Introduction. Coronary heart disease (CHD), leading among the causes of death in adulthood and old age, is an urgent medical and social problem. The pathogenesis of most forms of coronary heart disease is based on stenosing atherosclerosis of the coronary arteries, which develops against the background of dyslipidemia and arterial hypertension and is accompanied by the activation of immunocompetent cells (ICCs) of the vascular wall with the development of a subclinical inflammatory reaction, as well as the production of pro-inflammatory factors such as interleukins, chemokines, growth factors and etc. In turn, ICC activity is determined by the state of their intracellular molecular cascades, which transmit signals into the cell and ensure its reactivity to various external stimuli, such as mitogens, cytokines, pathogen components, etcIt has been shown that the central nervous system plays an important role in the regulation of ICC activity due to the production of neurohumoral molecules, such as melatonin, endorphin, sero-tonin, etc., which ensure the coordination of immune responses and their control by the central nervous system. The aim of this study was to study the relationship between melatonin production and intracellular factors that regulate the pro-inflammatory activi-ty of whole blood mononuclear cells and their metabolism in patients with coronary artery disease. Material and methods. As part of the cohort study, 58 patients of both sexes with coronary artery disease aged 49 to 67 years and 20 practically healthy individuals of both sexes were examined. In accordance with the purpose of the study, the concentration of focal adhesion protein kinase (FAK), 5'AMP-activated protein kinase (AMPK), AKT1 protein kinase, signal transducers and transcription activators (STAT) was determined in nuclear cy-toplasmic lysates of whole blood mononuclear cells: STAT3, STAT5A and STAT6, c-Jun N-terminal protein kinase 1 and 2 isoforms (JNK), mitogen-activated protein kinase p38 (p38), extracellular growth kinase 1 and 2 isoforms (ERK), Janus kinase type 2 (JAK2), nuclear transcription factor NF -kB, caspase-1, cyclooxygenase-2 (COX-2), p70-S6K1 protein kinase, p53, p27, p21 proteins. In addition, the concentration of cyclic adenosine monophos-phate (cAMP) and cyclic guanosine monophosphate (cGMP) was determined in cell supernatants. Melatonin concentration was determined in blood se-rum. The material for the study was venous blood taken from the cubital vein in the morning from 6.00 to 6.15. Results. The analysis showed that in patients with coronary artery disease, in comparison with practically healthy individuals, in MNCs of whole blood, there was an increased level of protein kinases FAK, AKT, JNK, ERK, p70-S6K1, factor STAT6, protein p21, against which there was a decrease in the content of STAT3, STAT5A, JAK2, transcription factor NF-kB and caspase-1. These changes were accompanied by increased levels of cGMP and cAMP. Against this background, a decrease in the content of factors was revealed in the MNC. A high concentration of melatonin in patients with CAD was as-sociated with a decrease in the content of protein kinases AMPK, AKT, Jak2, ERK1, protein p21, caspase-1, and cAMP in MNCs, which was observed against the background of an increase in the level of protein p27 and nuclear factor NF-kB. The results of the correlation analysis indicate a different na-ture of the relationship between the level of melatonin and such factors as caspase-1, protein kinases ERK, JAK2, as well as the transcription factor NF-kB and p21 protein, depending on the characteristics of melatonin production in patients with coronary artery disease. Conclusions. In patients with coronary artery disease, melatonin exhibits a modulating effect on the energy balance of ICCs and their metabolism, helps limit pro-inflammatory activity by limiting the functional activity of MAPK/SAPK signaling pathways in MNCs.

Introduction. The functional state of immunocompetent cells (ICC) plays an important role in the regulation of vasoactive mechanisms in patients with arterial hypertension (AH). In turn, an important role in the regulation of ICC metabolism plays an intracellular molecular sensor, adenosine monophosphate-dependent protein kinase (AMPK), which controls numerous intracellular processes as well as the production of biologically active molecules by cells depending on their energy balance. Aim: to assess the relationship between the content of AMPK protein kinase in MNCs and the state of the MAPK/SAPK signaling pathway as well as the level of vasoactive molecules and immunoregulatory factors in patients with hypertension. Materials and methods. We examined 55 patients of both sexes aged 47–67 years with primary hypertension with average and high cardiovascular risk. The control group consisted of 15 practically healthy individuals with normal blood pressure. The study material was venous blood samples taken from patients on the day of hospitalization. Results. The high level of protein kinase AMPK in the MNCs of patients with hypertension compared to the low level was associated with an increase in the production of prostaglandin E2, NO, and IL-4. An increase of eNOS, p38MAPK protein kinase, and HSP90 content was observed in MNCs. Along with this, there was a decrease in the production of proIL-1, IL-18, the soluble form of CD40L, and the content of protein kinase JNK, p70-S6K1, HSP70, and iNOS in MNCs. Conclusions. The high content of AMPK protein kinase in MNCs helps to reduce their pro-inflammatory activation, stimulates the production of NO, limits the activity of p38MAPK and JNK-dependent signaling pathways, promoting the normalization of the intracellular level of eNOS, HSP90 and the production of proinflammatory cytokines.

