Pathogenetic Features Research Articles

Immune system disturbances after a new coronavirus infection COVID-19

During the pandemic, a large number of works devoted to COVID infection have appeared, which have made it possible to understand the pathogenetic features of the disease and to accumulate significant clinical experience. However, the question remains about the degree of participation of humoral and cellular (primarily T-cell) immunity in the mechanisms of immune defense and resistance to COVID-19, the individual features of the immune response in different subjects. Post-COVID syndrome is currently a separate diagnosis included in the ICD-10 International Classification of Diseases, but the long-term effects of the SARS-CoV-2 on the immune system are not yet well established. At the same time, a long-term increased activity of the immune system can contribute to the development of autoimmune reactions. The review of the literature presents the results of studies, mainly devoted to immune system disorders after COVID infection. The changes in subpopulations of T-lymphocytes, B-lymphocytes, their functional properties, the complement system and other factors of humoral immunity, as well as the production of a number of cytokines are described. Data on immune disorders in post-COVID syndrome and during the convalescence period are presented in detail. Since COVID-19 is an infection that has a significant impact on the hematopoietic system and hemostasis, special attention is paid to the category of subjects with an increased risk of severe complications. Among the latter are elderly patients, persons suffering from diabetes mellitus, oncological and oncohematological patients, in particular, with hematopoietic and lymphoid tissue neoplasia, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma. The review pays special attention to the peculiarities of the course of COVID-19 and the response of the immune system to vaccination in patients with oncohematological diseases. Deciphering the significance of individual links of cellular and humoral immunity in patients who have undergone COVID-19 is an important issue in creating effective vaccines and improving therapeutic methods.

Endothelial dysfunction in patients with obesity

Endothelial dysfunction has been considered in the pathogenesis of obesity widespread in the population. The purpose of this review was to provide updated information about pathogenetic features and markers of endothelial dysfunction in obese patients. We mentioned systemic disorders in obesity, such as oxidative stress, an increase in pro-inflammatory cytokines – tumor necrosis factor alpha, interleukin-6, and arginase activity. We also discussed the role of insulin resistance in the development of endothelial dysfunction, as well as the product of adipose tissue metabolism – monocyte chemoattractant protein-1. The participation of perivascular adipose tissue, hyperoxia of adipose tissue in the regulation of inflammation was considered. We illustrated the influence of atherogenic concentrations of oxidized low-density lipoproteins, the asymmetric dimethyl-L-arginine level on endothelial function. Changes in laboratory parameters were analyzed: endothelin-1, levels of microalbuminuria, homocysteine and uric acid. We also described cytological (circulating vascular cells, endothelial microparticles) and instrumental (endothelium-dependent vasodilation, peripheral arterial tonometry, intima-media complex thickness of the common carotid artery, ultrasound kidneys examination with duplex scanning of the renal arteries) methods for assessing endothelial function. Factors that influence the risk of cardiovascular complications were arterial hypertension and arterial stiffness, high levels of low-density lipoprotein and triglycerides, reduced physical activity. The determination of endothelial function in patients with obesity can be important for predicting the pathology of the cardiovascular system. Information on the assessment of markers of endothelial dysfunction in such patients may expand the possibilities of early diagnosis and prevention of cardiovascular complications.

Influence of ZP2 peptide, a synthetic analogue of the GM-GSF active center on the anticytokine activity of bacteria from <i>Enterococcus</i> genus and their ability to produce cytokine-like substances

