NanoImpact
·
2025
·
IF 5.5
Yuan-Yuan Liu,Jie Liu,Yuan Guo,Qiangqiang Zhang,Aoneng Cao,Haifang Wang
Nanoplastics enter the human body mainly by ingestion through the gastrointestinal tract and thus the uptake and release of nanoplastics in intestinal cells have been studied. However, the fate of nanoplastics in intestinal cells remains poorly understood, particularly how they are exocytosed. Herein, we investigated the uptake, distribution, and exocytosis of nanoplastics in Caco-2 cells using 70 nm red fluorescent polystyrene (R70PS) as a nanoplastic model. The results show that R70PS readily enters Caco-2 cells and the content per cell peaks at around 24 h, but the total intracellular content in all cells increases continuously over 72 h. In addition, the uptake mechanisms change over incubation time, i.e. R70PS entered Caco-2 cells via both the energy-independent pathway and the energy-dependent caveolae-mediated endocytosis and macropinocytosis at 4 h incubation, but almost all R70PS entered cells in an energy-dependent manner via caveolae-mediated endocytosis, macropinocytosis, and clathrin-mediated endocytosis at 12 h incubation. Most of the intracellular R70PS accumulated in lysosomes, but R70PS also entered the mitochondria and its level increased over time. Approximately 45 % of the intracellular R70PS could be cleared from the cells within 12 h, mainly via the lysosomal pathway. Exocytosis was also associated with autophagy and was facilitated by the increase in the number of mitochondria and lysosomes, but inhibited by serum in the medium. Our findings deepen the understanding of the interaction between nanoplastics and intestinal cells, which is helpful for the risk assessment of nanoplastics.
研究领域:
生物学
·
医学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2017
·
IF 3.086
Yajing Fang,Fuqiang Liang,Kunyuan Liu,Shakeel Qaiser,Siyi Pan,Xiaoyun Xu
Flavonoids are a large group of polyphenols and widely distributed in plant foods. Flavonoids exhibit various biological activities, such as anti-cancer, antioxidant and anti-inflammatory while poor oral bioavailability has been considered as a major hurdle in their use as functional foods. Cellular uptake and efflux of flavonoid implicates their bioavailability. To investigate the cellular uptake and efflux of flavonoids, 27 flavonoids were measured for their cellular uptake in Caco-2 cells with (CUV) and without (CU) the inhibitor of P-glycoprotein (P-gp) verapamil. Then, a quantitative structure-absorption relationship (QSAR) model containing 21 compounds as training set was obtained from their corresponding CU. The model showed good robustness and predictivity with a high cross-validation coefficient (Q 2 ) value of 0.809 and Log of the octanol/water partition coefficient (SlogP) and atomic charge on carbon 5 (Q C5 ) were related to flavonoid uptake. The CUV of some flavonoids were significantly ( p < 0.05 or p < 0.01) higher than their CU, suggesting that specific flavonoids are pumped out by P-gp. The structure-affinity relationship of flavonoids as substrates of P-gp was determined with the presence of 4′-OCH 3 , 3′-OCH 3 and the absence of 3′-OH, 3-OH and 4′-OH favorable for the affinity of flavonoids. These results provide valuable information for screening flavonoids with good absorption and low affinity with transporters.
研究领域:
营养学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2014
·
IF 2.61
Jingze Duan,Yan Xie,Huilin Luo,Guowen Li,Tao Wu,Tong Zhang
Flavonoid isorhamnetin occurs in various plants and herbs, and demonstrates various biological effects in humans. This work will clarify the isorhamnetin absorption mechanism using the Caco-2 monolayer cell model. The isorhamnetin transport characteristics at different concentrations, pHs, temperatures, tight junctions and potential transporters were systemically investigated. Isorhamnetin was poorly absorbed by both passive diffusion and active transport mechanisms. Both trans- and paracellular pathways were involved during isorhamnetin transport. Active transport under an ATP-dependent transport mechanism was mediated by the organic anion transporting peptide (OATP); isorhamnetin’s permeability from the apical to the basolateral side significantly decreased after estrone-3-sulfate was added ( p < 0.01). Efflux transporters, P-glycoproteins (P-gp), breast cancer resistance proteins (BCRP) and multidrug resistance proteins (MRPs) participated in the isorhamnetin transport process. Among them, the MRPs (especially MRP2) were the main efflux transporters for isorhamnetin; transport from the apical to the basolateral side increased 10.8-fold after adding an MRP inhibitor (MK571). This study details isorhamnetin’s cellular transport and elaborates isorhamnetin’s absorption mechanisms to provide a foundation for further studies.
