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van der Tuin, S.J. (author), Kühnast, S. (author), Berbée, J. (author), Verschuren, L. (author), Pieterman, E.J. (author), Havekes, L.M. (author), van der Hoorn, J.W. (author), Rensen, P.C. (author), Jukema, J.W. (author), Princen, H.M. (author), Willems van Dijk, K. (author), Wang, Y. (author)Recently, we showed in APOE*3-Leiden.CETP mice that anacetrapib attenuated atherosclerosis development by reducing (V)LDL-C rather than by raising HDL-C. Here, we investigated the mechanism by which anacetrapib reduces (V)LDL-C and whether this effect was dependent on the inhibition of CETP. APOE*3-Leiden.CETP mice were fed a Western type diet...article 2015
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Kühnast, S. (author), Fiocco, M. (author), van der Hoorn, J.W.A. (author), Princen, H.M.G. (author), Jukema, J.W. (author)Non-HDL-cholesterol is well recognised as a primary causal risk factor in cardiovascular disease. However, despite consistent epidemiological evidence for an inverse association between HDL-C and coronary heart disease, clinical trials aimed at raising HDL-C (AIM-HIGH, HPS2-THRIVE, dal-OUTCOMES) failed to meet their primary goals. This...article 2015
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Busnadiego, O. (author), Gorbenko del Blanco, D. (author), González-Santamaría, J. (author), Habashi, J.P. (author), Calderon, J.F. (author), Sandoval, P. (author), Bedja, D. (author), Guinea-Viniegra, J. (author), Lopez-Cabrera, M. (author), Rosell-Garcia, T. (author), Snabel, J.M. (author), Hanemaaijer, R. (author), Forteza, A. (author), Dietz, H.C. (author), Egea, G. (author), Rodriguez-Pascual, F. (author)Patients with Marfan syndrome (MFS) are at high risk of life-threatening aortic dissections. The condition is caused by mutations in the gene encoding fibrillin-1, an essential component in the formation of elastic fibers. While experimental findings in animal models of the disease have shown the involvement of transforming growth factor-β (TGF...article 2015
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Kroese, E.D. (author), Bosgra, S. (author), Buist, H.E. (author), Lewin, G. (author), van der Linden, S.C. (author), Man, H.Y. (author), Piersma, A.H. (author), Rorije, E. (author), Schulpen, S.H.W. (author), Schwarz, M. (author), Uibel, F. (author), van Vugt-Lussenburg, B.M.A. (author), Wolterbeek, A.P.M. (author), van der Burg, B. (author)Previously we showed a battery consisting of CALUX transcriptional activation assays, the ReProGlo assay, and the embryonic stem cell test, and zebrafish embryotoxicity assay as 'apical' tests to correctly predict developmental toxicity for 11 out of 12 compounds, and to explain the one false negative [7]. Here we report on applying this battery...article 2015
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Buist, H.E. (author), Devito, S. (author), Goldbohm, R.A. (author), Stierum, R.H. (author), Venhorst, J. (author), Kroese, E.D. (author)Carbon capture and storage (CCS) technologies are considered vital and economic elements for achieving global CO2 reduction targets, and is currently introduced worldwide (for more information on CCS, consult for example the websites of the International Energy Agency (http://www.iea.org/topics/ccs/) and the Global CCS Institute (http://www...article 2015
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Wagner, A. (author), Cohen, N. (author), Kelder, T. (author), Amit, U. (author), Liebman, E. (author), Steinberg, D.M. (author), Radonjic, M. (author), Ruppin, E. (author)High-throughput omics have proven invaluable in studying human disease, and yet day-to-day clinical practice still relies on physiological, non-omic markers. The metabolic syndrome, for example, is diagnosed and monitored by blood and urine indices such as blood cholesterol levels. Nevertheless, the association between the molecular and the...article 2015
