Age-related changes of arginase activity and nitric oxide level in phagocytes and their modulation by thymic mesenchymal stromal cells

Arginine metabolism plays an important role in the activation of phagocytes, which are responsible for initiation, regulation, and resolution of inflammation. Deterioration of phagocyte functions is thought to cause the development of inflammaging and other age-related disorders. Mesenchymal stromal cells are well known for their immunoregulatory properties and ability to modulate activation status of mononuclear phagocytes. We aimed to compare arginase activity and NO production in phagocytes from different sources in young and aged animals, and to explore the effect of syngeneic thymic mesenchymal stromal cells on these parameters in tissue-resident phagocytes. We found that arginine metabolism of tissue-resident mononuclear phagocytes from aged mice is shifted to alternative or anti-inflammatory phenotype, due to a statistically significant arginase activity increase. Syngeneic co-culture with mesenchymal stromal cells greatly stimulates arginase activity and up-regulates nitric oxide generation by tissue mononuclear phagocytes regardless of cell donor age. Such bi-directional influence may be beneficial in clinical application for simultaneous inhibition of inflammation and infectious process

The effect of perioperative analgesia with omnopon and parecoxib on the endocytic activity of murine phagocytes on the model of tumor surgery

We used the model of surgical tumor removal to compare the effect of anesthesia with opioid analgesic omnopon and selective cyclooxygenase-2 inhibitor parecoxib on the endocytic activity of phagocytes of different localization sites. 50 C57/black mice were transplanted with Lewis lung carcinoma in the hind paw pad. After 22 days, the tumor paw was amputated. Analgesics (omnopon 10 mg/kg, parecoxib – 20 mg/kg) were administered 30 min before the operation and once per day for 3 days after the surgery. Assessment of the endocytic activity of phagocytes was performed by FACS analysis before the surgery, at days 1 and 3 after the surgery. It was found that parecoxib analgesia maintained the endocytic activity of blood and spleen phagocytes in the postoperative period. At day 3 after the surgery in parecoxib-treated animals phagocytic activity of splenic granulocytes were 2.2 times higher compared to that in the group receiving opioid analgesia. Phagocytic indices of monocytes in parecoxib-treated mice were also 1.6 and 2.5 times higher for blood and spleen monocytes, respectively. Thus, parecoxib analgesia maintained the activity of blood and spleen phagocytes in mice after the surgical tumor removal at a much higher level as compared with the omnopon analgesia

Complex of C₆₀ fullerene with doxorubicin as a promising agent in antitumor therapy

The main aim of this work was to evaluate the effect of doxorubicin in complex with C₆₀ fullerene (C₆₀ + Dox) on the growth and metastasis of Lewis lung carcinoma in mice and to perform a primary screening of the potential mechanisms of C₆₀ + Dox complex actio

Complex of C₆₀ fullerene with doxorubicin as a promising agent in antitumor therapy

The main aim of this work was to evaluate the effect of doxorubicin in complex with C₆₀ fullerene (C₆₀ + Dox) on the growth and metastasis of Lewis lung carcinoma in mice and to perform a primary screening of the potential mechanisms of C₆₀ + Dox complex actio

The effect of intranasally administered TLR3 agonist larifan on metabolic profile of microglial cells in rat with C6 glioma

Glioma-associated microglia/macrophages (GAM) represent an attractive therapeutic target for the development of the alternative methodology in the treatment of gliomas. This study was aimed to investigate the effect of intranasally administered TLR3 agonist Larifan on microglial cell metabolic profile in rats with C6 glioma. Our results demonstrate progressive generation microglial cell population with immunosuppressive and pro-inflammatory properties in C6 glioma-bearing brain. Intranasally delivered TLR3 agonist is capable to abrogate the creation of this pro-tumoral immune infiltrates, probably, through the effect on myeloid-derived suppressor cells, and can be considered as a promising agent for glioma therapy aimed the GAM re-education

EFFECT OF INTRACRANIAL CATHETER PLACEMENT ON MICROGLIA METABOLIC PROFILE OF RATS

The aim of the work was to investigate the effect of the intracranial catheter placement on the metabolic profile of rat microglia. Microglial cells were isolated by the centrifugation in Percoll gradient. Oxidative metabolism and phagocytic activity were investigated by flow cytometry. Arginase activity was examined by colorimetric method. Nitrite level was assayed in Griess reaction. It was found that intracranial catheter placement caused down-regulation of nitrite synthesis by 3 times, augmentation of the reactive oxygen species generation by 1.5 times, and slightly decreased microglia phagocytic activity. Thus, intracranial catheter placement causes long term anti-inflammatory shift of microglia metabolism in rats

