65 research outputs found

    Clinical significance of circulating dendritic cells in patients with systemic lupus erythematosus.

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    Dendritic cells are a complex group of mainly bone-marrow-derived leukocytes that play a role in autoimmune diseases. The total number of circulating dendritic cells (tDC), and their plasmacytoid dendritic cell (pDC) and myeloid dendritic cell (mDC1 and mDC2) subpopulations were assessed using flow cytometry. The number of tDC and their subsets were significantly lower in systemic lupus erythematosus patients than in the control group. The count of tDC and their subsets correlated with the number of T cells. The number of tDC and pDC subpopulation were lower in the patients with lymphopenia and leukopenia than in the patients without these symptoms. Our data suggest that fluctuations in blood dendritic cell count in systemic lupus erythematosus patients are much more significant in pDC than in mDC, what may be caused by their migration to the sites of inflammation including skin lesions. Positive correlation between dendritic cell number and TCD4+, TCD8+ and CD19+ B cells, testify of their interactions and influence on SLE pathogenesis. The association between dendritic cell number and clinical features seems to be less clear

    Effect of functionalization on the electrical properties of laser-structured hybrid carbon nanomaterials

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    Background and Objectives: An urgent task of field emission electronics is to reduce the operating voltage in order to obtain an emission current of a given density. To solve this problem, an emitter with a low work function is needed. Carbon nanomaterials are promising candidates for the role of field emitters; however, to reduce the work function of electrons from these nanomaterials, it is necessary to functionalize their surface with other nanostructures with a low work function. In this work, we experimentally studied the effect of functionalization of lanthanum hexaboride (LaB6) with nanoparticles on the electrical properties of nanomaterials based on an array of carbon nanotubes (CNTs). Materials and Methods: Using the developed technology of laser exposure, a hybrid nanomaterial was created based on a vertical array of CNTs functionalized with LaB6 nanoparticles. Pulsed laser action on an array of CNTs with an energy density of 0.15 J/cm2 made it possible to shorten, align, and structure the upper ends of the nanotubes perpendicular to the substrate. Results: The effect of the formation of a hybrid nanostructure by binding LaB6 nanoparticles to the CNT surface has been experimentally established. Registration of the emission current-voltage characteristics of hybrid nanomaterials has shown a decrease in the total work function of the hybrid nanomaterial by 78% after functionalization with LaB6 nanoparticles. Conclusion: Based on the results obtained, it is predicted that CNT+LaB6 hybrid nanostructures have a great potential for application as nanomaterials for field emission electronics

    Characterisation of feline renal cortical fibroblast cultures and their transcriptional response to transforming growth factor beta 1

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    Chronic kidney disease (CKD) is common in geriatric cats, and the most prevalent pathology is chronic tubulointerstitial inflammation and fibrosis. The cell type predominantly responsible for the production of extra-cellular matrix in renal fibrosis is the myofibroblast, and fibroblast to myofibroblast differentiation is probably a crucial event. The cytokine TGF-β1 is reportedly the most important regulator of myofibroblastic differentiation in other species. The aim of this study was to isolate and characterise renal fibroblasts from cadaverous kidney tissue of cats with and without CKD, and to investigate the transcriptional response to TGF-β1

    КОМПЛЕКСНЫЙ ХАРАКТЕР ВЛИЯНИЯ ПОЛИЦИКЛИЧЕСКИХ АРОМАТИЧЕСКИХ УГЛЕВОДОРОДОВ НА МЕТАБОЛИЧЕСКИЕ ПРОЦЕССЫ КАК ВАЖНЫЙ ФАКТОР, ОПРЕДЕЛЯЮЩИЙ ОСОБЕННОСТИ ИХ КАНЦЕРОГЕННОЙ АКТИВАЦИИ

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    In the article, the contribution of the monooxygenase component to the carcinogenic activation of a key procarcinogenic derivative of benzo(a)pyrene – 7,8-benzo(a)pyrenediol in lung adenocarcinoma cell line A549 was evaluated. It is shown that the contribution of the monooxygenase process under the experimental conditions in A549 cells is only 13 %, which corresponds to a relatively low level of the constitutive expression of CYP1A1 and CYP1B1. The situation changes significantly when cells are exposed to 20-methylcholanthrene. In this case, the monooxygenase component in the carcinogenic activation of 7,8-benzo(a)pyrenediol has reached 25 %. Moreover, 90 % is accounted for a "complete" carcinogen – diolepoxide-2. As 20-methylcholanthrene is a polycyclic aromatic compound and exists with a benzo(a)pyrene in the tobacco smoke, this suggests that the entry into the body a whole pool of polycyclic aromatic hydrocarbons may significantly affect not only the level but also the direction of the carcinogenic PAH activation of individual compounds.В работе оценен вклад монооксигеназной составляющей в канцерогенную активацию одного из ключевых проканцерогенных производных бензо(а)пирена – 7,8-бензо(а)пирен-диола в клеточной линии аденокарциномы легких А549. Количественное определение двух образующихся в результате монооксигеназной реакции диолэпоксидов и сопоставление с израсходованным количеством субстрата позволили заключить, что вклад монооксигеназного процесса в условиях эксперимента в клетках А549 составляет лишь 13 %, что в принципе согласуется с относительно низким уровнем конститутивной экспрессии CYP1A1 и CYP1B1. Картина существенно меняется при экспонировании клеток действию 20-метилхолантрена - полициклического ароматического углеводорода, входящего в состав табачного дыма: монооксигеназная составляющая в канцерогенной активации 7,8-бензо(а)пирен-диола достигает уже 25 %. Причем практически 90 % приходится на долю "полного" канцерогена – диолэпоксида-2. Это позволяет полагать, что попадание в организм не одного, а целого пула полициклических ароматических углеводородов может существенным образом влиять не только на уровень, но и на направление канцерогенной активации отдельных представителей полициклических ароматических соединений