Peptide ZP2, a synthetic analogue of the active center of granulocyte-macrophage colony stimulating factor (GM-CSF), exhibits a wide range of immunobiological effects, including antibacterial activity. At the same time, its effect (in sub-inhibitory concentrations) on the biological properties of Enterococcus spp., the causative agents of many infectious and inflammatory diseases remains poorly understood. The aim of our study was to analyze the nature of the effect of synthetic peptide ZP2 on anticytokine activity (ACA) and its ability to produce cytokine-like substances (CLS) in Enterococcus spp.
 18 clinical isolates of Enterococcus spp. were used. Over the experiments, the bacterial strains were cultured in Schaedlers broth with ZP2 peptide at 37 C for 24 hours. No specific peptide was added in the control. ACA for IL-8, TNF and IL-17A and the production of the corresponding CLS were determined by the ELISA method. To assess ACA, the proportion of cytokine inactivation in the experiment relative to the control was calculated and expressed in pg/ml; CLS production was evaluated by the level of cytokines in the experiment and control, expressed as pg/ml. The data were subjected to statistical processing.
 It was revealed that Enterococcus spp. strains are capable of secreting compounds that inactivate cytokines IL-8, IL-17A and TNF, and produce CLS in the culture medium. Intragenital and intraspecific variability was noted in the presence and frequency of occurrence and in the severity of these properties. It was found that the ZP2 peptide in E. faecium increases ACA with respect to all studied cytokines. When tested with E. faecalis, it either did not affect their ACA against TNF and IL-8, or completely inhibited ACA for IL-17A. At the same time, ZP2 blocked the production of CLS, e.g., IL-17A and IL-8 in E. faecium, but increased the production of CLS similar to TNF, and, with E. faecalis, it increased the number of IL-17A-producing isolates twofold, although the average level of production of these CLS was lower than in the control.
 Enterococcus spp strains are capable of secreting compounds that inactivate cytokines IL-8, TNF and IL- 17A, and may produce substances similar to these cytokines. The synthetic peptide ZP2 has a modifying effect on the manifestation of these properties by Enterococci. Further studies of biological and pathogenetic features of Enterococci and other bacterial species, as well as modifying effects of the ZP2 peptide are required.

Clinical Variations of Uveitis in Immuno-Inflammatory Diseases. Review of the Literature. Part 1

Non-infectious uveitis is one of the main and insufficiently studied causes of disability and blindness in patients with immuno-inflammatory diseases. Uveitis associated with spondyloarthritis, Behcet’s disease, juvenile idiopathic arthritis, systemic sarcoidosis and Vogt-Koyanagi-Harada syndrome are described more often and better than others, but the pathogenesis of different variants of their course is not well understood. Also, there remains a need to study the clinical and pathogenetic features of uveitis in rare autoimmune inflammatory diseases. Despite the currently existing diagnostic and therapeutic schemes, further study of the pathogenesis of uveitis associated with immune-inflammatory diseases is required, the research of a personalized approach and an algorithm for joint multidisciplinary diagnosis by specialists in various fields. A deeper understanding of the specific pathogenetic mechanisms will reveal new possibilities in the treatment of patients with autoimmune uveitis. This article is devoted to the current clinical and differential diagnostic aspects, common features and distinctive features associated with various variants of the course of non-infectious uveitis in patients with immuno-inflammatory diseases.

CLUSTER ANALYSIS AS A METHOD FOR TESTING THE HYPOTHESIS ABOUT THE INFLUENCE OF GLUCOSE METABOLISM DISORDERS ON THE COURSE OF ACUTE OTITIS MEDIA IN ADULTS