BACKGROUND: Among chronic noncommunicable diseases, cardiovascular diseases, particularly coronary heart disease (CHD), are the leading cause of death. The rennin-angiotensin-aldosterone system plays an important role in CHD development and progression; however, its role in the regulation of immunoneuroendocrine interactions requires further analysis. OBJECTIVE: To study the relationship between angiotensin II (AT II) and molecular regulators of the activity of whole blood mononuclear cells (MNCs) in patients with angina pectoris. MATERIALS AND METHODS: This cross-sectional study enrolled 65 patients with exertional angina aged 45–67 years, including 19 apparently healthy individuals. The levels of interleukins (ILs), transforming growth factor-β1 (TGF-β1), prostaglandin E2 (PG E2), serotonin, thyroid-stimulating hormone (TSH), and AT II in the blood serum were determined. In MNCs, the concentrations of protein kinases FAK, JNK, p38, and ERK, signal transducers, and activators of transcription (STAT 3, 5A, and 6) were determined. RESULTS: In patients with coronary artery disease, the production of TGF-β1 increased by 7.2% (p=0.00001), AT II by 136.9% (p=0.0001), serotonin by 129.0% (p=0.00001), IL-18 by 92.5% (p=0.00001), TSH by 51.7% (p=0.0012), ERK protein kinase content by 86.4% (p=0.0001), JNK by 56.8% (p=0.0001), and FAK by 55.3% (p=0.00002). The levels of IL-15 also decreased by 38.1% (p=0.0001), PG E2 by 39.5% (p=0.0001), and STAT3 by 52.5% (p=0.0001). CONCLUSION: The nature of the identified relationships among the analyzed factors allows us to consider AT II as a factor that ensures adaptive coupling of immune and neuroendocrine regulatory mechanisms in patients with coronary artery disease, contributing to a change in the balance between macrophages and T-helper types 1 and 2.

The aim of the investigation was to study the relationship between the content of whole blood in mononuclear leukocytes in pneumonia and in apparently healthy individuals of cytokine signaling suppressor 2 (SOCS2) with the production of cytokines (TNFα, TGFb, IFNα, IFNβ, IFNγ, IL-1β, IL-2, IL-4, IL-5, IL-10, IL-12, IL-17A, RAIL-1, RANTES) and individual factors of the NF-kB and JAK / STAT signaling pathways (NF-kB2, p65, p50, STAT1, STAT3, STAT5B, STAT6). Materials and research methods . The research material was mononuclear cells isolated from venous blood samples, as well as blood plasma of practically healthy individuals and patients with pneumonia. In nuclear-cytoplasmic lysates of mononuclear blood cells, the concentration of the components of the nuclear transcription factor NF-κB, p65, p50, NF-κB2, factors STAT1, STAT3, STAT5B, STAT6, and protein SOCS2, was assessed by enzyme immunoassay. We also determined the concentration of TNFα, IL-1β, TGFb, IFNα, IFNβ, IFNγ, IL-1β, IL-2, IL-4, IL-5, IL-10, IL-17A, RAIL-1, RANTES. The results of this study indicate that the stage of pneumonia convalescence is accompanied by dysregulation of the production of the main proinflammatory cytokines, manifested by a decrease in the level of TNFα, TGFb, RANTES, IL-4, IL-17A, IFNβ, IFNγ and an increase in the production of IL-2 and IFNα. Against this background, a decrease in the phosphorylation of the STAT3 and STAT4 factors was noted, as well as a decrease in the content of p50 and p65 proteins in MNCs. These changes were associated with an increased content of the SOCS2 factor in MNCs. The analysis showed that an increase in the content of SOCS2 in MNCs from the minimum level determined by the concentration corresponding to the 1st quartile of the sample (1.3 ng / ml) to the maximum, determined by the 4th quartile of the sample (1.7 ng / ml) is associated with a decrease in production IL-1β, IL-4, IL-4, IL-5, IL-10, IL-17A, TGFb, RANTES and IFNβ against the background of an increase in the level of INFα, INFγ and IL-2. Changes in cytokine production were accompanied by an increase in STAT5B, STAT4, and NF-kB2 levels and a decrease in STAT3 phosphorylation. a decrease in the content in the cell of the components of the nuclear transcription factor NF-κB, in particular, p50, p65. Conclusion . The peculiarities of the relationship of SOCS2 with the studied factors suggests that its high level helps to limit the production of proinflammatory cytokines, in particular those produced by type 2 T-helpers and Th17, stimulates an increase in ICC sensitivity to IL-2 and stimulation of type 1 T-helpers. These effects are realized due to an increase in the phosphorylation of the STAT5 and STAT4 factors, a decrease in the STAT3 activity, and a change in the ratio of the components p50, p65 and NF-κB2 of the nuclear transcription factor NF-κB in the cell.

