uptake

吸收量
  • 文章类型: Journal Article
    围绕荧蒽(FLN)不断升级的担忧,菲(Phe),和芘(Pyr),强调了在农业生态系统背景下调查其动态的紧迫性。油菜亚种。chinensis(Bokchoy),一种全球消费的蔬菜,在这种情况下具有特别重要的意义。本研究探讨了FLN的迁移和转化,Phe,和Pyr从土壤到芸苔属亚种。在它的生长过程中。这些处理中种子的发芽率各不相同,土壤+博克菜和土壤+FLN+博克菜处理显示出较高的比率(77.8%),而土壤+混合物+Bokchoy在3天后表现出最低的比率(11.1%)。分析FLN的分布,Phe,和Pyr在芸苔亚种中。30天后的中国部分显示茎>根>叶中的积累序列。这项研究提供了有关调节FLN的土壤-植物迁移和转化的实际意义的信息,Phe,还有Pyr,为农业环境中多环芳烃污染的迁移提供有价值的见解。
    The escalating concern surrounding fluoranthene (FLN), phenanthrene (Phe), and pyrene (Pyr), underscores the urgency to investigate their dynamics in the context of agricultural ecosystems. Brassica rapa subsp. chinensis (Bok choy), a globally consumed vegetable, holds particular significance in this scenario. This study explores the migration and transformation of FLN, Phe, and Pyr from soil to Brassica rapa subsp. chinensis during its growth. The germination rates of seeds in these treatments varied, with soil+Bok choy and soil+FLN+Bok choy treatments showing higher rates (77.8%), while soil+mix+Bok choy exhibited the lowest rate (11.1%) after 3 days. Analyzing the distribution of FLN, Phe, and Pyr in Brassica rapa subsp. chinensis parts after 30 days revealed a sequence of accumulation in stem> root> leaf. This study provides information on practical implications for regulating the soil-plant migration and transformation of FLN, Phe, and Pyr, offering valuable insights for migration of PAHs pollution in agricultural settings.
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  • 文章类型: Journal Article
    系统植物保护产品,如新烟碱(NIs),能够在整个植物中转移。尽管NIs对哺乳动物的毒性较小,鱼,和鸟,它们对微生物和非目标昆虫的影响令人担忧。这项研究调查了吸收,易位,和NI的积累,吡虫啉(IMI),在生菜中(LactucasativaL.var。longipolia)。将15天龄的幼苗暴露于“10毫克/升”的IMI,研究了对栽培(CS)和非栽培土壤(NCS)中微生物群落的影响以及植物组织内的IMI易位。初始施用后,土壤中IMI的浓度随时间和土壤类型之间的变化而变化,CS和NCS从采样第一天的2.0和7.7mg/kg下降到最终采样日(第35天)的0.5和2.6mg/kg,分别。在CS和NCS中,IMI土壤的半衰期分别为10.7天和72.5天,分别,表明IMI在CS中降解更快,可能是由于晶粒尺寸较小,曝气,微生物降解,和水流。在CS和NCS中,莴苣组织中IMI的累积浓度范围为12.4±0.2和18.7±0.9mg/kg,分别。在枝条中发现了最高浓度的IMI,其次是根,而在试验结束时,土壤显示出最低的IMI残差。通过IMI的应用改变了土壤细菌和真菌,细菌群落中的丰度指数较低,这表明对土壤中细菌的分布有负面影响。
    Systemic plant protection products, such as neonicotinoids (NIs), are capable of being translocated throughout a plant. Although NIs are less toxic to mammals, fish, and birds, their impact on microbial and non-target insects is of concern. This study investigates the uptake, translocation, and accumulation of the NI, imidacloprid (IMI), in romaine lettuce (Lactuca sativa L. var. longipolia). Exposing 15-day-old seedlings to \"10 mg/L\" of IMI, the effects on microbial communities in both cultivated (CS) and non-cultivated soil (NCS) were studied along with IMI translocation within plant tissues. The concentrations of IMI in soil varied temporally and between soil types after initial application, with a decrease from 2.0 and 7.7 mg/kg on the first day of sampling to 0.5 and 2.6 mg/kg on the final sampling day (day 35) for CS and NCS, respectively. The half-life of IMI soil was 10.7 and 72.5 days in CS and NCS, respectively, indicating that IMI degraded more quickly in CS, possibly due to smaller grain size, aeration, microbial degradation, and water flow. The accumulated concentrations of IMI in lettuce tissues ranged from 12.4 ± 0.2 and 18.7± 0.9 mg/kg in CS and NCS, respectively. The highest concentration of IMI was found in the shoots, followed by the roots, whereas the soil showed the lowest IMI residuals at the end of the trial. Soil bacteria and fungi were altered by the application of IMI, with a lower abundance index within the bacterial community, indicating a negative impact on the distribution of bacteria in the soil.
