Role of morphogenic proteins of the WNT signaling pathway in coronary artery disease

In recent years, researchers’ attention has been directed to the WNT signaling pathway study, which regulates embryogenesis processes and is involved in pathological condition development. The role of morphogenic proteins of WNT signaling pathway in the cardiovascular pathology genesis is practically not clear. The research aim was a comprehensive study of the main proteins of WNT signaling pathway (β-catenin, sclerostin, GSK-3α, GSK-3β, WIF-1 and DVL-1) in the blood serum of 353 patients with coronary artery disease acute forms who were treated at the Orel regional vascular center from 2019 to 2021, and 50 healthy individuals. A comprehensive analysis included an assessment of clinical, laboratory and instrumental parameters in the framework of current clinical guidelines, as well as an immunological examination to determine the morphogenic proteins of WNT signaling by enzyme immunoassay. The results showed a wide variability in the values of morphogenic proteins of WNT signaling pathway in the patient’s blood serum. The levels of β-catenin, WIF-1 and DVL-1 significantly exceeded those obtained in healthy individuals, while the concentrations of sclerostin and GSK-3β did not differ significantly from them. The level of GSK-3α of patients was twice lower than in healthy individuals. The highest sclerostin concentrations were found in patients with existing calcification of the aortic valve leaflets and aortic walls. Acute coronary syndrome unfavorable course was observed in patients with both extremely high and extremely low WIF-1 levels. Significant correlations were established between the level of morphogenic proteins of WNT signaling pathway and lipid metabolism, as well as myocardial remodeling. The obtained data on changes in the protein production of WNT signaling pathway allow us to expand our understanding of the molecular aspects of the immunopathogenesis of myocardial remodeling in coronary artery disease, increase the predictive potential for cardiovascular disease diagnosis and determine the vector for further development of cardioimmunology determination

ROLE OF GSK-3 IN Wnt/β-CATENIN SIGNALING PATHWAY IN OBESITY

The complexity of the adipogenesis mechanism results from the impact of multiple cues, among which an important place is held by the components of the Wnt signaling pathway. The search for potential markers of the development of diseases related to obesity aroused an interest in the study of GSK-3 (glycogen synthase kinase), β-catenin. GSK-3β is an intracellular serine / threonine kinase found in the cytoplasm, nucleus, mitochondria, synthesized in all body tissues and involved in regulating metabolic processes, cell proliferation, apoptosis etc. The first of the discovered functions of GSK-3β was the regulation of glycogen synthesis. Active GSK-3β phosphorylates and thereby inhibits glycogen synthase. As a result of the insulin binding to the cell receptor via inositol-3-phosphate, protein kinase B (Akt1) is activated, which, in turn, phosphorylates and inhibits GSK-3β. In addition, GSK-3β is involved in the regulating glucose metabolism. The most important function of GSK-3β is the inhibition of the β-catenin protein. In a resting cell, GSK-3β in complex with the APC and Axin proteins binds and phosphorylates the β-catenin transcription factor, which leads to its ubiquitination and degradation. When Wnt proteins act on the cell, the Dvl protein is activated, which, by binding to GSK-3β, releases β-catenin, preventing its degradation, however, the role of GSK3α/β in the adipocyte inflammatory response has not yet been fully investigated, therefore it seems promising to study the role of GSK-3 in the Wnt/β-catenin signaling pathway in obesityThe aim of the study was to assess the activity of the components of the Wnt signaling pathway in obese patients by measuring the serum level of GSK-3 and β-catenin. There were enrolled 32 patients with progressive forms of I-III degree obesity in the absence of diabetes mellitus. The concentration of serum GSK-3α, GSK-3β, and β-catenin was measured by enzyme-linked immunoassay. Data are presented as absolute and relative (%) number of patients; arithmetic mean; medians, 1 and 3 quartiles – Ме (Q0.25-Q0.75). Obese patients contained a 7.5-fold increased serum level of GSK-3α (785 (371-1317.5) pg/ml) compared to healthy individuals 105 (102.5-110) pg/ml, (p < 0.001), paralleled with increased amount of GSK-3β, which level in obese patients was 295 (190-695) pg/ml, which is by 18.3% higher than those in healthy individuals 241 (218.75-287.5) pg/ml, p = 0.111. Amount of GSK-3 depending on the degree of obesity tended to increase, most often coupled to decreased β-catenin level which is consistent with the literature data and can be considered as a prognostic criterion for the course of pathological processes in obesity

Non-invasive control of influence of polyethylene glycol on transport function of fluorescent colored liposomal nanoparticles

The studies were carried out on groups of clinically healthy mice line of outbred CD-1 stock. The model animals were divided into 2 groups and received experimental liposomal formulations. Using the method of fluorescence spectroscopy, we investigated the effectiveness of penetration into the circulatory system of fluorescently stained liposomes with polyethylene glycol (PEG) and without PEG when administered orally. Fluorescence channel with a fiber probe series of multifunctional laser non-invasive diagnostic system "LAKK-M" (SPE "LAZMA" Ltd, Russia) was used as the measuring equipment