PHYTOCHEMICAL SCREENING OF POLYHERBAL COMPOSITION BASED ON Portulaca oleracea AND IT’S EFFECT ON MACROPHAGE OXIDATIVE METABOLISM

The aim of the work was to explore phytochemical characteristics of water extract from polyherbal composition based on P. oleracea and it’s effect on oxidative metabolism of murine peritoneal macrophages. The qualitative phytochemical analysis was conducted by colorimetric method. Quantitative analysis of phenols was performed in the test with gallic acid as a standard. Murine peritoneal macrophages were isolated without previous sensitization. Leukotoxicity of the water extract from polyherbal composition leukotoxicity was evaluated in MTT test. Reactive oxygen species generation was assayed by the nitroblue tetrazolium reduction method. Phytochemical analysis revealed the presence of water-soluble and insoluble phenols, tannins, saponins, flavonoids, cardiac glycosides and coumarins in the studied plant mixture. The water extract from polyherbal composition used in a range of concentration 1–1000 μg/ml (lyophilisate in distilled H2O) didn’t exhibit any toxic effects on murine peritoneal macrophages. Water extract from polyherbal composition caused statistically significant dose-dependent increase in oxidative metabolism of murine peritoneal suggest modulatory effect of studied water extract from polyherbal composition on innate immunity cells

Systemic inflammation biomarkers in 6-OHDA- and LPS-induced Parkinson’s disease in rats

Hematological and immunological markers of systemic inflammation were studied in 6-hydroxydopamine (6-OHDA)- and lipopolysaccharide (LPS)-induced models of Parkinson’s disease (PD). Experiments were carried out on adult male Wistar rats: 1 – intact animals; 2 – sham-operated animals and 3 – 6-OHDA- and LPS-lesioned animals. PD development was confirmed by the results of behavioral testing (apomorphine test, open field test) and immunohistochemical detection of the loss of dopaminergic neurons. Hematological indices (complete blood count and differential leukocyte count (DLC)) were examined using hematological analyser. Immunological indices included phenotypic (CD206 and CD80/86) and metabolic (oxidative metabolism and phagocytic activity) characteristics of circulating monocytes (Mo) and granulocytes (Gr), which were determined by flow cytometry, as well as plasma levels of C-reactive protein, which were determined by ELISA. LPS-induced PD was associated with neutrophilia, 1.9 times increased neutrophil-to-lymphocyte ratio, 3 times increased platelet-to-lymphocyte ratio, and 3 times increased systemic immune inflammation index as compared to intact animals. Functional profile of circulating phagocytes from LPS-lesioned animals was characterized by the pro-inflammtory metabolic shift, as was indicated by 5 times increased oxidative metabolism indices and up-regulated CD80/86 expression along with decreased phagocytic activity and CD206 expression. 6-OHDA-lesioned rats demonstrated decreased DLC indices as compared to intact and sham-operated rats. Functional profile of circulating phagocytes in this model was characterized by anti-inflammatory shift. The results obtained from this study demonstrated that stereotaxic LPS-induced PD is appropriate rodent model for the study of systemic inflammation which is inherent for the disease pathophysiology

