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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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Stevens, L.J. (author), Donkers, J.M. (author), Dubbel, J. (author), Vaes, W.H.J. (author), van de Steeg, E. (author), Knibbe, C.A.J. (author), Alwayn, I.P.J. (author), van de Steeg, E. (author)To predict the absorption, distribution, metabolism and excretion (ADME) profile of candidate drugs a variety of preclinical models can be applied. The ADME and toxicological behavior of newly developed drugs are often investigated prior to assessment in humans, which is associated with long time-lines and high costs. Therefore, good predictions...article 2020
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Moné, M.J. (author), Pallocca, G. (author), Escher, S.E. (author), Exner, T. (author), Herzler, M. (author), Hougaard Bennekou, S. (author), Kamp, H. (author), Kroese, E.D. (author), Leist, M. (author), Steger-Hartmann, T. (author), van de Water, B. (author)In 2016, the European Commission launched the EU-ToxRisk research project to develop and promote animal-free approaches in toxicology. The 36 partners of this consortium used in vitro and in silico methods in the context of case studies (CSs). These CSs included both compounds with a highly defined target (e.g. mitochondrial respiratory chain...article 2020
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Verhoeckx, K. (author), lindholm Bøgh, K. (author), Constable, A. (author), Epstein, M.M. (author), hoffmann Sommergruber, K. (author), Holzhauser, T. (author), Houben, G. (author), Kuehn, A. (author), Roggen, E. (author), O'Mahony, L. (author), Remington, B. (author), Crevel, R. (author)The growing world population and increased pressure on agricultural resources are driving a shortage of dietary protein sources. As a result, industry is developing more sustainable novel food protein sources such as insects, algae and duckweed and using new processing techniques. Consumer exposure to these novel or processed proteins, could...article 2020
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Verhoeckx, K. (author), Bogh, K.L. (author), Dupont, D. (author), Egger, L. (author), Gadermaier, G. (author), Larre, C. (author), Mackie, A. (author), Menard, O. (author), Adel-Patient, K. (author), Picariello, G. (author), Portmann, R. (author), Smit, J. (author), Turner, P. (author), Untersmayr, E. (author), Epstein, M.M. (author)The current allergenicity assessment of novel proteins is based on the EFSA GMO guidance. Recently, EFSA launched a new guidance document on allergenicity assessment of GM plants (2017). This document describes, amongst other topics, the new scientific and regulatory developments on in vitro protein digestibility tests. The EFSA GMO Panel stated...article 2019
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Remington, B. (author), Broekman, H.C.H. (author), Blom, W.M. (author), Capt, A. (author), Crevel, R.W.R. (author), Dimitrov, I. (author), Faeste, C.K. (author), Fernandez-Canton, R. (author), Giavi, S. (author), Houben, G.F. (author), Glenn, K.C. (author), Madsen, C.B. (author), Kruizinga, A.K. (author), Constable, A. (author)The development and introduction of new dietary protein sources has the potential to improve food supply sustainability. Understanding the potential allergenicity of these new or modified proteins is crucial to ensure protection of public health. Exposure to new proteins may result in de novo sensitization, with or without clinical allergy, or...article 2018
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Wambaugh, J.F. (author), Hughes, M.F. (author), Ring, C.L. (author), MacMillan, D.K. (author), Ford, J. (author), Fennell, T.R. (author), Black, S.R. (author), Snyder, R.W. (author), Sipes, N.S. (author), Wetmore, B.A. (author), Westerhout, J. (author), Setzer, R.W. (author), Pearce, R.G. (author), Simmons, J.E. (author), Thomas, R.S. (author)Prioritizing the risk posed by thousands of chemicals potentially present in the environment requires exposure, toxicity, and toxicokinetic (TK) data, which are often unavailable. Relatively high throughput, in vitro TK (HTTK) assays and in vitro-to-in vivo extrapolation (IVIVE) methods have been developed to predict TK, but most of the in vivo...article 2018
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Botschuijver, S. (author), Welting, O. (author), Levin, E. (author), Maria-Ferreira, D. (author), Koch, E. (author), Montijn, R.C. (author), Seppen, J. (author), Hakvoort, T.B.M. (author), Schuren, F.H.J. (author), de Jonge, W.J. (author), van den Wijngaard, R.M. (author)Background: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder associated with altered gastrointestinal microflora and increased nociception to colonic distension. This visceral hypersensitivity can be reversed in our rat maternal separation model by fungicides. Menthacarin® is a proprietary combination of essential oils from...article 2018
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Raaphorst, R.M. (author), Savolainen, H. (author), Cantore, M. (author), van de Steeg, E. (author), van Waarde, A. (author), Colabufo, N.A. (author), Elsinga, P.H. (author), Lammertsma, A.A. (author), Windhorst, A.D. (author), Luurtsema, G. (author)Positron emission tomography (PET) imaging of P-glycoprotein (P-gp) in the blood-brain barrier can be important in neurological diseases where P-gp is affected, such as Alzheimer’s disease. Radiotracers used in the imaging studies are present at very small, nanomolar, concentration, whereas in vitro assays where these tracers are characterized,...article 2017
