BCG-INDUCED PRO-INFLAMMATORY PHENOTYPE OF MESENCHYMAL STEM CELLS: EFFECT OF IMMUNE MODULATORS

In case of mycobacterial infection the granulomatous infiltration foci contain the significant amount of mesenchymal stem cells (MSC), which functional phenotype and respective function in anti-tuberculosis immune defense remain unknown.Goal of the study: to characterize the MSC phenotype, formed by their interaction with BCG of M. bovis and to evaluate the changes in this phenotype caused by the action of inhibitors and stimulants of immune regulatory action.Materials and methods: MSC retrieved from bone marrow of mice were cultured with the presence and absence of BCG of M. bovis and/or poludanum TLR3 agonist; and the effect of two latter on the production of pro- and anti-inflammatory cytokines was evaluated by enzyme multiplied immunoassay. Flow cytometry and radioactive testing were used to evaluate the impact of cultured BCG fluid and poludanum-conditioned MSC on the proliferative and apoptotic activity of splenocytes. The inhibitors of indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2 (COG-2) or NO synthase were added to certain cultures alone with BCG and poludanum, and the contributions of IDO, COG-2 and NO to BCG and poludanum-induced response were assessed.Results. Pro-inflammatory polarization of MSC under the action of BCG and poludanum was demonstrated. Pro-inflammatory MSC phenotype correlated to their anti-apoptogenic and growth-stimulating actions on the splenocytes. It was demonstrated that IDO and NO restrained BCG-induced polarization and conversely COG-2 promoted BCG-induced pro-inflammatory polarization of MSC.Conclusions. 1. MSC actively participate in the formation of immunologic anti-mycobacterial resistance. 2. Targeted regulation of IDO and NO production can be feasibly applied for formation of anti-tuberculous vaccinal immunity and control mycobacterial infection

Functional System of Creative Thinking

In the article on the basis of electroencephalographic and psychological indicators the concept the mechanism of creative thinking was formulated. Creative thinking as a process involves operating images and searching similar tasks in memory (mental representations). High result in creative thinking is possible under the condition of high decision-making and low level of critical-controlling program

Relationship Between The Rhythmic Activity Of The Cerebral Cortex And The Manifestation Of Impulsivity / Reflexivity

The most significant EEG differences were obtained by us for the purpose of receiving the indicators of the coherence of the brain biopotentials in Δ-, θ-, β-frequency bands. These EEG differences were obtained in the course of performing tasks of the divergent type that are associated with the cognitive style of "impulsivity-reflexivity", which in its turn is based on the ability of an individual to make quick or slow decisions. It was established that in males, who are reflexive, the level of spatial synchronization was higher than the one of impulsive men in the Δ-, θ-, and β-frequency bands while performing the divergent task. And this was mainly achieved due to closer long-distance connections of the frontal areas of the cerebral cortex with occipital, temporal and parietal areas

Чрескожная неинвазивная вегетативная стимуляция: возможности и перспективы метода в практике специалистов по внутренним болезням

The article provides an overview of key studies on vagus nerve stimulation. The vagus nerve stimulation method affects the nerve fibers of the internal and external nerve plexuses, enhancing the parasympathetic effect. The positive therapeutic effect has been achieved in various experimental and clinical studies on the treatment of neurological and cardiac diseases, metabolic syndrome, and obesity. It has been shown that vagus nerve stimulation reduces epileptic seizures frequency, cardiac arrhythmias, and is prognostically favorable for the treatment of ischemia and reperfusion injury of the myocardium. Recent studies have examined the inflammatory reflex involved in the pathogenesis of obesity. The role of bioelectronic vagus nerve stimulation is being actively investigated for the treatment of obesity and metabolic syndrome.В статье приведен обзор ключевых исследований по стимуляции блуждающего нерва. Данный метод влияет на нервные волокна внутренних и наружных нервных сплетений, усиливая парасимпатическое действие. Благодаря такому воздействию в различных экспериментальных и клинических исследованиях достигнут положительный терапевтический эффект в лечении неврологических, кардиологических заболеваний, метаболического синдрома и ожирения. Показано, что стимуляция блуждающего нерва приводит к уменьшению количества приступов эпилепсии, нарушений ритма сердца, прогностически благоприятна для лечения ишемии и реперфузионного повреждения миокарда. В недавних исследованиях изучен воспалительный рефлекс, участвующий в патогенезе ожирения. Роль биоэлектронной стимуляции блуждающего нерва активно исследуется для лечения ожирения и метаболического синдрома

