Regulation of kisspeptin-54 activity of indolamine-2,3-dioxygenase and apoptosis of peripheral blood lymphocytes

Pregnancy is a phenomenon of natural semi-allogeneic transplantation, since the fetus is half alien due to the expression of paternal antigens. It was found that the hypothalamic hormone kisspeptin during pregnancy is produced by the syncytiotrophoblast of the placenta and participates in the formation of a new specific hormonal background. Several forms of the hormone circulate in the blood of pregnant women: kisspeptin-10, kisspeptin-14 and kisspeptin-54 (according to the number of amino acid residues in the hormone molecule), but the main active form is kisspeptin-54. The main mechanism for the formation of immune tolerance during pregnancy is the induction of the expression of the enzyme indolamine-2,3- dioxygenase (IDO) by antigen-presenting cells of peripheral blood, resulting in the catalysis of tryptophan (Trp) to kynurenins (KYN) blocking the activation and causing apoptosis of cytotoxic CD8+T lymphocytes in the zone of contact of maternal immune cells with placental-fetal complex antigens. In addition, during pregnancy, an important role is assigned to the process of apoptosis, since activated cells can be potentially dangerous for the developing fetus. Immunocompetent blood cells express a specific membrane receptor of kisspeptin (KISS-1R). Since kisspeptin-54 enters the systemic circulation only during pregnancy, the hormone has an effect on immune cells only during this period.The aim of this work was to evaluate the effect of kisspeptin-54 in concentrations comparable to its levelduring physiological pregnancy on IDO activity and apoptosis of peripheral blood lymphocytes.Peripheral blood mononuclear cells (PBMC) obtained from 10 healthy non-pregnant women of reproductive age (from 23 to 32 years) were used as the object of the study. Lymphocyte apoptosis was assessed in PBMC suspension by staining with annexin-V and propidium iodide. The determination of the number of cells in the early and late stages of apoptosis was carried out in the isolated gate of lymphocytes. IDO activity in PBMC was determined spectrophotometrically by changes in the concentration of KYN, the first stable metabolite of the Trp decay pathway.It was found that kisspeptin-54 at a concentration of 4.6 pM corresponding to the second trimester of pregnancy significantly enhances the activity of IDO, increases the number of cells in the early and late stages of apoptosis. Thus, kisspeptin-54 is an important mechanism for controlling these processes during pregnancy, aimed at protecting the semi-allogeneic fetus from adverse immune reactions of the mother and the favorable development of pregnancy

РАЗВИТИЕ КООРДИНАЦИОННЫХ СПОСОБНОСТЕЙ У ДОШКОЛЬНИКОВ 6–7 ЛЕТ НА ФИЗКУЛЬТУРНО-ОЗДОРОВИТЕЛЬНЫХ ЗАНЯТИЯХ С ИСПОЛЬЗОВАНИЕМ ВИБРАЦИОННЫХ ТРЕНАЖЁРОВ

The article proposes methodology of sports and recreational activities with the use of training systems “Tisa” among preschoolers. A comprehensive assessment of the level of development of coordination abilities in children aged 6–7 years is presented.В статье рассмотрена методика проведения физкультурно-оздоровительных занятий использованием тренажёрной системы «Тиса» у дошкольников. Представлена комплексная оценка уровня развития координационных способностей у детей 6–7 лет

The Effect of a Hydrocarbon Fragment in a Molecule on Depressant Activity of Resins

The effect of resins on solidification of paraffin solutions has been studied by vibration viscosimetry. This technique was used for studies of coagulating liquids, since the sample structure is less affected by mechanical oscillations compared to traditional rotary and linear shears. The installation developed for studies of thermo-induced phase transitions and the measurement procedure are described. The viscosimetric technique allows continuous registration of rheological properties with changing temperature, and has proved to be quite sensitive to small amounts of resins in model paraffin solutions. Measurements have been performed for resins extracted from methane-naphtene crudes of various West Siberia oil deposits. Dependencies of viscosity on temperature have been measured and are presented below for various concentrations of resins (up to 3 %) in paraffin solutions. It is demonstrated that increase of resin concentration results in a shift of the inflexion point on the viscosity-temperature curve to lower temperatures. A positive correlation has been found between depressant activity and average dimensions of aliphatic fragments of the resin molecul

Rational mucolytic therapy with ambroxol: controversial and indisputable. A review