研究领域:
药理学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
Nutrients
·
2017
·Vol. 9
·期 12
·1301
·
IF 3.55
Yajing Fang,Weiwei Cao,Mengmeng Xia,Siyi Pan,Xiaoyun Xu
Flavonoids exhibit a broad range of biological activities. However, poor absorption of some flavonoids is a major limitation for use of flavonoids as nutraceuticals. To investigate the structure requirements for flavonoids intestinal absorption, transepithelial transport and cellular accumulation (CA) of 30 flavonoids were determined using the Caco-2 cell monolayer. The bilateral permeation of five types of flavonoids followed the order: flavanones ≥ isoflavones > flavones ≥ chalcones > flavonols. The concentration of flavonoids accumulated in cells did not correlate with cell penetration since the correlation coefficient between the apparent permeability coefficient (Papp) and their corresponding CA was poor (R2< 0.3). Most flavonoids exhibited a ratio of 0.8–1.5 forPapp A to B/Papp B to A, suggesting passive diffusion pathways. However, luteolin, morin and taxifolin may involve the efflux mechanisms. The quantitative structure-permeability relationship (QSPR) study demonstrated that the intestinal absorption of flavonoids can be related to atomic charges on carbon 3′ (QC3′), molecule surface area (SlogP_V3), balance between the center of mass and position of hydrophobic region (vsurf_ID1) and solvation energy of flavonoids (E_sol). These results provide useful information for initially screening of flavonoids with high intestinal absorption.Keywords:Caco-2;flavonoids;intestinal absorption;permeability;QSPR
研究领域:
药理学
·
营养学
✓ 已验证
DOI
PubMed
高影响因子
Pharmaceuticals
·
2022
·Vol. 15
·期 4
·418
·
IF 5.215
Qiong Yang,Maochen Xing,Ke Wang,Qiang Wei,Jiarui Zhao,Yuan Wang,Kai Ji,Shuliang Song
The Caco-2 model is a common cell model for material intestinal absorption in vitro, which usually takes 21 days to establish. Although some studies have shown that adding puromycin (PM) can shorten the model establishment period to 7 days, this still requires a long modeling time. Therefore, exploring a shorter modeling method can reduce the experimental costs and promote the development and application of the model. Fucoidan is an acidic polysaccharide with various biological activities. Our study showed that the transepithelial electrical resistance (TEER) value could reach 600 Ω·cm2on the fourth day after the addition of fucoidan and puromycin, which met the applicable standards of the model (>500 Ω). Moreover, the alkaline phosphatase (AKP) activity, fluorescein sodium transmittance, and cell morphology of this model all met the requirements of model establishment. Fucoidan did not affect the absorption of macromolecular proteins and drugs. The results indicate that fucoidan can be applied to establish the Caco-2 model and can shorten the model establishment period to 5 days.Keywords:fucoidan;Caco-2 model;absorption of macromolecules
研究领域:
药理学
·
细胞生物学
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Xueli Yang,Zihao Zong,Ben Niu,Hangjun Chen,Weijie Wu,Xiangjun Fang,Ruiling Liu,Haiyan Gao,Honglei Mu
In this study, Shiitake mushroom-derived extracellular nanovesicles (SMDENVs) were isolated from fresh Shiitake mushrooms by ultracentrifugation and sucrose gradient ultracentrifugation. The morphological characteristics of SMDENVs were investigated via Transmission Electron Microscopy and Laser Scanning Confocal Microscopy. SMDENVs were spherical, hollow, and uniform in size, with an average diameter of 177.6 ± 51.4 nm. Based on the analysis of lipidomics and proteomics, 383 lipids species and 1290 proteins were identified in SMDENVs. Compared with the conventional liposomes, SMDENVs demonstrated higher stability in different environmental conditions. Furthermore, we observed that SMDENVs were cytocompatible and inhibited the proliferation of Caco-2 cells. SMDENVs could be phagocytized by Caco-2 cells in a time-dependent manner. Further, SMDENVs also inhibited the proliferation of Caco-2 cells in a dose-dependent manner, and the half-maximal inhibitory concentration (IC 50 ) was 236.2 ± 3.2 μg/mL. Additionally, SMDENVs induced cellular apoptosis by increasing the levels of reactive oxygen species and decreasing the mitochondrial membrane potential.