Relevance. Relevance of the research is caused by the clinical necessity to increase efficiency of diagnostics and treatment of acute otitis media (AOM) from the modern positions personalized medicine and the feasibility of statistical verification of the validity of the hypothesis about the influence of glucose metabolism disorders on the formation of clinical and pathogenetic features of acute otitis media in adults.
 Objective. To carry out statistical verification of the hypothesis about the influence of carbohydrate metabolism disorders on the complicated course of AOM on the basis of cluster analysis and to determine its informativity.
 Materials and methods. The cluster analysis included 73 with AOM. The 1 group (n=17) - patients with AOM; 2 group (n=15) - patients with AOM with presence of the sinus pathology; 3 group (n=20) - patients with AOM due to type 2 diabetes mellitus (DM2); 4 group (n=21) - patients with AOM due to transient glucose metabolism disorders. Apart from the clinical examination, all patients were tested for HbAlc, parathormone, osteocalcin, total calcium, IL-4, IL-6, FNP-α, and low-density lipoproteins (LDL). Cluster analysis on the basis of laboratory indicators was performed by the hierarchical method using the iterative algorithm of k-means and prior standardization of the data.
 Result. The hypothesis was tested at the level of stratification of patients into 4 and 2 clusters. In the first case, 28.8 %, 31.5 %, 15.6 %, and 24.6 % of the total number of patients were included in clusters I, II, III, and IV. Patients with AOM due to impaired glucose metabolism were predominantly in clusters I and II, comprising 51.2 % and 69.5 % of the cluster contingent respectively, while DM2 prevailed in cluster I and transient glucose metabolism disorders in cluster II (61.9 % and 62.5 % accordingly), 72.7 % and 94.4 % of patients with AOM without impaired glucose metabolism were stratified in clusters III and IV.
 The analysis of laboratory indicators using the k-means algorithm showed a general tendency for the increase in glucose, HbAlc, parathormone, TNF-α and LDL in patients with AOM in clusters I and II with increased levels of osteocalcin, calcium and IL-4 in patients in clusters III and IV with the presence of a significant difference (p˂0.05).
 At the level of patients' grouping into two clusters, cluster I included 41.9 % of the total number of patients due to the presence of all glucose metabolism disorders (of these, DM2 occurred in 57.6 % and transient glucose metabolism disorders in 43.3 %). The II cluster (58.9 % of patients) included all patients with AOM without impaired glucose metabolism, accounting for 74.4 % of its structure, and 25.6 % of patients with impaired glucose metabolism (6.97 % for DM2 and 18.6 % for transient impairments).
 The k-means algorithm revealed a clear and reliable distribution of clusters for all 9 studied indicators, which resulted in an increase in glucose content, HbAlc, levels of parathormone, IL-6, TNF-α and LDL and decreased osteocalcin, calcium and IL-4 in I cluster compared to II. Differences in the indicators at the group-group levels, group-cluster and cluster-cluster revealed a sufficient difference in the first and third cases (with the exception of osteocalcin) and their absence at the group-cluster level (with the exception of parathormone for cluster I, p˂0.01 and glucose and HbAlc for cluster II, p˂0.05).
 Conclusion. The cluster analysis was informative and confirmed the hypothesis about the influence of glucose metabolism disorders on peculiarities of AOM pathogenesis in adults according to laboratory indices. The principal importance of the presence or absence of impaired glucose metabolism in patients with AOM is confirmed by stratification of patients into two clusters. Thus, all patients without glucose metabolism disorders were included in one (II) cluster. The contingent of patients with impaired glucose metabolism was not homogeneous, with cluster I comprising only patients with impaired glucose metabolism, but 15 % of patients with DM2 and 38.1 % of patients with transient disorders were in cluster II. Therefore, to improve the quality of diagnostics of complicated course of acute otitis media on the basis of glucose metabolism disorders it is necessary to supplement the laboratory indicators with informative clinical criteria. Parathormone level, as well as the combination of IL-6, TNF-α and LDL levels can be used as a marker of impaired glucose metabolism.

Судинні порушення у хворих на ревматичні хвороби після перенесеного COVID-19

The article briefly summarizes data on the role of micro- and macrocirculatory disorders in the pathogenesis of COVID-19. Focused attention on similarities of clinical and pathogenetic features of rheumatic diseases, COVID-19 and its complications. The review analyzed and compared the data of the assessment of the main instrumental studies of the functional state of blood vessels in patients with rheumatic diseases in general and in patients with rheumatic diseases who suffered from COVID-19 (capillaroscopy and occlusion test). A conclusion was made about the presence of endothelial dysfunction in rheumatic diseases and its features in patients with rheumatic diseases after transmission of COVID-19. This leads to the opinion about the expediency of timely detection of secondary disorders of the functional state of blood vessels in patients with rheumatic diseases who are convalescents of COVID-19, and justifies the use of an occlusion test for this purpose. No conflict of interests was declared by the authors.

Association of VEGF cytokine levels and single nucleotide polymorphisms of the <i>VEGF-A</i> gene with the genital endometriosis in the female population of the Northwestern Federal District of Russia

Aim. To study the association of neoangiogenesis VEGF-A gene polymorphisms C(-460)T (rs833061), C(+936)T (rs3025039) with the risk of genital endometriosis in the population of the Northwestern Federal District; to examine the relationship of polymorphic variants of the VEGF-A neoangiogenesis gene C(-460)T (rs833061), C(+936)T (rs3025039) with the concentration of VEGF-A factor in the blood of females with genital endometriosis.
 Materials and methods. Eighty-five female volunteers aged from 19 to 44 (mean age 32.9 (5.8) years) with a histologically confirmed diagnosis of genital endometriosis were included in the stud; also, 79 females without endometriosis according to diagnostic laparoscopy for infertility or ectopic pregnancy, aged 20 to 42 (mean age 32.5 (7.2) years, p=0.71) were included in the study. The obtained data were analyzed using SPSS 20.0 statistical software package; 2 value and p value were estimated.
 Results. In our study, we found an association between the C allele and the CC genotype of the C(+936)T (rs3025039) polymorphism of the VEGF-A gene with genital endometriosis: odds ratio (OR) 2.35, 95% confidence interval (CI) 1.034.61, p=0.023; OR 1.89, 95% CI 1.034.61, p=0.048, respectively. The TT genotype of the C(-460)T (rs833061) polymorphisms and the TT genotype and the C(+936)T (rs3025039) allele of the VEGF-A gene were less common in patients with genital endometriosis: OR 0.43, 95% CI 0.141.29, p=0.023; OR 0.06, 95% CI 0.043.18, p=0.001; OR 0.43, 95% CI 0.231.29, p=0.023 respectively. The blood concentration of VEGF-A cytokine was lower in patients with genital endometriosis at all genotypes of C(-460)T (rs833061) locus of VEGF-A gene than that in females without endometriosis. The analysis of genotype frequency distribution of polymorphic site C(+936)T of the VEGF-A gene showed that the VEGF-A cytokine level was 1.5 times higher in the comparison group with heterozygous ST genotype versus that in homozygous genotypes. Enzyme immunoassay in the examined females showed a 2.5-fold decrease in the level of the VEGF-A angiogenic cytokine in blood serum in patients with endometriosis compared to those without endometriosis.
 Conclusion. To better understand the pathogenetic features of the endometriosis course and to make an individual prognosis of the course and therapy efficacy, an additional analysis of the associations between the polymorphisms of the listed genes and the angiogenesis factor level is required.