Влияние интерлейкина-21 на состояние внутриклеточных сигнальных механизмов в лейкоцитах у реконвалесцентов внебольничной пневмонииБ он дар ь С

Introduction. Antioxidants deficiency with excess of endoperoxides leads to damage of intracellular structures, aggravating the course of most diseases, including cardiovascular pathology. Given the important role of antioxidants in the regulation of physiological processes in cells, the aim of this research was to study the effect of the antioxidant status of blood serum on the expression of pro-inflammatory and vasoactive molecules by blood cells, as well as markers of the metabolic syndrome in the aspect of clarifying possible mechanisms of the pathogenesis of arterial hypertension (AH). Materials and methods. As part of the cohort study, 60 patients of both sexes with hypertension from 45 to 55 years and 15 practically healthy individuals were examined. During the study, we determined in the blood serum the concentrations of insulin, glucagon, apoA1, apoB100, nitric oxide (NO), angiotensin-II (AT-II), E-selectin, P-selectin, intercellular adhesion molecule ICAM1, vascular adhesion molecule VCAM1, VE-cadherin, epinephrine, norepinephrine, endothelin-1, vasopressin, brain natriuretic peptide (BNP), antioxidants (AOS), urokinase-type plasminogen (uPA), plasma endoperoxides (OXY), antiotensin II receptor type 1 (AT-IIR ), plasminogen inhibitor type 1 (PAI1), C-reactive protein (CRP). Results. In patients with AH an increase in the concentration of the studied adhesion molecules was revealed, with significant decrease in the level of VE-cadherin. An increase in the level of vasopressors and decrease NO production was also found. These changes were accompanied by a decrease in the level of apoA1, an increase of the levels of apoB100, insulin, BNP, uPA, PAI1, and CRP. At the same time, an increase in the level of OXY was noted, with a reduced concentration of AOS. It has been established that AOX promote decreasing of the adhesion molecules expression, as well as the production of studied vasopressors, including AT-II, endothelin-1, BNP, insulin, AROB, CRP and stimulates the level of VE-cadherin. Conclusions. AH proceed with activation of vasopressor mechanisms and sympathetic regulation, accompanied by an increase in the adhesive activity of blood cells and endothelium, as well as metabolic disorders and activation of peroxide oxidation of lipids. These changes are associated with AOS deficiency. A correlation between AOS deficiency, laboratory manifestations of a subclinical intravascular inflammatory process, increased aggregation of blood cells, dyslipidemia and dysmetabolic manifestations, as well as dysfunction of the vascular endothelium and myocardium has been established. At the same time, a high level of AOS, in comparison with its low level, is associated with a lower expression of adhesion molecules, a lower level of vasopressor molecules, especially AT-II, a decrease in the level of apoB100 and insulin, as well as a higher expression of VE-cadherin.

Objective is to study the relationship between clinical, laboratory and radiological manifestations of alveolar-bronchiolar dysfunction with the production of interleukin-20 in patients with community-acquired pneumonia. Materials and methods. We examined 60 patients of both sexes aged 18 to 45 years with bacterial community-acquired pneumonia in the first 3 days of the disease, as well as 15 practically healthy individuals. The material of the study was venous blood, in the serum of which the concentration of interleukins (IL) was determined: IL-1β, -2, -4, -8, -10, -17A, -20, -28A, -33, tumor necrosis factor-alpha (TNFα), interferon-gamma (IFNγ), Clara cell protein (CCP), surfactant protein D (SP-D), prostacyclin (PgI2), soluble form of the Fas-receptor (sFas), and its ligand (sFasL), leukotriene D4 (LTD4), thromboxane A2 (TA2). Results. The development of pneumonia is accompanied by an increase in the production of the studied mediators, which is more pronounced in patients with a severe course of the disease. An increase in the concentration of IL-20 from the minimum to the maximum level is accompanied by a significant proportional decrease in the concentration of IL-1β, TNFα, IL-33, TA2, LTD4, Fas, FasL. A high level of IL-20 was associated with a decrease in the concentration of CCP, indicating a weakening of the alveolar-bronchiolar dysfunction and a decrease in the intensity of the inflammatory reaction in the lung tissue. It was also found that a high level of IL-20 was associated with increased production of PgI2, IFNγ, IL-1RA, IL-17A, IL-8, IL-4, IL-28A, IL-10, SLPI. Conclusion. The results of the study indicate the important role of IL-20 in the development of inflammation of the lower respiratory tract, which consists in regulating the activity of the acute phase response, modulating the production of prostacyclin and leukotrienes, determining the limitation of alveolar-bronchiolar dysfunction in patients with pneumonia, as well as the restriction of proapoptogenic influences that determine the decrease in volumes. tissue and cellular damage in such patients.

