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61.
62.
Christos S. Mantzoros Antonios D. Liolios Nicholas A. Tritos Virginia G. Kaklamani Dimitrios E. Doulgerakis Ioannis Griveas Alan C. Moses Jeffrey S. Flier 《Obesity (Silver Spring, Md.)》1998,6(3):179-186
Objective : Leptin, an adipocyte-secreted hormone, has been shown to signal the status of energy stores to the brain, regulate energy homeostasis, and mediate the neuroendocrine response to food deprivation. Obesity is associated with increased leptin levels, and several hormones, including insulin and glucocorticoids, have been associated with leptin levels and expression in rodents. Although obesity has been strongly associated with increased leptin in humans, a significant percentage of leptin's variability remains unexplained. The role of endogenous hormones, demographic factors, or certain life-style factors in explaining the residual variability of leptin levels has not yet been clarified. We performed this cross-sectional study to document the relative importance of obesity, lifestyle factor, and endogenous hormones in determining serum leptin levels. Research Methods and Procedures : We measured serum concentrations of insulin, Cortisol, testosterone, growth hormone, and dehydroepiandrosterone sulfate; ascertained anthropometric, demographic, and lifestyle characteristics; and studied these variables in relationship to serum leptin concentrations in a sample of young healthy men. Results : Obesity and alcohol intake were independently and positively associated with circulating leptin concentrations. Additionally, cigarette smoking was negatively and independently associated with leptin concentrations. Finally, serum insulin concentration was an independent hormonal determinant of circulating leptin concentrations, whereas serum testosterone was negatively associated with leptin only by bivariate analysis. Discussion : We conclude that, in addition to obesity, cigarette smoking, alcohol intake, and serum insulin levels are associated with leptin levels in a population of healthy young men. 相似文献
63.
Paola Campagnolo Xuechong Hong Elisabetta di Bernardini Ioannis Smyrnias Yanhua Hu Qingbo Xu 《PloS one》2015,10(5)
Background and Purpose
Vessel graft failure is typically associated with arteriosclerosis, in which endothelial dysfunction/damage is a key event. Resveratrol has been shown to possess cardioprotective capacity and to reduce atherosclerosis. We aimed to study the influence of resveratrol on the behavior of resident stem cells that may contribute to graft arteriosclerosis.Experimental Approach
Vascular resident progenitor cells and embryonic stem cells were treated with resveratrol under differentiating conditions and endothelial markers expression was evaluated. Expression of miR-21 and β-catenin was also tested and exogenously modified. Effects of resveratrol treatment in an ex vivo re-endothelialization model and on mice undergone vascular graft were evaluated.Key Results
Resveratrol induced expression of endothelial markers such as CD31, VE-cadherin and eNOS in both progenitor and stem cells. We demonstrated that resveratrol significantly reduced miR-21 expression, which in turn reduced Akt phosphorylation. This signal cascade diminished the amount of nuclear β-catenin, inducing endothelial marker expression and increasing tube-like formation by progenitor cells. Both the inhibition of miR-21 and the knockdown of β-catenin were able to recapitulate the effect of resveratrol application. Ex vivo, progenitor cells treated with resveratrol produced better endothelialization of the decellularized vessel. Finally, in a mouse model of vessel graft, a resveratrol-enhanced diet was able to reduce lesion formation.Conclusions and Implications
We provide the first evidence that oral administration of resveratrol can reduce neointimal formation in a model of vascular graft and elucidated the underpinning miR-21/Akt/β-catenin dependent mechanism. These findings may support the beneficial effect of resveratrol supplementation for graft failure prevention. 相似文献64.
Dimitrios Draganidis Athanasios Chatzinikolaou Alexandra Avloniti José C. Barbero-álvarez Magni Mohr Paraskevi Malliou Vassilios Gourgoulis Chariklia K. Deli Ioannis I. Douroudos Konstantinos Margonis Asimenia Gioftsidou Andreas D. Flouris Athanasios Z. Jamurtas Yiannis Koutedakis Ioannis G. Fatouros 《PloS one》2015,10(7)
65.