THE INFLUENCE OF AN INFECTIOUS AGENT ON THE DEVELOPMENT OF HYPERPLASTIC PROCESSES OF THE ENDOMETRY IN THE EARLY REPRODUCTIVE AGE

The problem of hyperplastic processes of the endometrium (HPE) in women of reproductive age is a potential cause of reduced fertility and the risk of developing oncological pathology, which has been steadily increasing in recent years, attracting the increased attention of clinicians.
 The aim: to analyze the role of an infectious agent in the development of hyperplastic processes of the uterine mucosa in women of early reproductive age for the formation of risk groups for the occurrence of endometrial hyperplasia and polyps.
 Materials and Methods: 90 patients in early reproductive age were examined, who were divided into groups: the main group included patients with histologically verified atypical hyperplastic pathology of the endometrium (polyps of the uterine body and atypical hyperplasia of the endometrium) (n = 60). The control group consisted of 30 healthy volunteer patients of the same age category. The patients of the main group underwent a diagnostic hysteroscopy with endometrial biopsy, material was collected from women of the control group with prior consent using Peipel-biopsy with subsequent examination of the material. Bacteriological analysis of the material from the uterine cavity included the study of aerobic and anaerobic flora using a set of selective differential diagnostic nutrient media.
 Results and Discussion: Data on the role of microbial and viral factors in the development of atypical endometrial hyperplasia in women of early reproductive age are given. The structure of microbial insemination of the uterine cavity in such women has been established. Cytomegalovirus antigens in hyperplastic endometrium were found in 38.3 % of cases. The obtained data make it necessary to carry out high-quality infectious screening for the formation of risk groups regarding the occurrence of hyperplastic changes of the uterine mucosa.
 Conclusions: In patients of early reproductive age with atypical hyperplasia of the endometrium, the persistence of bacterial agents in the uterine cavity in insignificant concentration was noted in all examined, viral - in 38.3 %, which reflects the significant etiological role of bacterial and viral infection, which participates in the implementation of the inflammatory process and formation of hyperplastic pathology. Pathogenetic features of bacterial-viral infection of the genital tract of patients with hyperplastic endometrial pathology determine the need for high-quality infectious screening with the formation of risk groups and subsequent etiopathogenetic treatment.

New aspects of the pathogenesis of psoriasis

Psoriasis is a chronic multi-factorial immune-mediated inflammatory disease of skin and joints. The variety of clinical forms of dermatosis is consistent with various pathogenetic features of the disease progress which have been significantly supplemented and reviewed recently. Knowledge of these mechanisms will improve and personalize the prescribed therapy.
 This study places the emphasis on modern ideas about the formation of T cell memory, the role of melanocytes and innate lymphoid cells. Development mechanisms of guttate and paradoxical psoriasis with important distinguishing characteristics are described separately.
 Today, knowledge of the molecular basis of the disease progression has led to the creation and introduction of a number of highly effective targeted drugs into clinical practice. Further developments related to the inhibition of resident memory cells, innate lymphoid cells, as well as the study of guttate psoriasis perpetuation and the occurrence of paradoxical psoriasis will significantly increase the effectiveness of the therapy.

Gut Microbiome and Mycobiome Alterations in an In Vivo Model of Alzheimer's Disease.

