorly examined. Because NK cells can produce cytokines, one of putative options for their participation in eliminating prokaryotic pathogens may be coupled to regulation of immune system cells such as dendritic cells, macrophages, etc. However, there have been also described variants of contact cytolysis of cells infected with intracellular bacteria enabled due to cytotoxic proteins perforin, granzymes, granulisin found in NK cells. In recent years, it has become known that NK cells take part in development of immune response against extracellular bacteria including the ESKAPE group bacteria, which includes opportunistic prokaryotes that most actively develop antibiotic resistance and cause nosocomial infections. Here, we attempted to review the data on the role NK cells play in antibacterial immunity. Assessing a crosstalk between ESKAPE group bacteria and NK cells also attracts researchers due to the ability of prokaryotes to alter functions of immune cells, but very little is known about the effects they exert on NK cells. At the same time, such data could be applied to seek out for new ways to treat oncological diseases as well as pave the basis for new approaches to regulating NK cell characteristics in reproductive pathologies. As mentioned earlier, the latter occur in the decidual membrane, where they can interact with fetal cells including trophoblast cells. It is believed that cells can mutually regulate each others properties necessary for the course of physiological pregnancy. Probably, imbalance in this system can lead to development of reproductive pathologies. The review summarizes the currently available data on the effects of ESKAPE group bacteria on NK cells, and also considers putative mechanisms for emergence of impaired interaction between NK cells and trophoblasts exposed to ESKAPE group bacteria. Owing to few publications available on this phenomenon, the experimental study assessing an impact of ESKAPE group bacteria on NK cell properties is envisioned as a necessary stage in development of contemporary biology.

Hypertrophic cardiomyopathy is characterized by genetic and phenotypic heterogeneity which manifests in different variants of localization and extent of myocardial hypertrophy.Aim: to evaluate specifics of left ventricular hypertrophy, the prevalence and characteristics of clinical and instrumental features of phenotypic variants of hypertrophic cardiomyopathy.Materials and methods. The study includes 295 patients with hypertrophic cardiomyopathy aged 18 to 88 years (60.3±13.4 years), 183 men (62 %), and women 112 (38 %). The diagnosis of which was established by 2D echocardiography. The severity, localization and extent of myocardial hypertrophy, the maximum thickness of the hypertrophied segment, left ventricular myocardial mass, left ventricular myocardial mass index, the presence and severity of mid-ventricular and left ventricular outflow tract obstruction were evaluated. Depending on the predominant localization and extent of hypertrophy, patients were divided into 8 groups according to the recommendations for hypertrophic cardiomyopathy of the Ministry of Health of the Russian Federation. The analysis and comparison of the obtained results are carried out.Results. The average duration of the disease is 10.5±7.52 years. The mean values of the body mass index in patients — 28.2±2.82 kg/m2. The phenotype with basal hypertrophy of the septum (n=130, 44.1 %), group 1 was most often noted. In 47 (15.9 %) patients, hypertrophy of the septum of “reverse curve” (2 group) was detected, in 41 (13.9 %) — “neutral septum” (3 group), in 36 (12.2 %) — symmetrical hypertrophy of the left ventricle (8 group), 11 (3.7 %) of patients had combined hypertrophy of the septum and other parts of the left or right ventricle (4 group) and the free left ventricular wall (7 group), in 10 (3.4 %) — middle ventricular hypertrophy of the left ventricle (6 group) and in 9 (3.1 %) — apical hypertrophy (5 group). The highest value of the maximum thickness of the myocardium was noted in patients of the 6th group 19.3 (1920.4 mm). Mid-ventricular obstruction was detected in group 6 (90 %), left ventricular outflow tract obstruction was more often registered in groups 4 and 8 (81.8 % and 77.8 %), and less often in group 5 (22.2 %) (p

Aim: to provide a literature review of the current conсepts on phenotypic heterogeneity of left ventricular (LV) remodeling in heart failure (HF), and highlight the significance of such a diversity for an implementation of personalized patients` management. This paper is a second part of the review, devoted to the current state of pathophysiology of LV remodeling in HF. Material and methods. The thematic scientific papers, published predominantly during the last decade, constituted the study material. The research methodology involved bibliosemantic method and structural and logical analysis. Results and discussion. HF is a heterogeneous, multifactorial and rising epidemic syndrome. To date, the LV ejection fraction (EF) is used as a substantial criterion for HF classification and management. However, the existing research data has revealed the significant overlapping between different LV EF-based HF patterns in terms of the risk factors, comorbidities and disease modifiers; bidirectional transitions of LV EF due to disease treatment and progression; myocardial fibrosis and dysfunction; effectiveness of neurohumoral inhibitors etc. Moreover, the «spectrum» paradigm has been recently proposed, positioning HF as a spectrum across different phenotypes. Particularly, each HF phenotype is the result of a patient-specific trajectory, being an exceptional and unique «track» for the heart transition towards different remodeling patterns. The HF phenotyping may be an innovative approach to the study of myocardial remodeling and HF, which is potentially an important prerequisite for the development of individualized patients` treatment. Personalized medicine can offer the particular options for managing HF patients, that, in turn, will better identify responders, non-responders, and those at high risk of adverse events, and ultimately improve of the treatment efficacy and safety. Conclusions. The baseline heterogeneity of the structural and functional patients` characteristics, including those describing the LV remodeling, and their dynamic change over time, creates a spectrum across overlapping HF phenotypes, challenging a categorical HF classification based solely on LV EF. Such an approach to treat the HF phenotypic heterogeneity may provide further insights into the pathomechanisms, related to LV remodeling in HF, and has the potential to improve the personalized patients` management.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a heterogeneous disease. Determination of different T2DM phenotypes will improve the prediction of metabolic disorders, the risk of complications and individual diabetes therapy.AIM: To identify clusters of T2DM in patients with different duration of diabetes with a study of the frequency of diabetic complications and drug therapy in the Novosibirsk region.MATERIALS AND METHODS: The study was carried out at Diamodul in the period 2013–2017 in the Novosibirsk region. K-means cluster analysis was performed in 2805 T2DM patients aged 44 to 75 years with a duration of diabetes of 7.84±6.53 years based on 5 variables — HbA1c, age at diagnosis, BMI, C-peptide, sex.RESULTS: Cluster analysis identified three clusters: cluster 1 in 1003 patients (35.7%) with preserved β-cell function, age of T2DM diagnosis 51.72±8.29 years and BMI 33.50±5.74 kg/m2, in men there was a 27% higher risk of developing diabetic nephropathy compared to women. Cluster 2 in 432 patients (15.4%) with increased function of β-cells, the age of diagnosis of T2DM was older — 52.91±7.75 years, patients had a higher BMI of 35.64±7.21 kg/m2 and more high diastolic blood pressure, earlier development of diabetic retinopathy, nephropathy and polyneuropathy, and better response to metformin therapy and combined therapy with metformin and sulfonylurea. Cluster 3 in 1370 patients (48.8%) with reduced function of β-cells, the age of diagnosing T2DM was younger — 49.63±8.32 years, patients had a lower BMI of 33.09±6.36 kg/m2 and had longer diabetes, high fasting glucose levels, males were associated with a higher risk of developing diabetic nephropathy (by 26%) compared with women, the first line of therapy was insulin therapy in 52.8% of patients.CONCLUSION: The conducted study in T2DM patients with different duration of diabetes confirmed the possibility of using cluster analysis to identify phenotypes of T2DM in the Russian population by five variables (HbA1c, age at the time of diagnosis, BMI, C-peptide, gender). A high incidence of early development of diabetic polyneuropathy, nephropathy and retinopathy was revealed in a cluster with increased function of β-cells, male gender was risk factor for diabetic nephropathy and polyneuropathy.

Left ventricular (LV) hypertrophy implies structural cardiac changes and, as a consequence, an increase in myocardial mass. Currently, there are many causes of this condition as follows: hypertension, aortic stenosis, hypertrophic cardiomyopathy, exercise, storage diseases (AL, ATTR amyloidosis, Danon disease, Anderson-­Fabry disease, etc.), metabolic disorders. Despite the currently existing diagnostic algorithms for LV hypertrophy, establishing a correct diagnosis can take a long time, and controversial research results can lead to false conclusions. This article presents a case report of a patient with LV hypertrophy, an atypical clinical performance and ambiguous paraclinical data, which led to certain diagnostic difficulties.

The article is dedicated to the new method for early diagnostics of pathological conditions under the action of physiologically active substances with genotoxic properties. The method allows the evaluation of microsomal system of the liver under the action of xenobiotic alkylating type and the condition of microsomal oxidiation system in vivo. It is supposed to asses preliminary the norm of the reaction of organism (phenotype of bio-object) by the intensity of microsomal oxidiation during the study of the toxicological characteristics of physiologically active substances influencing the organism at low doses. The method includes the characteristics of hereditary intensity of epoxidiation (hydroxyliation) reactions of metabolism. Carbamazepine is used as a pharmacological probe. The article formulates the definition of the concept of norm, threshold for the harmful effect and prepatological state of organism.