Vassilis Stavrakas Ioannis N. Melas Theodore Sakellaropoulos Leonidas G. Alexopoulos 《PloS one》2015,10(5)
Modeling of signal transduction pathways is instrumental for understanding cells’ function. People have been tackling modeling of signaling pathways in order to accurately represent the signaling events inside cells’ biochemical microenvironment in a way meaningful for scientists in a biological field. In this article, we propose a method to interrogate such pathways in order to produce cell-specific signaling models. We integrate available prior knowledge of protein connectivity, in a form of a Prior Knowledge Network (PKN) with phosphoproteomic data to construct predictive models of the protein connectivity of the interrogated cell type. Several computational methodologies focusing on pathways’ logic modeling using optimization formulations or machine learning algorithms have been published on this front over the past few years. Here, we introduce a light and fast approach that uses a breadth-first traversal of the graph to identify the shortest pathways and score proteins in the PKN, fitting the dependencies extracted from the experimental design. The pathways are then combined through a heuristic formulation to produce a final topology handling inconsistencies between the PKN and the experimental scenarios. Our results show that the algorithm we developed is efficient and accurate for the construction of medium and large scale signaling networks. We demonstrate the applicability of the proposed approach by interrogating a manually curated interaction graph model of EGF/TNFA stimulation against made up experimental data. To avoid the possibility of erroneous predictions, we performed a cross-validation analysis. Finally, we validate that the introduced approach generates predictive topologies, comparable to the ILP formulation. Overall, an efficient approach based on graph theory is presented herein to interrogate protein–protein interaction networks and to provide meaningful biological insights. 相似文献
66.
George Pentheroudakis Georgia Raptou Vassiliki Kotoula Ralph M. Wirtz Eleni Vrettou Vasilios Karavasilis Georgia Gourgioti Chryssa Gakou Konstantinos N. Syrigos Evangelos Bournakis Grigorios Rallis Ioannis Varthalitis Eleni Galani Georgios Lazaridis George Papaxoinis Dimitrios Pectasides Gerasimos Aravantinos Thomas Makatsoris Konstantine T. Kalogeras George Fountzilas 《PloS one》2015,10(5)
Background
Although host immune response is an emerging prognostic factor for colorectal cancer, there is no consensus on the optimal methodology, surrogate markers or tissue for study.Patients and Methods
Tumour blocks were prospectively collected from 344 patients with stage II/III colorectal cancer (CRC) treated with adjuvant chemotherapy. Whole section lymphocytic infiltration was studied along with mRNA expression of CD3Z, CD8, CD4, CXCL9, CXCL13, IGHM, FOXP3, SNAI2 and ESR1 by qRT-qPCR in tissue microarray (TMA) cores from the centre of tumour, invasive margin and adjacent normal mucosa.Results
Lymphocytic infiltration, deficient MMR (10.9%), KRAS (40.7%) and BRAF (4.9%) mutations or single mRNA gene expression were not prognostic. Tumour ESR1 gene expression (Hazard Ratio [HR] for relapse 2.33, 95% CI 1.35-4.02; HR for death 1.74, 95% CI 1.02-2.97) and absence of necrosis (HR for relapse 1.71, 95% CI 1.05-2.71; HR for death 1.98, 95% CI 1.14-3.43) were adverse prognostic features. We used CD3Z and CD8 expression in order to devise the mRNA-based Immune Score (mIS) and proceeded to partitioning analysis in 267 patients, with age, stage, tumour site (Right vs Left CRC), KRAS mutation and tumour mIS as input factors. Only in patients with stage III right-sided colon cancer, a low immune response was associated with inferior disease-free survival (mIS-low, HR for relapse 2.28, 95% CI 1.05-8.02). No prognostic significance was seen for tumour mIS in any other stage or site of CRC, or for a similar mIS score derived from adjacent normal mucosa. Independent adverse prognostic significance was retained in multivariable analysis for absence of necrosis, tumour ESR1 expression in all patients and low tumour mIS in stage III right-sided CRC.Conclusions
In localised CRC, mRNA-based CD3Z/CD8 profiling of tumour immune response may have stage, site and tissue-specific prognostic significance, along with ESR1 expression.Trial Registration
ANZCTR.org.au ACTRN12610000509066 相似文献67.