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  • 文章类型: Journal Article
    食品级二氧化钛E171已用于糖果等产品,面团和面粉,以增强感官特性。欧盟警告说,口服对人类的不利影响。口腔暴露后,E171到达血流,这引起了人们对单核细胞等血细胞的影响的关注。这些细胞的主要功能之一是巨噬细胞的分化,导致外源颗粒的吞噬作用。这项研究的目的是评估E171暴露对单核细胞(THP-1)吞噬能力和向巨噬细胞分化过程的影响。对E171的理化性质进行了评估,和THP-1单核细胞暴露于4、40和200μg/ml。细胞活力,吸收能力,细胞因子释放,分化过程,测定细胞骨架排列和E171内化。结果表明,E171颗粒在细胞培养基中呈无定形形状,平均流体动力学尺寸为〜46nm。细胞活力下降,直到暴露的第9天,而单核细胞的摄取能力以浓度依赖性方式下降高达62%。此外,E171暴露增加了促炎细胞因子的释放,并使巨噬细胞的细胞分化减少了61%.E171诱导细胞骨架排列的变化,一些E171颗粒位于细胞核内。我们得出结论,THP-1单核细胞中的E171暴露诱导了炎症反应,吞噬能力受损,并干扰细胞从单核细胞分化为巨噬细胞。
    Food grade titanium dioxide E171 has been used in products such as confectionery, doughs and flours to enhance organoleptic properties. The European Union has warned about adverse effects on humans due to oral consumption. After oral exposure, E171 reaches the bloodstream which raises the concern about effects on blood cells such as monocytes. One of the main functions of these cells is the differentiation of macrophages leading to the phagocytosis of foreign particles. The aim of this study was to evaluate the effect of E171 exposure on the phagocytic capacity and differentiation process of monocytes (THP-1) into macrophages. Physicochemical E171 properties were evaluated, and THP-1 monocytes were exposed to 4, 40 and 200 μg/ml. Cell viability, uptake capacity, cytokine release, the differentiation process, cytoskeletal arrangement and E171 internalization were assayed. Results showed that E171 particles had an amorphous shape with a mean of hydrodynamic size of ∼46 nm in cell culture media. Cell viability decreased until the 9th day of exposure, while the uptake capacity decreased up to 62% in a concentration dependent manner in monocytes. Additionally, the E171 exposure increased the proinflammatory cytokines release and decreased the cell differentiation by a 61% in macrophages. E171 induced changes in cytoskeletal arrangement and some of the E171 particles were located inside the nuclei. We conclude that E171 exposure in THP-1 monocytes induced an inflammatory response, impaired the phagocytic capacity, and interfered with cell differentiation from monocytes to macrophages.
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  • 文章类型: Journal Article
    研究纳米材料与它们可能在体内遇到的细胞之间的相互作用是设计用于成像和治疗应用的纳米药物的关键方面。免疫细胞如树突状细胞,巨噬细胞,骨髓来源的抑制细胞在识别和清除体内异物方面具有前线作用,相互作用严重依赖于纳米颗粒尺寸等变量,charge,表面化学。相互作用,如细胞缔合或纳米颗粒的摄取可导致功能减弱或从体内快速清除,这使得在设计和合成从药物递送到成像和生物传感的生物医学应用的纳米材料时考虑这些相互作用变得至关重要。我们研究了聚乙二醇化的有机二氧化硅纳米颗粒与从小鼠骨髓中的干细胞生长的天然内吞免疫细胞之间的相互作用。具体来说,我们改变了颗粒大小从60纳米到1000纳米,并研究了大小对免疫细胞结合的影响,激活,和这些关键的看门人细胞的成熟。这些结果将有助于为利用有机二氧化硅纳米粒子的体外和体内生物医学应用提供未来的设计参数。
    Investigating the interactions between nanomaterials and the cells they are likely to encounter in vivo is a critical aspect of designing nanomedicines for imaging and therapeutic applications. Immune cells such as dendritic cells, macrophages, and myeloid derived suppressor cells have a frontline role in the identification and removal of foreign materials from the body, with interactions shown to be heavily dependent on variables such as nanoparticle size, charge, and surface chemistry. Interactions such as cellular association or uptake of nanoparticles can lead to diminished functionality or rapid clearance from the body, making it critical to consider these interactions when designing and synthesizing nanomaterials for biomedical applications ranging from drug delivery to imaging and biosensing. We investigated the interactions between PEGylated organosilica nanoparticles and naturally endocytic immune cells grown from stem cells in murine bone marrow. Specifically, we varied the particle size from 60 nm up to 1000 nm and investigated the effects of size on immune cell association, activation, and maturation with these critical gatekeeper cells. These results will help inform future design parameters for in vitro and in vivo biomedical applications utilizing organosilica nanoparticles.
