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Suchowerska, A.K. (author), Stokman, G. (author), Palmer, J.T. (author), Coghlan, P.A. (author), Pieterman, E.J. (author), Keijzer, N. (author), Lambert, G. (author), Chemello, K. (author), Jaafar, A.K. (author), Parmar, J. (author), Yan, L. (author), Tong, Y. (author), Mu, L. (author), Princen, H.M.G. (author), Bonnar, J. (author), Evison, B.J. (author)Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibits the clearance of low-density lipoprotein (LDL) cholesterol (LDL-C) from plasma by directly binding with the LDL receptor (LDLR) and sending the receptor for lysosomal degradation. As the interaction promotes elevated plasma LDL-C levels, and therefore a predisposition to...article 2022
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Onder, S. (author), van Grol, M. (author), Fidder, A. (author), Xiao, G. (author), Noort, D. (author), Yerramalla, U. (author), Tacal, O. (author), Schopfer, L.M. (author), Lockridge, O. (author)Chronic low-dose exposure to organophosphorus pesticides is associated with the risk of neurodegenerative disease. The mechanism of neurotoxicity is independent of acetylcholinesterase inhibition. Adducts on tyrosine, lysine, threonine, and serine can occur after exposure to organophosphorus pesticides, the most stable being adducts on tyrosine....article 2021
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Kuper, C.F. (author), Pieters, R.H.H. (author), van Bilsen, J.H.M. (author)The thoracic and peritoneal cavities are lined by serous membranes and are home of the serosal immune system. This immune system fuses innate and adaptive immunity, to maintain local homeostasis and repair local tissue damage, and to cooperate closely with the mucosal immune system. Innate lymphoid cells (ILCs) are found abundantly in the...article 2021
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Kuper, C.F. (author), van Bilsen, J. (author), Wijnands, M.V.W. (author)The thoracic cavities receive increasing attention in toxicology, because inhaled fibers and (nano)particles can reach these cavities and challenge the local lymphoid tissues. The thoracic and abdominopelvic cavities are controlled by the serosal immune system with its special, loosely organized lymphoid clusters, namely the fat-associated...article 2018
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Detection of the mechanism of immunotoxicity of cyclosporine A in murine in vitro and in vivo modelsSchmeits, P.C.J. (author), Schaap, M.M. (author), Luijten, M. (author), van Someren, E. (author), Boorsma, A. (author), van Loveren, H. (author), Peijnenburg, A.A.C.M. (author), Hendriksen, P.J.M. (author)Transcriptomics in combination with in vitro cell systems is a powerful approach to unravel modes of action of toxicants. An important question is to which extent the modes of action as revealed by transcriptomics depend on cell type, species and study type (in vitro or in vivo). To acquire more insight into this, we assessed the transcriptomic...article 2015
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Bodin, J. (author), Kocbach Bølling, A. (author), Wendt, A. (author), Eliasson, L. (author), Becher, R. (author), Kuper, F. (author), Løvik, M. (author), Nygaard, U.C. (author)Type 1 diabetes mellitus (T1DM) is an autoimmune destruction of insulin producing pancreatic beta-cells due to a genetic predisposition and can be triggered by environmental factors. We have previously shown that bisphenol A (BPA) accelerates the spontaneous development of diabetes in non-obese diabetic (NOD) mice. Here, we hypothesized that...article 2015
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Raiten, D.J. (author), Sakr Ashour, F.A. (author), Ross, A.C. (author), Meydani, S.N. (author), Dawson, H.D. (author), Stephensen, C.B. (author), Brabin, B.J. (author), Suchdev, P.S. (author), van Ommen, B. (author), Ahluwalia, N. (author), Ahmed, T. (author), Allen, L. (author), Beck, M. (author), Blanchard, H. (author), Brindle, E. (author), Brown, K. (author), Calder, P. (author), Checkley, W. (author), Claycombe, K. (author), Coles, C. (author), Esamai, F. (author), Friis, H. (author), Gardner, E. (author), Grinspoon, S. (author), Guerrant, R. (author), Hellerstein, M. (author), Hunt, J. (author), King, J. (author), Klasing, K. (author), Kramer, B. (author), Koski, K. (author), Northrop-Clewes, C. (author), Pfeiffer, C. (author), Prentice, A. (author), Ramirez-Zea, M. (author), van Rheenan, P. (author), Rink, L. (author), Srinivasa, S. (author), Benn, C.S. (author), Stephensen, C. (author), Suchdev, P. (author), Sullivan, K. (author), Thurnham, D. (author), Varadhan, R. (author), Van Der Ven, A. (author), Walston, J. (author), Xia, J. (author)An increasing recognition has emerged of the complexities of the global health agenda-specifically, the collision of infections and noncommunicable diseases and the dual burden of over- and undernutrition. Of particular practical concern are both 1) the need for a better understanding of the bidirectional relations between nutritional status and...article 2015