Many years of experience in the use of ambroxol is based on its ability to regulate the basic mechanisms of physiological production and transport of bronchial mucus. The main indication for ambroxol is the mucolytic therapy of acute and chronic bronchopulmonary diseases associated with hypersecretion and impaired mucus transport. Ambroxol has a number of the following properties: high secretolytic activity (promotes mucus clearance, facilitates expectoration of sputum, reduces productive cough); anti-inflammatory and antioxidant activity; local analgesic (anesthetic) effect through the blockade of sodium channels of cell membranes. The effect of anesthesia of the mucous membranes is attributed to the new pharmacological action of ambroxol, useful in the treatment of acute respiratory tract infections. The efficacy and safety of ambroxol in clinical practice has been confirmed by half a century of experience in its administration. The purpose of this publication was an up-to-date assessment of the controversial and indisputable chemical, pharmacological, clinical data on the properties of ambroxol in the concept of modern recovery mucolytic therapy that can improve the therapy and prognosis of patients with tracheobronchial secretion hypersecretion, impaired mucociliary clearance and unproductive cough

The multifaceted erdostein: facts on the desk. A review

Erdostein is a mucoactive agent belonging to the group of thiol drugs with antioxidant, anti-inflammatory and antibacterial activity against a number of major respiratory pathogens. After transformation in the liver, erdostein is metabolized to a compound with an open ring M1 (MET-1) having unique properties. In the RESTORE study (2022), it was confirmed that erdostein significantly reduces the risks of severe exacerbations in patients with chronic obstructive pulmonary disease (COPD), reduces their duration, and reduces the number of hospitalizations with acute respiratory failure (ARF). The unique preventive properties of erdostein do not depend on the administration of inhaled (ICS) or systemic (SCS) corticosteroids to COPD patients, as well as on the level of eosinophilia in the blood. The results obtained contrast with the available therapy strategy, where thiol mucolytics are indicated in patients who do not use ICS-therapy and/or SCS-therapy. Moreover, this confirms the assumption about the use of erdostein in COPD patients as a drug for the phased withdrawal of ICS-therapy

Galectin-9 influences the Tim-3 molecule expression in natural killer different subpopulations

Galectin-9 is a b-galactoside binding lectin with expressed immunoregulatory activity. During pregnancy galectin-9 is produced by trophoblast cells and regulates the function of natural killer (NK) cells at the maternal-fetal interface via binding to Tim-3 (T-cell Ig and mucin domain-containing protein 3) molecules. Natural killer (NK) lymphocytes belong to the innate lymphoid cells, which have a cytotoxic effect on target cells and are capable of producing a large number of regulatory factors (cytokines, chemokines). Decidual NK have a tolerant phenotype and play a leading role in the regulation of invasive trophoblast growth and provide peripheral immune tolerance in the area of uteroplacental contact. Peripheral NK cells express Tim-3 molecules. Galectin-9 concentration is increased in peripheral blood during physiologic pregnancy. At pregnancy phenotype and functions of peripheral NK cells are changed to maintain the maternal–fetal immune tolerance. Peripheral NK cells migrate to the maternal-fetal interface and are transformed into a decidual NK-like phenotype cells. Galectin-9 concentration is decreased in women with a  complicated  pregnancy and miscarriage. However the galectin-9 effects on different NK cell subpopulations of peripheral blood are not investigated. Therefore, we studied the galectin-9 influence on phenotype transformation and Tim-3 expression of NK cells isolated from peripheral blood of healthy non-pregnant fertile women. CD56+NK cells were obtained by immunomagnetic separation and cultivated in vitro during 72 hours with cytokines (IL-2 and IL-15). Galectin-9 (5 ng/mL) and anti-Tim-3 (10 mg) antibodies were added to the NK cultures. Galectin-9 concentration is corresponded to its level during first trimester of physiologic pregnancy. The number of regulatory NK (CD16-CD56bright), cytotoxic NK (CD16+CD56dim/-) cells and Tim-3 expression on different NK subpopulations were assessed by flow cytometry. It was found that Tim-3 was expressed on all subpopulations of peripheral blood NK cells (CD16-CD56brightNK, CD16+CD56dimNK, CD16+CD56-NK). Incubation with galectin-9 increased the expression of Tim-3 on regulatory CD16-CD56brightNK cells and did not change on cytotoxic CD16+CD56dim/-NK cells. Galectin-9 reduced the percentage of cytotoxic CD16+CD56dimNK in culture, but did not influence the number of regulatory CD16-CD56bright NK and cytotoxic CD16+CD56-NK cells. Thus, galectin-9 regulates Tim-3 molecule expression and NK cell subpopulation distributions in vitro culture

