马泰克的科学家们正在参加并展示海报 2021年Eurotox国会 在哥本哈根,丹麦. 阅读更多，看看我们一直在做什么，并索取我们的海报副本.
IN VITRO MODELING OF INFLAMMATION-INDUCED INTESTINAL BARRIER DAMAGE AND REPAIR WITH THERAPEUTIC CANDIDATES
马库斯·简1, Letasiova西尔维亚1, Belich莫妮卡2， Robas Nicola2, Kanumilli Srinivasan2马查多卡2, Ayehunie塞尤姆3
3 华体会网页版, Ashland, MA - USA
Proper functioning of the gastrointestinal tract depends on the functional physiology and intactness of the mucosa lining of the gut. Disruption of the intestinal barrier integrity can cause inflammation in patients that can lead to chronic diseases such as trauma or inflammatory bowel diseases. 为了模拟体外肠道屏障的破坏，我们暴露 Epi肠 (in vitro reconstructed 3D human small intestine epithelium) to various combinations of cytokines that were previously shown to play a role in the pathogenesis of inflammatory bowel disease. Prolonged exposure of Epi肠 tissue to the combination of tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ) results in an approximate 30% decrease in barrier integrity as established by measurement of trans-epithelial electric resistance (TEER). This decline was associated with the induction of several proinflammatory cytokines including interleukins 6 and 8 (IL6, IL8). 除了对完整的肠上皮细胞的影响, treatment with TNFα and IFNγ hindered the reconstitution of mechanically injured/wounded tissues. In cytokine treated tissues wounds were healing much slower than controls and newly grown tissue appeared structurally different. To test if this model of inflammation-induced barrier disruption can be used to screen potential therapeutic compounds, we exposed wounded tissues to relevant concentrations of anti-inflammatory compounds. Most of the tested candidate drugs were capable to counteract the disruption of barrier integrity. In addition two of them also shown the ability to promote healing of tissues exposed to the combination of mechanical wounds and cytokines. 简而言之, the reconstructed 3D small intestine epithelium model (Epi肠) can be used to mimic the intestinal barrier disruption associated with chronic inflammation, 哪些可能有助于识别潜在的治疗药物.
关键词: reconstructed tissue; intestine; macrophage; tissue engineering; innate immunity
ALT4EI: DETERMINATION OF EYE IRRITATING POTENTIAL OF 59 CHEMICALS USING EPIOCULAR™ TIME-TO-TOXICITY NEAT AND DILUTION PROTOCOLS
3 Adriaens Consulting BVBA, Bellemdorpweg 95,9981 Aalter，比利时
4 VITO NV, UNI Health, Boeretang 200，摩尔2400，比利时
Determination of acute eye irritation potential is part of international regulatory requirements for the testing of chemicals. The objective of ALT4EI (ALTernatives for Eye Irritation) project was to confirm the testing strategy developed in CON4EI (CONsortium for in vitro Eye Irritation testing strategy)project. These projects focused on the development of tiered testing strategies for eye irritation assessment for all drivers of classification and evaluation of whether the test methods can discriminate chemicals not requiring classification for serious eye damage/eye irritancy (No Category) from chemicals requiring classification and labeling for Category 1 (Cat 1) and Category 2 (Cat 2). 在CON4EI项目中，提出了一种新的测试策略 Epi眼 time-to-toxicity开发, 预测GHS Cat 1和GHS Cat 2化学物质的敏感性分别为73%和64%, 分别, 97%的特异度得到了保持. 没有一种Cat 1类化学物质被低估为GHS No Category. Plus the goal of the ALT4EI project was to fill the remaining data gaps and strengthen the data set. 一套新的59种化学品(41种液体:未稀释), 用重建的人角膜样上皮细胞检测18个固体), Epi眼, 在两次Epi眼毒性时间测试中(纯和稀释). The set of chemicals contained 32 chemicals not requiring classification (No Cat) and 27 chemicals requiring classification (16 Cat 2 and 11 Cat 1). 华体会网页版在两次独立的试验中对这些化学物质进行了盲法测试. 在这项研究中, a testing strategy to achieve optimal prediction for all three classes developed in the CON4EI project (combining the most predictive time-points of both protocols and which tests liquids and solids separately) was used. 使用CON4EI测试策略, 我们能正确地辨认出63,6%的第一类化学物质,56,6%的猫2, 和76年,6%的无猫化学物质. 两组的重现性为88.7%. The combination of the Epi眼 time-to-toxicity neat and dilution protocols seems to be promising in integrated testing strategy (ITS) for eye irritation assessment.
关键词: ALT4EI; Epi眼; ocular irritation assay; in vitro; testing strategy
NOVEL APPROACH FOR CHARACTERIZING EXPOSURE AND RESPONSE TO ENGINEERED NANOMATERIALS IN THE GUT
S. Ayehunie P. 大草原，简·马库斯，M. 时,才具有. Armento 华体会网页版, Ashland MA, USA
尽管工程纳米颗粒(ENPs)的应用数量不断增加，, 人们对与摄入纳米颗粒有关的人类健康问题知之甚少. 在本研究中，我们利用 三维人体小肠组织模型 to develop a physiologically relevant test system to assess toxicological profiles of ingestible nanomaterials. We examined barrier integrity and cytotoxicity of the human 3D intestinal tissue model following exposure (4 doses of each nanoparticle to Cupric (II) oxide (CuO) (50 nm in size), 氧化锌纳米, 尺寸35- 45nm), 和氧化钛(TiO .2，尺寸为40纳米). To monitor the reproducibility of the test method the 纳米粒子 were tested using 3-4 intestinal tissue lots. 测定纳米颗粒对小肠组织的影响, 我们检查了1)屏障完整性(TEER), 2)组织活力(MTT), 炎症反应(ELISA检测). 在各种实验中进行, the tissues were exposed to 40 ul of different doses of sonicated 纳米粒子 under rocking conditions for 4 hr. 4小时后，给药的组织在静态条件下进一步培养过夜. Using IC15 (concentration that reduces barrier function or tissue viability by 15%) as a cut-off, we observed a dose-response reduction of barrier integrity and tissue viability for CuO and ZnO. 然而，氧化钛对测试浓度没有诱导毒性. 此外, culture supernatants collected from at 24 hr of the culture period were also analyzed for inflammatory response and the result showed a dose-dependent release of IL-8 for CuO and ZnO but not for TiO2 纳米粒子. Overall, the TEER measurement was a sensitive endpoint compared to the MTT tissue viability assay. 总之, the use SMI tissue model to examine the toxicity profile of ingestible nanotoxicity will also enhance our understanding of nanoparticle-host cell interaction, 提高剂量/设计, 生成一个生理相关的数据集, 并对纳米颗粒暴露的体内反应提供了更深入的了解.