研究领域:
食品科学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Ruihong Dong,Yuting Wang,David Julian McClements,Qiang Yu,Jianhua Xie,Huijie Zhang,Lizhi Huang,Bin Li,Jinlong Tian,Yi Chen
This study investigated intestinal absorption and cellular antioxidant efficacy of anthocyanin (ACN)-loaded ovalbumin (OVA)-carrageenans (ι-, λC)/dextran sulfate (DS) nanocomplexes. Utilizing Caco-2 cells, we assessed endocytic pathways, intracellular trafficking, and delivery efficacy of ternary nanocomplexes. ACN-loaded nanocomplexes could be internalized by cells in a time-, dose-, energy-dependent manner, with macropinocytosis, lipid raft/caveolae, and actin co-mediated endocytosis routes playing pivotal roles. Nanocomplexes inhibited P-glycoprotein efflux of Rhodamine-123, enhancing the apparent permeability of ACN into cells, especially for OVA-ιC-ACN. Transport pathways of ACN-loaded nanocomplexes through Caco-2 monolayers involved different organelles including microtubules, Golgi complexes, endoplasmic reticulum, and lysosomes. Compared to free ACN, nanocomplexes exhibited more efficiency in recovering cellular viability and endogenous antioxidant enzyme activities under oxidative stress. Our findings provide a more comprehensive understanding of internalization, transport mechanisms of protein-polysaccharide-anthocyanin nanocomplexes across epithelial cell monolayers, and provide valuable insights for designing efficient ACN-loaded nanocomplex systems with high transportation efficiency and intestinal absorption.
研究领域:
生物化学
·
药剂学
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细胞生物学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Foods
·
2023
·Vol. 12
·期 6
·1318
·
IF 5.2
Dan Su,Jiawen Lu,Chunchao Nie,Ziyan Guo,Chang Li,Qiang Yu,Jianhua Xie,Yi Chen
Acrylamide (AA) and ochratoxin A (OTA) are contaminants that co-exist in the same foods, and may create a serious threat to human health. However, the combined effects of AA and OTA on intestinal epithelial cells remain unclear. The purpose of this research was to investigate the effects of AA and OTA individually and collectively on Caco-2 cells. The results showed that AA and OTA significantly inhibited Caco-2 cell viability in a concentration- and time-dependent manner, decreased transepithelial electrical resistance (TEER) values, and increased the lucifer yellow (LY) permeabilization, lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) levels. In addition, the levels of IL-1β, IL-6, and TNF-α increased, while the levels of IL-10 decreased after AA and OTA treatment. Western blot analysis revealed that AA and OTA damaged the intestinal barrier by reducing the expression of the tight junction (TJ) protein. The collective effects of AA and OTA exhibited enhanced toxicity compared to either single compound and, for most of the intestinal barrier function indicators, AA and OTA combined exposure tended to produce synergistic toxicity to Caco-2 cells. Overall, this research suggests the possibility of toxic reactions arising from the interaction of toxic substances present in foodstuffs with those produced during processing.Keywords:acrylamide;ochratoxin A;Caco-2 cells;tight junction;interactive effects
研究领域:
毒理学
·
细胞生物学
·
食品安全
✓ 已验证
DOI
PubMed
高影响因子
CHINESE CHEMICAL LETTERS
·
2021
·
IF 6.779
Min Xie,Chaobo Huang,Yongqi Liang,Shuang Li,Liping Sheng,Yi Cao
MoS 2 nanosheets (NSs) are novel 2D nanomaterials (NMs) with potential uses in many areas, and therefore oral exposure route to MoS 2 NSs is plausible. Currently, MoS 2 NSs are considered as biocompatible NMs , but there is lacking of systemic investigations to study the interactions of MoS 2 NSs with intestinal cells. In this study, we exposed the 3D Caco-2 spheroids to MoS 2 NSs or MoS 2 powders (denoted as MoS 2 -bulk), and investigated the potential adverse effects of MoS 2 -materials based on transcriptomics and lipidomics analysis. As expected, both MoS 2 NSs and MoS 2 -bulk were dose-dependently internalized into 3D Caco-2 spheroids but did not induce cytotoxicity, membrane disruption or decrease of thiols. However, the Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) analysis indicated that nutrient absorption and metabolism was decreased. One of the most significantly decreased KEGG pathways is fat digestion and absorption (map04975), and Western blotting analysis further showed that fatty acid binding protein 1 and apolipoprotein A1 , key proteins involved in fat digestion and absorption, were down-regulated by MoS 2 NSs or MoS 2 -bulk. In addition, BODIPY 493/503 staining suggested that exposure to MoS 2 NSs and MoS 2 -bulk decreased lipid levels in the spheroids. However, lipidomics data indicated that MoS 2 materials only decreased 8 lipid classes, including lysophosphatidylcholine , lysodimethylphosphatidylethanolamine, N -acylethanolamine, ceramide phosphoethanolamines , gangliosides , lysosphingomyelin and sulfatide, whereas most of the lipid classes were indeed increased. In addition, MoS 2 NSs was more potent to decrease the lipid classes compared with MoS 2 -bulk. Combined, the results from this study showed that MoS 2 NSs and bulk materials were non-cytotoxic but altered lipid profiles in 3D Caco-2 spheroids.
