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51.
Tibor Maliar Mária Maliarová Ján Kraic Miroslav Ondrejovič Ivana Pšenáková Michaela Havrlentová 《Biologia》2013,68(1):99-104
Beneficial effects of whole grains of cereals and pseudocereals and their fractions to human physiology are well known and broadly published. Especially secondary metabolites, dominantly from the category of phenolics (or polyphenols), beneficially influence the health physiology and/or prevent disease progress. Within the frame of this study, ten genotypes of four cereals or pseudocereals, respectively, were chosen for their antioxidant activity, determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and β-carotene-linoleic acid bleaching model (BCLM) mechanisms. Tested genotypes were selected from primary collection based on their antioxidant activity values, as well as higher level of flavonoids or phenolic acids. The stability of antioxidant properties after thermic, acidic, and basic treatments was evaluated. The oat cultivar Sirene and buckwheat cultivar Bogatyr expressed high level of the antioxidant activity, but they lost it due to all types of treatment. Oppositely, treatments increased antioxidant activities in some samples, especially in oat cultivar Maris Oberon, wheat cultivar Ines and Karolinum, or partially in barley cultivars Kompakt (after basic treatment) and Jubilant (acidic and basic treatments). The lack of the antioxidant activity could be observed due to destruction of the key compounds responsible for the antioxidant effect, whereas the increasing activity could be seen due to release of the aglycons from glycosidic forms after treatment. The stability of antioxidant properties could be a valuable parameter of the raw material for manufacturing special foods with functional properties. 相似文献
52.
Anna Lehner Viktor Magdolen Tibor Schuster Matthias Kotzsch Marion Kiechle Alfons Meindl Fred C. G. J. Sweep Paul N. Span Eva Gross 《PloS one》2013,8(4)
HTRA1 is a highly conserved serine protease which has been implicated in suppression of epithelial-to-mesenchymal-transition (EMT) and cell motility in breast cancer. Its prognostic relevance for breast cancer is unclear so far. Therefore, we evaluated the impact of HTRA1 mRNA expression on patient outcome using a cohort of 131 breast cancer patients as well as a validation cohort including 2809 publically available data sets. Additionally, we aimed at investigating for the presence of promoter hypermethylation as a mechanism for silencing the HTRA1 gene in breast tumors. HTRA1 downregulation was detected in more than 50% of the breast cancer specimens and was associated with higher tumor stage (p = 0.025). By applying Cox proportional hazard models, we observed favorable overall (OS) and disease-free survival (DFS) related to high HTRA1 expression (HR = 0.45 [CI 0.23–0.90], p = 0.023; HR = 0.55 [CI 0.32–0.94], p = 0.028, respectively), with even more pronounced impact in node-positive patients (HR = 0.21 [CI 0.07–0.63], p = 0.006; HR = 0.29 [CI 0.13–0.65], p = 0.002, respectively). Moreover, HTRA1 remained a statistically significant factor predicting DFS among established clinical parameters in the multivariable analysis. Its impact on patient outcome was independently confirmed in the validation set (for relapse-free survival (n = 2809): HR = 0.79 [CI 0.7–0.9], log-rank p = 0.0003; for OS (n = 971): HR = 0.63 [CI 0.48–0.83], log-rank p = 0.0009). In promoter analyses, we in fact detected methylation of HTRA1 in a small subset of breast cancer specimens (two out of a series of 12), and in MCF-7 breast cancer cells which exhibited 22-fold lower HTRA1 mRNA expression levels compared to unmethylated MDA-MB-231 cells. In conclusion, we show that downregulation of HTRA1 is associated with shorter patient survival, particularly in node-positive breast cancer. Since HTRA1 loss was demonstrated to induce EMT and cancer cell invasion, these patients might benefit from demethylating agents or histone deacetylase inhibitors previously reported to lead to HTRA1 upregulation, or from novel small-molecule inhibitors targeting EMT-related processes. 相似文献
53.
54.