Noninvasive control of the transport function of fluorescent coloured liposomal nanoparticles

The use of liposomal nanoparticles with an incorporated active substance is an innovative and promising approach to diagnostics and therapy. The application of liposomal nanoparticle-based drugs allows for targeted localized delivery, overcomes the natural barriers within the body effectively, and minimizes possible side effects. Liposomes are able to contain a variety of ingredients with practically no limitations to their chemical composition, chemical properties, or size of constituent molecules. This study evaluated the ability to control the passage of fluorescent dye-filled liposomes through the intestinal mucosal barrier after oral administration. For this purpose, the increase in transcutaneous registered fluorescence from tetrabromofluorescein dye was recorded and analysed. Fluorescence intensity was measured at the proximal end of the tail of an animal model after oral administration of the liposomes. Measurements were taken at the excitation wavelengths of 365 and 450 nm. The fluorescence intensity in the group treated with the fluorescent contrast agent encapsulated in liposomal particles increased 140% of the initial level, but in the group treated with pure contrast agent, the increase in detected fluorescence intensity did not exceed 110%. Mice that received empty liposomes as well as the control group did not demonstrate statistically significant changes in fluorescence intensity. A potential application of our results is an express laser optical method of monitoring the transport of orally administered liposomal particles. The results can be used to help create new optical tools for use in the development of new drugs and in high-throughput screening used during their testing

Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021

IntroductionThe J Project (JP) physician education and clinical research collaboration program was started in 2004 and includes by now 32 countries mostly in Eastern and Central Europe (ECE). Until the end of 2021, 344 inborn errors of immunity (IEI)-focused meetings were organized by the JP to raise awareness and facilitate the diagnosis and treatment of patients with IEI.ResultsIn this study, meeting profiles and major diagnostic and treatment parameters were studied. JP center leaders reported patients’ data from 30 countries representing a total population of 506 567 565. Two countries reported patients from JP centers (Konya, Turkey and Cairo University, Egypt). Diagnostic criteria were based on the 2020 update of classification by the IUIS Expert Committee on IEI. The number of JP meetings increased from 6 per year in 2004 and 2005 to 44 and 63 in 2020 and 2021, respectively. The cumulative number of meetings per country varied from 1 to 59 in various countries reflecting partly but not entirely the population of the respective countries. Altogether, 24,879 patients were reported giving an average prevalence of 4.9. Most of the patients had predominantly antibody deficiency (46,32%) followed by patients with combined immunodeficiencies (14.3%). The percentages of patients with bone marrow failure and phenocopies of IEI were less than 1 each. The number of patients was remarkably higher that those reported to the ESID Registry in 13 countries. Immunoglobulin (IgG) substitution was provided to 7,572 patients (5,693 intravenously) and 1,480 patients received hematopoietic stem cell therapy (HSCT). Searching for basic diagnostic parameters revealed the availability of immunochemistry and flow cytometry in 27 and 28 countries, respectively, and targeted gene sequencing and new generation sequencing was available in 21 and 18 countries. The number of IEI centers and experts in the field were 260 and 690, respectively. We found high correlation between the number of IEI centers and patients treated with intravenous IgG (IVIG) (correlation coefficient, cc, 0,916) and with those who were treated with HSCT (cc, 0,905). Similar correlation was found when the number of experts was compared with those treated with HSCT. However, the number of patients treated with subcutaneous Ig (SCIG) only slightly correlated with the number of experts (cc, 0,489) and no correlation was found between the number of centers and patients on SCIG (cc, 0,174).Conclusions1) this is the first study describing major diagnostic and treatment parameters of IEI care in countries of the JP; 2) the data suggest that the JP had tremendous impact on the development of IEI care in ECE; 3) our data help to define major future targets of JP activity in various countries; 4) we suggest that the number of IEI centers and IEI experts closely correlate to the most important treatment parameters; 5) we propose that specialist education among medical professionals plays pivotal role in increasing levels of diagnostics and adequate care of this vulnerable and still highly neglected patient population; 6) this study also provides the basis for further analysis of more specific aspects of IEI care including genetic diagnostics, disease specific prevalence, newborn screening and professional collaboration in JP countries

Automated system-cognitive analysis of the dependence of export and import of agricultural machinery on its production (the case of Russia)