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Lukovac, S. (author), Belzer, C. (author), Pellis, L. (author), Keijser, B.J. (author), de Vos, W.M. (author), Montijn, R.C. (author), Roeselers, G. (author)The gut microbiota is essential for numerous aspects of human health. However, the underlying mechanisms of many host-microbiota interactions remain unclear. The aim of this study was to characterize effects of the microbiota on host epithelium using a novel ex vivo model based on mouse ileal organoids. We have explored the transcriptional...article 2014
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Eijckelhof, B.H.W. (author), Huysmans, M.A. (author), Blatter, B.M. (author), Leider, P.C. (author), Johnson, P.W. (author), van Dieën, J.H. (author), Dennerlein, J.T. (author), van der Beek, A.J. (author)This field study examined associations between workplace stressors and office workers' computer use patterns. We collected keyboard and mouse activities of 93 office workers (68F, 25M) for approximately two work weeks. Linear regression analyses examined the associations between self-reported effort, reward, overcommitment, and perceived stress...article 2014
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Wei, W. (author), Clockaerts, S. (author), Bastiaansen-Jenniskens, Y.M. (author), Gierman, L.M. (author), Botter, S.M. (author), Bierma-Zeinstra, S.M.A. (author), Weinans, H. (author), Verhaar, J.A.N. (author), Kloppenburg, M. (author), Zuurmond, A.M. (author), van Osch, G.J.V.M. (author)Objective: Since statins and fibrates are capable of improving the metabolic profile of patients as well as decreasing inflammation, they are considered as potential drugs for preventing osteoarthritis (OA). The goal of the present study was to investigate the effect of these drugs in the STR/Ort spontaneous OA mouse model. Design: Male STR/Ort...article 2014
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Boon, M.R. (author), Kooijman, S. (author), van Dam, A.D. (author), Pelgrom, L.R. (author), Berbée, J.F.P. (author), Visseren, C.A.R. (author), van Aggele, R.C. (author), van den Hoek, A.M. (author), Sips, H.C.M. (author), Lombès, M. (author), Havekes, L.M. (author), Tamsma, J.T. (author), Guigas, B. (author), Meijer, O.C. (author), Jukema, J.W. (author), Rensen, P.C.N. (author)The endocannabinoid system is an important player in energy metabolism by regulating appetite, lipolysis, and energy expenditure. Chronic blockade of the cannabinoid 1 receptor (CB1R) leads to long-term maintenance of weight loss and reduction of dyslipidemia in experimental and human obesity. The molecular mechanism by which CB1R blockade...article 2014
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Neumann, A. (author), Berends, E.T.M. (author), Nerlich, A. (author), Molhoek, E.M. (author), Gallo, R.L. (author), Meerloo, T. (author), Nizet, V. (author), Naim, H.Y. (author), von Köckritz-Blickwede, M. (author)NETs (neutrophil extracellular traps) have been described as a fundamental innate immune defence mechanism. Duringformation of NETs, the nuclear membrane is disrupted by an asyet unknown mechanism. In the present study we investigated the role of human cathelicidin LL-37 in nuclear membrane disruption and formation of NETs. Immunofluorescence...article 2014
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Commissaris, D.A.C.M. (author), Könemann, R. (author), Hiemstra-van Mastrigt, S. (author), Burford, E.M. (author), Botter, J. (author), Douwes, M. (author), Ellegast, R.P. (author)Sedentary work entails health risks. Dynamic (or active) workstations, at which computer tasks can be combined with physical activity, may reduce the risks of sedentary behaviour. The aim of this study was to evaluate short term task performance while working on three dynamic workstations: a treadmill, an elliptical trainer, a bicycle ergometer...article 2014
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Kim, E.S. (author), Cha, Y. (author), Ham, M. (author), Jung, J. (author), Kim, S.G. (author), Hwang, S. (author), Kleemann, R. (author), Moon, A. (author)A crucial role of the inflammatory lipid sphingosine-1-phosphate (S1P) in breast cancer aggressiveness has been reported. Recent clinical studies have suggested that C-reactive protein (CRP) has a role in breast cancer development. However, limited information is available on the molecular basis for the expression of CRP and its functional...article 2014