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  • 文章类型: Journal Article
    确定新药是否是底物,外排或摄取膜转运蛋白的抑制剂或诱导剂已成为药物发现和开发过程中的常规过程。体外测定用于确定新药是否有可能成为目标(底物)或沉淀剂(抑制剂,诱导剂)在转运蛋白介导的临床药物相互作用中。然后将这些体外实验的发现用于确定新药是否需要进一步的体内药物相互作用研究。
    本文提供了有关体外转运蛋白测定的最新信息,专注于转染细胞的新用途,时间依赖性抑制,转运蛋白诱导,和复杂的模型系统。
    较新的体外测定法在定义新药作为转运底物时增加了工具箱,抑制剂,或诱导物。复杂的模型,如球体,类器官,和微生理系统需要标准化和进一步研究模型转运蛋白底物和抑制剂。在药物发现中,更传统的转运蛋白测定可以用作底物和抑制剂筛选测定。在药物开发中,更复杂的细胞模型可以在以后的药物开发中使用,以更好地了解转运蛋白如何参与吸收,分布,以及新药的排泄.
    UNASSIGNED: Determining whether a new drug is a substrate, inhibitor or inducer of efflux or uptake membrane transporters has become a routine process during drug discovery and development. In vitro assays are utilized to establish whether a new drug has the potential to be an object (substrate) or precipitant (inhibitor, inducer) in transporter-mediated clinical drug-drug interactions. The findings from these in vitro experiments are then used to determine whether further in vivo drug interaction studies are necessary for a new drug.
    UNASSIGNED: This article provides an update on in vitro transporter assays, focusing on new uses of transfected cells, time-dependent inhibition, transporter induction, and complex model systems.
    UNASSIGNED: The newer in vitro assays add to the toolbox in defining new drugs as transporter substrates, inhibitors, or inducers. Complex models such as spheroids, organoids, and microphysiological systems require standardization and further research with model transporter substrates and inhibitors. In drug discovery, the more traditional transporter assays may be employed as substrate and inhibitor screening assays. In drug development, more complex cell models can be employed in later drug development to better understand how transporter(s) are involved in the absorption, distribution, and excretion of new drugs.
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  • 文章类型: Journal Article
    2022年,法国的人乳头瘤病毒(HPV)疫苗覆盖率<50%,在社会弱势群体中甚至更低。我们旨在评估HPV疫苗意识的社会人口统计学决定因素,摄取,以及青少年父母的意愿,以及相关的态度和知识项目。在法国各地上中学的青少年家长,参加随机试验的人对匿名基线调查做出了回应,在2021年11月至2022年2月期间进行。我们使用逻辑回归模型来调整儿童的年龄和性别,以探索社会人口统计学决定因素(包括在家使用多种语言,职业类别,当地剥夺指数和城市化)对HPV疫苗的认识,摄取,和意图。在来自61所学校的1889名参与者中,与高管/专业人员相比,作为工厂工人/农民工作的父母对疫苗的认识几率大大降低,如果他们报告(OR=0.07;0.03-0.15)或不报告(OR=0.20;0.11-0.36)在家里也说法语以外的另一种语言。具有多语言家庭的较低职业类别的父母不太可能打算给孩子接种疫苗(OR=0.19;0.07-0.56)。最近的医生访问或疫苗提供是意识的强烈积极决定因素,吸收和意图。关于HPV疫苗有用性的态度和知识在职业类别中观察到了很大的梯度,安全,和可访问性。这项研究证实了法国HPV疫苗摄取的差异,并提供了对HPV疫苗意识的社会差异机制的见解。访问和意图。
    Human Papillomavirus (HPV) vaccine coverage was <50% in France in 2022 and even lower among socially disadvantaged populations. We aimed to evaluate socio-demographic determinants of HPV vaccine awareness, uptake, and intention among parents of adolescents, and related attitudes and knowledge items. Parents of adolescents attending middle schools across France, who participated in a randomized trial responded to an anonymous baseline survey, conducted between November 2021 and February 2022. We used logistic regression models adjusting for a child\'s age and sex to explore sociodemographic determinants (including at-home multilingualism, occupational categories, local deprivation index and urbanity) of HPV vaccine awareness, uptake, and intention. Among the 1889 participants from 61 schools, parents working as factory workers/farmers had significantly lower odds of vaccine awareness compared to executives/professionals, both if they reported (OR = 