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Vogt, L.M. (author), Meyer, D. (author), Pullens, G. (author), Faas, M.M. (author), Venema, K. (author), Ramasamy, U. (author), Schols, H.A. (author), de Vos, P. (author)Dietary fiber intake is associated with lower incidence and mortality from disease, but the underlying mechanisms of these protective effects are unclear.We hypothesized that β2→1-fructan dietary fibers confer protection on intestinal epithelial cell barrier function via Toll-like receptor 2 (TLR2), and we studied whether β2→1-fructan chain...article 2014
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de Lange-Brokaar, B.J.E. (author), Ioan-Facsinay, A. (author), van Osch, G.J.V.M. (author), Zuurmond, A.-M. (author), Schoones, J. (author), Toes, R.E.M. (author), Huizinga, T.W.J. (author), Kloppenburg, M. (author)Objective: Although osteoarthritis (OA) is considered a non-inflammatory condition, it is widely accepted that synovial inflammation is a feature of OA. However, the role of immune cells and their cytokines in OA is largely unknown. This narrative systematic review summarizes the knowledge of inflammatory properties, immune cells and their...article 2012
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Mariman, R. (author), Kremer, S.H.A. (author), van Erk, M. (author), Lagerweij, T. (author), Koning, F. (author), Nagelkerken, L. (author)Background: Host-microbiota interactions in the intestinal mucosa play a major role in intestinal immune homeostasis and control the threshold of local inflammation. The aim of this study was to evaluate the efficacy of probiotics in the recurrent trinitrobenzene sulfonic acid (TNBS)-induced colitis model and gain more insight into protective...article 2012
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Tonk, E.C.M. (author), de Groot, D.M.G. (author), Penninks, A.H. (author), Waalkens - Berendsen, I.D.H. (author), Wolterbeek, A.P.M. (author), Slob, W. (author), Piersma, A.H. (author), van Loveren, H. (author), TNO Kwaliteit van Leven (author)Current developmental and reproductive toxicity protocols include only a limited set of parameters for effects on the developing immune system. In this study, a wide range of immunological parameters were included in a pre- and postnatal developmental toxicity study. Dose-response data were compared to determine the relative sensitivity of...article 2010
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Willemsen, G. (author), de Geus, E.J.C. (author), Bartels, M. (author), van Beijsterveldt, C.E.M.T. (author), Brooks, A.I. (author), Estourgie-van Burk, G.F. (author), Fugman, D.A. (author), Hoekstra, C. (author), Hottenga, J.-J. (author), Kluft, K. (author), Meijer, P. (author), Montgomery, G.W. (author), Rizzu, P. (author), Sondervan, D. (author), Smit, A.B. (author), Spijker, S. (author), Suchiman, H.E.D. (author), Tischfield, J.A. (author), Lehner, T. (author), Slagboom, P.E. (author), Boomsma, D.I. (author), TNO Kwaliteit van Leven (author)In 2004 the Netherlands Twin Register (NTR) started a large scale biological sample collection in twin families to create a resource for genetic studies on health, lifestyle and personality. Between January 2004 and July 2008, adult participants from NTR research projects were invited into the study. During a home visit between 7:00 and 10:00 am...article 2010
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van Riet, E. (author), Everts, B. (author), Retra, K. (author), Phylipsen, M. (author), van Hellemond, J.J. (author), Tielens, A.G.M. (author), van der Kleij, D. (author), Hartgers, F.C. (author), Yazdanbakhsh, M. (author), TNO Defensie en Veiligheid (author)Background: Recognition of pathogens by dendritic cells (DCs) through interaction with pattern recognition receptors, including Toll like receptors (TLR), is crucial for the initiation of appropriate polarized T helper (Th) cell responses. Yet, the characteristics and differences in molecular profiles of DCs with different T cell polarizing...article 2009