Gut microbiota has emerged as an important key regulator of health and disease status. Indeed, gut microbial dysbiosis has been identified in an increasing number of diseases, including neurodegenerative disorders. Accordingly, microbial alterations have been reported also in Alzheimer’s disease (AD), suggesting possible pathogenetic mechanisms contributing to the development of specific AD hallmarks and exacerbating metabolic alterations and neuroinflammation. The identification of these mechanisms is crucial to develop novel, targeted therapies and identify potential biomarkers for diagnostic purposes. Thus, the possibility to have AD in vivo models to study this microbial ecosystem represents a great opportunity for translational applications. Here, we characterized both gut microbiome and mycobiome of 3xTg-AD mice, one of the most widely used AD models, to identify specific microbial alterations with respect to the wild-type counterpart. Interestingly, we found a significant reduction of the Coprococcus and an increased abundance of Escherichia_Shigella and Barnesiella genera in the AD mice compatible with a pro-inflammatory status and the development of AD-related pathogenetic features. Moreover, the fungal Dipodascaceae family was significantly increased, thus suggesting a possible contribution to the metabolic alterations found in AD. Our data point out the strict connection between bacterial dysbiosis and AD and, even if further studies are required to clarify the underlining mechanisms, it clearly indicates the need for extensive metagenomic studies over the bacterial counterpart.

Pathomorphological and pathochemical characteristic of the osteomyelitis focus in patients with diabetic osteoarthropathy (Charcot foot)

BACKGROUND: Osteomyelitis in diabetic osteoarthropathy occurs in 65 % of cases, and it is the main cause of non-traumatic amputations. The choice of optimal treatment technologies should be based on understanding the pathogenetic characteristics of this disease.AIM: To study the pathomorphological and pathochemical picture of osteomyelitic focus in patients with diabetic neuroosteoarthropathy.MATERIALS AND METHODS: Object — 20 patients (55.3±9.33 years) with Type 2 diabetes mellitus, diabetic neuroosteoarthropathy, chronic osteomyelitis of the foot bones. The treatment consisted in surgical debridement of the purulent focus with the material collection for pathomorphological and biochemical studies, and in reposition and alignment of bone fragments with the leg and foot fixation using the Ilizarov fixator in order to form bone ankylosis of the compromised joint.RESULTS: Subacute and acute course of chronic osteomyelitis was registered in 80 % of cases. As for the pathohistological changes in bone tissue, the following ones were the most significant: necrosis and the presence of an inflammatory infiltrate of varying severity depending on the phase of the inflammatory process. The articular cartilage structure was broken in all the cases. Activation of osteoclasts was observed in the osteomyelitis focus, especially in the subchondral zone. There was no subchondral bone plate in most cases, or only its fragments remained. Pathohistological examination of the soft tissues associated with the osteomyelitis focus indicated the presence of mirocirculatory and denervation disorders due to necrosis and hyalinosis of a significant part of microvessels against the background of compensatory hypervascularisation and chronic inflammation, narrowing and obliteration of the lumens of feeding arteries, almost complete absence of nerve elements in the tissues or their destructive changes. An increase in the activity of lytic enzymes was revealed in the interstitial environment of the tissues surrounding the osteomyelitis focus (138-fold increase in the activity of acid phosphatase, interstitial osteolytic index was 7.2-fold higher than blood serum index).CONCLUSION: The pathomorphological signs of chronic osteomyelitis subacute and acute processing were observed in most patients. Breaking the articular cartilage structure was accompanied by invasion of vessels, inflammatory infiltrate, and by activation of osteoclasts in the subchondral zone. Destructive changes of vessels and nerves in the soft tissues associated with the osteomyelitis focus can be etiopathogenetic factors of this disease development. The technologies for stopping this process should be based on obligatory debridement of the focus with sequestrnecrectomy, with regular monitoring of the operated segment condition.

Comprehensive analysis reveals a 5-gene signature and immune cell infiltration in Alzheimer's disease with qPCR validation.