Chronic pelvic inflammatory disease (PID) in women remains a problem due to the importance of medical consequences. The study of the receptor apparatus of neutrophilic granulocytes (NG) involved in anti-infective protection in diseases of various etiologies seems to be relevant. Aim: to clarify the features of variants of quantitative and phenotypic changes in subsets of NG CD11b+CD64-CD32+CD16+, CD11b+CD64+CD32+CD16+ of immunocompromised women during exacerbation of chronic PID of various etiologies. We were tested women 20-40 years: Study Group 1 (SG1, n = 20) – chronic PID during the exacerbation with mono- or mixed latent/recurrent various viral infections (chronic herpes-virus infections, papillomavirus infection, recurrent ARVI); Study Group 2 (SG2, n = 30) – chronic PID of bacterial etiologies; Comparison Group (CG)– 20 healthy women. The number of subsets CD11b+CD64-CD32+CD16+NG (major) and CD11b+CD64+CD32+CD16+NG (minor), receptor expression density (MFI) was determined (FC500, USA). It was found that in PID during the period of exacerbation, diagnostically significant differences in the subset composition of NG were revealed. We got a decrease in the CD11b+СD64-СD32+СD16+NG subset and in 7,6 times increase in the CD11b+CD64+CD32+CD16+NG subset in SG2 with chronic PID of bacterial etiology, in contrast to chronic PID occurring in combination with recurrent/persistent viral infection SG1. Negative transformation of NG subsets is associated with a predominant decrease in the level of expression of the activation CD16. The absence of an adequate response to the infectious and inflammatory process was revealed – the absence of an increase in the expression of the activation CD11b in the major subset in SG1, as well as in the minor subset in groups SG1 and SG2. In the major subset of NG in groups SG2 a decrease in the expression of the activation marker CD11b. In the various viral infections and PID (SG1), in the negatively altered minor subset of NG we got a decrease of expression of CD16, an increase of expression of CD64 and CD32. Determination of subsets of CD11b+СD64-СD32+СD16+, CD11b+CD64+CD32+CD16+NG and their phenotype can be used as diagnostic markers for the differential diagnosis of PID of viral and bacterial etiology, and for the development of new methods of targeted immunomodulatory therapy.

The key role of neutrophilic granulocytes (NG) in the pathogenesis of COVID-19 makes them new targets for therapeutic approaches and of influencing the course and outcome of the disease, restoring changes in the phenotype and functions of NG. Synthetic peptides or polypeptide complexes of action are the most promising in the treatment of COVID-19. Aim: to reveal the effects of the influence of the hexapeptide (HP) – Arginyl-alpha-Aspartyl-Lysyl-Valyl-Tyrosyl-Arginine on the phenotype of functionally significant NG subsets in moderate COVID-19.The study examined patients 61 (57-71) years old (n = 45) in the acute period of COVID-19 – study group1 (SG1). In vitro, samples SG1 were incubated with HP (106 g/L, 60 min, 37 °C) – study group2 (SG2). The number of NG subsets was evaluated: CD16+IFNα/βR1+CD119+, CD16+IFNα/βR1+CD119- , CD16+IFNα/βR1+CD119+, CD64- CD16+CD32+CD11b+, CD64+CD16+CD32+CD11b+ and phenotype by membrane receptor expression density (MFI) (FC 500, Beckman Coulter, USA); NG phagocytic activity was tested before and after incubation with HP. The comparison group (GS) – of 22 volunteers examined in the pre-COVID period.It was revealed that unidirectional effects of HP in vitro contributing to the restoration of the phenotype of subsets CD16+IFNα/βR1- CD119+, CD16+IFNα/βR1+CD119- to CG indicators. There was a decrease in MFI CD16 (p < 0.05) in both subsets; MFI CD119 (p < 0.05) in the CD16+IFNα/βR1- CD119+NG subset, MFI IFNa/βR1 in the CD16+IFNα/βR1+CD119- NG subset. The effects of HP on the phenotype of CD16+IFNα/βR1+CD119+NG subsets in 76% of cases were manifested by a decrease in MFI CD16 (p

Currently, a large number of studies on genetic modification of cord blood NK cells (UCB-NK) are carried out at both clinical and preclinical levels. Immunotherapy based on UCB-NK cells has great potential for antitumor therapy. However, despite having known several advantages over peripheral blood NK cells (PB- NK), including a high concentration in cord blood and low virulence rate, UCB-NK cells are predominantly characterized in the scientific literature as immature and low-functioning NK cells. In this work, we studied the phenotypic characteristics of UCB-NK cells and the possibility of stimulatory compensation of the decreased functional activity of UCB-NK cells. Our studies revealed UCB-NK cells can be characterized as poorly differentiated and weakly activated cells with high level of inhibitory receptor NKG2A and low level of activating receptor NKG2C and HLA-DR, accordingly with the literature data. Two types of stimuli were chosen to stimulate freshly isolated UCB-NK cells: 1) 100 units of IL-2; 2) combinations of 100 units IL-2 and K-562 feeder cells expressing membrane-bound IL-21 (K562-mbIL21). It was shown the degranulation (LAMP-1) and proliferative activity was higher than for parallel cultured ex vivo PB-NK cells under the same conditions for UCB-NK cells stimulated for 7 days with IL-2 + K562-mbIL21. Moreover, stimulation in the way of IL-2 + K562-mbIL21 seemed to be a more perspective way to obtain a large number of proliferatively active UCB-NK cells compared to stimulation with IL-2 only. Since genetic modification of NK cells is a promising way to improve the antitumor properties of NK cells, retroviral transduction procedure was performed to study of the stimulated UCB-NK cells. UCB-NK cells stimulated with IL-2 + K562-mbIL21 were transduced on day 8 of cultivation. In this study, we used targeted overexpression of the adaptor molecule DAP12, which is involved in the signaling of activating NK cell receptors. PB-NK cells and UCB-NK cells were transduced under the equal experimental conditions in same volume of viral particles. As a result, the transduction efficiency was found to be more than 4-fold higher for UCB-NK cells compared to PB-NK cells. Thus, UCB-NK cells appear to be a promising tool for further research in cancer immunotherapy.

Transthyretin amyloidosis (ATTR-amyloidosis) is a systemic disorder associated with extracellular deposition in the tissues and organs of amyloid fibrils, transthyretin-containing insoluble protein-polysaccharide complexes. The change in transthyretin conformation, leading to its destabilization and amyloidogenicity, can be acquired (wild type, ATTRwt) and hereditary due to mutations in the TTR gene (variant, ATTRv) [1, 2]. Hereditary ATTR-amyloidosis has an earlier onset and greater phenotypic diversity. The age of the manifestation, the predominant phenotype, and the prognosis are often determined by the genetic variant. To date, more than 140 variants in the TTR gene have been identified; however, most of them are described in single patients and do not have clear evidence of pathogenicity. The prospects of a new pathogenetic treatment of ATTR-amyloidosis [3], especially effective in the early stages of the disease, increases the relevance of timely diagnosis, which is challenging due to physicians' lack of awareness. This article presents a clinical case of ATTRv-amyloidosis associated with a rare pathogenic variant in the TTR gene and a newly described skin symptom. This article is a literature review.

Mesenchymal stem cells (MSCs) are multipotent stromal cells that can differentiate into various cell types, including adipocytes, osteocytes, chondrocytes, etc. MSCs can be isolated from various human and animal tissues. MSCs are characterized by high proliferative capacity, differentiation in the connective-tissue direction, paracrine and trophic activity (they produce a wide range of biologically active molecules), are capable of migrating to the zone of organ and tissue damage, and exhibit immunosuppression. There are similarities and differences between human and mammalian MSCs in phenotype and functional activity. The therapeutic potential of MSCs has been shown on experimental models and in clinical trials, which allows us to consider the MSC-oriented cell technologies as an alternative to traditional methods of treatment. The article presents a review and analysis of the literature devoted to the study of MSCs properties, signaling pathways involved in the regulation of cell activity, the prospects for the use of MSCs in the treatment of inflammatory and degenerative diseases. During preparation of the review full-text, free access articles for the period from 2006 to 2022 were taken from eLibrary and National Center for Biotechnology Information (NCBI) databases.

A clinical case of a familial form of peroxisomal D-bifunctional protein (DBP) deficiency (OMIM 261515) with an unfavorable (fatal) outcome caused by a mutation in type 4 17ß-hydroxysteroid dehydrogenase (HSD17B4) with a nucleotide replacement of chr5:118788316G>A in the homozygous state is presented. (D-bifunctional protein deficiency or 17-beta-hydroxysteroid dehydrogenase IV deficiency). Bifunctional protein deficiency is an autosomal recessive birth defect of peroxisomal fatty acid oxidation. The total incidence of morbidity is one case per 50,000 newborns. Most peroxisomal disorders manifest in the early neonatal period with an extremely severe course and phenotypic features, which facilitates their diagnosis. This is the difference between them and diseases with a milder and prolonged course, which debuted at different age periods, often had no neonatal or infantile symptoms and were accompanied, in some cases, by satisfactory cognitive functions. The purpose of the report was to highlight the clinical manifestations, variants of the course and complexity of the diagnosis of peroxisomal disorders to a wide range of doctors of different specialization: in the field of perinatology, pediatrics, neurology, genetics, endocrinology.

