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Gayban, A.J.B. (author), Souza, L.A.C. (author), Cooper, S.G. (author), Regalado, E. (author), Kleemann, R. (author), Earley, Y.F. (author)Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of liver damage directly related to diabetes, obesity, and metabolic syndrome. The (pro)renin receptor (PRR) has recently been demonstrated to play a role in glucose and lipid metabolism. Here, we test the hypothesis that the PRR regulates the development of diet-induced hepatic...article 2023
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Eslami Amirabadi, H. (author), Donkers, J.M. (author), Wieringa, E. (author), Ingenhut, B. (author), Pieters, L. (author), Stevens, L. (author), Donkers, T. (author), Westerhout, J. (author), Masereeuw, R. (author), Bobeldijk-Pastorova, I. (author), Nooijen, I. (author), van de Steeg, E. (author)The majority of intestinal in vitro screening models use cell lines that do not reflect the complexity of the human intestinal tract and hence often fail to accurately predict intestinal drug absorption. Tissue explants have intact intestinal architecture and cell type diversity, but show short viability in static conditions. Here, we present a...article 2022
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Ostendorf, R. (author), Erpelinck, S. (author)The Organ-on-a-Chip Early Research Program enables TNO to offer state-of-the-art technologies that help the pharmaceutical industry advance drug development. An accurate, viable alternative to animal testing, on-a-chip technologies model human tissue functioning and accelerate compound development and testing. The Intestinal Epithelial Barrier...other 2022
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Ostendorf, R. (author)The Organ-on-a-Chip Early Research Program (ERP) has enabled TNO to offer a number of state-of-the-art technologies to help pharmaceutical and biotech companies advance and accelerate drug development. An accurate, viable alternative to animal testing, on-a-chip technologies model the workings of human tissue and accelerate compound development...other 2022
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Donkers, J.M. (author), Hoppener, E.M. (author), Grigoriev, I. (author), Will, L. (author), Melgert, B.N. (author), van der Zaan, B. (author), van de Steeg, E. (author), Kooter, I.M. (author)Micro- and nanoplastics (MNP) can be found virtually everywhere around us in the biosphere and food chain, therefore humans are continuously exposed to MNP, mainly via inhalation and ingestion. Here, we have applied physiologically relevant human-based advanced in vitro models representing the lung (MucilAir™) and gut (InTESTine™ and Intestinal...article 2022
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Giordano, L. (author), Mihaila, S.M. (author), Eslami Amirabadi, H. (author), Masereeuw, R. (author)Chronic kidney disease (CKD) typically appears alongside other comorbidities, highlighting an underlying complex pathophysiology that is thought to be vastly modulated by the bidirectional gut–kidney crosstalk. By combining advances in tissue engineering, biofabrication, microfluidics, and biosensors, microphysiological systems (MPSs) have...article 2021
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Kim, C. (author), Colborn, K. (author), van Buuren, S. (author), Loar, T. (author), Stevens-Lapsley, J.E. (author), Kittelson, A.J. (author)The purpose of this study was to develop and test personalized predictions for functional recovery after Total Knee Arthroplasty (TKA) surgery, using a novel neighbors-based prediction approach. We used data from 397 patients with TKA to develop the prediction methodology and then tested the predictions in a temporally distinct sample of 202...article 2021
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Gart, E. (author), van Duyvenvoorde, W. (author), Toet, K. (author), Caspers, M.P.M. (author), Verschuren, L. (author), Nielsen, M.J. (author), Leeming, D.J. (author), Lima, E.S. (author), Menke, A. (author), Hanemaaijer, R. (author), Keijer, J. (author), Salic, K. (author), Kleemann, R. (author), Morrison, M.C. (author)In obesity-associated non-alcoholic steatohepatitis (NASH), persistent hepatocellular damage and inflammation are key drivers of fibrosis, which is the main determinant of NASH-associated mortality. The short-chain fatty acid butyrate can exert metabolic improvements and anti-inflammatory activities in NASH. However, its effects on NASH...article 2021
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van Bilsen, J.H.M. (author), van den Brink, W. (author), van den Hoek, A.M. (author), Dulos, R. (author), Caspers, M.P.M. (author), Kleeman, R. (author), Wopereis, S. (author), Verschuren, L. (author)Metabolic disorders, such as obesity and type 2 diabetes have a large impact on global health, especially in industrialized countries. Tissue-specific chronic low-grade inflammation is a key contributor to complications in metabolic disorders. To support therapeutic approaches to these complications, it is crucial to gain a deeper understanding...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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Ruiz-Zapata, A.M. (author), Heinz, A. (author), Kerkhof, M.H. (author), van de Westerlo-van Rijt, C. (author), Schmelzer, C.E.H. (author), Stoop, R. (author), Kluivers, K.B. (author), Oosterwijk, E. (author)Fibroblast to myofibroblast differentiation is a key feature of wound-healing in soft tissues, including the vagina. Vaginal fibroblasts maintain the integrity of the vaginal wall tissues, essential to keep pelvic organs in place and avoid pelvic organ prolapse (POP). The micro-environment of vaginal tissues in POP patients is stiffer and has...article 2020
