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van Gemert, Y. (author), Kozijn, A.E. (author), Pouwer, M.G. (author), Kruisbergen, N.N.L. (author), van den Bosch, M.H.J. (author), Blom, A.B. (author), Pieterman, E.J. (author), Weinans, H. (author), Stoop, R. (author), Princen, H.M.G. (author), van Lent, P.L.E.M. (author)Objective: High systemic cholesterol levels have been associated with osteoarthritis (OA) development. Therefore, cholesterol lowering by statins has been suggested as a potential treatment for OA. We investigated whether therapeutic high-intensive cholesterol-lowering attenuated OA development in dyslipidemic APOE*3Leiden.CETP mice. Methods:...article 2021
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Pouwer, M.G. (author)The thesis discussed several strategies that may contribute to further CVD risk reduction in the future. We described two novel lipid-lowering strategies, we unraveled (part of) the etiology of the cardiovascular safety issues of TKIs that are used for the treatment of CML, and we investigated the dose effects of PFOA on lipoprotein metabolism....doctoral thesis 2020
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van Esch, B.C.A.M. (author), van Bilsen, J.H.M. (author), Gros- van Hest, M. (author), Kleinjans, L. (author), Belzer, C. (author), Jeurink, P.V. (author), Garssen, J. (author), Smit, J.J. (author), Pieters, R.H.H. (author), Knippels, L.M. (author)Introduction This 4-center study is part of a project to validate a food allergy murine model for safety testing of hydrolyzed infant formulas. Aim The aim of the current multi-center experiment was to evaluate the residual allergenicity of three partial hydrolyzed whey proteins (pWH) in a multiple-parameter cow’s milk allergy murine model and...article 2020
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van Ginneken, V. (author), Verheij, E.R. (author), de Vries, E. (author), Schouten, F. (author), van der Greef, J. (author)There are currently two main directions with regard to nutritional supplements with PUFAs. The first research school recommends enriching the diet with the essential fatty acid (EFA) obtained from vegetable sources, the C18 lipid omega-3 molecule α-linolenic acid and then via the elongase/desaturase activity naturally in omega-3 Eicosapentaenoic...article 2020
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He, M. (author), Harms, A.C. (author), van Wijk, E. (author), Wang, M. (author), Berger, R. (author), Koval. S., (author), Hankemeier, T. (author), van der Greef, J. (author)Background. Rheumatoid arthritis (RA) is a complex, chronic autoimmune disease characterized by various inflammatory symptoms, including joint swelling, joint pain, and both structural and functional joint damage. The most commonly used animal model for studying RA is mice with collagen‐induced arthritis (CIA); the wide use of this model is due...article 2019
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Kozijn, A.E. (author), Gierman, L.M. (author), van der Ham, F. (author), Mulder, P. (author), Morrison, M.C. (author), Kühnast, S. (author), van der Heijden, R.A. (author), Stavro, P.M. (author), van Koppen, A. (author), Pieterman, E.J. (author), van den Hoek, A.M. (author), Kleemann, R. (author), Princen, H.M.G. (author), Mastbergen, S.C. (author), Lafeber, F.P.J.G. (author), Zuurmond, A.M. (author), Bobeldijk, I. (author), Weinans, H. (author), Stoop, R. (author)Objective. Human cohort studies have demonstrated a role for systemic metabolic dysfunction in osteoarthritis (OA) pathogenesis in obese patients. To explore the mechanisms underlying this metabolic phenotype of OA, we examined cartilage degradation in the knees of mice from different genetic backgrounds in which a metabolic phenotype was...article 2018
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van de Steeg, E. (author), Läppchen, T. (author), Aguilera, B. (author), Jansen, H.T. (author), Muilwijk, D. (author), Vermue, R. (author), van der Hoorn, J.W. (author), Donato, K. (author), Rossin, R. (author), de Visser, P.C. (author), Vlaming, M.L.H. (author)Antisense oligonucleotides (AONs) are promising candidates for treatment of Duchenne muscular dystrophy (DMD), a severe and progressive disease resulting in premature death. However, more knowledge on the pharmacokinetics of new AON drug candidates is desired for effective application in the clinic. We assessed the feasibility of using...article 2017
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Smit, J. (author), Zeeuw-Brouwer, M.L.D. (author), van Roest, M. (author), de Jong, G. (author), van Bilsen, J. (author)The current methodology to identify allergenic food proteins is effective in identifying those that are likely to cross-react with known allergens. However, most assays show false positive results for low/non-allergens. Therefore, an ex vivo/in vitro DC-T cell assay and an in vivo mouse model were used to distinguish known allergenic food...article 2016
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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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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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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