Aim. To develop individualized approaches to the treatment of irritable bowel syndrome (IBS) based on the interaction of genetic and epigenetic factors, to characterize the phenotypes of the disease. Materials and methods. According to the formulated concept of the authors, from the cohort of patients with IBS, subgroups were distinguished post-infectious IBS (n=45), IBS in overweight and obese people (n=49), comorbid IBS (n=75) and essential IBS (n=51). In each subgroup the prevalence of candidate gene polymorphisms associated with IBS (COMT, SLC6A4, FTO), nutritional habits, levels of anxiety and depression, secretion of cortisol, serotonin, dopamine and zonulin levels in feces were studied. Results. Patients with post-infectious IBS are characterized by the carriage of the S allele of the SLC6A4 gene, the val/val genotype of the COMT gene, the prevalence of diarrhea, a high level of anxiety and frequent refusal of milk and dairy products. The phenotype IBS in overweight and obese individuals is characterized by L/L genotypes of the SLC6A4 gene, met/met of the COMT gene and A/A of the FTO gene, constipation, low plasma dopamine levels, signs of depression, frequent episodes of overeating, addiction to fatty and sweet foods, excessive consumption of sugar, lack of vegetables in the diet. The comorbid IBS phenotype is characterized by more frequent detection of the val/val genotype of the COMT gene and the carriage of the S allele of the SLC6A4 gene, clinically pronounced anxiety and depression, early onset of the disease, severe course, significant food restrictions and significant increase in epithelial permeability. With the essential phenotype, there are no bright stigmas of the disease; it is not possible to identify distinctive genetic and epigenetic factors, as well as the leading pathogenetic mechanism. Conclusion. The analysis of genetic and epigenetic factors, the leading mechanisms of the formation and course of IBS allows us to identify additional (except for postinfectious) phenotypes of the disease: IBS in overweight and obese people, comorbid and essential.

The review presents the data on domestic and foreign phenotypic classifications of Yersinia pestis strains developed in the XX century; genetic classifications of the XXI century; as well as on the genealogy of ancient strains of the plague microbe, reconstructed using paleogenomic technologies. Since the discovery of the plague agent in 1894, many classifications were created that corresponded to the level of development of microbiology at that time. The intraspecific classification schemes of the XX century were based on three principles: phenotypic differences between strains, features of the species composition of carriers, and geographical affiliation. With the development of molecular microbiology early on in the XXI century, a genetic nomenclature of the branches of the pathogen evolution was developed and a number of classifications based on the analysis of the population structure of Y. pestis were created. Through the prism of the genetic diversity of Y. pestis strains from natural plague foci in Russia, near and far abroad countries, an improved classification with a division into seven subspecies has been developed: pestis, tibetica, caucasica, qinghaica, angolica, central asiatica, ulegeica, which allocates the subspecies according to the phylogenetic principle and epidemic significance. With the advancements in paleomicrobiology, prehistoric lineages of evolution have been included in the genealogy of Y. pestis, which expand the data on the intraspecific diversity of the plague microbe.

At present, it is vital to examine adverse effects produced on gene expression by negative environmental factors and nutrients. In this study, our aim was to generalize data available in literature on an association between health risks and polymorphisms of genes that participated in xenobiotic detoxification and allergic status, food intolerance included, in adults and children. We also considered influence exerted by various components in diets on gene expression. Available research data indicate that GSTP1 and SOD gene polymorphisms have their effects on a decline in detoxification and antioxidant functions and early development of allergic, occupational and oncological diseases under exposure to harmful chemicals. Micronutrients in diets that can protect from adverse effects produced by chemicals can act not only as substrates but also as detoxification enzyme inducers. Great quantities of biologically active compounds in the Mediterranean diet are assumed to be able to modulate functional activity of certain genes. Such nutrients as polyphenols, flavonoids, catechins, glucosinolates, anthocyanins, stilbenes, carotinoids, polyamines, spermidine and spermine produce anti-genotoxic and anti-carcinogenic effects. Use of combined nutrigenetic and phenotypic data seems a promising trend in effective modeling of a healthy diet. The research data outlined in this review indicate there is solid evidence that health risks can depend on a genotype, phenotype and quality of the environment. These risks also differ depending on a diet. Modeling a healthy diet based on available knowledge on nutritional genetic and nutritional genomics is a promising trend within non-carcinogenic health risk management, including risks of oncological diseases caused by exposure to adverse environmental factors.

The aim of our study was to investigate the main characteristics of peripheral blood NKT cell phenotype in patients with disseminated purulent peritonitis (DPP) in dynamics of postoperative period, depending on the disease outcome. Fifty-two patients with acute surgical diseases and injuries of the abdominal organs complicated by DPP, and 68 healthy individuals in control group, were examined. Blood sampling was performed before surgery (preoperative period), as well as on the day 7, 14 and 21 of postoperative period. All patients with DPP were divided into two groups depending on disease outcome in postoperative period: patients with favorable disease outcome (n = 34); and patients with unfavorable outcome (n = 18). Study of the phenotype of blood NKT lymphocytes was performed by flow cytometry using direct immunofluorescence of whole peripheral blood samples with monoclonal antibodies. The low relative and absolute level of NKT cells was observed in DPP patients regardless of outcome disease in preoperative period. At the same time, the absolute level of NKT cells returned to normal only in patients with favorable DPP outcome and only by day 21 after surgery. Patients with favorable DPP outcome by the end of examination period had normalized quantity of mature NKT-lymphocytes and significantly decreased level of cytotoxic cells which was apparently associated with migration of such cell subsets to site of inflammation. A reduced level of non-classical (expressing CD8 marker) mature and cytokine-producing NKT cells was detected only in patients with favorable DPP outcome in preoperative period which returned to normal by the end of postoperative period. At the same time, patients with unfavorable disease outcome had reduced quantity of NKT cells of these subsets by day 21 of postoperative treatment. Patients with favorable outcome had high level of mature and cytotoxic CD11b+ NKT cells already in the preoperative period, while patients with unfavorable DPP outcome had increased level of cytotoxic CD11b+ NKT cells only by day 21 after surgery. The proportion of NKT cells expressing activation markers (CD28 and CD57) was reduced in patients in preoperative period that returned to normal immediately after surgery with favorable outcome, while it recovered with unfavorable outcome closer to the end of postoperative examination. The defined features of NKT cell phenotype in patients with unfavorable DPP outcome characterize disturbances in subset ratio and mechanisms of functioning of this cell fraction. This determines a need to develop immunotherapeutic methods aimed at stimulating immunoregulatory activity of NKT cells.

Background. Many factors influence the development of atopic dermatitis (AD): genetic, environmental (including exposure to allergens), skin barrier damage, and activation of the T2-pathway immune response. Patients with AD, including those with severe disease, are prone to sensitization to various allergens, including fungal ones. Fungal sensitization (FS) promotes autoreactivity to the body's own structures due to shared epitopes with homologous fungal allergens. It can contribute to the development of allergic diseases, including AD, asthma, and rhinitis, as well as to their exacerbation and uncontrolled course. Since FS can be considered a factor aggravating AD, it is relevant to distinguish patients with FS and AD into a separate phenotype. Aim. To characterize the phenotype of patients with severe AD and FS using retrospective data analysis from a digital analytics platform in a real-world clinical setting. Materials and methods. A retrospective observational single-center study was conducted between 01.06.2017 and 01.07.2022. The study cohort included 88 patients with severe AD who were candidates for therapy or received treatment with either dupilumab or upadacitinib. FS was confirmed in 49 patients from the study group. Part of the cohort without FS (n=39) was used as a comparison group. Inclusion criteria: the age over 18 years old; severe AD (SCORAD40 points at the beginning of therapy); determination of specific immunoglobulin E to a panel of fungal allergens or individual fungi (or by the ImmunoCAP ISAC method to fungal allergen components). A digital analytics platform was used to generate primary data. Results. The phenotype of a patient with severe AD and confirmed FS was described. The patient profile is characterized by an extended sensitization spectrum (at least 34 allergen groups) with the most typical combination of pollen, epidermal, and FS. If there is a food allergy, it is of the classic "big eight" nature. Besides exacerbation of the skin disorder, its manifestations include angioedema of life-threatening localization and bronchospasm. Markers of T2 inflammation (high levels of immunoglobulin E and blood eosinophilia) are observed according to the test results, and the T2 endotype of allergy-related abnormalities is typical. Conclusion. Apparently, the presence of FS in patients with AD may exacerbate parenteral sensitization mechanisms, expanding its spectrum, including food allergens. Therefore, distinguishing the phenotype of severe AD with FS needs further detailing with a subsequent adaptation of monitoring and treatment methods of severe AD.