In the pathogenesis of arterial hypertension (AH), the renin-angiotensin-aldosterone system plays a key role in helping to maintain elevated blood pressure. At the same time, the state of angiotensin-II production (AT II) and the expression level of its receptors on target cells determine the formation of most of the effects underlying the pathogenesis of associated clinical conditions in such patients. Thus, the study of the pathogenesis of AH, namely the study of the role of the AT II axis, the AT II receptor, is an actual scientific and practical task. Aim. Given the important role of type 1 receptors for AT II in the formation of pathological changes in arterial hypertension, the purpose of this study was to study the peculiarities of the effect of their expression on biochemical processes in patients with arterial hypertension. Material and methods. In the course of the clinical study, 60 patients of both sexes with hypertension aged 45 to 55 years old were admitted to the clinic for planned treatment. Depending on the initial level of expression of receptors for AT II (AT1R), determined by the serum concentration of the soluble form of type 1 receptors for AT II, the patients were divided into two subgroups with conditionally low (corresponding to the concentration of the soluble form of the receptor for AT II 0.66 ng/ml) and conditionally high (1.57 ng/ml) expression. The analysis showed that high expression of AT1R is associated with elevated plasma levels of renin by 30.8% (p=0.0005), AT II by 48.1% (p=0.00001), E-selectin by 47.9% (p=0.0001), VCAM-1 by 29.1% (p=0.00001), ICAM-1 by 52.9% (p=0.00001), VE-cadherin by 50.9% (p=0.00001), endothelin-1 by 48.8% (p=0.0005), an ACE inhibitor by 13.6% (p=0.047), and CRP by 74.1% (p=0.00002 ) and endoperoxide by 29.7% (p=0.009). Against this background, there was a decrease in the level of apoA1 by 21.6% (p=0.027), ACE by 20.1% (p=0.1), the level of antioxidants by 22.3% (p=0.00001). The analysis showed that in the group with initially high expression of AT1R, there was an increased blood pressure, the level of which, on average, exceeded the values of patients with low expression of the indicated receptor by 24.5 mm Hg (p=0.011). Against the background of therapy in the group with high expression of AT1R, plasma renin activity decreased by 20.3% (p=0.013), endoperoxide by 8.4% (p=0.038), an ACE inhibitor by 14.6% (p=0.02). At the same time, the level of apoA1 increased by 8.5% (p=0.036), antioxidants by 8.6% (p=0.036), ICAM-1 by 5.3% (p=0.05), VE-cadherin by 2.5% (p=0.07). The level of the remaining factors was not statistically significant. In the subgroup with low expression of the AT II receptor, during treatment, there was a decrease in endoperoxide by 12.8% (p=0.031), an ACE inhibitor by 5.5% (p=0.044) without significant changes in other indicators. Conclusion. In hypertensive patients, higher expression of AT1R is associated with high activation of immune-inflammatory mechanisms, dyslipidemia, an imbalance of the lipid peroxidation system and antioxidant protection, as well as higher renin-angiotensin-aldosterone system activity and increased arterial pressure. On the background of antihypertensive therapy, partial compensation of the identified changes is achieved, including a moderate increase in the level of antioxidants, a decrease in the concentration of endoperoxide, renin activity and an increase in the level of apoA1, while maintaining an increased level of AT II, high expression of receptors to it. These changes indicate the need for further search for effective antihypertensive therapy strategies aimed at limiting the activity of renin-angiotensin-aldosterone system in patients with hypertension.