Over 50 million people around the world currently are suffering from Alzheimer’s disease (AD) without any effective therapy. Neuroinflammation plays a pivotal role in AD, which leads us to probe the profile of immune cell infiltration in AD. Here, we analyzed a microarray dataset (GSE44770) containing 115 AD and 115 control samples to determine biomarkers and immune infiltration characteristics of AD by multiple bioinformatics methods. First, we identified 3,840 DEGs (1892 upregulated and 1948 downregulated) by using the limma package and 2,697 hub genes by constructing a weighted gene correlation network, and they had a total of 2,167 intersecting genes. Second, combining the LASSO logistic regression and SVM-RFE, we obtained five biomarkers (DGKG, MAP3K7IP2, NFKBIE, VIP, and PCCB), which may reveal the key pathogenetic features of AD and serve as diagnostic markers assessed by the ROC curve (AUC = 0.9716) and validation of another AD dataset (GSE33000) (AUC = 0.9388). Third, immune cell infiltration analysis revealed that compared with control samples, plasma cells, CD8 T cells, T follicular helper cells, and activated NK cells infiltrated less in AD; Monocytes, M2 macrophages, and neutrophils infiltrated more in AD. Neutrophils and activated NK cells demonstrated the most significant and negative correlation. Then, Spearman correlation analysis between the five biomarkers and immune infiltrating cells revealed that all of them were significantly associated with plasma cells. Finally, mRNA levels of VIP and PCCB were conformed in a murine AD model. In conclusion, DGKG, MAP3K7IP2, NFKBIE, VIP, and PCCB may be used as diagnostic markers of AD, and the disruption of the delicate immune balance may be a key process in the onset and development of AD.

Treatment of patients with heart failure and preserved ejection fraction: reliance on clinical phenotypes

The article discusses the problem of improving the effectiveness of treatment of heart failure with preserved left ventricular ejection fraction (HFpEF). The relative "failure" of early studies with renin-angiotensin-aldosterone system inhibitors was largely due to the lack of understanding that patients with HFpEF represent a heterogeneous group with various etiological factors and pathogenetic mechanisms of the disease. Therefore, the so-called personalized approach should be used in the treatment of these patients. This approach is based on the identification of clearly defined disease phenotypes, each characterized by a set of demographic, pathogenetic, and clinical characteristics. Based on the literature and own experience, the authors consider four main phenotypes of HFpEF: 1) phenotype with brain natriuretic peptide "deficiency" syndrome associated with moderate/severe left ventricular hypertrophy; 2) cardiometabolic phenotype; 3) phenotype with mixed pulmonary hypertension and right ventricular failure; and 4) cardiac amyloidosis phenotype. In the treatment of patients with phenotype 1, it seems preferable to use the valsartan + sacubitril (possibly in combination with spironolactone) combination treatment; with phenotype 2, the empagliflozin treatment is the best; with phenotype 3, the phosphodiesterase type 5 inhibitor sildenafil; and with phenotype 4, transthyretin stabilizers. Certain features of different phenotypes overlap and may change as the disease progresses. Nevertheless, the isolation of these phenotypes is advisable to prioritize the choice of drug therapy. Thus, the diuretic treatment (preferably torasemide) should be considered in the presence of congestion, regardless of the HFpEF phenotype; the valsartan + sacubitril and spironolactone treatment is appropriate not only in the shortage of brain natriuretic peptide but also in the presence of concentric left ventricular hypertrophy (except for the amyloidosis phenotype); and the treatment with empagliflozin and statins may be considered in all situations where pro-inflammatory mechanisms are involved.

Potential roles of non-lymphocytic cells in the pathogenesis of IgG4-related disease.

Studies have confirmed the involvement of a variety of lymphocyte subsets, including type 2 helper T lymphocytes (Th2) and IgG4+ B lymphocytes, in the pathogenesis of IgG4-related disease (IgG4-RD). Those lymphocytes contribute to the major pathogenetic features of IgG4-RD. However, they are not the only cellular components in the immunoinflammatory environment of this mysterious disease entity. Recent studies have suggested that various non-lymphocytic components, including macrophages and fibroblasts, may also play an important role in the pathogenetic process of IgG4-RD in terms of contributing to the chronic and complex progress of the disease. Therefore, the potential role of non-lymphocyte in the pathogenesis of IgG4-RD is worth discussing.

Pathogenetic features of experimental osteoarthrosis induced by dexamethasone and talc