The aim of the present study was to evaluate the subpopulation profile of T and B lymphocytes, and their relationships during therapy of the patients with Graves’ disease (GD) treated by means of radioactive iodine. We have examined 36 women with verified diagnosis of GD. The contents of thyroid hormones were determined by immunoradiometric analysis. The levels of thyroid-stimulating hormone receptor autoantibodies (rTSH) were evaluated by enzyme-linked immunosorbent assay. On the basis of comprehensive pre-therapeutic examination, all patients were exposed to the fixed-activity therapy with radioactive iodine-131 at a dose of 400 to 700 MBq administered orally in isotonic aqueous solution of sodium iodide. 56 practically healthy women were examined as a control group. The phenotype of T and B cells in whole blood was studied by flow cytometry using direct immunofluorescence. It was shown that the patients, prior to treatment with radioactive iodine, had high levels of cellular functional activity, as determined by expression of CD25 antigen on T cells and CD23-antigen on B lymphocytes. Higher functional activity of the cells responsive for adaptive immunity in the patients with GD manifests in the presence of increased levels of autoantibodies to rTSH. By means of correlation analysis, we found that the patients with GD examined before the therapy had the thyroid status may determine the functional stimulation of T and B cells, thus increasing the levels of autoimmune processes. One month after radioiodine therapy (RIT), the GD patients, along with transient hyperthyroidism with increased concentration of autoantibodies to rTSH, showed a reduction of activated T lymphocyte contents (including T helpers and cytotoxic T cells) to control values. However, the level of cytotoxic T lymphocytes in the blood remained low, and the content of Treg cells was significantly increased in the patients. Decreased contents of B cells activated memory B cell to the control levels were found in patients with GD over 1 month after RIT when studying the phenotype of blood B lymphocytes. In this case, increased levels of naive B lymphocytes and B2 cells were detected, as well as decreased numbers of activated B1 lymphocytes. The observed changes in the subpopulation composition of T and B cells, and in their phenotype developed against the background of complete absence of relationships between the studied parameters, thus suggesting loss of thyroid control of immune processes and cooperative cell interaction during the development of the immune response. Generally, the phenotypic changes of T and B lymphocyte subsets in the blood of patients with GD through 1 month after treatment with radioactive iodine may reflect a trend for decreased functional activity of adaptive cellular immunity which may also account for inhibition of autoimmune processes.

Aim of the study was to investigate the most typical phenotypes and to study cardiovascular risk factors and assess of the clinical angiographic picture in stable angina patients with intermedium coronary artery stenosis. Material and methods. 236 stable angina functional class I–III patients (190 men) aged 49–59 with intermedium (40–70 %) coronary artery stenosis were examined. A general clinical examination, ultrasound examination and coronary angiography were performed. Study design – non-randomized descriptive study of four parallel groups. Differences in the compared parameters were considered statistically significant at p < 0.05. Results. The prevailing phenotypes in stable angina patients with intermedium coronary artery stenosis turned out to be coronary artery disease (CAD) without a previous myocardial infarction (MI); CAD with previous MI less than a 6 months ago; CAD with metabolically unhealthy obesity phenotype (MUOP) without diabetes mellitus (DM), and CAD with DM type 2. Patients of different phenotypes did not significantly differ in the frequency of past MI. CAD and MUOP patients with previous MI were characterized by the earliest age of its occurrence. Despite the 100 % availability of hypertension in different phenotypes groups, in CAD and DM type 2 patients were largest left ventricle myocardium mass values. They also had the most frequently recorded multivessel lesion during the coronary angiography study. Despite ongoing outpatient treatment for one year, the values of lipid and inflammation indices (content of low-density cholesterol, triglyceride, C-reactive protein) were high in all phenotypes patients as well as number of people with insufficient blood pressure control. Conclusions. In stable angina patients with intermedium coronary artery stenosis despite the absence of obstructive coronary artery lesion, the cardiovascular complications risk is due to the presence of 100 % arterial hypertension, high body mass index, significant frequency of obesity, dyslipidemia, carbohydrates metabolism disorders. That is why such patients represent a rather serious group in terms of prognosis. The clinical and angiographic picture, as well as residual risk levels, vary depending on the clinical phenotype.

The rainbow trout, or mykiss Oncorhynchus mykiss, is one of the most important aquaculture and introduced species worldwide. For the rational use and management of salmon stocks, various methods are used, of which phenetic analysis is one of the simplest, but effective. The authors analyzed the variability of color (spots) in trout populations from 1) Lake Kolsay, which originated from a cultural form from farms in Europe; 2) from the Kopak River, which originated from the wild populations of Kamchatka; 3) farmed trout of Danish and Polish origin. Data on the frequency of occurrence of various phenes and the proportion of rare morphs are given, and the index of similarity of populations is calculated. The dendrograms were constructed based on the similarity score using the complete linkage and unweighted pair-group similarity (UPGMA) methods. Significant differences between the trout from the Kokpak River and all other studied forms and the absence of variability in the stock of trout of Polish origin were revealed. The data obtained can be used to identify the sources of rainbow trout entering new water bodies and assess the risk for native ichthyofauna, as well as provide a preliminary assessment of the existing genotypic diversity of this alien species. [ABSTRACT FROM AUTHOR]

The aim of the research was to identify promising biochemical markers of blood associated with the intensity of live weight gain in young cattle. The work was carried out in 2021...2022 in the conditions of the dairy farm of LLC Severnaya Niva in the Kortkerossky district of the Komi Republic. A group of newborn heifers of the Kholmogorsky breed (n = 30) was selected for the experiment. It has been established that on the first day after birth, calves with intensive growth rates had lower AsAT activity (r = -0.510) and iron concentration (r = -0.650) in blood serum, and vice versa a higher level of SMLMM рlasma (0.626). At later stages of the analysis, a pronounced correlation of the intensity of body weight gain was observed with respect to the activity of alkaline phosphatase: -0.639 and -0.744 on day 7 and 14, respectively. It was determined that many of the calculated coefficients obtained during the blood test on the 14th day after birth had a more noticeable correlation with the intensity of growth. Such markers included: Alkaline phosphatase/Calcium (-0.746), Alkaline phosphatase/Magnesium (-0.756), Magnesium/Alkaline Phosphatase (-0.760), Calcium×Phosphorus/Alkaline Phosphatase (0.758) and Alkaline Phosphatase/(Calcium+Magnesium) (-0.753). At the next stage, the analysis of the rate of live weight gain in heifers ranked by the increase in the values of the developed coefficients was carried out. It is proved that the use of coefficients contributed to a more pronounced differentiation of the rate of weight gain in comparison with the values established with the use of one alkaline phosphatase. Thus, the calculated index of Alkaline phosphatase/Calcium/ Magnesium on the 1st, 7th and 14th days of postnatal ontogenesis provided a difference between the phenotypes of the 1st and 3rd groups by 74.1(P≤0.05), 92.6 (P≤0.01) and 90.7 (P≤0.001) g of weight gain per day, whereas the difference when using one alkaline phosphatase was 33.3; 16.0 and 12.2 % less. Thus, the use of these coefficients to predict the rate of live weight gain in calves can increase the accuracy of the selection of animals with the desired phenotype in early postnatal ontogenesis.

Adoptive immunotherapy using NK cells has become a promising therapeutic area. NK cells are a component of the innate immune system, act as key regulators, and have potent antitumor cytolytic activity. In order to be able to evaluate the therapeutic effect of adoptive NK cell immunotherapy at preclinical stages, there is a need for reliable protocols for in vitro production of NK cells. There are a large number of publications on methods for activating and generating human NK cells, including using feeder-cells and various cytokines. The article describes the experience of cultivation of NK cells from cancer patients or donors with feedercells and without feeder-cells (control group). The K562 cell line was used as a feeder after irradiation of two types: after gene modification of K562 (gmK562) with membrane-bound mbIL15, mbIL21 and without it. NK cells donors and cancer patients were mixed with K562 in a ratio of 1:1, 1:2 and 1:5 on 0, 7 and 14 days respectively. Daily morphological assessment showed that, NK cells donors and cancer patients began to proliferate and increase in size, while the viability of feeder cells began to decrease after 3 days of cultivation, and they were less than 20% on 21 days. NK cells of donors and cancer patients went into apoptosis, their viability level decreased to 70% in the control group (without feeder-cells) after 3 days of cultivation. A comparative evaluation of two different methods of obtaining human NK cells was carried out. It was shown when NK cells were isolated by magnetic selection, the proportion of CD3-CD56+CD16+ cells were more than 90%, and after the removal of adherent cells, it was at least 60%. When cultivating NK cells cancer patients (after magnetic separation) together with gmK562 on the 21st day, it was possible to increase the number of NK cells up to 85 times. When cultivating NK cells donors (after adhesion) together with non-genetically modified K562 cells on 21 days, it was possible to increase the number of NK cells up to 8 times. It was shown that in the supernatants collected during the cultivation of NK cells with feeder cells (both irradiated with K562 and genetically modified with K562), the concentrations of TNFα and IFNγ increased many times relative to the control group. The optimal conditions for culturing NK cells were experimentally selected to obtain a large number of NK cells.