Біологічна ефективність вирощування культур агроценозу

Purpose. To study the biological efficiency of growing crops by using different fertilizer systems.Methods. Field, laboratory.Results. The influence of the fertilizer system on the productivity of crops of short crop rotation with a four-year rotation cycle, which provides for the cultivation of the following crops: soybeans – winter wheat – sugar beets – corn for grain. A high level of productivity and product quality can be achieved through biologization measures, and not only through the intensification of cultivation technologies. Under the industrial fertilizer system, only mineral fertilizers are applied, and therefore the role of vegetation fertilizers increases significantly, aimed at the formation of the crop and in the future and to ensure a high level of quality. However, due to the influence of weather conditions in the years of research to conduct high-quality fertilization of vegetation with mineral fertilizers was impossible due to lack of moisture or in some years due to significant rainfall at the time of harvest. At the same time, nitrogen available to plants from biological and ecological fertilizer systems allowed to ensure the formation of acceptable quality indicators. Thus, the cultivation of crop rotations with the use of ecological and biological fertilizer systems allows forming high-quality yield indicators at a good level.Conclusions. The maximum yield of soybeans was provided by industrial (4.21 t/ha) and biological fertilizer system (4.18 t/ha). Also, under the industrial fertilizer system, the maximum grain yield of winter wheat was obtained (7.9 t/ha). However, in the biological system of fertilization of sugar beets for sugar yield, under the conditions of the experiment, the highest efficiency was obtained (12.7 t/ha). At the same time, the maximum yield of corn grain (11.7 t/ha) was obtained in the variant of the industrial fertilizer system.Цель. Изучить биологическую эффективность выращивания культур севооборота при использовании различных систем удобрения.Методы. Полевые, лабораторные.Результаты. Изучено влияние системы удобрения на продуктивность культур короткоротационного севооборота с четырехлетним циклом ротации, предусматривающего выращивание следующих культур: соя – пшеница озимая – сахарная свекла – кукуруза на зерно. Высокого уровня продуктивности и качества продукции можно достигать за счет мероприятий биологизации, а не исключительно благодаря интенсификации технологий выращивания. В промышленной системе удобрения вносят только минеральные удобрения, поэтому значительно возрастает роль подкормок по вегетации – направленных на формирование урожая и в дальнейшем, и на обеспечение высокого уровня качества. А вот за счет влияния погодных условий, сложившихся в годы исследований, провести качественно подкормки по вегетации минеральными удобрениями было невозможно из-за отсутствия влаги или в отдельные годы значительных ливневых осадков. В то же время, доступный растениям азот биологической и экологической систем удобрения позволил обеспечить формирование приемлемых показателей качества. Итак, выращивание культур севооборота при применении экологической и биологической систем удобрения позволяет сформировать качественные показатели урожая на хорошем уровне.Выводы. Максимальную урожайность сои обеспечивала промышленная – 4,21 т/га и биологическая система удобрения – 4,18 т/га. Также при промышленной системе удобрения было получено максимальные показатели урожайности зерна озимой пшеницы – 7,9 т/га. А вот при биологической системе удобрения сахарной свеклы по сбору сахара, в условиях опыта, получено наибольшую эффективность – 12,7 т/га. В то же время максимальную урожайность зерна кукурузы получено в варианте промышленной системы удобрения – 11,7 т/га.Мета. Вивчити біологічну ефективність вирощування культур сівозміни за використання різних систем удобрення.Методи. Польові, лабораторні.Результати. Вивчено вплив системи удобрення на продуктивність культур короткоротаційної сівозміни з чотирирічним циклом ротації, що передбачає вирощування таких культур: соя – пшениця озима – буряки цукрові – кукурудза на зерно. Високого рівня продуктивності та якості продукції можна досягати і за рахунок заходів біологізації, а не виключно завдяки інтенсифікації технологій вирощування. За промислової системи удобрення вносять лише мінеральні добрива, а тому значно зростає роль підживлень по вегетації – спрямованих на формування врожаю та в подальшому і на забезпечення високого рівня якості. А от за рахунок впливу погодних умов, що склались в роки досліджень, провести якісно підживлення по вегетації мінеральними добривами було неможливо з-за відсутності вологи або ж в окремі роки значних зливових опадів на час формування врожаю. В той же час, доступний рослинам азот біологічної та екологічної систем удобрення дозволив забезпечити формування прийнятних показників якості. Отже, вирощування культур сівозміни за застосування екологічної та біологічної систем удобрення дозволяє сформувати якісні показники врожаю на хорошому рівні.Висновки. Максимальну урожайність сої забезпечувала промислова – 4,21 т/га та біологічна система удобрення – 4,18 т/га. Також за промислової системи удобрення було отримано максимальні показники урожайності зерна пшениці озимої – 7,9 т/га. А от за біологічної системи удобрення буряків цукрових за збором цукру, в умовах досліду, отримано найбільшу ефективність – 12,7 т/га. В той же час максимальну урожайність зерна кукурудзи отримано у варіанті промислової системи удобрення – 11,7 т/га

Complex of C₆₀ fullerene with doxorubicin as a promising agent in antitumor therapy

The main aim of this work was to evaluate the effect of doxorubicin in complex with C₆₀ fullerene (C₆₀ + Dox) on the growth and metastasis of Lewis lung carcinoma in mice and to perform a primary screening of the potential mechanisms of C₆₀ + Dox complex actio