О фотокаталитической активности систем типа диоксид титана/(Fe(II, III)) в водных суспензиях

. The photocatalytic activity of three systems, promising for chemical water purification technologies, was experimentally compared, based on a combination of titanium dioxide/(Fe(II, III)), applying to the model oxidation reaction of methylorange organic dye in an aqueous medium. Herewith the cases of photocatalytic systems were investigated, which are based on: a) titania hydrosol obtained by hydrolysis of titanium isobutylate; b) a similar hydrosol with addition of Fe(III) ions; c) suspension of ilmenite powder based on FeTiO3. As a result of the investigation, the increase of the rate of destruction of methylorange by more than two times was found in the system with the introduction of a small amount of iron ions into initial suspension of the TiO2 hydrosol (at the obtaining a medium with the Fe3+ concentration up to 3.7 × 10–5 M). In the photocatalytic system, based on the suspension of pretreated (with suphation and calcination) ilmenite powder, enough high photocatalytic activity (the degree of methylorange decomposition up to 77 %) was measured but at a higher exposure than for the case of systems based on the TiO2 hydrosol. For the photocatalytic systems of the type being investigated, a possible mechanism of increasing their oxidative activity was briefly considered, which requires an additional physico-chemical analysis.Экспериментальным методом проведено сравнение фотокаталитической активности трех систем, перспективных для технологий химической водоочистки, на основе комбинации диоксид титана/(Fe(II, III)) применительно к модельной реакции окисления органического красителя метилоранжа в водной среде. Изучены фотокаталитические системы на основе: гидрозоля диоксида титана, полученного гидролизом изобутилата титана; аналогичного гидрозоля с добавлением ионов Fe(III); водной суспензии порошка природного титансодержащего минерала ильменита (основной компонент FeTiO3). В результате исследования в системе с введением в исходную суспензию гидрозоля TiO2 небольшого количества ионов железа (с получением среды с концентрацией Fe3+ до 3,7 × 10–5 М) обнаружено увеличение скорости деструкции метилоранжа более чем в два раза. В фотокаталитической системе на основе суспензии предварительно обработанного (сульфатированием и прокаливанием) порошка ильменита зарегистрирована достаточно высокая фотокаталитическая активность (степень разложения метилоранжа до 77 %), но при большей экспозиции, чем в случае систем на основе гидрозоля TiO2. Для фотокаталитических систем изученного типа рассмотрен возможный механизм увеличения их окислительной активности, требующий дополнительного физико-химического исследования

The Role of Pollution in the Formation of Tropospheric Ozone

При рассмотрении безопасности экосистемы планеты в учебных программах высшей школы достаточно много внимания уделяется роли стратосферного озонового слоя в защите всего живого от ультрафиолетового излучения. Однако вопрос образования тропосферного озона и его взаимодействия с присутствующими в приземном пространстве загрязнителями изучен недостаточно. В статье рассмотрены пути образования, трансформации тропосферного озона и его участия в формировании фотохимического смога.When considering the safety of the planet's ecosystem in the curricula of higher education, a lot of attention is paid to the role of the stratospheric ozone layer in protecting all living things from ultraviolet radiation. However, the issue of tropospheric ozone formation and its interaction with pollutants present in the surface space has not been sufficiently studied. The article considers the ways of formation, transformation of tropospheric ozone and its participation in the formation of photochemical smog