Microvesicles are membrane-derived formations ranging in size from 100 to 1000 nm, being produced by a variety of resting and activated cells. They can transfer their cargo to target cells, regulate physiological processes, and participate in the development of clinical disorders. Among the microvesicles of different origin, natural killers are of special interest. They represent a subpopulation of lymphocytes that eliminate aberrant cells, including virally infected and malignant cells, and participate in regulation of angiogenesis. By producing various stimuli and inhibitors of the latter process, natural killers are able to change functional activity of endothelial cells by means of microvesicle-mediated contacts. There are only scarce literature data on ability of the extracellular vesicles to influence endothelial functions, depending on the intrinsic balance of pro- and anti-angiogenic factors. Therefore, the aim of our study was to evaluate the effect of protein fractions derived from microvesicle lysate of the NK-92 natural killer cell line upon phenotype and functional characteristics of EA.hy926 endothelial cell line under in vitro experimental conditions. Using chromatographic micro-preparatory separation, twelve protein fractions (inducers) were obtained from the lysate. It was found that proliferation and migration of EA.hy926 cells after their cultivation with 10 of 12 protein fractions, were changed in different directions. These effects were dose-dependent, or remained unchanged, at distinct concentrations of active components in the fractions. The inducing factors from these fractions exerted predominantly stimulating effects on proliferation of the target cells, thus suggesting presence of proteins which are able of regulating endothelial functions. However, the size of residual area free of migrating endothelial cells treated by the inducers did not always correlate with the migration intensity and did not inversely correlate with the number of migrating cells. Moreover, it was found that the obtained protein fractions had no effect upon expression of CD54 (ICAM-1), CD34, CD31 (PECAM-1) and CD119 (IFNγR1) receptors by EA.hy926 cells. The data obtained confirm an involvement of microvesicles in communications between natural killer cells and endothelial cells, and presume different participation modes of microvesicle-derived effector proteins in the angiogenesis machinery.

The classifications of the World Health Organization, the European Society of Car­-diology and the American Heart Association indicate the existence of several pheno­types of myocardial non-compaction (MnC) with specific structural and func­tional abnormalities. The MnC+dilated cardiomyopathy (DCM) phenotype is considered one of the most severe variants. Disputes continue about whether to regard MnC as an independent disease or as a consequence of DCM and heart failure. In other words, MnC remains one of the most mysterious heart diseases. As an illustration of MnC+DCM phenotype, the authors offer a case of a patient with cardiovascular disease from her youth, but maintained a satisfactory state of health and performance until her old age. Symptoms of arrhythmia and heart failure with massive pericardial effusion were first described in her at the age of 66, which is uncharacteristic for this MnC phenotype. Attention is drawn to the difficulties of differential diagnosis of MnC due to the non-specificity of clinical performance, the role of echocardiography in the recognition of the disease and predictors of its unfavorable outcome. The fact that the patient, even when typical signs of MnC were detected during echocardiography, initially had coronary artery disease as the main diagnosis, indicates the relevance of publishing another case report on this rare pathology in order to improve the awareness of cardiologists and general practitioners.

Objective: to evaluate the impact of undifferentiated connective tissue dysplasia (CTD) on the clinical manifestations of primary osteoarthritis (OA) in postmenopausal women.Patients and methods. The case-control study included 38 postmenopausal women with primary knee OA, radiological stage II. The main group included 19 patients who met the criteria for CTD, the control group included 19 patients without CTD.Results and discussion. Patients in the control group had significantly higher values of body mass index, hip circumference and more pronounced clinical manifestations of menopausal syndrome. Patients in the control group had all clinical components and laboratory criteria of the metabolic syndrome, they also had greater limitations of joint function compared to patients of the main group. In patients with CTD pathogenetic mechanisms of development and progression of OA differ from the metabolic phenotype of OA.Conclusion. The dysplastic phenotype of OA develops in the absence of metabolic syndrome and with less functional impairment than the metabolic phenotype. The metabolic phenotype of OA is associated with insulin resistance, more pronounced functional and psycho-emotional disturbances.

Background. Fungal sensitization (FS) often escapes the attention of clinicians when assessing the spectrum of sensitization in patients with atopic diseases. According to cohort studies is found in 310% of the general population and in 720% of asthmatics; the proportion of patients with severe bronchial asthma (SBA) with HS ranges from 35 to 75%. Fungal conidia have a 1000-fold higher exposure and are among the most important clinically relevant allergens in asthma. Exposure to fungal allergens is capable of generating a sustained T2 response with production of proinflammatory cytokines such as IL-5 and 13, which is indirectly related to the severity of airway eosinophilia. The identification of specific serum IgE is considered the benchmark diagnostic sign of FS, and the encapsulated hydrophobic carrier polymer system is considered preferable to skin prick tests. The process of reclassifying diseases with fungal lung lesions is confusing treatment strategies, leaving the FS problem underestimated. A series of publications have shown that omalizumab and other biologics targeting IL-5 or IL-5 receptor (IL5R) alpha are effective in treating SBA with FS. However, there remains an unmet need in real clinical practice for standardized approaches to genetically engineered biological therapies (BT) for different phenotypes of SBA, especially those associated with impaired microbiological homeostasis and this type of sensitization. Aim. Using retrospective analysis of clinical-dynamic observational data from patients on BT treatment in a real clinical setting to determine phenotypic features of severe allergic bronchial asthma with FS and to perform additional detailed analysis of a cohort of patients on anti-IgE therapy. Materials and methods. A retrospective observational single-center registry study was conducted between June 2017 and August 2021 at the City Reference Center for Allergology and Immunology. The baseline cohort consisted of 198 patients with severe allergic AD who were in the initial phase of BT. Inclusion criteria: age of patients over 18 years; presence of severe allergic bronchial asthma. Complex initial examination of patients included determination of FS by two methods: ImmunoCap ISAC to fungal allergic components alt a1, alt 6 (fungi of genus Alternaria) and asp f1, asp f3, asp f6 (fungi of genus Aspergillus). Specific IgE determinations on fungal panels. Sensitization to fungi was detected in 47 people during allergy examination. The following criteria were considered in evaluation of response to omalizumab: AST score less than 19 and/or difference between initial AST score and this score in dynamics less than 3 points; FEV 1 score less than 80; combination of 2 listed criteria. The minimum period of BT was 16 weeks. Nonparametric methods of descriptive statistics were used: median, interquartile range. Differences were considered significant at p0.05. Data were statistically processed using nonparametric methods in IBM SPSS Statistics V-22 program. MannWhitney U-test and KruskalWallis one-way analysis of variance were used to compare quantitative characteristics. Fisher's 2 test was used to compare qualitative characteristics. Results. Characteristics of the eosinophilic phenotype of SBA combined with FS: middle-aged patients, more often women, with relatively early onset of AD and high baseline eosinophil levels before prescription of biological drug therapy. Concomitant atopic dermatitis and food allergies are additional frequent features of this phenotype. Analysis of the effect of FS on achieving response to omalizumab and further consideration of switching to alternative therapy in SBA and FS patients showed the need to avoid premature revision and perform no earlier than the 10th month of therapy due to delayed response formation. Given the aggressive impact of FS on the barrier functions of the bronchial tree epithelium, it is advisable to test patients for FS at the initial diagnosis of AD. In the presence of atopic dermatitis and/or food allergy as T2 comorbidities in patients with SBA, early testing for FS and increased control of local and systemic inflammation are appropriate, which may improve long-term outcomes and reduce risks of further damage to natural barriers. Conclusion. Further research on various aspects of FS and its role in allergic diseases is extremely relevant in the current context.

The review provides data on severe bronchial asthma. Frequent exacerbations of asthma significantly reduce the quality of life of patients, cause disability, disability and death. The heterogeneity of severe bronchial asthma fits into the concepts of phenotype and endotype, the identification of which in clinical practice has limitations, but is necessary for personalized therapy. Analysis of the literature reflecting experience in patient data management is needed to form holistic perceptions of severe bronchial asthma and develop ways to optimize therapy.

The aim of the study was to investigate the phenotype of effector T lymphocytes in patients with chronic viral hepatitis C (CVHC) before and after of treatment with direct antiviral drugs depending on the genotype of the virus. 50 patients with CVHC without signs of liver cirrhosis were examined. The diagnosis was made on the basis of epidemiological and clinical laboratory data as recommended by the European Association for the Study of the Liver when specific serological markers of CHCV and RNA of hepatitis C virus (HCV) were detected (EASL, 2016). The determination of HCV RNA was carried out by the method of quantitative polymerase chain reaction in real time. The degree of liver fibrosis in patients with CVHC was assessed using ultrasound elastography. Patients were treated for 3 months with direct antiviral drugs according to the recommendations of the European Association for the Study of the Liver (2016). The control group included 46 practically healthy individuals with severe chronic diseases of various organs and systems excluded during a routine examination, no health complaints, having normal clinical and biochemical blood tests in the absence of markers for viral hepatitis B and C, antibodies to opisthorchis and denying history of alcohol abuse. The study of the subpopulation composition of helper and cytotoxic T lymphocytes was carried out by direct immunofluorescence of whole peripheral blood. We obtained a 100% sustained virological response in patients with 1, 2 and genotypes of CHCV without signs of liver cirrhosis when using therapy with Sofosbuvir (400 mg) and Daclatasvir (60 mg) for 12 weeks. It was found that in CVHC patients were found characteristic features in the phenotypic composition of effector T lymphocytes before and after treatment with direct antiviral drugs in depending on the genotype of HCV. Patients with HCV genotypes 1 and 3 had an increase in the content of terminal differentiated effector (TEMRA) T helpers and effector memory (EM). Only patients with HCV genotype 2 had a decrease in the level of EM T-helper cells in the blood. A decrease in the relative number of T helpers of central memory (СM) was independent of the HCV genotype. The level of effector subpopulations of cytotoxic T lymphocytes in patients with CVHC was consistent with or exceeded control levels in depending on the genotype of HCV. The level of all investigated subpopulations of effector cytotoxic T lymphocytes in patients with HCV genotype 1 was equal to the control values. The number of naïve cytotoxic T cells and CM in peripheral blood in patients with HCV genotype 2 was increased. The content of naïve cytotoxic T lymphocytes, CM and TEMRA in patients with genotype 3 HCV in the blood was increased. The highest viral load was detected in patients with CVHC with genotype 1 HCV. Liver fibrosis was most pronounced in patients with CVHC infection with HCV genotypes 2 and 3. After 3 months of treatment with direct antiviral drugs the patients with CVHC had a reduced content of CM T helpers regardless of the HCV genotype. In addition, patients with HCV genotypes 1 and 3 had a decrease in the number of naïve T helpers and patients with HCV genotypes 2 and 3 had a normalization of the content of naïve cytotoxic T lymphocytes.