Ischemic heart disease (IHD) represents significant medical issues, due to high prevalence of the disorder, permanent progressive course, being a leading cause of mortality. With respect to important role of vascular wall inflammation in IHT sipported by the inflammatory macrophages, Т cells and NK cells, one should conclude that their activation markers may play certain role in evaluation of intensity of immune inflammation, and, therefore, they could be used for prediction of health consequences for the patients. Hence, the aim of this study was to assess diagnostic value of soluble co-stimulatory molecules, as well as adhesion molecules in the patients with effort angina and acute coronary syndrome. In the course of controlled clinical study, we have examined 48 patients with IHD, of both genders at the age of 55 to 70 years, as well as 15 healthy persons aged 50 to 70 лет. The main group of IHD patients was divided into 2 subgroups: the 1st subgroup included 25 cases with effort angina, functional class 2-3; the 2nd subgroup consisted of 23 patients admitted to the clinic with acute coronary syndrome with ST elevation on ECG, and GRACE score of 125 to 140 points. The mean age of the observed patients was 68.5±5.0 years old). In the course of the study, serum contents of adhesion molecules (sICAM-1, sVCAM-1, leukocyte (L) and platelet (P) selectins), like as sCD28, sCD40, sCD40L, sCD80, sCD152, sFas, sFasL were measured by means of immunoenzyme technique. The data analysis has shown an increase of sCD152 levels by 77.8% (р = 0.026); sCD40 elevated by 22.2% (р = 0.038), and sVCAM was increased 1.98-fold (р = 0.011) in the effort angina patients. Similarly, we revealed a decrease in L- and P-selectins, respectively, by 51.6% (р = 0.029), and 29.0 % (р = 0.04), as well as decrease of sСD80 by 77.1% (р = 0.026); sCD40L by 30.8% (р = 0.041), sFas by 54.4 (р = 0.038), sFasL на 32.5% (р = 0.043). In acute coronary syndrome, if compared to control group, an increase in sCD152 was found by 61.1% (р = 0.029); sCD40 by 29.6% (р = 0.041); sVCAM-1 was elevated 3.16-fold (р = 0.001), along with decreased concentrations of L-selectin by 71.6% (р = 0.025); P-selectin by на 32.1% (р = 0.043); sCD80 by 76.4% (р = 0.023); sCD28 by 48.1% (р = 0.038); sCD40 by 29.6% (р = 0.046); sCD40L by 28.2% (р = 0.045); sFas by 48.5% (р = 0.041); sFasL by 12.5% (р = 0.05). The patients with acute coronary syndrome, in comparison with effort angina, exhibited a diminished L-selectin expression by 41.3% (р = 0.033); sCD28 by 30.1% (р = 0.036); sFasL by 29.6% (р = 0.041); sFas by 12.5% (р = 0.06), whereas sVCAM-1 levels were increased by 59.0% (р = 0.027). The examined patients with IHD exhibited increased levels of serum sCD152, sCD40 and sVCAM-1, along with decreased expression of L- and P-selectins, sCD80, sCD40L, as well as sFas and sFasL. In presence of acute coronary syndrome, a more pronounced drop in L-selectin, sVCAM-1, sCD28, sFasL and sFas expression like as relative increase of FasL over Fas levels. L-selectin is the most precise marker of acute coronary syndrome, with informativity of 91% and diagnostic threshold of 7.7 ng/mL (95% CI, 78-98%), as well as FasL with informativity of 93% (84-99%) and diagnostic value of 3.1 ng/mL. The detected changes of the markers studied in acute coronary syndrome, in particular, increased FasL levels and diminished CD28 presume a possible pathogenetic relation between development of the IHD exacerbation and imbalance between T-regulatory lymphocytes and Th17 helper cells as well as pronounced apoptosis activation of endotheliocytes in coronary arteria.

Цель - изучение влияния тимозина 1 альфа на состояние внутриклеточных сигнальных механизмов, в частности, на состояние терминальных компонентов MAPK/SAPK и JAK/STAT-сигнальных путей в мононуклеарных лейкоцитах периферической крови у пациентов с артериальной гипертензией. Методика. Методом иммуноферментного анализа в мононуклеарных клетках пациентов определяли уровень фосфорилирования факторов STAT5A, STAT6, ERK1/2, p38, а также содержание ядерного фактора транскрипции NF-κB. Взаимосвязи между исследованными факторами оценивали методом линейного регрессионного анализа. Критериями включения в исследование являлись: возраст 45-55 лет, информированное согласие на участие в исследовании, окружность талии более 80 см у женщин и более 94 см у мужчин, артериальная гипертензия (АД ≥ 140/90 мм рт. ст.), а также уровень С-реактивного белка в сыворотке крови, определяемого высокочувствительным методом, в пределах ≥ 2,5 и <5,0 мг/дл), отсутствие в течение предшествующих 3 мес госпитализации, острых бактериальных и вирусных инфекций. Критериями исключения из исследования являлись обострения воспалительных заболеваний внутренних органов, декомпенсация углеводного обмена, отказ от участия в исследовании. Результаты. Повышение сывороточной концентрации Тα1 ассоциируется с активацией в мононуклеарных клетках факторов STAT5A, STAT6, а также протеинкиназ ERK и p38 и ядерного фактора транскрипции NF-κB. Высокая концентрация Тα1 ассоциировалась с повышением активности ядерного фактора транскрипции NF-κB, STAT6 и ERK. На этом фоне повышенный уровень продукции Тα1 сопровождался усилением активности факторов STAT6, STAT5A, а также протеинкиназ ERK и р38, не влияя при этом на активность NF-κB. Заключение. В физиологических концентрациях (0,9-2,85 пг/мл) Тα1 является иммуномодулятором, регулирующим активность MAPK/SAPK и JAK/STAT сигнальных путей через изменение реактивности иммунокомпетентных клеток к сигналам цитокинов, факторов роста и гормонам, в том числе, лептину, инсулину, соматотропину, не обладая при этом прямым активирующим влиянием на продукцию цитокинов. Полученные результаты позволяют рассматривать Тα1 в качестве иммунотропного регулятора, потенциальные эффекты которого (иммуномодулирующие, либо противовоспалительные) определяются его концентрацией в сыворотке, способствуя либо ограничению, либо прогрессированию иммунометаболических нарушений, лежащих в основе патогенеза атеросклероза и артериальной гипертонии.The aim of this work was to study effects of thymosin 1 alpha on intracellular signaling mechanisms, specifically, the state of terminal components of MAPK/SAPK and JAK/STAT signaling pathways in peripheral blood mononuclear leukocytes of patients with arterial hypertension. Methods. The level of phosphorylation of factors STAT5A, STAT6, ERK1/2, and p38 and the content of the nuclear transcription factor NF-κB were measured using the enzyme immunoassay. Relationship between the studied factors was assessed by the linear regression analysis. Results. The increase in serum Tα1 concentration was associated with activation of STAT5A and STAT6 as well as ERK and p38 protein kinases and the nuclear transcription factor NF-κB in mononuclear cells. A high concentration of Tα1 was associated with increased activity of the nuclear transcription factor NF-κB, STAT6, and ERK. In this process, the increased production of Tα1 was associated with increased activity of STAT6 and STAT5A as well as ERK and p38 protein kinases but with unchanged activity of NF-κB. Conclusion. At physiological concentrations (0.9-2.85 pg/ml), Tα1 is an important immunomodulator that regulates activities of the MAPK SAPK and JAK/STAT signaling pathways, thereby changing responses of immunocompetent cells to signals of cytokines, growth factors, and hormones, including leptin, insulin, and somatotropin without a direct activating effect on cytokine production by immunocompetent cells. The results of the study suggested that Tα1 is an immunomodulator potentially capable of correcting respective immunometabolic disorders in patients with hypertension.