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van Esch, B.C.A.M. (author), van Bilsen, J.H.M. (author), Jeurink, P.V. (author), Garssen, J. (author), Penninks, A.H. (author), Smit, J.J. (author), Pieters, R.H.H. (author), Knippels, L.M.J. (author)This study describes two phases of a multi-phase project aiming to validate a mouse model for cow's milk allergy to assess the potential allergenicity of hydrolysed cow's milk based infant formulas (claim support EC-directive 2006/141/E). The transferability and the discriminatory power of this model was evaluated in 4 research centers. Mice...article 2013
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Verschuren, L. (author), Radonjic, M. (author), Wielinga, P.Y. (author), Kelder, T. (author), Kooistra, T. (author), van Ommen, B. (author), Kleemann, R. (author)AIMS: Combination-drug therapy takes advantage of the complementary action of their individual components, thereby potentiating its therapeutic effect. Potential disadvantages include side effects that are not foreseen on basis of the data available from drug monotherapy. Here, we used a systems biology approach to understand both the efficacy...article 2012
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Wong, M.C. (author), van Diepen, J.A. (author), Hu, L. (author), Guigas, B. (author), de Boer, H.C. (author), van Puijvelde, G.H. (author), Kuiper, J. (author), van Zonneveld, A.J. (author), Shoelson, S.E. (author), Voshol, P.J. (author), Romijn, J.A. (author), Havekes, L.M. (author), Tamsma, J.T. (author), Rensen, P.C.N. (author), Hiemstra, P.S. (author), Berbée, J.F.P. (author)Objective: The liver is the key organ involved in systemic inflammation, but the relation between hepatic inflammation and atherogenesis is poorly understood. Since nuclear factor-κB (NF-κB) is a central regulator of inflammatory processes, we hypothesized that chronically enhanced hepatic NF-κB activation, through hepatocyte-specific expression...article 2012
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de Vries-van der Weij, J. (author), Toet, K. (author), Zadelaar, A.S.M. (author), Wielinga, P.Y. (author), Kleemann, R. (author), Rensen, P.C.N. (author), Kooistra, T. (author), TNO Kwaliteit van Leven (author)Objective: Inflammation plays an important role in all stages of atherosclerosis, but little is known about the therapeutic effects of quenching inflammation in already existing atherosclerotic lesions. Putative beneficial effects of salicylate, an inhibitor of NF-κB activation, were studied in mice with established lesions. Methods: ApoE*3...article 2010
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TNO Kwaliteit van Leven (author), Bijland, S. (author), Pieterman, E.J. (author), Maas, A.C.E. (author), van der Hoorn, J.W.A. (author), van Erk, M.J. (author), van Klinken, J.B. (author), Havekes, L.M. (author), van Dijk, K.W. (author), Princen, H.M.G. (author), Rensen, P.C.N. (author)The peroxisome proliferator-activated receptor alpha (PPARalpha) activator fenofibrate efficiently decreases plasma triglycerides (TG), which is generally attributed to enhanced very low density lipoprotein (VLDL)-TG clearance and decreased VLDL-TG production. However, because data on the effect of fenofibrate on VLDL production are...article 2010
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Oranje, A.P. (author), Verbeek, R. (author), Verzaal, P. (author), Haspels, I. (author), Prens, E. (author), Nagelkerken, L. (author), TNO Kwaliteit van Leven (author)Background: Wet-wrap treatment (WWT) with diluted topical steroids is widely used in atopic dermatitis (AD). Mice with transgenic overexpression of human apolipoprotein C1 (APOC1) in the liver and the skin are not only characterized by hyperlipidaemia and raised IgE levels, but also by pruritic dermatitis and a disturbed skin barrier function,...article 2009
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Hu, C. (author), van Dommelen, J. (author), van der Heijden, R. (author), Spijksma, G. (author), Reijmers, T.H. (author), Wang, M. (author), Slee, E. (author), Lu, X. (author), Xu, G. (author), van der Greef, J. (author), Hankemeier, T. (author), TNO Kwaliteit van Leven (author)A reversed-phase liquid chromatography-linear ion trap-Fourier transform ion cyclotron resonance-mass spectrometry method was developed for the profiling of lipids in human and mouse plasma. With the use of a fused-core C<sub>8</sub> column and a binary gradient, more than 160 lipids belonging to eight different classes were detected in a single...article 2008
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Zadelaar, A.S.M. (author), Kleemann, R. (author), Verschuren, L. (author), de Vries-van der Weij, J. (author), van der Hoorn, J. (author), Princen, H.M. (author), Kooistra, T. (author), TNO Kwaliteit van Leven (author)Atherosclerosis is a multifactorial highly-complex disease with numerous etiologies that work synergistically to promote lesion development. The ability to develop preventive and ameliorative treatments will depend on animal models that mimic the human subject metabolically and pathophysiologically and will develop lesions comparable to those in...article 2007
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TNO Kwaliteit van Leven (author), Westerterp, M. (author), de Haan, W. (author), Berbée, J.F.P. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)Previous studies have shown that overexpression of human apolipoprotein C-I (apoC-I) results in moderate hypercholesterolemia and severe hypertriglyceridemia in mice in the presence and absence of apoE. We assessed whether physiological endogenous apoC-I levels are sufficient to modulate plasma lipid levels independently of effects of apoE on...article 2006
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