Dukgyu Lee Tatsujiro Oka Beth Hunter Alison Robinson Sylvia Papp Kimitoshi Nakamura Wattamon Srisakuldee Barbara E. Nickel Peter E. Light Jason R. B. Dyck Gary D. Lopaschuk Elissavet Kardami Michal Opas Marek Michalak 《PloS one》2013,8(2)
Background
Calreticulin, a Ca2+-buffering chaperone of the endoplasmic reticulum, is highly expressed in the embryonic heart and is essential for cardiac development. After birth, the calreticulin gene is sharply down regulated in the heart, and thus, adult hearts have negligible levels of calreticulin. In this study we tested the role of calreticulin in the adult heart.Methodology/Principal Findings
We generated an inducible transgenic mouse in which calreticulin is targeted to the cardiac tissue using a Cre/loxP system and can be up-regulated in adult hearts. Echocardiography analysis of hearts from transgenic mice expressing calreticulin revealed impaired left ventricular systolic and diastolic function and impaired mitral valve function. There was altered expression of Ca2+ signaling molecules and the gap junction proteins, Connexin 43 and 45. Sarcoplasmic reticulum associated Ca2+-handling proteins (including the cardiac ryanodine receptor, sarco/endoplasmic reticulum Ca2+-ATPase, and cardiac calsequestrin) were down-regulated in the transgenic hearts with increased expression of calreticulin.Conclusions/Significance
We show that in adult heart, up-regulated expression of calreticulin induces cardiomyopathy in vivo leading to heart failure. This is due to an alternation in changes in a subset of Ca2+ handling genes, gap junction components and left ventricle remodeling. 相似文献55.
Sara Vandenwijngaert Peter Pokreisz Hadewich Hermans Hilde Gillijns Marijke Pellens Noortje A. M. Bax Giulia Coppiello Wouter Oosterlinck Agnes Balogh Zoltan Papp Carlijn V. C. Bouten Jozef Bartunek Jan D'hooge Aernout Luttun Erik Verbeken Marie Christine Herregods Paul Herijgers Kenneth D. Bloch Stefan Janssens 《PloS one》2013,8(3)
Background
The intracellular second messenger cGMP protects the heart under pathological conditions. We examined expression of phosphodiesterase 5 (PDE5), an enzyme that hydrolyzes cGMP, in human and mouse hearts subjected to sustained left ventricular (LV) pressure overload. We also determined the role of cardiac myocyte-specific PDE5 expression in adverse LV remodeling in mice after transverse aortic constriction (TAC).Methodology/Principal Findings
In patients with severe aortic stenosis (AS) undergoing valve replacement, we detected greater myocardial PDE5 expression than in control hearts. We observed robust expression in scattered cardiac myocytes of those AS patients with higher LV filling pressures and BNP serum levels. Following TAC, we detected similar, focal PDE5 expression in cardiac myocytes of C57BL/6NTac mice exhibiting the most pronounced LV remodeling. To examine the effect of cell-specific PDE5 expression, we subjected transgenic mice with cardiac myocyte-specific PDE5 overexpression (PDE5-TG) to TAC. LV hypertrophy and fibrosis were similar as in WT, but PDE5-TG had increased cardiac dimensions, and decreased dP/dtmax and dP/dtmin with prolonged tau (P<0.05 for all). Greater cardiac dysfunction in PDE5-TG was associated with reduced myocardial cGMP and SERCA2 levels, and higher passive force in cardiac myocytes in vitro.Conclusions/Significance
Myocardial PDE5 expression is increased in the hearts of humans and mice with chronic pressure overload. Increased cardiac myocyte-specific PDE5 expression is a molecular hallmark in hypertrophic hearts with contractile failure, and represents an important therapeutic target. 相似文献56.
Helena J. M. van Alphen Karin M. Volkers Christiaan G. Blankevoort Erik J. A. Scherder Tibor Hortobágyi Marieke J. G. van Heuvelen 《PloS one》2016,11(3)
Purpose
Self-reported data suggest that older adults with dementia are inactive. The purpose of the present study was to objectively assess the physical activity (PA) levels of community-dwelling and institutionalized ambulatory patients with dementia, and to compare with the PA levels of cognitive healthy older adults.Methods
We used actigraphy to assess the PA levels in institutionalized (n = 83, age: 83.0 ± 7.6, Mini-Mental-State Examination (MMSE): 15.5 ± 6.5) and community-dwelling dementia patients (n = 37, age: 77.3 ± 5.6, MMSE-score: 20.8 ± 4.8), and healthy older adults (n = 26, age: 79.5 ± 5.6, MMSE-score: 28.2 ± 1.6). We characterized PA levels based on the raw data and classified <100 counts/min as sedentary behavior.Results
Institutionalized dementia patients had the lowest daily PA levels (1.69 ± 1.33 counts/day), spent 72.1% of the day sedentary, and were most active between 8:00 and 9:00 am. Institutionalized vs. community-dwelling dementia patients had 23.5% lower daily PA levels (difference M = 0.52, p = .004) and spent 9.3% longer in sedentariness (difference M = 1.47, p = .032). Community-dwelling dementia patients spent 66.0% of the day sedentary and were most active between 9:00 to 10:00 am with a second peak between 14:00 to 15:00. Community-dwelling dementia patients vs healthy older adults’ daily PA levels and sedentary time were 21.6% lower and 8.9% longer, respectively (difference M = 0.61, p = .007; difference M = 1.29, p = .078).Conclusions
Institutionalized and community-dwelling dementia patients are sedentary for most of the day and the little PA they perform is of lower intensity compared to their healthy peers. Their highest PA peak is when they get out of bed in the morning. In addition, it seems that institutionalized living is associated with lower PA levels in dementia patients. These are the first results that objectively characterize institutionalized as well as community-dwelling dementia patients’ PA levels and confirm that dementia patients are inactive. 相似文献57.