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Bar, A. (author), Kieronska-Rudek, A. (author), Proniewski, B. (author), Suraj-Prazmowska, J. (author), Czamara, K. (author), Marczyk, B. (author), Matyjaszczyk-Gwarda, K. (author), Jasztal, A. (author), Kus, E. (author), Majka, Z. (author), Kaczor, A. (author), Kurpinska, A. (author), Walczak, M. (author), Pieterman, E.J. (author), Princen, H.M.G. (author), Chlopicki, S. (author)Background Long-term feeding with a high-fat diet (HFD) induces endothelial dysfunction in mice, but early HFD-induced effects on endothelium have not been well characterized. Methods and Results Using an magnetic resonance imaging-based methodology that allows characterization of endothelial function in vivo, we demonstrated that short-term (2...article 2020
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Peters, R.J.B. (author), Oomen, A.G. (author), van Bemmel, G. (author), van Vliet, L. (author), Undas, A.K. (author), Munniks, S. (author), Bleys, R.L.A.W. (author), Tromp, P.C. (author), Brand, W. (author), van der Lee, M. (author)Silicon dioxide (silica, SiO2, SAS) and titanium dioxide (TiO2) are produced in high volumes and applied in many consumer and food products. As a consequence, there is a potential human exposure and subsequent systemic uptake of these particles. In this study we show the characterization and quantification of both total silicon (Si) and titanium...article 2020
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Oosterman, J.E. (author), Wopereis, S. (author), Kalsbeek, A. (author)Obesity and type 2 diabetes (T2D) have become a global health concern. The prevalence of obesity and T2D is significantly higher in shift workers compared to people working regular hours. An accepted hypothesis is that the increased risk for metabolic health problems arises from aberrantly timed eating behavior, that is, eating out of synchrony...article 2020
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Stevens, L.J. (author), van Lipzig, M.M.H. (author), Erpelinck, S.L.A. (author), Pronk, A. (author), van Gorp, J. (author), Wortelboer, H.M. (author), van de Steeg, E. (author)A majority of the preclinical intestinal screening models do not properly reflect the complex physiology of the human intestinal tract, resulting in low translational value to the clinical situation. The often used cell lines such as Caco-2 or HT-29 are not well suited to investigate the different processes that predict oral bioavailability in...article 2019
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Kubbinga, M. (author), Augustijns, P. (author), Garcia, M.A. (author), Heinen, C. (author), Wortelboer, H.M. (author), Verwei, M. (author), Langguth, P. (author)Chitosan is object of pharmaceutical research as a candidate permeability enhancer. However, chitosan was recently shown to reduce the oral bioavailability of acyclovir in humans. The effect of chitosan on two processes determining the oral bioavailability of acyclovir, bioaccessibility and intestinal absorption, was now investigated. Acyclovir...article 2019
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Tans, R. (author), van Diepen, J.A. (author), Bijlsma, S. (author), Verschuren, L. (author), Suppers, A. (author), Stienstra, R. (author), Wevers, R.A. (author), Tack, C.J. (author), Gloerich, J. (author), van Gool, A.J. (author)Background: Overweight and obesity can lead to adipose tissue inflammation, which causes insulin resistance and on the long-term type 2 diabetes mellitus (T2D). The inflammatory changes of obese-adipose tissue are characterized by macrophage infiltration and activation, but validated circulating biomarkers for adipose tissue inflammation for...article 2019
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Abe, N. (author), Kato, S. (author), Tsuchida, T. (author), Sugimoto, K. (author), Saito, R. (author), Verschuren, L. (author), Kleemann, R. (author), Oka, K. (author)Non-alcoholic steatohepatitis (NASH) is a fast-growing liver disease in the Western world. Currently, only a few animal models show both the metabolic and histological features of human NASH. We aimed to explore murine NASH models in a time dependent manner that exhibit metabolic, histological and transcriptomic hallmarks of human NASH. For this...article 2019
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Gart, E. (author), Souto Lima, E. (author), Schuren, F, (author), de Ruiter, C.G.F. (author), Attema, J. (author), Verschuren, L. (author), Keijer, J. (author), Salic, K. (author), Morrison, M.C. (author), Kleemann, R. (author)Development of non-alcoholic fatty liver disease (NAFLD) is linked to obesity, adipose tissue inflammation, and gut dysfunction, all of which depend on diet. So far, studies have mainly focused on diet-related fecal microbiota changes, but other compartments may be more informative on host health. We present a first systematic analysis of...article 2019
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Kuhnt, T. (author), marroquín García, R. (author), Camarero-Espinosa, S. (author), Dias, A. (author), ten Cate, A.T. (author), van Blitterswijk, C.A. (author), Moroni, L. (author), Baker, M.B. (author)To exploit the usability of Digital Light Processing (DLP) in regenerative medicine, biodegradable, mechanically customizable and well-defined polyester urethane acrylate resins were synthesized based on poly(caprolactone-co-trimethlenecarbonate). By controlling the monomer ratio, the resultant fabricated constructs showed tunable mechanical...article 2019