Natural killer cells (NK cells) are innate immunity lymphocytes. NK cell differentiation is controlled by the cellular microenvironment and locally produced cytokines, including IL-2, IL-15 and IL-18. NK cells are present in various tissues, forming pools of tissue-resident NK cells, e.g., decidual NK cell pool. Peripheral blood NK cells (pNK cells) are considered a supposed source of cells for decidual NK cell differentiation. In the uterus, NK cells contact with trophoblast cells, which can affect their phenotype. Contribution of trophoblast cells and IL-2, IL-15 and IL-18 cytokines to the pNK cell phenotype regulation is scarcely studied. In this regard, the aim of our research was to evaluate the effect of trophoblast cells on the phenotype of pNK cells when cultured in medium with IL-2, IL-15, and IL-18. We used mononuclear cells obtained from peripheral blood of healthy non-pregnant women at their reproductive age, with regular menstrual cycle (n = 21). Mononuclear cells were cultured in presence of IL-2, and either of cytokines regulating NK cell differentiation (IL-15, or IL-18). JEG-3 cells were used as trophoblast cells. We evaluated expression of CD45, CD3, CD56, CD14, KIR3DL1, KIR2DL3, KIR2DL4, KIR2DS4, NKp44, CD215, CD122, CD127, NKG2D, KIR2DL1, NKG2C receptors by pNK cells. It was found that pNK cells cultured in presence of trophoblast cells (JEG-3 cell line) were characterized by lower intensity of CD56 receptor expression, compared to pNK cells cultured without trophoblast cells. These changes were detected upon culturing both in medium supplied by IL-15, and with IL-18. A reduced number of NKG2C+ pNK cells was detected in presence of JEG-3 trophoblast cells, compared to NK cells cultured without trophoblast cells in medium with IL-15. The detected changes in the CD56 and NKG2C expression by pNK cells in presence of trophoblast cells proved to be opposite to those previously detected for NK cells derived from NK-92 cell line. Along with trophoblast cells, the monocytes isolated among mononuclear cells and being affected by cytokines, can apparently influence the phenotype of pNK cells in the model system used. Since monocytes/macrophages are present in decidua, further research is required to study the effect of cytokines and cellular microenvironment, including monocytes, on pNK cells.

The aim of current study was to compare profiles of T cell subsets in the patients with ankylosing spondylitis (AS) who received different modes of genetically engineered biological therapy (GEBT). The research involved 58 patients aged 20 to 58 years diagnosed with AS and treated with anti-TNFα and antiIL-17 drugs, as well as those receiving common anti-inflammatory therapy. The AS diagnostics was based on the modified New York criteria. Disease activity was assessed by means of nomenclature approved by the Assessment of Spondyloarthritis International Society and Outcome Measures in Rheumatology. 45 healthy people aged 18 to 57 were included into the control group. Peripheral blood T cell subsets were analysed by multicolor flow cytometry. It was found that the T lymphocyte subpopulation profiles in AS patients showed significant differences depending on the therapy type. First, T lymphocyte counts were decreased in AS patients receiving traditional anti-inflammatory therapy, whereas relative numbers of T cells with high levels of effector potential and cytokine secretion were increased. Negative correlations between the levels of effector memory and pre-effector cytotoxic T cells and other laboratory and clinical indexes of inflammatory activity in AS may reflect lower efficiency of traditional therapy. Next, the levels of main T cell subsets in AS patients during antiIL-17 therapy fully corresponded to the control values. However, based on numerous correlations between immunological and clinical laboratory parameters, it was concluded that anti-IL-17 therapy had an inhibitory effect on the joint inflammation activity, while the state of T cell subsets was mainly dependent on standard anti-inflammatory therapy. The most pronounced changes in T cell subsets were found in AS patients during anti-TNFα therapy was associated with decreased effector potential of Th cells and cytotoxic T lymphocytes. At the same time, the lowest frequency of extraskeletal manifestations was found in AS patients treated with anti-TNFα drugs. Finally, the higher efficiency of GEBT, compared with conventional methods of therapy, is determined by the effects upon immune targets of AS pathogenesis which manifested, e.g., by changes in the T lymphocyte subpopulation profile. Moreover, usage of anti-TNFα versus anti-IL-17 inhibitors was associated with greater effect upon phenotypic profile of T cells.

Clinical and molecular heterogeneity of bronchial asthma has been documented in recent years. The search for novel solutions to enhance efficient patient support related first of all to understanding of asthma heterogenic nature and allows to personalize each patient treatment. Biological therapy application can influence to achieve better control at greater extent for patients with severe uncontrolled asthma. Nowadays 5 biological drugs are registered on Russian Federation territory and implemented according to severe asthma phenotypes: anti-IgE, anti-IL-4,13 and anti-IL-5 class therapies. Omalizumab become the first target drug for uncontrolled allergic asthma patients (monoclonal antibody against IgE). This medication is prescribed for uncontrolled moderate and severe allergic (atopic) asthma in patients on basic asthma therapy according GINA step 4 and 5 (Level of evidence A). Clinical trials confidently reported that anti- IgE-therapy reduces the rate of asthma exacerbations, severity of disease in patients with chronic severe asthma on high doses of inhaled steroids or systemic steroids and allows to reduce or withdraw systemic steroids doses in case of steroid-dependent asthma. For the last years special attention led to and demonstrated omalizumab positive effect on airways remodeling and modification of bronchial asthma natural course in adults and children. Antiinflammatory effect of omalizumab is documented. Omalizumab significantly reduces eosinophilic infiltration of submucosal bronchi layer among patients with atopic asthma, sputum eosinophilia, which correlates with reduction of FeNO during biologic treatment, reduces mast cells infiltration of smooth muscle cells in bronchi. Omalizumab significantly reduces the thickness of the bronchial wall, increases the lumen of the bronchi (positive dynamics of CT-scan parameters), which is clinically manifested by increased of FEV1.

Aim. A study of abdominal pain incidence in young adults in relation to dietary habits and psychological profile for advancement of health-promoting technologies.Materials and methods. An anonymous quiz survey covered 3,634 students enrolled at Omsk State Medical University in higher and secondary vocational education programmes via online use of the GSRS and WHO CINDI programme questionnaires to assess eating patterns and dietary preferences, as well as a brief multifactor personality inventory scale. Respondents with abdominal pain were divided into subcohorts by pain severity according to GSRS scores (mild, moderate or severe pain).Results. Abdominal pain was reported by 2,300 (63.29%) respondents, of whom 1,243 (54.0%) rated symptoms as mild, 996 (43.3%) and 61 (2.7%) — as moderate to severe. Abdominal pain complaints were more frequent in women (2I = 33.96, p

Introduction: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. It is characterized by damaged epidermal barrier, skin dysbiosis and pruritus. It affects up to 20% of the population of developed countries. AD represents a heterogeneous condition belonging to the spectrum of atopic diseases. It occurs in the form of multiple phenotypes with varied pathogenesis requiring different therapeutic strategies. Aim of the study: To summarize the current state of knowledge on AD phenotypes and related therapeutic options. Methods and materials: A review of the literature available in PudMed and Google Scholar databases was conducted. The following keywords were used: "atopic dermatitis", "atopic dermatitis phenotypes", "atopic dermatitis current treatment". Results: There are many phenotypes of AD. However, due to the lack of a consistent classification system, identifying phenotypes is greatly hindered. It is possible to use the division of phenotypes into groups based on age, lesion topography, lesion morphology and patient ethnicity. Various drugs are available for the treatment of AD, but therapeutic strategies for specific phenotypes are sparse and insufficiently understood due to the problem of identifying phenotypes and the complexity of the endotypes behind them. Treatment of AD is not currently based on phenotype-specific targeted therapy. Conclusion: Development of personalized therapy for the treatment of AD requires additional research using uniform definitions of phenotypes and endotypes. It is necessary to create a classification system for AD phenotypes.