Ischemic heart disease (IHD) represents significant medical issues, due to high prevalence of the disorder, permanent progressive course, being a leading cause of mortality. With respect to important role of vascular wall inflammation in IHT sipported by the inflammatory macrophages, Т cells and NK cells, one should conclude that their activation markers may play certain role in evaluation of intensity of immune inflammation, and, therefore, they could be used for prediction of health consequences for the patients. Hence, the aim of this study was to assess diagnostic value of soluble co-stimulatory molecules, as well as adhesion molecules in the patients with effort angina and acute coronary syndrome. In the course of controlled clinical study, we have examined 48 patients with IHD, of both genders at the age of 55 to 70 years, as well as 15 healthy persons aged 50 to 70 лет. The main group of IHD patients was divided into 2 subgroups: the 1st subgroup included 25 cases with effort angina, functional class 2-3; the 2nd subgroup consisted of 23 patients admitted to the clinic with acute coronary syndrome with ST elevation on ECG, and GRACE score of 125 to 140 points. The mean age of the observed patients was 68.5±5.0 years old). In the course of the study, serum contents of adhesion molecules (sICAM-1, sVCAM-1, leukocyte (L) and platelet (P) selectins), like as sCD28, sCD40, sCD40L, sCD80, sCD152, sFas, sFasL were measured by means of immunoenzyme technique. The data analysis has shown an increase of sCD152 levels by 77.8% (р = 0.026); sCD40 elevated by 22.2% (р = 0.038), and sVCAM was increased 1.98-fold (р = 0.011) in the effort angina patients. Similarly, we revealed a decrease in L- and P-selectins, respectively, by 51.6% (р = 0.029), and 29.0 % (р = 0.04), as well as decrease of sСD80 by 77.1% (р = 0.026); sCD40L by 30.8% (р = 0.041), sFas by 54.4 (р = 0.038), sFasL на 32.5% (р = 0.043). In acute coronary syndrome, if compared to control group, an increase in sCD152 was found by 61.1% (р = 0.029); sCD40 by 29.6% (р = 0.041); sVCAM-1 was elevated 3.16-fold (р = 0.001), along with decreased concentrations of L-selectin by 71.6% (р = 0.025); P-selectin by на 32.1% (р = 0.043); sCD80 by 76.4% (р = 0.023); sCD28 by 48.1% (р = 0.038); sCD40 by 29.6% (р = 0.046); sCD40L by 28.2% (р = 0.045); sFas by 48.5% (р = 0.041); sFasL by 12.5% (р = 0.05). The patients with acute coronary syndrome, in comparison with effort angina, exhibited a diminished L-selectin expression by 41.3% (р = 0.033); sCD28 by 30.1% (р = 0.036); sFasL by 29.6% (р = 0.041); sFas by 12.5% (р = 0.06), whereas sVCAM-1 levels were increased by 59.0% (р = 0.027). The examined patients with IHD exhibited increased levels of serum sCD152, sCD40 and sVCAM-1, along with decreased expression of L- and P-selectins, sCD80, sCD40L, as well as sFas and sFasL. In presence of acute coronary syndrome, a more pronounced drop in L-selectin, sVCAM-1, sCD28, sFasL and sFas expression like as relative increase of FasL over Fas levels. L-selectin is the most precise marker of acute coronary syndrome, with informativity of 91% and diagnostic threshold of 7.7 ng/mL (95% CI, 78-98%), as well as FasL with informativity of 93% (84-99%) and diagnostic value of 3.1 ng/mL. The detected changes of the markers studied in acute coronary syndrome, in particular, increased FasL levels and diminished CD28 presume a possible pathogenetic relation between development of the IHD exacerbation and imbalance between T-regulatory lymphocytes and Th17 helper cells as well as pronounced apoptosis activation of endotheliocytes in coronary arteria.