0.07; 0.03-0.15) or not (OR = 0.20; 0.11-0.36) speaking also another language than French at home. Parents in lower occupational categories with multilingual families were less likely to have the intention to vaccinate their child (OR = 0.19; 0.07-0.56). Recent physician visit or vaccine offer was strong positive determinants of awareness, uptake and intention. A substantial gradient across occupational categories was observed for attitudes and knowledge around HPV vaccine usefulness, safety, and accessibility. This study confirms the disparities on HPV vaccine uptake in France and provides insight into mechanisms of social disparities in HPV vaccine awareness, access and intention.
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  • 文章类型: Journal Article
    东非湖泊,尤其是苏打水湖,是大量野生动物如火烈鸟的栖息地,哺乳动物,和鱼。由于当地高温,这些湖泊以其高初级产量而闻名,光强度,和碱度(无机碳)。然而,这些湖泊,通常在偏远地区,接受低营养输入。铵(NH4)再循环和/或固氮可以成为浮游植物的主要氮供应机制。然而,人为干扰最小的湖泊中微生物氮营养的驱动力仍然知之甚少。使用稳定同位素示踪技术,在2020年初的旱季期间,在东非(坦桑尼亚和肯尼亚)的18个湖泊和水库中测量了NH4回收率。三个功能基因(nifH,gdh,和UreC)也测量了与微生物氮营养有关的信息。NH4+再生支持高达71%的NH4+吸收。所有湖泊和水库的群落生物NH4需求(CBAD)正表明微生物群落对氮的需求明显。我们的研究提供了明确的证据,表明微生物NH4+吸收速率与溶解有机物(DOM)特性密切相关(例如,254nm处的吸收系数,微生物腐殖质样和蛋白质样成分贡献的总荧光强度百分比),并且水的停留时间通过调节湖内DOM处理的持续时间和影响藻类的生长来驱动微生物NH4再循环。浮游植物,尤其是蓝藻科,在一定的水停留时间范围内显示出最大的生物量和更高的NH4+回收率(例如,5-8年)。然而,随着水停留时间的延长,CBAD呈下降趋势,这可能会受到藻类群落组成变化的影响(例如,%蓝藻与%芽孢杆菌科)。这些结果表明,水的停留时间和DOM动力学有可能促进对东非湖泊中微生物氮供应机制的理解。
    East African lakes, especially soda lakes, are home habitats for massive numbers of wildlife such as flamingos, mammals, and fishes. These lakes are known for their high primary production due to local high temperatures, light intensities, and alkalinity (inorganic carbon). However, these lakes, normally within remote areas, receive low nutrient inputs. Ammonium (NH4+) recycling and/or nitrogen fixation can become the major N supply mechanisms for phytoplankton. However, the driving forces on microbial N nutrition in lakes with minimal anthropogenic disturbance remain poorly understood. Using stable isotope tracer techniques, NH4+ recycling rates were measured in 18 lakes and reservoirs in East Africa (Tanzania and Kenya) during the dry season in early 2020. Three functional genes (nifH, gdh, and ureC) relating to microbial N nutrition were also measured. The regeneration of NH4+ supported up to 71 % of the NH4+ uptake. Positive community biological NH4+ demands (CBAD) for all lakes and reservoirs indicate an obvious N demand from microbial community. Our study provides clear evidence that microbial NH4+ uptake rates linked closely to the dissolved organic matter (DOM) properties (e.g., the absorption coefficient at 254 nm, percents of total fluorescence intensity contributed by microbial humic-like and protein-like components) and that water residence time drives microbial NH4+ recycling by regulating the duration of in-lake DOM processing and influencing algal growth. Phytoplankton, especially those of Cyanophyceae, showed maximum biomass and higher NH4+ recycling rates at a certain range of water residence time (e.g., 5-8 years). However, CBAD showed a decreasing trend with longer water residence time, which may be influenced by changes in the algal community composition (e.g., % Cyanophyceae vs. % Bacillariophyceae). These results indicate that DOM dynamics and the water residence time have the potential to facilitate the understanding of microbial nitrogen supply status in East African lakes.