Panagiotis D. Dimitriou Nafsika Papageorgiou Christos Arvanitidis Georgia Assimakopoulou Kalliopi Pagou Konstantia N. Papadopoulou Alexandra Pavlidou Paraskevi Pitta Sofia Reizopoulou Nomiki Simboura Ioannis Karakassis 《PloS one》2015,10(10)
A large data set from the Eastern Mediterranean was analyzed to explore the relationship between seawater column variables and benthic community status. Our results showed a strong quantitative link between the seawater column variables (Chlorophyll a and Eutrophication Index) and various indicators describing benthic diversity and community composition. The percentage of benthic opportunistic species increased significantly in the stations with high trophic status of the seawater column and so did the strength of the coupling between values of seawater column and benthic indicators. The Eutrophication Index threshold level of 0.85, separating the “Bad and Poor” from “Moderate to High” conditions could serve as an acceptable critical value above which there is a readily observable change in benthic community composition. 相似文献
68.
Katharina M. Katsaros Walter S Speidl Svitlana Demyanets Stefan P. Kastl Konstantin A. Krychtiuk Anna Wonnerth Gerlinde Zorn Ioannis Tentzeris Serdar Farhan Gerald Maurer Johann Wojta Kurt Huber 《PloS one》2015,10(11)
Granulocyte-colony-stimulating-factor (G-CSF) induces mobilization of progenitor cells but may also exert pro-inflammatory and pro-thrombotic effects. Treatment with recombinant G-CSF after acute myocardial infarction is currently under examination and has been associated with in-stent restenosis. However, it is not known whether plasma levels of endogenous G-CSF are also associated with an increased cardiovascular risk. Therefore we included 280 patients with angiographically proven stable coronary artery disease. G-CSF was measured by specific ELISA and patients were followed for a median of 30 months for the occurrence of major adverse cardiovascular events (MACE: death, myocardial infarction, re-hospitalization). Those with cardiac events during follow-up showed significant higher G-CSF levels (32.3 pg/mL IQR 21.4–40.5 pg/mL vs. 24.6 pg/mL IQR 16.4–34.9 pg/mL; p<0.05) at baseline. Patients with G-CSF plasma levels above the median had a 2-fold increased risk for MACE (p<0.05). This was independent from established cardiovascular risk factors. In addition, G-CSF above the median was a predictor of clinical in-stent restenosis after implantation of bare-metal stents (6.6% vs. 19.4%; p<0.05) but not of drug-eluting stents (7.7% vs. 7.6%; p = 0.98). This data suggests that endogenous plasma levels of G-CSF predict cardiovascular events independently from established cardiac risk factors and are associated with increased in-stent restenosis rates after implantation of bare metal stents. 相似文献
69.
Anastasia Chasapi Paulina Wachowicz Anne Niknejad Philippe Collin Andrea Krapp Elena Cano Viesturs Simanis Ioannis Xenarios 《PloS one》2015,10(8)
Cytokinesis in fission yeast is controlled by the Septation Initiation Network (SIN), a protein kinase signaling network using the spindle pole body as scaffold. In order to describe the qualitative behavior of the system and predict unknown mutant behaviors we decided to adopt a Boolean modeling approach. In this paper, we report the construction of an extended, Boolean model of the SIN, comprising most SIN components and regulators as individual, experimentally testable nodes. The model uses CDK activity levels as control nodes for the simulation of SIN related events in different stages of the cell cycle. The model was optimized using single knock-out experiments of known phenotypic effect as a training set, and was able to correctly predict a double knock-out test set. Moreover, the model has made in silico predictions that have been validated in vivo, providing new insights into the regulation and hierarchical organization of the SIN. 相似文献
70.
Georgios Hadjigeorgiou Efthimios Dardiotis Georgios Tsivgoulis Triantafyllos Doskas Damianos Petrou Nikolaos Makris Nikolaos Vlaikidis Thomas Thomaidis Athanasios Kyritsis Nikolaos Fakas Xoulietta Treska Clementine Karageorgiou Stefania Sotirli Christos Giannoulis Dimitra Papadimitriou Ioannis Mylonas Evaggelos Kouremenos George S. Vlachos Dimitrios Georgiopoulos Despoina Mademtzoglou Michalis Vikelis Elias Zintzaras 《PloS one》2015,10(10)