The key role in the antiviral and antimicrobial defense of the body is played by the RIG-I and NF-kB signaling pathways. The RIG-I signaling pathway activates interferon-regulated factors IRF3 and IRF7, and the central component of the NF-kB signaling pathway, the nuclear transcription factor NF-kB, determines the production of endogenous antimicrobial peptides and interferons by cells. One of the key regulators of the RIG-I signaling pathway is the mitochondrial protein MAVS, which integrates signals from receptors that recognize pathogenicity patterns. The influence of various factors, such as bacterial toxins, free radicals, reactive oxygen species, leads to MAVS dysfunction, impaired antiviral resistance and the progression of viral infection. However, despite the important role of the proteins of the RIG-I-pathway and the components of the NF-KB-signaling pathway in ensuring the body's resistance to infections and sanogenesis, their significance in the postclinical phase has not been fully studied. The aim of the study was to evaluate the content of the components of RIG-I and NF-kB signaling pathways in mononuclear cells of whole blood of healthy individuals and pneumonia convalescents after exposure to a complex mitogen. The enzyme-linked immunosorbent assay determined the content of components of the NF-kB signaling pathway (p50, p65, c-Rel, RelB, NF-kB2), protein kinases of the NF-kB nuclear transcription factor inhibitor (IkB), and RIG-I- proteins in mononuclear cells of whole blood the signal path (TAK1, TBK1, TRIM25, TMEM173, RNF125, IRF3, IRF7, MAVS), RIG-I-dependent helicase (LGP2), the level of phosphorylation of protein kinase p38 and IkB, as well as the production of whole blood cells IL-4, IL-, were evaluated 12, RANTES, cathelicidin and interferons (IFN-p and IFNa). It was established that in the subclinical phase of community-acquired bacterial pneumonia in mononuclear cells of whole blood after stimulation with a complex mitogen containing lipopolysaccharide, the content of RelB, MaVS, DHX58, and IRF7 decreased compared to practically healthy individuals, p38 protein kinase dephosphorylation was noted. In contrast, the concentrations of IKKa, IKKp, the level of phosphorylation of kBa, the protein content of TRIM25, TMEM173, OTuD5, RNF125 and tBk1 were increased. These changes were accompanied by a statistically significant decrease in the production of IL-4, IL-12, RANTES, cathelicidin and IFN-p against the background of an increase in the level of IFNa. The effect on the mononuclear cells of whole blood of a complex mitogen led to a change in the ratio of the components of the signaling pathways that determine the antibacterial and antiviral defense of the body. In patients with pneumonia, against the background of mitogenic stimulation, the production of cathelicidin,

The study discusses the relationship of thiol concentrations in intercellular fluid with the level of peripheral blood mononuclear cells (MNCs) in convalescents with community-acquired pneumonia (CAP) components MAPK/SAPK and JAK/STAT-signaling pathways, nuclear transcription factor NF-KB. The content and level of phosphorylation of JAK2 protein kinase, signal transducers and transcription activators STAT3, STAT5A, STAT6, NFKB nuclear transcription factor inhibitor (IkBa), stress-activated protein kinases JNK, ERK, the level of the p50 subunit of nuclear transcription factor NF-κB were determined by enzyme immunoassay in MNC. The results of the study indicate that the stage of reconvalescence of CAP is characterized by a lack of antioxidant protection, manifested by a decrease in the concentration of thiol compounds in the supernatant against which there is a decrease in the level of phosphorylation of protein kinase JAK2, factors STAT3, STAT5, STAT6, JNK, which is also associated with an increase in the level of phosphorylation of protein kinase ERK. The analysis showed that the thiol status is characterized by a positive relationship with the activity of STAT5A, JNK, p50. The level of thiols and ERK, as well as STAT3, was characterized by a negative relationship. Thus, the increase in the level of thiols contributes to the increase in the activity of the transcription factor STAT5A and decrease-STAT3 with a corresponding change in cell reactivity with respect to specific cytokines, as well as a specific effect on the differentiation of individual populations of immunocompetent cells.