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Blink, M. (author), Buitenkamp, T.D. (author), van Wouwe, J.P. (author), van Wering, E.R. (author), van der Velden, V.H.J. (author), Zwaan, C.M. (author), TNO Kwaliteit van Leven (author)Children with Down syndrome (DS) have an increased risk for developing both acute myeloid as well as acute lymphoblastic leukemia. These leukemias differ in clinical characteristics and biology compared to leukemias in non-DS children. Moreover, children with DS have an increased risk of side-effects from cytostatic therapy, which complicates...article 2009
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Boele, L.C.L. (author), Bajramovic, J.J. (author), de Vries, A.M.M.B.C. (author), Voskamp-Visser, I.A.I. (author), Kaman, W.E. (author), van der Kleij, D. (author), TNO Defensie en Veiligheid (author)Activation of pattern recognition receptors such as Toll-like receptors (TLRs) by pathogens leads to activation and maturation of dendritic cells (DC), which orchestrate the development of the adaptive immune response. To create an overview of the effects of a broad range of pathogenic bacteria, their capacity to activate TLRs and to affect DC...article 2009
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Liu, J. (author), O'Brien, K.L. (author), Lynch, D.M. (author), Simmons, N.L. (author), La Porte, A. (author), Riggs, A.M. (author), Abbink, P. (author), Coffey, R.T. (author), Grandpre, L.E. (author), Seaman, M.S. (author), Landucci, G. (author), Forthal, D.N. (author), Montefiori, D.C. (author), Carville, A. (author), Mansfield, K.G. (author), Havenga, M.J. (author), Pau, M.G. (author), Goudsmit, J. (author), Barouch, D.H. (author), TNO Kwaliteit van Leven (author)A recombinant adenovirus serotype 5 (rAd5) vector-based vaccine for HIV-1 has recently failed in a phase 2b efficacy study in humans. Consistent with these results, preclinical studies have demonstrated that rAd5 vectors expressing simian immunodeficiency virus (SIV) Gag failed to reduce peak or setpoint viral loads after SIV challenge of rhesus...article 2009
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TNO Kwaliteit van Leven (author), Lindeman, J.H.N. (author), Abdul-Hussien, H. (author), van Bockel, J.H. (author), Wolterbeek, R. (author), Kleemann, R. (author)Background-Doxycycline has been shown to effectively inhibit aneurysm formation in animal models of abdominal aortic aneurysm. Although this effect is ascribed to matrix metalloproteinase-9 inhibition, such an effect is unclear in human studies. We reevaluated the effect of doxycycline on aortic wall protease content in a inical trial and found...article 2009
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van Noort, J.M. (author), TNO Kwaliteit van Leven (author)Stress proteins or heat shock proteins (HSPs) are ubiquitous cellular components that have long been known to act as molecular chaperones. By assisting proper folding and transport of proteins, and by assisting in the degradation of aberrant proteins, they play key roles in cellular metabolism. The frequent accumulation of insoluble protein...article 2008
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Lindeman, J.H.N. (author), Abdul-Hussien, H. (author), Schaapherder, A.F.M. (author), van Bockel, J.H. (author), von der Thüsen, J.H. (author), Roelen, D.L. (author), Kleemann, R. (author)Inflammation plays a key role in the pathogenesis of an AAA (abdominal aortic aneurysm); however, the nature of the inflammatory factors and cellular response(s) involved in AAA growth is controversial. In the present study, we set out to determine the aortic levels of inflammatory cytokines in relation to downstream inflammatory transcription...article 2008
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Kel, J.M. (author), Slütter, B. (author), Drijfhout, J.W. (author), Koning, F. (author), Nagelkerken, L. (author), TNO Kwaliteit van Leven (author)Tolerance to experimental autoimmune encephalomyelitis (EAE) in SJL mice can be induced by immunization with a mannosylated form of the proteolipid protein (M-PLP139-151), despite the presence of CFA. The state of tolerance is characterized by poor delayed-type hypersensitivity responses and the absence of clinical EAE symptoms. In vivo...article 2008