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  • 文章类型: Journal Article
    性健康和生殖健康对所有个人都至关重要,包括LGBTQ+个人。然而,女同性恋者和双性恋女性往往缺乏量身定制的服务,导致利用不足。这项研究旨在评估女同性恋和双性恋Bulawayo妇女的性健康和生殖健康服务的可用性和吸收。
    一项横断面研究调查了通过“无声组织之声”招募的67名女同性恋和双性恋女性。参与者填写了一份关于现有服务的结构化问卷,影响它们摄取的因素,和访问挑战。交叉制表用于检查变量之间的关联。数据使用MicrosoftExcel和STATA第15版S.E.
    大多数受访者是35岁的双性恋女性。交叉表格显示,延迟或避免的服务与缺乏针对女同性恋者和双性恋妇女的特定服务之间存在重大关联,以及存在性别认同非歧视政策。
    性健康和生殖健康计划在满足女同性恋和双性恋女性的需求方面发挥着至关重要的作用。改善服务吸收需要加强诊所和性健康教育计划之间的联系,提供女同性恋和双性恋女性友好的临床服务,并确保获得全面的信息。
    UNASSIGNED: Sexual and reproductive healthcare is essential for all individuals, including LGBTQ+ individuals. However, lesbians and bisexual women often lack tailored services, leading to underutilization. This study aimed to assess the availability and uptake of sexual and reproductive health services for lesbian and bisexual Bulawayo women.
    UNASSIGNED: A cross-sectional study surveyed 67 lesbian and bisexual women recruited through the Voice of the Voiceless Organization. The participants completed a structured questionnaire on available services, factors influencing their uptake, and access challenges. Cross-tabulation was used to examine the associations between variables. Data were analyzed using Microsoft Excel and STATA Version 15 S.E.
    UNASSIGNED: Most respondents were bisexual women aged 35 years. Cross-tabulations revealed significant associations between delayed or avoided services and the absence of specific services for lesbians and bisexual women as well as the presence of gender identity nondiscrimination policies.
    UNASSIGNED: Sexual and reproductive health programs play a vital role in meeting lesbian and bisexual women\'s needs. Improving service uptake requires strengthening the linkages between clinics and sexual health education programs, providing lesbian and bisexual women-friendly clinical services, and ensuring access to comprehensive information.
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  • 文章类型: Journal Article
    估计蚯蚓中农药生物浓度的现有模型在不同化学品中的适用性有限,土壤和物种限制了它们作为替代品的潜力,风险评估的中间层。我们使用了三种蚯蚓(Lumbricusterrestriris,卡利吉诺萨立克托底,费蒂达艾塞尼亚),五种农药(logKow1.69-6.63)和五种土壤(有机质含量=0.972-39.9wt%)产生一级动力学积累模型。根据文献报道的402个内部蚯蚓浓度的数据集评估了模型的适用性,其中包括用于产生模型的数据范围之外的化学和土壤性质。我们的模型使用孔隙水或整体土壤浓度准确预测身体负荷,身体负荷预测的至少93.5%和84.3%在相应观测值的10和5倍内,分别。这表明,在预测蚯蚓生物浓缩时,无需区分孔隙水和土壤暴露途径,也无需考虑不同的吸收和消除途径。我们的新模型不仅在表征土壤中蚯蚓暴露于农药的特征方面优于现有模型,但是,它也可以与模型相结合,这些模型可以解释蚯蚓的运动以及由于降解和运输而导致的土壤农药浓度的波动。
    Existing models for estimating pesticide bioconcentration in earthworms exhibit limited applicability across different chemicals, soils and species which restricts their potential as an alternative, intermediate tier for risk assessment. We used experimental data from uptake and elimination studies using three earthworm species (Lumbricus terrestris, Aporrectodea caliginosa, Eisenia fetida), five pesticides (log Kow 1.69-6.63) and five soils (organic matter content = 0.972-39.9 wt %) to produce a first-order kinetic accumulation model. Model applicability was evaluated against a data set of 402 internal earthworm concentrations reported from the literature including chemical and soil properties outside the data range used to produce the model. Our models accurately predict body load using either porewater or bulk soil concentrations, with at least 93.5 and 84.3% of body load predictions within a factor of 10 and 5 of corresponding observed values, respectively. This suggests that there is no need to distinguish between porewater and soil exposure routes or to consider different uptake and elimination pathways when predicting earthworm bioconcentration. Our new model not only outperformed existing models in characterizing earthworm exposure to pesticides in soil, but it could also be integrated with models that account for earthworm movement and fluctuating soil pesticide concentrations due to degradation and transport.