The issue raised in the article is the study of the dependence of export and import of agricultural machinery on its production in Russia. The Russian agricultural machinery market is influenced by three groups of factors: 1) own production of agricultural machinery; 2) export of agricultural machinery of Russian production; 3) import of agricultural machinery of foreign production. Traditionally, such problems are solved using multivariate analysis. However, in this case, the use of this method is problematic for a number of reasons: the source data is dimensional and measured in different units, the number of observations is less than the number of factors, the factors depend on each other, and the number of factors is too large. These restrictions are proposed to be overcome by applying automated system-cognitive analysis and its software tools of the intellectual system “Eidos”. For this purpose the following tasks were solved: 1) formulation of the idea and the concept of problem solving; 2) justification of the choice of the method and tool for solving the problem; 3) application of the selected method and tool to solve the problem; 4) evaluation of the effectiveness of the proposed solution of the problem; 5) consideration of the restrictions and disadvantages of the proposed solution of the problem and the prospects for its development by overcoming these restrictions and disadvantages. Some results of solving these problems are briefly summarized in this article

Noninvasive control of the transport function of fluorescent coloured liposomal nanoparticles

Abstract The use of liposomal nanoparticles with an incorporated active substance is an innovative and promising approach to diagnostics and therapy. The application of liposomal nanoparticle-based drugs allows for targeted localized delivery, overcomes the natural barriers within the body effectively, and minimizes possible side effects. Liposomes are able to contain a variety of ingredients with practically no limitations to their chemical composition, chemical properties, or size of constituent molecules. This study evaluated the ability to control the passage of fluorescent dye-filled liposomes through the intestinal mucosal barrier after oral administration. For this purpose, the increase in transcutaneous registered fluorescence from tetrabromofluorescein dye was recorded and analysed. Fluorescence intensity was measured at the proximal end of the tail of an animal model after oral administration of the liposomes. Measurements were taken at the excitation wavelengths of 365 and 450 nm. The fluorescence intensity in the group treated with the fluorescent contrast agent encapsulated in liposomal particles increased 140% of the initial level, but in the group treated with pure contrast agent, the increase in detected fluorescence intensity did not exceed 110%. Mice that received empty liposomes as well as the control group did not demonstrate statistically significant changes in fluorescence intensity. A potential application of our results is an express laser optical method of monitoring the transport of orally administered liposomal particles. The results can be used to help create new optical tools for use in the development of new drugs and in high-throughput screening used during their testing

CHRONIC PHARYNGITIS: ETIOLOGY, PATHOGENESIS, TREATMENT. NEW APPROACHES TO THE ESTIMATION OF ETIOPATOGENESIS

The work discusses modern issues of etiopathogenesis, treatment of chronic pharyngitis. The results of the application of a modern method for the diagnosis of mass spectrometry of microbial markers (MSMM), which allows to detect the microorganisms in a biofilm, in a “sleeping state” under the protection of mucin are presented. With the help of this express method, it is possible to conduct a determination of the content in a smear from the pharynx 57 biomarkers of microorganisms at the same time 2 hours after delivery to the laboratory. It was found that 100% of the examined patients with a recurring course of HF (n = 62) increased the total content of microorganisms, which indicates the need for antibacterial therapy; 87% of patients have elevated levels of endotoxin, which is a sign of general intoxication; 71% of patients have reduced plasmalogene content and these patients may be at increased risk for lipid metabolic disturbances; in 100% of the examined patients with frequent exacerbations of CP in the pharynx the nasopharyngeal microflora (coccal) is determined, as well as new etiopathogenetically significant microorganisms (not detected by PCR and cultures), among which there are 7 transient microorganisms (normally in the orifice their level = 0), 11 resident (6- found in the throat in the norm in the minimum level and 5 in the high content). Also, with the help of MSMM, a significant or moderate increase in the content of herpes, cytomegalovirus was detected in the majority (75%) of patients, which indicates the important role of the viruses of the herpes group in the etiopathogenesis in the recurrent course of CP; level of Candida spp. elevated in half of patients; the content of normal microflora is increased in 71% of patients, which indicates the preservation of local resistance in patients with chronic HF, examined by the authors. Thus, the use of MSMM for chronic fever allows to identify new etiopathogenetic microorganisms, on this basis to prescribe a more effective therapy. Thus? it is possible to carry out personified, more effective treatment