Клиническое значение лептина при системной красной волчанке

Objective: to study the frequency of hyperleptinemia in patients with systemic lupus erythematosus (SLE), its relationship with clinical and laboratory manifestations of the disease, drug therapy, and other metabolic disorders.Patients and methods. The cross-sectional study included 46 women with a definite diagnosis of SLE (median age 40 [31; 48] years) and disease duration 3.0 [0.9; 9.0] years. Glucocorticoids (GC) were received by 38 (83%) patients, hydroxychloroquine – by 35 (76%), immunosuppressants – by 10 (22%), biologic disease-modifying antirheumatic drugs – by 5 (11%). In all patients, fasting levels of glucose, leptin, apoliproprotein B (ApoB) and immunoreactive insulin were determined, and homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. Concentration of leptin ≥11.1 ng/ml, ApoB – >1.6 mg/ml were considered an elevated level. HOMA-IR index ≥2.77 corresponded to the presence of insulin resistance (IR).Results and discussion. Hyperleptinemia was found in 34 (74%) patients with SLE, an increased level of ApoB – in 19 (41%), IR – in 10 (22%). In patients with hyperleptinemia, serositis, positivity for anti-double-stranded DNA (aDNA) and hypocomplementemia were less common, overweight and obesity were more frequent, the SLEDAI-2K index was lower, the aDNA level was lower, and the concentration of the C3 component of complement, insulin, HOMA-IR index, body mass index (BMI) and disease duration were higher (p<0.05 for all cases). BMI <25 kg / m2 had 26 (57%) women, 14 (54%) of whom had hyperleptinemia. In patients with BMI <25 kg / m2, we found a relationship between leptin concentration and disease duration (r=0.4, p=0.04), SLE activity according to SLEDAI-2K (r=-0.6, p=0.003), levels of aDNA (r=-0.6, p<0.001), C3 component of complement (r=0.5, p=0.01), maximum (r=0.7, p<0.001) and supporting (r=0,5, p=0.023) GC doses.In patients with BMI ≥25 kg/m2 (n=20), no such relationship was observed.Conclusion. Hyperleptinemia was found in the majority of women with SLE; elevated levels of ApoB and IR were much less common. Patients with hyperleptinemia are characterized by a longer duration and less activity of the disease, as well as the presence of overweight and obesity and an increase in the HOMA-IR index. In SLE patients with normal body weight, the concentration of leptin increased along with GC dose elevation.Цель исследования – изучение частоты гиперлептинемии у пациентов с системной красной волчанкой (СКВ), ее взаимосвязи с клинико-лабораторными проявлениями заболевания, лекарственной терапией, а также другими метаболическими нарушениями.Пациенты и методы. В поперечное исследование включено 46 женщин с достоверным диагнозом СКВ (медиана возраста 40 [31; 48] лет) и длительностью заболевания 3,0 [0,9; 9,0] года. Глюкокортикоиды (ГК) получали 38 (83%) больных, гидроксихлорохин – 35 (76%), иммуносупрессанты – 10 (22%), генно-инженерные биологические препараты – 5 (11%). У всех больных определены натощак уровни глюкозы, лептина, аполипропротеина В (АпоВ) и иммунореактивного инсулина, рассчитан индекс оценки гомеостатической модели резистентности к инсулину (HOMA-IR). Повышенной считали концентрацию лептина ≥11,1 нг/мл, АпоВ – >1,6 мг/мл.Индекс HOMA-IR ≥2,77 соответствовал наличию инсулинорезистентности (ИР).Результаты и обсуждение. Гиперлептинемия обнаружена у 34 (74%) больных СКВ, повышенный уровень АпоВ – у 19 (41%), ИР – у 10 (22%). При гиперлептинемии реже встречались серозит, позитивность по антителам к двуспиральной ДНК (аДНК) и гипокомплементемия, чаще – избыточная масса тела и ожирение, были ниже индекс SLEDAI-2K, уровень аДНК, выше – концентрация С3-компонента комплемента, инсулина, индекс HOMA-IR, индекс массы тела (ИМТ) и длительность заболевания (р<0,05 для всех случаев). ИМТ<25 кг/м2 имели 26 (57%) женщин, у 14 (54%) из которых обнаружена гиперлептинемия. У пациенток с ИМТ <25 кг/м2 выявлена взаимосвязь концентрации лептина с длительностью заболевания (r=0,4, p=0,04), активностью СКВ по SLEDAI-2K (r=-0,6, p=0,003), уровнем аДНК (r=-0,6, p<0,001), С3-компонента комплемента (r=0,5, p=0,01), максимальной (r=0,7, p<0,001) и поддерживающей (r=0,5, p=0,023) дозами ГК. У больных с ИМТ ≥25 кг/м2 (n=20) подобной взаимосвязи не отмечено.Заключение. Гиперлептинемия выявлена у большинства женщин с СКВ, повышенный уровень АпоВ и ИР встречались гораздо реже.Для пациенток с гиперлептинемией характерны большая длительность и меньшая активность заболевания, а также наличие избыточной массы тела и ожирения, увеличение индекса HOMA-IR. У больных СКВ с нормальной массой тела концентрация лептина нарастала по мере увеличения дозы ГК