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  • 文章类型: Journal Article
    原代人肝细胞(3DPHH)的3D球体在培养中保留了数周的分化表型,具有很大程度上保守的代谢功能和蛋白质组学指纹。因此,3DPHH作为机械性肝脏稳态研究的模型以及在药物发现中的体外至体内外推(IVIVIVE)越来越重要。然而,尚未在3DPHH中评估药物转运蛋白的动力学和调节。这里,我们使用有机阳离子转运蛋白1(OCT1/SLC22A1)作为模型来研究转运动力学和通过相关信号通路对转运蛋白活性的长期调节。使用荧光模型底物4-(4-(二甲基氨基)苯乙烯基)-N-甲基吡啶(ASP)和已知的OCT1抑制剂在单个3DPHH中研究了OCT1转运蛋白的动力学。对于长期研究,3DPHH用异生物质处理7天,之后评估蛋白质表达和OCT1功能。全局蛋白质组学分析用于追踪肝脏表型以及其他调节蛋白的原型变化。如P-糖蛋白和细胞色素P450.3A4。ASP+动力学表明来自三个供体的Km值为14±4.0µM的全功能OCT1转运蛋白。与已知OCT1抑制剂的共孵育使3DPHH球状体中ASP+的摄取降低了35-52%。长期暴露研究表明,OCT1在激活核受体信号或暴露于可诱导炎症的化合物后相对稳定,脂肪变性或肝损伤。我们的结果表明,3DPHH球体表达生理相关水平的完全活性OCT1,并且可以在3DPHH构型中准确研究其转运蛋白动力学。我们还证实OCT1在改变其他药物转运蛋白和药物代谢酶的表达和功能的关键代谢途径的激活过程中保持稳定和功能。这些结果将扩大可以使用3DPHH进行的研究范围。
    3D spheroids of primary human hepatocytes (3D PHH) retain a differentiated phenotype with largely conserved metabolic function and proteomic fingerprint over weeks in culture. As a result, 3D PHH are gaining importance as a model for mechanistic liver homeostasis studies and in vitro to in vivo extrapolation (IVIVE) in drug discovery. However, the kinetics and regulation of drug transporters have not yet been assessed in 3D PHH. Here, we used organic cation transporter 1 (OCT1/SLC22A1) as a model to study both transport kinetics and the long-term regulation of transporter activity via relevant signalling pathways. The kinetics of the OCT1 transporter was studied using the fluorescent model substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP+) and known OCT1 inhibitors in individual 3D PHH. For long-term studies, 3D PHH were treated with xenobiotics for seven days, after which protein expression and OCT1 function were assessed. Global proteomic analysis was used to track hepatic phenotypes as well as prototypical changes in other regulated proteins, such as P-glycoprotein and Cytochrome P450 3A4. ASP+ kinetics indicated a fully functional OCT1 transporter with a Km value of 14 ± 4.0µM as the mean from three donors. Co-incubation with known OCT1 inhibitors decreased the uptake of ASP+ in the 3D PHH spheroids by 35-52%. The long-term exposure studies showed that OCT1 is relatively stable upon activation of nuclear receptor signalling or exposure to compounds that could induce inflammation, steatosis or liver injury. Our results demonstrate that 3D PHH spheroids express physiologically relevant levels of fully active OCT1 and that its transporter kinetics can be accurately studied in the 3D PHH configuration. We also confirm that OCT1 remains stable and functional during the activation of key metabolic pathways that alter the expression and function of other drug transporters and drug-metabolizing enzymes. These results will expand the range of studies that can be performed using 3D PHH.
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