The aim of the study was to investigate the pathogenesis of experimental osteoarthrosis induced by dexamethasone and talc by examining the structure and defining the morphometric and metabolic features of knee joint skeletal connective tissues in rats.Materials and methods. We performed a morphometric evaluation of articular cartilages (their thickness, extracellular matrix arrangement, spatial arrangement of the main components, distribution density, and main cellular indices of chondrocytes), as well as changes in subchondral bones (the presence of trabeculae in the basal layer of the articular cartilage and individual osteophytes) in 30 rats with a model of primary osteoarthrosis induced by sequential administration of 0.5 ml dexamethasone (2 mg) and 1 ml 10% sterile talc suspension mixed with normal saline into the joint cavity. We studied the histologic specimens of the knee joints stained with hematoxylin – eosin, Alcian blue (рН 1.0 and 2.5), as well as with Van Gieson’s, Masson’s, and Mallory’s trichome stains. The metabolic features of the articular cartilage and bone tissues were investigated by determining the hyaluronan, osteocalcin, and type I collagen levels in the serum of the rats.Results. In the rats with dexamethasone- and talc-induced osteoarthrosis, the thickness of cartilages in their weight-bearing areas decreased by 50%, the spatial arrangement of chondrocytes was impaired, and the nuclear – cytoplasmatic ratio (р < 0.01) decreased to 0.3. Besides, a rise in the serum levels of hyaluronan (p < 0.001) to 110.2 ng / ml, type I collagen fragments (p < 0.001) to 217.9 ng / ml, and osteocalcin (p < 0.001) to 231.1 ng / ml was detected.Conclusion. The main pathogenetic features of experimental osteoarthrosis induced by dexamethasone and talc include impaired distribution density, morphological characteristics, and functional activity of chondrocytes, which results in inhibited synthesis of extracellular matrix components in the articular cartilage and activated destruction of proteoglycans containing unsulphated glycosaminoglycans. The subchondral bone remodeling in experimental osteoarthrosis induced by dexamethasone and talc is characterized by intensification of synthetic activity of osteoblasts.

PATHOGENETIC FEATURES OF PREECLAMPSIA CLINICAL COURSE CONTROL IN PREGNANT WOMEN AND ITS EFFECT ON THE CARDIOVASCULAR SYSTEM (LITERATURE REVIEW)

Objective – to analyze modern views on the pathogenetic features of control over theclinical course of preeclampsia in pregnant, NT-proBNP role and its pathogenesis andthe possibilities of prevention.Conclusion. The necessity of further investigation of this problem, with the aim of prolongingthe term of pregnancy in women with preeclampsia to avoid preterm labor, has been shown.

Mental Disorders of the Female Reproductive Cycle

Background: Mental disorders associated with the female reproductive cycle (premenstrual period, pregnancy, lactation, infertility, perimenopause) have been a clinical reality throughout the history of the study of psychosomatic health factors in women. The most recent ICD-11 classication distinguishes an independent categories, “Mental or behavioral disorders associated with pregnancy, childbirth and the puerperium, with/without psychotic symptoms”. The clinical and etiological variety of mental disorders associated with female reproductive cycle (MDFRC) requires an integrated approach to diagnostics and choice of treatment methods. Objective: to analyze the results of the main scientic studies concerning pathogenetic and clinical characteristics of MDFRC. Material and methods: the key words “mental disorders, premenstrual syndrome, pregnancy, infertility, lactation, perimenopause, involution” were used to search the databases of articles of domestic and foreign authors (PubMed, eLibrary, Scopus and ResearchGate) published over the past 25 years. Conclusion : The presented review analyzed the results of studies showing that a variety of psychoemotional stresses and endocrinological abnormalities at different stages of the female generative cycle are risk factors for the development of psychiatric disorders. MDFRC include heterogeneous and polymorphous anxiety, affective, dysmorphic, and psychotic symptom complexes. However, the lack of a clear understanding of their pathogenesis leads to persistent disagreement as to whether MDFRC (postpartum psychosis, involutionary melancholia/hysteria, etc.) are independent psychiatric disorders or provoked exacerbations of other psychiatric diseases in predisposed women. The presented review allows to improve understanding of MDFRC, their risk factors and clinical variants, which has important practical value in diagnostics and choice of treatment methods.

Pathogenetic Features of Restoring of Urinary Reservoir Function, Which Was Replaced by an Ileum Implant (Experimental Study)