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Mariman, R. (author), Kremer, S.H.A. (author), Koning, F. (author), Nagelkerken, L. (author)Probiotic bacteria express a wide range of molecular structures that bind to receptors on innate immune cells and mediate health-promoting effects in the host. We have recently demonstrated in a colitis model that favourable effects of the probiotic mixture VSL#3 may in part be due to the suppression of intestinal chemokine expression. To obtain...article 2014
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Kooijman, S. (author), Boon, M.R. (author), Parlevliet, E.T. (author), Geerling, J.J. (author), van de Pol, V. (author), Romijn, J.A. (author), Havekes, L.M. (author), Meurs, I. (author), Rensen, P.C.N. (author)The melanocortin system is an important regulator of energy balance, and melanocortin 4 receptor (MC4R) deficiency is the most common monogenic cause of obesity. We investigated whether the relationship between melanocortin system activity and energy expenditure (EE) is mediated by brown adipose tissue (BAT) activity. Therefore, female APOE∗3...article 2014
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Kühnast, S. (author), van der Hoorn, J.W.A. (author), Pieterman, E.J. (author), van den Hoek, A.M. (author), Sasiela, W.J. (author), Gusarova, V. (author), Peyman, A. (author), Schäfer, H.L. (author), Schwahn, U. (author), Jukema, J.W. (author), Princen, H.M.G. (author)Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is a potential novel strategy for treatment of CVD. Alirocumab is a fully human PCSK9 monoclonal antibody in phase 3 clinical development. We evaluated the antiatherogenic potential of alirocumab in APOE∗3Leiden. CETP mice. Mice received a Western-type diet and were treated with...article 2014
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Zimmer, B. (author), Pallocca, G. (author), Dreser, N. (author), Foerster, S. (author), Waldmann, T. (author), Westerhout, J. (author), Julien, S. (author), Krause, K.H. (author), van Thriel, C. (author), Hengstler, J.G. (author), Sachinidis, A. (author), Bosgra, S. (author), Leist, M. (author)Developmental toxicity in vitro assays have hitherto been established as stand-alone systems, based on a limited number of toxicants. Within the embryonic stem cell-based novel alternative tests project, we developed a test battery framework that allows inclusion of any developmental toxicity assay and that explores the responses of such test...article 2014
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Gierman, L.M. (author), Kühnast, S. (author), Koudijs, A. (author), Pieterman, E.J. (author), Kloppenburg, M. (author), van Osch, G.J.V.M. (author), Stojanovic-Susulic, V. (author), Huizinga, T.W.J. (author), Princen, H.M.G. (author), Zuurmond. A.M., (author)Objective Hypercholesterolaemia, a risk factor for atherosclerosis (ATH), has been suggested to have a role in the development of osteoarthritis (OA). To test this hypothesis, the effect of cholesterol and different cholesterol-lowering treatments on OA was investigated in a mouse model resembling human lipoprotein metabolism. Methods Female...article 2014
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Gvaramia, D. (author), Blaauboer, M.E. (author), Hanemaaijer, R. (author), Everts, V. (author)Fibrosis underlies the pathogenesis of numerous diseases and leads to severe damage of vital body organs and, frequently, to death. Better understanding of the mechanisms resulting in fibrosis is essential for developing appropriate treatment solutions and is therefore of upmost importance. Recent evidence suggests a significant antifibrotic...article 2013
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van Diepen, J.A. (author), Berbée, J.F.P. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)Dyslipidemia and inflammation are well known causal risk factors the development of atherosclerosis. The interplay between lipid metabolism and inflammation at multiple levels in metabolic active tissues may exacerbate the development of atherosclerosis, and will be discussed in this review. Cholesterol, fatty acids and modified lipids can...article 2013