85 research outputs found
Apocynum venetum L. and Apocynum pictum Schrenk (Apocynaceae) as multi-functional and multi-service plant species in Central Asia: a review on biology, ecology, and utilization
During the second half of the 20th century cotton was strongly promoted along the rivers of Central Asia. The irrigation agriculture resulted in wide spread soil salinization and severe water shortages within the river systems. Most prominent example is the desiccation of the Aral Sea. The natural vegetation along the rivers of Central Asia is adapted to periods of water shortage, is very productive, and contains plant species with valuable utilization opportunities. We reviewed the literature about Apocynum venetumL. and A. pictum Schrenk, two plant species of those riparian ecosystems, which are used as fibre and medicinal plants. A. venetum and A. pictum yield fibres, which can be used as textiles, though the fibres best are blended with cotton and/or chemical fibres. Though, the fibre extraction process needs more research attention. Furthermore, the literature shows that Apocynum leafs are used to produce antihypertonic tea and medicine. Both species grow under the arid climate of Central Asia without irrigation, because they exploit groundwater. Furthermore, both species can withstand higher soil salinization levels than cotton. Both species can be used and provide an income to local people under conditions, which are unfavourable to grow crops under irrigation. Such conditions are unreliable water supply for irrigation systems and/or saline soils
Экспрессия провоспалительных и костимулирующих молекул на макрофагах in vitro у больных туберкулезом легких
The aim of this study was to identify features of the expression of pro-inflammatory and co-stimulatory molecules on the surface of macrophages in vitro in patients with pulmonary tuberculosis, depending on the clinical form of the disease and sensitivity of the pathogen to anti-TB drugs.Materials and methods. 40 patients (36 men and 4 women) with pulmonary tuberculosis (TB) were examined: 18 patients (16 men and 2 women, average age (44.56 ± 8.10) years) with disseminated tuberculosis (DTB) and 22 patients (20 men and 2 women, average age (46.54 ± 5.24) years) with infiltrative tuberculosis (ITB). Of those, 30 patients secreted Mycobacterium tuberculosis (MBT) sensitive to the basic anti-TB drugs (ATBD), and 10 patients secreted MBT resistant to first-line anti-TB drugs. Venous blood was the study material. To isolate monocytes from the whole blood in order to transform them into macrophages, ficoll density gradient centrifugation with gradient density of 1.077 g/cm3 was used followed by immunomagnetic separation of CD14+ cells. Monocytes were cultured in a complete culture medium X-VIVO 10 with gentamicin and phenol red with the addition of the macrophage colony-stimulating factor (M-CSF) (5 ng/ml) at a concentration of 1×106 cells/ml with the following stimulators: interleukin (IL) 4 (10 ng/ml) and interferon (IFN) γ (100 ng/ml). Immunophenotyping of macrophages was performed using monoclonal antibodies to CD80, CD86, and HLA-DR on a Beckman Coulter CytoFLEX LX flow cytometer (Beckman Coulter, USA). The analysis of the obtained data was carried out using the CytExpert 2.0 software application. The results were analyzed using statistical methods.Results. The number of intact and cytokine-stimulated (IL-4 and IFNγ) CD80-positive macrophages in patients with ITB and drug-resistant TB (DR TB) exceeded their number not only in healthy donors, but also in patients with DTB and drug-sensitive TB (DS TB), respectively. In addition, an increase in CD86 expression on the surface of macrophages was registered in patients with ITB and DR TB after adding IFNγ (M1-activation inducer) to the suspension culture. In contrast, in patients with DTB and DS TB, the number of macrophages with expression of B7 family co-stimulating molecules decreased or remained within the normal values in the absence of a reaction to cytokines during cytokine induction. Deficiency of HLA-DR-positive macrophages was found in all TB patients. The minimal number of macrophages expressing HLA-DR was found in patients with DTB and DS TB after cell incubation with IL-4 (M2-activation inducer).Conclusion. Evaluation of the expression of B7 (CD80/86) and HLA-DR membrane molecules on macrophages in TB patients allows to conclude that anti-TB immune response is impaired at stages of antigen presentation (in all examined patients with TB) and co-stimulation (in DTB and DS TB). An increase in the expression of macrophage surface molecules CD80 (with M1- and M2-stimulation) and CD86 (with M1-stimulation) in patients with ITB and DR TB indicates an increase in cell reactivity in these forms of TB. In addition, deficit of expression of HLA-DR (a key marker of pro-inflammatory cell activation) on the surface of macrophages in TB can be considered as a general (independent of the clinical form of the disease and drug sensitivity of the pathogen) pathogenetic factor of immune imbalance in pulmonary tuberculosis.Цель работы – установить особенности экспрессии провоспалительных и костимулирующих молекул на макрофагах in vitro у больных туберкулезом легких в зависимости от клинической формы заболевания и чувствительности возбудителя к противотуберкулезным лекарственным средствам.