研究领域:
毒理学
·
生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Marine Drugs
·
2021
·Vol. 19
·期 2
·92
·
IF 5.118
Yue Sui,Yue Gu,Yujing Lu,Chenxu Yu,Jie Zheng,Hang Qi
Fucoxanthin (FX), a natural carotenoid found in seaweed with multiple functional activities, is unstable with a poor water solubility that limits its utilization. This study aimed to improve FX’s stability and bioavailability via the nano-encapsulation of FX in polyvinylpyrrolidone (PVP)-coated[email protected]nanoparticles (NPs). The[email protected]NPs were evaluated in terms of their morphology, stability, encapsulation efficiency (EE), loading capacity (LC), and in vitro release to optimize the encapsulation parameters, and a 1:8 FX:PVP ratio was found to perform the best with the highest EE (85.50 ± 0.19%) and LC (10.68 ± 0.15%) and improved FX stability. In addition, the[email protected]NPs were shown to effectively deliver FX into Caco-2 cancer cells, and the accumulation of FX in these cancer cells showed pro-oxidative activities to ameliorate H2O2-induced damage and cell death. The[email protected]NPs could potentially become a new therapeutical approach for targeted cancer treatment.Keywords:fucoxanthin;nanoparticles;Caco-2 cells;pro-oxidation;targeted cell death
研究领域:
药学
·
癌症研究
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2017
·
IF 3.154
Qianzhu Zhao,Yueyu Zou,Caihuan Huang,Ping Lan,Jie Zheng,Shiyi Ou
Adducts of 5-hydroxymethylfurfural (HMF)-amino acids are formed during food processing and digestion; the elimination capacity of in vitro intestinal digests of biscuits, instant noodles, and potato crisps for HMF is 652, 727, and 540 μg/g, respectively. However, the safety of these adducts is unknown. In this study, an HMF–cysteine adduct named 1-dicysteinethioacetal-5-hydroxymehtylfurfural (DCH), which was found to be produced in the gastrointestinal tract after HMF intake, was prepared to test its effect toward Caco-2 cells. Compared with HMF, the adduct displayed lower cytotoxicity against Caco-2 cells with an IC50 value of 31.26 mM versus 14.95 mM (HMF). The DCH did not induce cell apoptosis, whereas HMF significantly increased the apoptosis rate after incubation at concentrations of 16, 32, and 48 mM for 72 h. DCH showed an absorption rate considerably lower than that of HMF by Caco-2 cells. Lower absorption of DCH may result in lower toxicity compared with HMF against Caco-2 cells. Intracellular transformation of DCH has been observed.
研究领域:
食品科学
·
毒理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Foods
·
2022
·Vol. 11
·期 23
·3793
·
IF 5.561
Yang Liu,Jiali Lin,Tiantian Cheng,Yangjie Liu,Fuliang Han
Anthocyanins are substances with multiple physiological activities widely present in red wine, but the influence of structure (methylation, hydroxylation, acylation, glycosylation) on the transport remains ill-defined. In the present study, Caco-2 monolayers were used as an in vitro model of the absorptive intestinal epithelium to transport different types of anthocyanin samples. Results showed that both methylation and acetylation promote the level of transport. Monoglycoside standard exhibited higher transport amount and rate compared to diglycoside standard while the transport level of the monoglycoside mixture was unexpectedly lower than that of the diglycoside mixture. Caco-2 monolayers appeared to be more capable of transporting the single standard than the mixed standard. Meanwhile, the transport of anthocyanins in Caco-2 cell model showed time- and concentration-dependent trends. Anthocyanin treatment had a greater effect on sodium-dependent glucose transporter 1 (SGLT1) mRNA expression than glucose transporter 2 (GLUT2), and significantly down-regulated the protein expression of SGLT1. Although the low bioavailability of anthocyanins requires much more research, further evidence of the role of structure is provided.Keywords:wine;anthocyanins;Caco-2 cell monolayer;absorption;SGLT1;GLUT2
研究领域:
食品科学
·
药理学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）