DataSheet_2_Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021.docx

IntroductionThe J Project (JP) physician education and clinical research collaboration program was started in 2004 and includes by now 32 countries mostly in Eastern and Central Europe (ECE). Until the end of 2021, 344 inborn errors of immunity (IEI)-focused meetings were organized by the JP to raise awareness and facilitate the diagnosis and treatment of patients with IEI.ResultsIn this study, meeting profiles and major diagnostic and treatment parameters were studied. JP center leaders reported patients’ data from 30 countries representing a total population of 506 567 565. Two countries reported patients from JP centers (Konya, Turkey and Cairo University, Egypt). Diagnostic criteria were based on the 2020 update of classification by the IUIS Expert Committee on IEI. The number of JP meetings increased from 6 per year in 2004 and 2005 to 44 and 63 in 2020 and 2021, respectively. The cumulative number of meetings per country varied from 1 to 59 in various countries reflecting partly but not entirely the population of the respective countries. Altogether, 24,879 patients were reported giving an average prevalence of 4.9. Most of the patients had predominantly antibody deficiency (46,32%) followed by patients with combined immunodeficiencies (14.3%). The percentages of patients with bone marrow failure and phenocopies of IEI were less than 1 each. The number of patients was remarkably higher that those reported to the ESID Registry in 13 countries. Immunoglobulin (IgG) substitution was provided to 7,572 patients (5,693 intravenously) and 1,480 patients received hematopoietic stem cell therapy (HSCT). Searching for basic diagnostic parameters revealed the availability of immunochemistry and flow cytometry in 27 and 28 countries, respectively, and targeted gene sequencing and new generation sequencing was available in 21 and 18 countries. The number of IEI centers and experts in the field were 260 and 690, respectively. We found high correlation between the number of IEI centers and patients treated with intravenous IgG (IVIG) (correlation coefficient, cc, 0,916) and with those who were treated with HSCT (cc, 0,905). Similar correlation was found when the number of experts was compared with those treated with HSCT. However, the number of patients treated with subcutaneous Ig (SCIG) only slightly correlated with the number of experts (cc, 0,489) and no correlation was found between the number of centers and patients on SCIG (cc, 0,174).Conclusions1) this is the first study describing major diagnostic and treatment parameters of IEI care in countries of the JP; 2) the data suggest that the JP had tremendous impact on the development of IEI care in ECE; 3) our data help to define major future targets of JP activity in various countries; 4) we suggest that the number of IEI centers and IEI experts closely correlate to the most important treatment parameters; 5) we propose that specialist education among medical professionals plays pivotal role in increasing levels of diagnostics and adequate care of this vulnerable and still highly neglected patient population; 6) this study also provides the basis for further analysis of more specific aspects of IEI care including genetic diagnostics, disease specific prevalence, newborn screening and professional collaboration in JP countries.</p

Image_1_Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021.jpeg

IntroductionThe J Project (JP) physician education and clinical research collaboration program was started in 2004 and includes by now 32 countries mostly in Eastern and Central Europe (ECE). Until the end of 2021, 344 inborn errors of immunity (IEI)-focused meetings were organized by the JP to raise awareness and facilitate the diagnosis and treatment of patients with IEI.ResultsIn this study, meeting profiles and major diagnostic and treatment parameters were studied. JP center leaders reported patients’ data from 30 countries representing a total population of 506 567 565. Two countries reported patients from JP centers (Konya, Turkey and Cairo University, Egypt). Diagnostic criteria were based on the 2020 update of classification by the IUIS Expert Committee on IEI. The number of JP meetings increased from 6 per year in 2004 and 2005 to 44 and 63 in 2020 and 2021, respectively. The cumulative number of meetings per country varied from 1 to 59 in various countries reflecting partly but not entirely the population of the respective countries. Altogether, 24,879 patients were reported giving an average prevalence of 4.9. Most of the patients had predominantly antibody deficiency (46,32%) followed by patients with combined immunodeficiencies (14.3%). The percentages of patients with bone marrow failure and phenocopies of IEI were less than 1 each. The number of patients was remarkably higher that those reported to the ESID Registry in 13 countries. Immunoglobulin (IgG) substitution was provided to 7,572 patients (5,693 intravenously) and 1,480 patients received hematopoietic stem cell therapy (HSCT). Searching for basic diagnostic parameters revealed the availability of immunochemistry and flow cytometry in 27 and 28 countries, respectively, and targeted gene sequencing and new generation sequencing was available in 21 and 18 countries. The number of IEI centers and experts in the field were 260 and 690, respectively. We found high correlation between the number of IEI centers and patients treated with intravenous IgG (IVIG) (correlation coefficient, cc, 0,916) and with those who were treated with HSCT (cc, 0,905). Similar correlation was found when the number of experts was compared with those treated with HSCT. However, the number of patients treated with subcutaneous Ig (SCIG) only slightly correlated with the number of experts (cc, 0,489) and no correlation was found between the number of centers and patients on SCIG (cc, 0,174).Conclusions1) this is the first study describing major diagnostic and treatment parameters of IEI care in countries of the JP; 2) the data suggest that the JP had tremendous impact on the development of IEI care in ECE; 3) our data help to define major future targets of JP activity in various countries; 4) we suggest that the number of IEI centers and IEI experts closely correlate to the most important treatment parameters; 5) we propose that specialist education among medical professionals plays pivotal role in increasing levels of diagnostics and adequate care of this vulnerable and still highly neglected patient population; 6) this study also provides the basis for further analysis of more specific aspects of IEI care including genetic diagnostics, disease specific prevalence, newborn screening and professional collaboration in JP countries.</p