    Оценка уровня экспрессии и каталитической активности изоэнзимов цитохрома Р450 в опухолевой клеточной линии А549

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    The contribution of monooxygenase component in carcinogenic activation of a key procarcinogenic derivative of benzo(a) pyrene - 7,8-benzo(a)pyrenediol in lung adenocarcinoma cell line A549 has been evaluated. It has been shown that the contribution of monooxygenase process under the experimental conditions in A549 cells is only 13 %, which corresponds with the relatively low level of constitutive expression of CYP1A1 and CYP1B1. When cells are exposed to 20-methylcholanthrene, monooxygenase component in carcinogenic activation of 7,8-benzo(a)pyrenediol has reached 25 %. Moreover, 90 % is accounted for a "complete" carcinogen - diolepoxide-2. As 20-methylcholanthrene is a polycyclic aromatic compound and exists with a benzo(a) pyrene in the tobacco smoke, this suggests a whole pool of polycyclic aromatic hydrocarbons entering the organism may significantly affect not only the level but also the direction of carcinogenic PAH activation of individual compounds.Оценен вклад монооксигеназной составляющей в канцерогенную активацию одного из ключевых прокан-церогенных производных бензо(а)пирена - 7,8-бензо(а)пирен-диола в клеточной линии аденокарциномы легких А549. Количественное определение двух образующихся в результате монооксигеназной реакции диолэпокси-дов и сопоставление с израсходованным количеством субстрата позволило заключить, что вклад монооксиге-назного процесса в условиях эксперимента в клетках А549 составляет лишь 13 %, что в принципе согласуется с относительно низким уровнем конститутивной экспрессии CYP1A1 и CYP1B1. Картина существенно меняется при экспонировании клеток действию 20-метилхолантрена. В этом случае монооксигеназная составляющая в канцерогенной активации 7,8-бензо(а)пирен-диола достигает уже 25 %. Причем практически 90 % приходится на долю «полного» канцерогена - диолэпоксида-2. Напомним, что 20-метилхоантрен является полициклическим ароматическим соединением и наряду с бензо(а)пиреном входит в состав табачного дыма. Это позволяет полагать, что попадание в организм не одного, а целого пула полициклических ароматических углеводородов может существенным образом влиять не только на уровень, но и на направление канцерогенной активации отдельных представителей полициклических ароматических углеводородов

    Quality of life and satisfaction with life in SLE patients—the importance of clinical manifestations

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    To assess the correlation between quality of life (QoL) and satisfaction with life (SL) in SLE patients and correlate both with clinical symptoms of the disease. The study was performed in 83 patients. QoL was assessed by Short Form 36, and SL was assessed by the Satisfaction with Life Scale. Clinical manifestations presented at the time of examination were taken into consideration. SLE patients assessed their QoL and SL as rather low. Those with photosensitivity as well as neurological symptoms presented lower QoL in particular domains, while those with renal manifestation of SLE assessed their QoL as higher. Similar observations were made for SL only in relation to neurological symptoms. Moreover, our findings show that although SL is a part of QoL, both these parameters should be distinguished in order to fully assess the state of the patient

    Expression of Human Frataxin Is Regulated by Transcription Factors SRF and TFAP2

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    Friedreich ataxia is an autosomal recessive neurodegenerative disease caused by reduced expression levels of the frataxin gene (FXN) due to expansion of triplet nucleotide GAA repeats in the first intron of FXN. Augmentation of frataxin expression levels in affected Friedreich ataxia patient tissues might substantially slow disease progression.We utilized bioinformatic tools in conjunction with chromatin immunoprecipitation and electrophoretic mobility shift assays to identify transcription factors that influence transcription of the FXN gene. We found that the transcription factors SRF and TFAP2 bind directly to FXN promoter sequences. SRF and TFAP2 binding sequences in the FXN promoter enhanced transcription from luciferase constructs, while mutagenesis of the predicted SRF or TFAP2 binding sites significantly decreased FXN promoter activity. Further analysis demonstrated that robust SRF- and TFAP2-mediated transcriptional activity was dependent on a regulatory element, located immediately downstream of the first FXN exon. Finally, over-expression of either SRF or TFAP2 significantly increased frataxin mRNA and protein levels in HEK293 cells, and frataxin mRNA levels were also elevated in SH-SY5Y cells and in Friedreich ataxia patient lymphoblasts transfected with SRF or TFAP2.We identified two transcription factors, SRF and TFAP2, as well as an intronic element encompassing EGR3-like sequence, that work together to regulate expression of the FXN gene. By providing new mechanistic insights into the molecular factors influencing frataxin expression, our results should aid in the discovery of new therapeutic targets for the treatment of Friedreich ataxia
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