БЦЖ-ИНДУЦИРОВАННЫЙ ПРОВОСПАЛИТЕЛЬНЫЙ ФЕНОТИП МЕЗЕНХИМАЛЬНЫХ СТВОЛОВЫХ КЛЕТОК: ВЛИЯНИЕ ИММУНОМОДУЛЯТОРОВ

In case of mycobacterial infection the granulomatous infiltration foci contain the significant amount of mesenchymal stem cells (MSC), which functional phenotype and respective function in anti-tuberculosis immune defense remain unknown.Goal of the study: to characterize the MSC phenotype, formed by their interaction with BCG of M. bovis and to evaluate the changes in this phenotype caused by the action of inhibitors and stimulants of immune regulatory action.Materials and methods: MSC retrieved from bone marrow of mice were cultured with the presence and absence of BCG of M. bovis and/or poludanum TLR3 agonist; and the effect of two latter on the production of pro- and anti-inflammatory cytokines was evaluated by enzyme multiplied immunoassay. Flow cytometry and radioactive testing were used to evaluate the impact of cultured BCG fluid and poludanum-conditioned MSC on the proliferative and apoptotic activity of splenocytes. The inhibitors of indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2 (COG-2) or NO synthase were added to certain cultures alone with BCG and poludanum, and the contributions of IDO, COG-2 and NO to BCG and poludanum-induced response were assessed.Results. Pro-inflammatory polarization of MSC under the action of BCG and poludanum was demonstrated. Pro-inflammatory MSC phenotype correlated to their anti-apoptogenic and growth-stimulating actions on the splenocytes. It was demonstrated that IDO and NO restrained BCG-induced polarization and conversely COG-2 promoted BCG-induced pro-inflammatory polarization of MSC.Conclusions. 1. MSC actively participate in the formation of immunologic anti-mycobacterial resistance. 2. Targeted regulation of IDO and NO production can be feasibly applied for formation of anti-tuberculous vaccinal immunity and control mycobacterial infection. При микобактериальной инфекции в очагах гранулематозной инфильтрации содержится большое количество мезенхимальных стволовых клеток (МСК), функциональный фенотип которых и, соответственно, функция в противотуберкулезном иммунитете неизвестны.Цель исследования: охарактеризовать фенотип МСК, формирующийся при их взаимодействии с M. bovis БЦЖ, и оценить изменения этого фенотипа под действием ингибиторов и стимуляторов иммунорегуляторной активности.Материалы и методы: МСК, полученные из костного мозга мышей, культивировали в присутствии или отсутствии M. bovis БЦЖ и/или агониста TLR3 полудана и методами иммуноферментного анализа оценивали влияние последних на продукцию про- и антивоспалительных цитокинов. Методами проточной цитометрии и радиоактивного анализа оценивали влияние культуральной жидкости БЦЖ- и полудан-кондиционированных МСК на пролиферативную и апоптотическую активность спленоцитов. В часть культур вместе с БЦЖ или полуданом добавляли ингибиторы индоламин-2,3-диоксигеназы (ИДО), циклооксигеназы-2 (ЦОГ-2) или NO синтазы и оценивали вклад ИДО, ЦОГ-2 и NO в БЦЖ- и полудан-индуцированный ответ.Результаты. Показана провоспалительная поляризация МСК под действием БЦЖ и полудана. Провоспалительный фенотип МСК коррелировал с их антиапоптогенной и ростостимулирующей активностью по отношению к спленоцитам. Продемонстрировано, что ИДО и NO сдерживают БЦЖ-индуцированную поляризацию, а активность ЦОГ-2, наоборот, способствует БЦЖ-индуцированной провоспалительной поляризации МСК.Выводы. 1. МСК являются активными участники формирования иммунологической антимикобактериальной резистентности. 2. Таргетное регулирование продукции ИДО и оксида азота может быть целесообразно для формирования противотуберкулезного вакцинального иммунитета и для борьбы с микобактериальной инфекцией