Материалы и методы. Обследованы 40 пациентов (36 мужчин и 4 женщины): 18 пациентов с диссеминированным туберкулезом легких (ДТБ) (16 мужчин и 2 женщины, средний возраст (44,56 ± 8,10) лет) и 22 пациента с инфильтративным туберкулезом легких (ИТБ) (20 мужчин и 2 женщины, средний возраст (46,54 ± 5,24) лет) c туберкулезом легких (ТБ). Из них было 30 пациентов, выделяющих Mycobacterium tuberculosis (MBT), чувствительные к основным противотуберкулезным средствам (ПТС), и 10 пациентов, выделяющих MBT, устойчивые к лекарственным средствам основного ряда противотуберкулезной терапии. Группу сравнения составили 15 здоровых доноров с сопоставимыми характеристиками по полу и возрасту.Материалом исследования являлась венозная кровь. Для выделения моноцитов из цельной крови с целью их трансформации в макрофаги использовали метод центрифугирования в градиенте фиколла плотностью 1,077 г/см3 с последующей иммуномагнитной сепарацией CD14+ клеток. Моноциты культивировали в полной питательной среде X-VIVO 10 с добавлением колониестимулирующего фактора макрофагов (M-CSF) (5 нг/мл) в концентрации 1×106 клеток/мл со стимуляторами: интерлейкином (IL) 4 (10 нг/мл) и интерфероном (IFN) γ (100 нг/мл). Иммунофенотипирование макрофагов проводили с использованием моноклональныхантител к CD80, CD86, HLA-DR на проточном цитометре Beckman Coulter CytoFLEX LX (Beckman Coulter, США). Анализ полученных данных осуществляли при помощи программного приложения CytExpert 2.0 (Beckman Coulter, США). Полученные результаты анализировали статистическими методами.Результаты. Количество интактных и стимулированных цитокинами (IL-4 и IFNγ) CD80- позитивных макрофагов у больных ИТБ и с лекарственно-устойчивым ТБ (ЛУ ТБ) превышало их число не только у здоровых доноров, но и у больных ДТБ и с лекарственно-чувствительным ТБ (ЛЧ ТБ) соответственно. Кроме того, у больных ИТБ и ЛУ ТБ регистрировалось повышение экспрессии CD86 на макрофагах после добавления в суспензионную культуру IFNγ (индуктор М1-активации). У больных ДТБ и ЛЧ ТБ количество макрофагов с экспрессией костимулирующих молекул семейства В7 при индукции цитокинами, напротив, снижалось или сохранялось в пределах нормы в отсутствие реакции на цитокины. Дефицит HLA-DR-позитивных макрофагов обнаруживался у всех больных ТБ. Минимальное число макрофагов, экспрессирующих HLADR, установлено у больных ДТБ и ЛЧ ТБ после инкубации клеток с IL-4 (индуктор М2-активации).Заключение. Оценка экспрессии мембранных молекул B7 (CD80/86) и HLA-DR на макрофагах у больных ТБ позволяет сделать вывод о нарушениях противотуберкулезного иммунного ответа на стадии презентации антигена (у всех обследованных больных ТБ) и костимуляции (при ДТБ и ЛЧ ТБ). Увеличение экспрессии макрофагами поверхностных молекул CD80 (при М1- и М2-стимуляции) и CD86 (при М1-стимуляции) у больных ИТБ и ЛУ ТБ свидетельствует о повышении реактивности клеток при данных формах течения ТБ. Наряду с этим дефицит экспрессии на макрофагах HLA-DR (ключевого маркера провоспалительной активации клеток) при ТБ можно рассматривать как общий (не зависящий от клинической формы болезни и лекарственной чувствительности возбудителя) патогенетический фактор иммунного дисбаланса при туберкулезе легких.
Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression
Fibrosis compromises pancreatic ductal carcinoma (PDAC) treatment and contributes to patient mortality yet anti-stromal therapies are controversial. We found that human PDACs with impaired epithelial transforming growth factor β (TGF-β) signaling have elevated epithelial Stat3 activity and develop a stiffer, matricellular-enriched fibrosis associated with high epithelial tension and shorter patient survival. In several Kras-driven mouse models, both the loss of TGF-β signaling and elevated β1-integrin mechanosignaling engaged a positive feedback loop whereby Stat3 signaling promotes tumor progression by increasing matricellular fibrosis and tissue tension. In contrast, epithelial Stat3 ablation attenuated tumor progression by reducing the stromal stiffening and epithelial contractility induced by loss of TGF-β signaling. In PDAC patient biopsies, higher matricellular protein and activated Stat3 associated with SMAD4 mutation and shorter survival. The findings implicate epithelial tension and matricellular fibrosis in the aggressiveness of SMAD4 mutant pancreatic tumors, and highlight Stat3 and mechanics as key drivers of this phenotype
AMP Affects Intracellular Ca2+ Signaling, Migration, Cytokine Secretion and T Cell Priming Capacity of Dendritic Cells
The nucleotide adenosine-5′-monophosphate (AMP) can be released by various cell types and has been shown to elicit different cellular responses. In the extracellular space AMP is dephosphorylated to the nucleoside adenosine which can then bind to adenosine receptors. However, it has been shown that AMP can also activate A1 and A2a receptors directly. Here we show that AMP is a potent modulator of mouse and human dendritic cell (DC) function. AMP increased intracellular Ca2+ concentration in a time and dose dependent manner. Furthermore, AMP stimulated actin-polymerization in human DCs and induced migration of immature human and bone marrow derived mouse DCs, both via direct activation of A1 receptors. AMP strongly inhibited secretion of TNF-α and IL-12p70, while it enhanced production of IL-10 both via activation of A2a receptors. Consequently, DCs matured in the presence of AMP and co-cultivated with naive CD4+CD45RA+ T cells inhibited IFN-γ production whereas secretion of IL-5 and