Bladder cancer accounts for 50–70% of all malignant diseases of genital urinary system and 4% of all oncological diseases. It is well known, that in Ukraine men have such pathology 4 times more often than women and, unfortunately, up to 22% of patients die within the first year after confirmed diagnosis. The basic criteria of treatment effectiveness of the patients with oncological diseases are not only the rate of their survival, but also their quality of life. One of the main types of treatment for muscle-invasive bladder cancer is radical cystectomy with different variants of urinary diversion. The morphological changes in the muscle layer of the neobladder can cause deviations in the regulations of its contractility. This evolution of the smooth muscle wall demonstrates the electrophysiological contractility features of the neobladder compared to the ileum. The objective: to analyze the pathogenetic moments of the smooth muscle contractility regulation of the artificial bladder. Materials and methods. The experimental study on female mini-pigs aged 16–19 months, with weight 30–40 kg, the duration of the study was 12 months. The experimental model of the artificial bladder was performed by cystectomy in animals following by the terminal ileum of the neocyst, its anastomosis with the ureters, urethra under the anesthesia. After the forming of the neobladder the experimental animals had anesthesia with tiopental, and the neocyst and part of the ileum were removed, in one year. The experiments were carried put on the 18 pairs of specimens: isolated strips of the small intestine of mini-pigs and strips of the wall of the artificial bladder. Results. It was determined that spontaneous activity of the ileum and neobladder smooth muscles in 12 months has different indices. During the experiment the spontaneous activities of longitudinal smooth muscles (SM) of the ileum and neobladder were compared. It was determined that the spontaneous contractions of the neobladder SM are significantly different from the strip ileum contraction in control by larger amplitude and the complex shape. Conclusions. The hypertrophic growth of smooth muscles (SM) is a complex dynamic phenomenon that includes not only the structural changes, but also the complex physiological processes, namely aimed at transforming the part of the intestines to perform a new function of the urinary reservoir. The artificial bladder performs the functions of the natural bladder, there by making the life easier for a patient. The study of smooth muscle contractive activity regulation mechanisms under the influence of nervous and humoral systems will allow to expand the methods of its correction.

Spices as one of the important agents to enhance dietary rehabilitation of patients with the phenomena of poly- and comorbidity and infectious processes in the context of the latest achievements. Literature review and discussion

The authors substantiate the wider use of spices in the dietary rehabilitation of patients with the phenomena of poly‑ and comorbidity, infectious processes based on the analysis of the latest scientific research on their pharmacological properties. An information search has been carried out in print and electronic publications, search scientific databases using methods of analysis, comparison and generalization of the obtained data. It has been established that in recent years the world medical and biological community has significantly increased interest in spices such as ginger, turmeric, cinnamon, garlic, parsley, onion, basil, cloves, coriander, cardamom, peppers, dill, cumin, blackberries, nutmeg, rosemary. It has been revealed that all of them possess the following actions with various intensity: anti‑inflammatory, antispasmodic, analgesic, antioxidant, antibacterial, antiviral, antifungal, hypocholesterolemic. Some of them have antitumor, hypoglycemic, anticoagulant, antidepressant, nootropic, diuretic effects. According to the dominant properties, the authors grouped spices, which allows doctors to use them in dietary rehabilitation in a differentiated way, according to the pathogenetic features of different diseases, especially in the phenomena of poly‑ and comorbidity. Prospects for wider use of spices in tumors, diabetes, immunodeficiency and chronic infectious diseases are noted. The authors elucidated their own experience of successful use of species in the complex rehabilitation of patients with post‑COVID syndrome. The novel scientific data on the pharmacological, metabolic, poly‑organ, system‑regulatory properties of spices enable their wide application in the comprehensive rehabilitation of patients with poly‑ and comorbidities and infectious processes.

The epithelial-to-mesenchymal transition in cancer: pathogenetic features

The epithelial‑to‑mesenchymal transition (EMT) is a cellular biological process, that occurs in a wide range of cells and tissues and is triggered by complex regulatory networks involving transcriptional control with SNAIL, ZEB1, ZEB2, Twist, SLUG, E‑cadherin, vimentin, tumor microenvironment and genetic characteristics. EMT is represented by the multi‑stage development and transformation of cells of the epithelial phenotype into cells that acquire mesenchymal features of various severity. These quasi‑mesenchymal cells are characterized by stemness, tumor heterogeneity, increasing invasiveness, drug resistance and a tendency to distant metastasis, which leads to the proliferation of neoplastic cells, tumor dissemination and initiation of metastasis, which induces the therapy resistance and the oncological recurrence.This review is based on the latest scientific publications about the EMT phenomenon, indexed in PubMed. The aim of the study was to evaluate the biochemical and molecular pathogenetic mechanisms of EMT and the effect of EMT markers on the progression of neoplastic processes and the effectiveness of the treatment. Nowadays the proper EMT scheme that combines all the molecular transformations of sells with quasi‑mesenchymal phenotype doesn’t exist. But analyzing the features of this cellular program, we can find the proper therapy, that could be able to suppress the plasticity of cancer cells, prevent EMT induction by blocking contextual signals, and induce mesenchymal‑epithelial transition. All these aspects will lead to the reduction of the risk of tumor dissemination and the increase of the effectiveness of cancer treatment.