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Luijten, M. (author), Olthof, E.D. (author), Hakkert, B.C. (author), Rorije, E. (author), van der Laan, J.-W. (author), Woutersen, R.A. (author), van Benthem, J. (author)Assessment of genotoxic and carcinogenic potential is considered one of the basic requirements when evaluating possible human health risks associated with exposure to chemicals. Test strategies currently in place focus primarily on identifying genotoxic potential due to the strong association between the accumulation of genetic damage and cancer...article 2016
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Higuera, G.A. (author), Fernandes, H. (author), Spitters, T.W.G.M. (author), van de Peppel, J. (author), Aufferman, N. (author), Truckenmueller, R. (author), Stoop, R. (author), van Leeuwen, J.P. (author), de Boer, J. (author), Subramaniam, V. (author), Karperien, M. (author), van Blitterswijk, C. (author), van Boxtel, A. (author), Moroni, L. (author)Cells and tissues are intrinsically adapted to molecular gradients and use them to maintain or change their activity. The effect of such gradients is particularly important for cell populations that have an intrinsic capacity to differentiate into multiple cell lineages, such as bone marrow derived mesenchymal stromal cells (MSCs). Our results...article 2015
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Reinen, J. (author), Nematollahi, L. (author), Fidder, A. (author), Vermeulen, N.P.E. (author), Noort, D. (author), Commandeur, J.N.M. (author)Tri-ortho-cresyl phosphate (ToCP) is a multipurpose organophosphorus compound that is neurotoxic and suspected to be involved in aerotoxic syndrome in humans. It has been reported that not ToCP itself but a metabolite of ToCP, namely, 2-(ortho-cresyl)-4H-1,2,3-benzodioxaphosphoran-2-one (CBDP), may be responsible for this effect as it can...article 2015
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Bosgra, S. (author), Westerhout, J. (author)In the EU collaborative project ChemScreen an alternative, in vitro assay-based test strategy was developed to screen compounds for reproductive toxicity. A toxicokinetic modeling approach was used to allow quantitative comparison between effective concentrations in the in vitro test battery and observations of developmental toxicity in vivo....article 2015
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Johnson, D. (author), Carter, M.D. (author), Crow, B.S. (author), Isenberg, S.L. (author), Graham, L.A. (author), Erol, H.A. (author), Watson, C.M. (author), Pantazides, B.G. (author), van der Schans, M.J. (author), Langenberg, J.P. (author), Noort, D. (author), Blake, T.A. (author), Thomas, J.D. (author), Johnson, R.C. (author)Tri-ortho-cresyl phosphate (ToCP) is an anti-wear, flame retardant additive used in industrial lubricants, hydraulic fluids and gasoline. The neurotoxic effects of ToCP arise from the liver-activated metabolite 2-(o-cresyl)-4H-1,3,2-benzodioxaphosphoran-2-one (cresyl saligenin phosphate or CBDP), which inhibits esterase enzymes including...article 2015
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Walczak, A.P. (author), Hendriksen, P.J.M. (author), Woutersen, R.A. (author), van der Zande, M. (author), Undas, A.K. (author), Helsdingen, R. (author), van den Berg, H.H.J. (author), Rietjens, I.M.C.M. (author), Bouwmeester, H. (author)The likelihood of oral exposure to nanoparticles (NPs) is increasing, and it is necessary to evaluate the oral bioavailability of NPs. In vitro approaches could help reducing animal studies, but validation against in vivo studies is essential. Previously, we assessed the translocation of 50 nm polystyrene NPs of different charges (neutral,...article 2015
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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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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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Aguirre, M. (author), Ramiro-Garcia, J. (author), Koenen, M.E. (author), Venema, K. (author)This study investigated the stability and the activity of the microbiota from a single and a pool of donors in the TNO in vitro model of the colon (TIM-2 system). Our findings demonstrate the suitability of the preparation of a pool of fecal sample to be used for fermentation experiments. Chemicals/CAS: isobutyric acid, 5711-69-3, 79-31-2;...article 2014
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Bosgra, S. (author), van de Steeg, E. (author), Vlaming, M.L. (author), Verhoeckx, K.C. (author), Huisman, M.T. (author), Verwei, M. (author), Wortelboer, H.M. (author)In contrast to primary hepatocytes, estimating carrier-mediated hepatic disposition by using a panel of single transfected cell-lines provides direct information on the contribution of the individual transporters to the net disposition. The most direct way to correct for differences in transporter abundance between cell-lines and tissue is by...article 2014
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Kostewicz, E.S. (author), Abrahamsson, B. (author), Brewster, M. (author), Brouwers, J. (author), Butler, J. (author), Carlert, S. (author), Dickinson, P.A. (author), Dressman, J. (author), Holm, R. (author), Klein, S. (author), Mann, J. (author), McAllister, M. (author), Minekus, M. (author), Muenster, U. (author), Müllertz, A. (author), Verwei, M. (author), Vertzoni, M. (author), Weitschies, W. (author), Augustijns, P. (author)Accurate prediction of the in vivo biopharmaceutical performance of oral drug formulations is critical to efficient drug development. Traditionally, in vitro evaluation of oral drug formulations has focused on disintegration and dissolution testing for quality control (QC) purposes. The connection with in vivo biopharmaceutical performance has...article 2014