Aim. To study and compare genotypic and phenotypic signs in patients with non-compaction cardiomyopathy (NCM) and dilated cardiomyopathy (DCM), to conduct a comparative analysis of clinical outcomes and 5-year cumulative survival of patients with NCM and DCM.Material and methods. The study included 144 unrelated patients with cardiomyopathy: NCM (n=74) and DCM (n=70). Mean age was 39 [30; 49] years (men, 96 (66,7%); left ventricular ejection fraction (LVEF) was 30,5 [24; 46]%. A comprehensive clinical examination included electrocardiography, Holter monitoring, echocardiography, cardiac magnetic resonance imaging, coronary angiography, DNA diagnostics (NGS+Sanger), cascade screening, and cosegregation analysis. To assess clinical outcomes, the NCM group was divided into 2 subtypes according to baseline LV systolic function (NCM/DCM phenotype — 50 individuals with LVEF ≤49%; and isolated NCM — 24 patients with LVEF ≥50%). The following adverse events were assessed as the composite endpoint: cardiovascular death, heart transplantation (HT), sustained ventricular tachycardia, ventricular fibrillation, successful cardiopulmonary resuscitation, cerebral thromboembolism. The follow-up period was 62 months.Results. Among patients with LVEF ≤49% at a 5-year follow-up, 37 (74,0%) of 50 patients with the NCM/DCM phenotype and 41 (58,6%) of 70 patients with DCM achieved composite endpoint. Out of 24 patients with NCM with LVEF ≥50% (median LVEF, 56 [51; 61]%), 2 (8,3%) patients achieved composite endpoint (χ2=28,8; p=0,001). In the NCM/DCM group with LVEF ≤49%, a higher level of pathogenic genetic variants (64% vs 41,4%/DCM vs 29,2%/NCM; χ2=11,4; p=0,003), cerebral thromboembolism (χ2=11,8; p=0,003) and HT (χ2=10,6; p=0,005). The results of the 5-year survival analysis (Kaplan-Meier) showed a worse prognosis for NCM with LVEF ≤49% compared with DCM (log rang: χ2=11,5; p=0,001) and isolated NCM (log rang: χ2=17,02; p=0,0001). In the overall cohort (n=144), gene-positivity was also associated with worse prognosis (log rang: χ2=5,38; p=0,02).Conclusion. In the present study, patients with dilated subtype of NCM showed a worse prognosis compared with DCM and isolated NCM. Heart failure progression and cerebral thromboembolism were the most common complications in patients with NCM/DCM.

Aim. To analyze and demonstrate various phenotypes in patients with familial left ventricular noncompaction (LVNC). Materials and methods. In 2013 was created a multicenter registry of LVNC patients. On its basis 30 families with a familial LVNC were selected. Results. 30 LVNC families were selected from the register. From a total of 115 people (probands and relatives) in 71 (61.7%) LVNC was diagnosed (30 probands and 41 relatives with non-compact myocardial criteria). The most common type of remodeling in patients was the dilated type (DT) (n=30), the isolated LVNC with preserved ejection fraction (EF) was slightly less common (n=23), and the hypertrophic type (GT) was detected in 8 patients. 4 patients were diagnosed with the isolated LVNC with a reduced EF. 3 patients were with a combination of non-compact myocardium with congenital heart disease and with a combination of DT and GT (DT+GT). During the analysis of cases a combination of different phenotypes in the same family was observed. The largest number of families was diagnosed with a combination of DT and the isolated LVNC with preserved EF. The development of cardiovascular complications was associated with DT. Conclusion. Family cases of LVNC had different types of myocardial remodeling and variants of clinical course. In one family a combination of different types of left ventricular remodeling is possible. DT is associated with the most severe clinical manifestations. The clinical picture of the isolated LVNC with preserved EF, is the most favorable, but in rare cases, serious clinical manifestations were observed.

The review provides data on one of the phenotypes of severe bronchial asthma it is asthma with fixed airway obstruction. According to data published today, there is no single pathway for the formation of fixed airway obstruction in patients with severe asthma. Increasing knowledge of the pathophysiology of fixed airway obstruction, as well as identifying the most significant risk factors, is essential for the successful treatment of such patients. In addition, the development of fixed obstruction is associated with a worse and sometimes fatal prognosis. Expanding the existing views is also necessary to overcome the difficulties of differential diagnosis between bronchial asthma with fixed airway obstruction and bronchial asthma in combination with COPD. All this will optimize the approach to the management of patients with bronchial asthma to prevent the formation of fixed airway obstruction.

In recent years, there has been an increase in the prevalence of allergic diseases in children. Allergic rhinitis (AR) ranks first among other allergic diseases in terms of prevalence and impact on the health and quality of life patients. In various countries of the world, according to various sources, from 10 to 40% of the population suffers. Allergic rhinitis is a serious medical, social and economic problem. In addition, allergic rhinitis, especially with multiple sensitization and insufficiently controlled course, is an independent risk factor for recurrence of respiratory infections and the development of bronchial asthma, and also significantly reduces the quality of life patients.AR is a multifactorial disease in the development of which many factors play a role. The basis of the pathological process in AR is IgE--dependent mucosal inflammation, which is realized under the influence of specific and nonspecific mechanisms and has a Th2 character. The tissues and organs involved in the process determine the formation of complex mechanisms of interaction between the immune, microcirculatory and autonomic nervous systems.The inflammatory process in AR is characterized by a number of features, for example, the presence of minimal persistent inflammation and the priming effect, which in turn is a predisposing factor for the clinical onset and progression of AR. Microcirculatory mechanisms are of great pathogenetic significance in the development of allergic inflammation, including in AR.Depending on the leading pathognomonic trait, it is now customary to distinguish individual phenotypes and endotypes of AR.The phenotype covers the clinically significant properties of AR, but does not reveal the detailed mechanisms of its development, on the basis of which a personalized algorithm for prevention, treatment and prognosis can be created.And the autonomic nervous system is responsible for setting links between the body, ambient and internal environment through the regulation of metabolism, functioning of organs and tissues based on changes in this environment; it also provides the integration of all organs into a single whole acting as one of the main body’s adaptive systems.Since the autonomic nervous system governs the body and homeostasis uniting separate pathogenetic links of disease progression and sets the basis for structural and functional unity. In light of this, the failure of neuroregulatory mechanisms takes the lead among the causes of systemic changes in the microvasculature, which, in turn, reflects general pathogenetic processes in the body. The regulatory mechanism is implemented through nerves and reflexes by different neurohumoral factors, their nature has been studied under experimental conditions and is beyond doubt to date.The study of the main indicators of microcirculation and the autonomic nervous system among children with allergic rhinitis in various combinations with concomitant pathology will highlight new AR phenotypes and select an individual treatment and rehabilitation plan for these children.

A search for new targeted therapeutic strategies based on examining immunopathogenetic mechanisms for emerging co-infections is relevant and may further contribute not only to optimizing choice of immunotropic drugs, but also to achieving positive clinical and immunological remission for abnormal infectious processes. Previously, our studies found that recurrent viral-bacterial respiratory infections are associated with dysfunction of neutrophilic granulocytes (NG) with varying degree of intensity in altered effector properties. NG dysfunctions are often associated with diverse phenotypic profiles characterized by varying density for expression level of functionally significant trigger receptors. The aim of the study was to pinpoint phenotype transformation in CD64-CD32+CD16+CD11b+, CD64+CD32+CD16+CD11b+ neutrophilic granulocytes in experimental model of viral-bacterial infection in vitro. We examined 52 peripheral blood samples collected from 13 healthy adult volunteers. Viral, bacterial and virus-bacterial infection was modelled in vitro by incubating blood-derived cell samples with formyl-methionyl-leucyl-phenylalanine (fMLP), double-stranded RNA (dsRNA) or in combination followed by assessing changes in immunophenotyping of CD64-CD32+CD16+CD11b+NG, CD64+CD32+CD16+CD11b+NG by using using MAbs CD16-ECD, CD64-FITC, CD32-PE, CD11b-PC5 conjugates (Beckman Coulter International SA, France). It was demonstrated that NGs from healthy adult volunteers were dominated by CD64-CD32+CD16+CD11b+NG as well as minor subset СD64+CD32+CD16+CD11b+ NG varying in expression density of membrane molecules. Percentage of the minor subset СD64+CD16+CD32+CD11b+ NG was significantly increased after exposure with dsRNA, fMLP and dsRNA+fMLP compared to untreated samples. Comparative analysis revealed that various immunotropic agents differed in affecting expression of surface receptor molecules CD16, CD32 and unidirectional effects, but of varying magnitude altering CD11b marker both in major and minor subsets. Preincubation with dsRNA followed by adding fMLP allowed to find that they co-stimulated expression of surface receptors in both NG subsets. We generated an experimental model of viral-bacterial co-infection in vitro by using fMLP and dsRNA and observed types of phenotype transformation in CD64-CD32+CD16+CD11b+ NG and CD64+CD32+CD16+CD11b+ NG subsets. This model can be used to evaluate transformation of other NG subset phenotypes, NG functional activity, features of NET formation as well as impact of various immunotropic agents on NG.

Aim. To determine the prevalence of refractory hypertension (RfH) in patients with and without type 2 diabetes mellitus (DM), as well as to evaluate whether diabetic patients with RfH significant differ from those with uncontrolled resistant hypertension (RH) in clinical phenotype, metabolic profile and endothelial function. Materials and methods. The study included 193 patients with RH: RH 74 patients with diabetes and 119 patients without DM. Uncontrolled RH and RfH were defined by the presence of uncontrolled blood pressure BP (140 and/or 90 mm Hg) despite the use of 3 but 5 antihypertensive drugs (for RH) and 5 antihypertensive drugs, including a mineralocorticoid receptor antagonist (for RfH). Clinical examination, lab tests were performed. Flow-mediated dilation (FMD) and vasoreactivity of middle cerebral artery (MCA) using both breath-holding and hyperventilation test were measured by high-resolution ultrasound. Results. The prevalence of refractory hypertension in patients with and without DM was similar (30% vs 28%, respectively). No differences in BP levels, data of echocardiography and clinical phenotype were found between the diabetic groups, but value of HOMA index, plasma resistin level and postprandial glycaemia were higher in patients with RfH. FMD and MCA reactivity to the breath-holding test were worse in patients with RfH, and they had a more pronounced vasoconstrictor response of MCA to the hyperventilation test compared to patients with RH. Conclusion. The prevalence of RfH is the same in patients with and without diabetes. Diabetic patients with refractory hypertension have a more unfavorable metabolic profile and greater impairment of endothelial function than patients with uncontrolled resistant hypertension.