The study discusses the relationship between the content of NF-KB and cytokine signaling suppressor 7 (SOCS7) in mononuclear peripheral blood cells (MNC) phosphorylated form of nuclear transcription factor inhibitor (NF-KB) and the production of MNC cytokines (TNF, IFN, IL-1β, IL-4, IL-10, IL-12) determining the state of congenital and adaptive immune response.The content and level of phosphorylation of the nuclear transcription factor NF-KB (Ikba) inhibitor and the SOCS7 protein concentration were determined by enzyme immunoassay in MNC. In addition, the concentration of TNF, IFN, IL-1β, IL-4, IL-10, IL-12 was determined in cellular supernatants. The interrelations between the studied factors were evaluated by the method of linear regression analysis.The results of the study indicate that the stage of recovery of community-acquired pneumonia is accompanied by a decrease in the level of IL-1, TNF and IL-4 and an increase in the production of Information. Also in the stage of convalescence there is a decrease in phosphorylation of Ikba and an increase in the concentration of SOCS7 in the OLS. The analysis revealed a significant effect on the level of phosphorylation of Ikba content in the cell SOCS7. Thus, a strong negative relationship between SOCS7 and phosphorylation of Ikba can be mediated by inhibition under its influence of STAT3/5 and MARK / SAPK-dependent cytokine production mechanisms, which allows to consider this factor as a therapeutic target for limiting excessive immunosuppression in pneumonia.

Background. Hypertension (HTN) associated with metabolic syndrome is an important issue of preventive medicine. The modulation of biochemical activity of immune cells might be a solution, as immune cells play crucial role in atherosclerosis progression and vascular inflammation. Among factors regulating molecular processes, e. g. activity of signaling pathways and cell proinflammatory sensitivity, low-intensity microwave (1GHz) therapy attracts attention. The purpose of this study was the assessment of the low-intensity microwave therapy in the management of hypertensive patientsin order to influence the biochemical components of metabolic syndrome. Design and methods. In a randomized double-blinded controlled study, we included 60 patients with hypertension (HTN) aged 45–55 years old. The patients of the comparison group (n = 30) received medication therapy according to the current guidelines, while patients from the study group (n = 30) additionally underwent physiotherapy with the use of microwave therapy (frequency 1 GHz, device “Aquaton”). Control group included 15 otherwise healthy subjects. Serum insulin, glucagon, apoA1 and apoB100 were measured by immuneenzyme assay. Hugh-sensitive C‑reactive potein (hsCRP) was assessed to evaluate the inflammatory response. Results. HTN patients compared to the healthy group demonstrated higher levels of insulin by 23,0% (p = 0,051), apoВ100 by 35,1% (p = 0,001), hsCRP by 43,4% (p = 0,05), and lower levels of glucagon by 5,0% (p = 0,8) and apoА1 by 32,8% (p = 0,000002). Patients of the comparison group who received only medication therapy showed an increase in glucagon level by 2,2% (p = 0,018), apoА1 by 0,96% (p = 0,063), insulin by 3,5% (p = 0,11) with the decrease in apoВ100 by 2,7% (p = 0,083) and hCRP by 2,4% (p = 0,18). Those who additionally underwent the low-intensity microwave therapy showed an increase in glucagon by 1,3% (p = 0,028), apoА1 by 11,1% (p = 0,028), while insulin level decreased by 5,1% (p = 0,06), apoВ100 by 5,4% (p = 0,015) and hsCRP by 5,3% (p = 0,05). There was no significant impact of microwave therapy on the central hemodynamics. Conclusions. The patients who received low-intensity microwave therapy demonstrate higher apoА1 level and lower levels of insulin, apoВ100 and hsCRP. The number of patients to be treated for the planned effect achievement was the following: for the change in the levels of apoА1 — 2,0 patients, change in insulin level — 3,7, change in апоВ100 level — 5,5, change in hsCRP — 5,8. Therefore, low-intensity microwave therapy positively affects metabolism in HTN patients without significant impact in central hemodynamics.

We evaluated the levels of protein p53, retinoblastoma protein (RB), β-catenin, SMAD2, protein kinases AKT and focal adhesion kinase (FAK), and transcription factor CREB using ELISA in mononuclear leukocytes of patients with community-acquired pneumonia on days 15–17 of the disease. The research results showed that the subclinical immune-inflammatory process was characterized by a higher content of β-catenin by 19.8%, CREB by 23.3%, RB protein by 14.7%, increased phosphorylation level of protein kinase FAK by 19.8%, АKТ1 at serine-473 by 65.6%, and RB by 13.7%. In the cells, there was a decrease in p53 of 15.7%, SMAD2 of 16.9%, and protein kinase АKТ1 of 31.2%. Three hours after 1-GHz microwave irradiation, MNCs displayed a statistically significant increase in their content of the p53 protein of 20.0‰, RB of 9.35‰, β-catenin of 10.9‰, protein kinase FAK of 10.0‰, and CREB of 8.55‰. A day after a single irradiation of the cultures of whole blood cells, in irradiated cells compared to nonirradiated control, we observed a statistically significant increase in the content of p53 of 24.2‰, β-catenin of 15.1‰, SMAD2 of 20.4‰, RB of 9.8‰, as well as a reduction of the initially elevated levels of protein kinase AKT1 of 25.1‰, its phosphorylated form at serine-473 of 16.5‰, and a decrease in the phosphorylated form of the transcription factor CREB at serine-133 of 4.1‰. The research results indicate that a low-intensity microwave frequency of 1 GHz can be considered as a factor in molecular immune rehabilitation in conditions of community-acquired pneumonia.