58.
László?K?lesEmail author Erzsébet?Kató Adrienn?Hanuska Zoltán?S.?Zádori Mahmoud?Al-Khrasani Tibor?Zelles Patrizia?Rubini Peter?IllesEmail author 《Purinergic signalling》2016,12(1):1-24
Glutamate is the main excitatory neurotransmitter of the central nervous system (CNS), released both from neurons and glial cells. Acting via ionotropic (NMDA, AMPA, kainate) and metabotropic glutamate receptors, it is critically involved in essential regulatory functions. Disturbances of glutamatergic neurotransmission can be detected in cognitive and neurodegenerative disorders. This paper summarizes the present knowledge on the modulation of glutamate-mediated responses in the CNS. Emphasis will be put on NMDA receptor channels, which are essential executive and integrative elements of the glutamatergic system. This receptor is crucial for proper functioning of neuronal circuits; its hypofunction or overactivation can result in neuronal disturbances and neurotoxicity. Somewhat surprisingly, NMDA receptors are not widely targeted by pharmacotherapy in clinics; their robust activation or inhibition seems to be desirable only in exceptional cases. However, their fine-tuning might provide a promising manipulation to optimize the activity of the glutamatergic system and to restore proper CNS function. This orchestration utilizes several neuromodulators. Besides the classical ones such as dopamine, novel candidates emerged in the last two decades. The purinergic system is a promising possibility to optimize the activity of the glutamatergic system. It exerts not only direct and indirect influences on NMDA receptors but, by modulating glutamatergic transmission, also plays an important role in glia-neuron communication. These purinergic functions will be illustrated mostly by depicting the modulatory role of the purinergic system on glutamatergic transmission in the prefrontal cortex, a CNS area important for attention, memory and learning. 相似文献
59.
Voller Jiří Béres Tibor Zatloukal Marek Džubák Petr Hajdúch Marián Doležal Karel Schmülling Thomas Miroslav Strnad 《Phytochemistry Reviews》2019,18(4):1101-1113
Phytochemistry Reviews - Cytokinins are plant hormones and play essential roles in regulating plant growth and development. They also have diverse pharmacological effects in animals and humans.... 相似文献
60.
Muscles are formed by fusion of individual postmitotic myoblasts to form multinucleated syncytial myotubes. The process requires a well-coordinated transition from proliferation, through migratory alignment and cycle exit, to breakdown of apposed membranes. Connexin43 protein and cell-cycle inhibitor levels are correlated, and gap junction blockers can delay muscle regeneration, so a coordinating role for gap junctions has been proposed. Here, wild-type and dominant-negative connexin43 variants (wtCx43, dnCx43) were introduced into rat myoblasts in primary culture through pIRES-eGFP constructs that made transfected cells fluoresce. GFP-positive cells and vitally-stained nuclei were counted on successive days to reveal differences in proliferation, and myotubes were counted to reveal differences in fusion. Individual transfected cells were injected with Cascade Blue, which permeates gap junctions, mixed with FITC-dextran, which requires cytoplasmic continuity to enter neighbouring cells. Myoblasts transfected with wtCx43 showed more gap-junctional coupling than GFP-only controls, began fusion sooner as judged by the incidence of cytoplasmic coupling, and formed more myotubes. Myoblasts transfected with dnCx43 remained proliferative for longer than either GFP-only or wtCx43 myoblasts, showed less coupling, and underwent little fusion into myotubes. These results highlight the critical role of gap-junctional coupling in myotube formation. 相似文献