IL-13 was up-regulated. An enhancement of Th2-driven immune response could also be observed when OVA-pulsed murine DCs were pretreated with AMP prior to co-culture with OVA-transgenic naïve OTII T cells. An effect due to the enzymatic degradation of AMP to adenosine could be ruled out, as AMP still elicited migration and changes in cytokine secretion in bone-marrow derived DCs generated from CD73-deficient animals and in human DCs pretreated with the ecto-nucleotidase inhibitor 5′-(alpha,beta-methylene) diphosphate (APCP). Finally, the influence of contaminating adenosine could be excluded, as AMP admixed with adenosine desaminase (ADA) was still able to influence DC function. In summary our data show that AMP when present during maturation is a potent regulator of dendritic cell function and point out the role for AMP in the pathogenesis of inflammatory disorders
Purinergic signalling links mechanical breath profile and alveolar mechanics with the pro-inflammatory innate immune response causing ventilation-induced lung injury
Severe pulmonary infection or vigorous cyclic deformation of the alveolar epithelial type I (AT I) cells by mechanical ventilation leads to massive extracellular ATP release. High levels of extracellular ATP saturate the ATP hydrolysis enzymes CD39 and CD73 resulting in persistent high ATP levels despite the conversion to adenosine. Above a certain level, extracellular ATP molecules act as danger-associated molecular patterns (DAMPs) and activate the pro-inflammatory response of the innate immunity through purinergic receptors on the surface of the immune cells. This results in lung tissue inflammation, capillary leakage, interstitial and alveolar oedema and lung injury reducing the production of surfactant by the damaged AT II cells and deactivating the surfactant function by the concomitant extravasated serum proteins through capillary leakage followed by a substantial increase in alveolar surface tension and alveolar collapse. The resulting inhomogeneous ventilation of the lungs is an important mechanism in the development of ventilation-induced lung injury. The high levels of extracellular ATP and the upregulation of ecto-enzymes and soluble enzymes that hydrolyse ATP to adenosine (CD39 and CD73) increase the extracellular adenosine levels that inhibit the innate and adaptive immune responses rendering the host susceptible to infection by invading microorganisms. Moreover, high levels of extracellular adenosine increase the expression, the production and the activation of pro-fibrotic proteins (such as TGF-β, α-SMA, etc.) followed by the establishment of lung fibrosis
Purinergic signalling and immune cells
This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells
Context modulates the ERP signature of contour integration
We investigated how the electrophysiological signature of contour integration is changed by the context in which a contour is embedded. Specifically, we manipulated the orientations of Gabor elements surrounding an embedded shape outline. The amplitudes of early visual components over posterior scalp regions were changed by the presence of a contour, and by the orientation of elements surrounding the contour. Differences in context type had an effect on the early P1 and N1 components, but not on the later P2 component. The presence of a contour had an effect on the N1 and P2 components, but not on the earlier P1 component. A modulatory effect of context on contour integration was observed on the N1 component. These results highlight the importance of the context in which contour integration takes place
Context modulates the ERP signature of contour integration
We investigated how the electrophysiological signature of contour integration is changed by the context in which a contour is embedded. Specifically, we manipulated the orientations of Gabor elements surrounding an embedded shape outline. The amplitudes of early visual components over posterior scalp regions were changed by the presence of a contour, and by the orientation of elements surrounding the contour. Differences in context type had an effect on the early P1 and N1 components, but not on the later P2 component. The presence of a contour had an effect on the N1 and P2 components, but not on the earlier P1 component. A modulatory effect of context on contour integration was observed on the N1 component. These results highlight the importance of the context in which contour integration takes place
ASSOCIATIONS OF INTERFERON GENE POLYMORPHISMS OAS-1, OAS-3, PKR WITH CHRONIC VIRAL HEPATITIS C
Abstract. Present work is devoted to analyzing possible associations of single-nucleotide gene polymorphisms (SNPs) with liver pathology in patients with chronic hepatitis C. SNP genotypes and allele frequencies were identified for some genes of interferon system, i.e., oligoadenilatsynthetase-1 (-1A/G), oligoadenilatsynthetase-3 (+1314C/T), and protein kinase R (+244A/G), using DNA samples from healthy donors and patients with chronic hepatitis C representing population of Tomsk and Tomsk Region. An association has been shown between SNPs of oligoadenilatsynthetase-1 and protein kinase R genes, and clinical activity of inflammatory process in the liver, as well as an impact of certain SNPs of protein kinase R and oligoadenilatsynthetase-3 genes upon fibrogenesis. (Med. Immunol., 2011, vol. 13, N 1, pp 93-100
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