Mechanisms of recognition and effector responses of immune system upon initiation and maintenance of immune-mediated inflammation and tissue damage in inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis (UC), have been actively studied over recent time. Existing evidence suggests these diseases to be caused by abnormal immune response against intestinal flora microorganisms in genetically susceptible individuals. Despite available data on the features of immune disorders in ulcerative colitis and Crohn’s disease, there are still many questions about the involved minor lymphocyte subpopulations and contribution of various functionally active molecules, which play a key role in recognition and initiation of the immune response and can be considered biomarkers of a pathological process in inflammatory bowel diseases. The populations of T lymphocytes with γδT cell receptor, B1 cells and NK T lymphocytes are of greatest interest, as well as functionally active TLRs (Toll-like receptors), CD89, CD314, etc. Due to substantial progress in studying the nature of recognition and activation of the immune cells, the paper presents phenotypic and functional characteristics of major and minor subpopulations of peripheral blood lymphocytes observed in 25 patients treated at the Surgery Department of the State Institution “Minsk Regional Clinical Hospital” (Republic of Belarus) from 2018 to 2020. The detected changes in peripheral blood lymphocyte phenotype of inflammatory bowel diseases patients suggest distinct immunological profiles prevailing in the damage mechanisms in Crohn’s disease and ulcerative colitis. I.e., in Crohn’s disease patients, B1 lymphocytes with CD19+CD5+ and NK cells in combination with increased CD56bright population, as well as NK T cells with anti-inflammatory and regulatory activity are involved into genesis of the disease. In ulcerative colitis, T, B, NK lymphocytes with pro-inflammatory phenotype and T lymphocytes with γδ T cell receptor may play a pathogenetic role in maintenance of chronic inflammation. With respect to functional significance of activating receptors, the number of TLR4- и CD89-positive cells may be used for developing immunological criteria/ biomarkers of therapeutic efficacy of new drugs. Studying interactions between innate and adaptive immunity will open new perspectives in understanding immunological disorders associated with chronic gastrointestinal inflammation.

Defects in the functioning of neutrophilic granulocytes (NG) are accompanied by various purulent-inflammatory diseases that have a persistent-relapsing course. The bactericidal activity of NG, the processes of intracellular and extracellular killing of bacteria, is directly dependent on their phenotypic features: the expression level of functionally significant membrane receptors CD64, CD16, CD32, CD11b triggering effector processes. It was shown that there are subsets of NG with different phenotypic characteristics and the course and outcome of infectious and inflammatory diseases directly depends on their usefulness. Despite the large amount of accumulated information, the question of the transformation of NG subpopulations phenotype during NG response formation in children with local purulent processes of soft tissues - a small purulent infection (SPI) remains poorly understood. Purpose: to evaluate the local and systemic effector function of neutrophilic granulocytes (phagocytosis, NET formation) with clarification of the phenotype of functionally significant CD64-CD16+CD32+CD11b+, CD64+CD16+CD32+CD11b+ and CD64-CD16+CD32-CD11b+ NG subpopulations in peripheral blood (PB) in children with SPI. Materials and methods. We evaluated the phagocytic function of NG in 60 PB samples of children 5-9 years old, on the 2-3rd day of acute purulent process, before surgery, in smears - prints taken from the local focus of purulent inflammation and 17 PB samples of conditionally healthy children. Also the ability to form NET was additionally determined in smears-prints in children with SPI. In parallel, in PB we evaluated:% NG simultaneously carrying CD64, CD16, CD32, CD11b receptors and their expression density (MFI) by flow cytometry (CYTOMICS FC500, Beckman Coulter, USA). Statistical data processing was performed in the Microsoft Exel 2016 and Stat Plus 2010 software packages. Nonparametric criteria were used: median (Me) and interquartile range (Q1; Q3), Mann-Whitney U-test and Wilcoxon test. Results . We found a significant increase in the content of the NG subpopulation with a negatively transformed phenotype CD64-CD16+CD32-CD11b+ with defects in the expression of CD64 and CD32 receptors, which is the cause of inadequate inclusion of NG in inflammatory processes, disruption of phagocytic activity at the systemic and local levels and the occurrence of SPI in children. The formation of NET in the first stage is necessary to supplement the effector function of NG in order to compensate for disorders of phagocytosis.

The aim of the present study was to analyze the relationships between expression of activation and adhesion receptors on peripheral blood neutrophils, and intracellular activity of some neutrophil enzymes in patients with kidney cancer (KC). Patients and methods: the KC patients (n = 72) (T3N0M0, clear-cell type) were examined prior to surgical treatment at the Krasnoyarsk Regional Oncology Center. The diagnosis was verified histologically for all KC patients. The phenotype of blood neutrophils was studied using flow cytometry. The surface receptor expression levels of the neutrophils were evaluated by mean fluorescence intensity. NAD and NADP-dependent dehydrogenases activities in purified peripheral blood neutrophils were measured by bioluminescent method. Results: we have found that the phenotypic alterations in circulating KC patients’ neutrophils appeared along with inhibition of main intracellular metabolic processes and were closely linked with them. The features of the phenotypic imbalance in the neutrophils from KC patients were associated with a decrease in blood cells expressing adhesive (CD11b and CD62L) and functional (CD64 and HLA-DR) receptors. Moreover, the patient’s neutrophils expressed CD11b, CD16 and HLA-DR on their cell surface more intensively, than neutrophilic leukocytes from control group. These phenotypic changes in KC patients’ blood neutrophils occurred in parallel with pronounced decrease in immature cells numbers. The metabolic changes of neutrophil cytoplasmic compartment in KC patients were determined by a decrease in Glu6PDH activity (a key and initializing enzyme of the pentose phosphate cycle) and NADH-LDH (anaerobic glycolysis). Mitochondrial metabolism in neutrophils of KC patients was characterized by multidirectional changes in the activity of NAD- and NADP-dependent glutamate dehydrogenases (decreased activity of NAD-dependent and increased activity of NADP-dependent) and a decrease in NADH-MDH activity. The established features in mitochondrial enzymes activities suggest some disturbances of NAD-dependent processes that could lead to down-regulation of aerobic energy processes. We guess that the decreased activity of plastic and energy processes in blood neutrophils of KC patients could affect the receptor expression levels. By means of correlation analysis, we have found that the relationships in KC patients were determined by negative effects of NADHGDH and NADH-LDH activities upon expression of activation and adhesion receptors in blood neutrophils. Of these enzymes, only glutathione reductase activity in neutrophils from KC patients was positively linked with the CD23 and HLA-DR expression. Thus, an increase in activity of energy processes (e.g., coupling the tricarboxylic acid cycle to amino acid metabolism) in blood neutrophils from the patients with kidney cancer could stimulate expression levels of activation and adhesion receptors and potentially increase antitumor activity of neutrophils.

Hyperproliferative diseases of the endometrium play an important role in the structure of gynecological pathology, which are a spectrum of irregular morphological changes. Particularly difficult is evaluation of the phenotypic characteristics of the endometrium hyperplastic processes (EHP) in premenopausal women in the presence of an unstable menstrual cycle. Diagnosis and EHP prognosis remains a difficult task given that it can occur as focal or diffuse lesions with various structural and cytological differences. Objective of the study: to evaluate the immunohistochemical features (phenotypic variants) of benign endometrial hyperplasia in premenopausal women. Material and methods. 33 premenopausal women with abnormal uterine bleeding and verified benign endometrial hyperplasia were examined. Expression of the α-receptors for estrogens type 1 (ER1), progesterone receptors and Ki-67 nuclear protein in the endometrium stroma and glands was analyzed. Micromorphometry was performed and the D-score was calculated. Results. Prevalence of comorbid lesions in patients was the combination of endometrial hyperplasia and fibroids (51.4%), cases of abnormal uterine bleedings against submucosal fibroids (13.5%), endometrial polyps (8.1%), combinations of EHP and peritoneal endometriosis (10.8%), adenomyosis and myoma (8.1%), or other combinations of endometrial and myometrial proliferative pathology. D-score for surgery averaged 1.78 ± 0.11 indicating a low risk of malignancy. There were changes after treatment in the quantitative presentation of the studied proteins in stroma and endometrial glands. Thus, before treatment in the glands was determined up to 100% of cells containing ER1 in large quantities, while after treatment their number decreased by an average of 20%. Similar dynamics was observed with progesterone receptors activity. Conclusions. The main prognostic significant phenotypes of endometrial proliferative pathology have been identified. After removing of pathologically chanced endometrium and subsequent treatment with dydrogesterone during 6 months there is prognostically positive decreasing in the ER1 density as well as the Ki-67 protein expression