APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
·
2013
·Vol. 97
·期 15
·6943-6955
·
IF 3.689
Deng Xudong,Zhang Guoliang,Shen Chong,Yin Jian,Meng Qin
Caco-2 cells usually require 21 days of culture for developing sufficient differentiation in traditional two-dimensional Transwell culture, deviating far away from the quick differentiation of enterocytes in vivo. The recently proposed three-dimensional cultures of Caco-2 cells, though imitating the villi/crypt-like microstructure of intestinal epithelium, showed no effect on accelerating the differentiation of Caco-2 cells. In this study, a novel culture of Caco-2 cells on hollow fiber bioreactor was applied to morphologically mimic the human small intestine lumen for accelerating the expression of intestine functions. The porous hollow fibers of polyethersulfone (PES), a suitable membrane material for Caco-2 cell culture, successfully promoted cells to form confluent monolayer on the inner surface. The differentiated functions of Caco-2 cells, represented by alkaline phosphatase, γ-glutamyltransferase, and P-glycoprotein activity, were greatly higher in a 10-day hollow fiber culture than in a 21-day Transwell culture. Moreover, the Caco-2 cells on PES hollow fibers expressed higher F-actin and zonula occludens-1 protein than those on Transwell culture, indicative of an increased mechanical stress in Caco-2 cells on PES hollow fibers. The accelerated differentiation of Caco-2 cells on PES hollow fibers was unassociated with membrane chemical composition and surface roughness, but could be stimulated by hollow fiber configuration, since PES flat membranes with either rough or smooth surface failed to enhance the differentiation of Caco-2. Therefore, the accelerated expression of Caco-2 cell function on hollow fiber culture might show great values in simulation of the tissue microenvironment in vivo and guide the construction of intestinal tissue engineering apparatus.
研究领域:
细胞生物学
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组织工程
·
药学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2022
·
IF 5.895
Fanghua Guo,Rong Tsao,Chuyao Li,Xiaoya Wang,Hua Zhang,Li Jiang,Yong Sun,Hua Xiong
Green pea hulls are a byproduct of the processing of green pea and are rich in phenolic substances. In the present study, in vitro digestion, human colonic adenocarcinoma cell line (Caco-2) monolayer, and the Caco-2/macrophage cell lines of the murine origin (Raw264.7) coculture model were established to investigate the release of polyphenols, absorption, and transport of digestive products and their effects on inflammation and intestinal barrier. During the digestive process, polyphenols were constantly released from the pea hulls, reaching the maximum amount in the small intestine (total phenolic content (TPC): 5.41 ± 0.04 mg gallic acid (GAE)/g dry weight (DW)), and the digestive products (800 μg/mL) could reduce the secretion of NO (50.9%), IL-6 (50.6%), and TNF-α (24.6%) and inhibit the mRNA expression of cyclooxygenase-2 (COX-2) (37.2%) and inducible nitric oxide synthase (iNOS) (91.1%) compared with the lipopolysaccharide (LPS) group. A total of 12 phenolic components were quantified by ultraperformance liquid chromatography-linear ion trap orbitrap tandem mass spectrometry (UHPLC-LTQ-OrbiTrap-MS) technology. Kaempferol trihexoside in digestive products could be absorbed and transported (1.25 ± 0.13 ng quercetin/mL). The digestive products could promote the expression of claudin-1 (210.8%), occludin (64.9%), and zonulin occludin-1 (ZO-1) (52.0%) compared with the LPS group and exert anti-inflammatory effects after being absorbed. The results indicated that pea hull polyphenols could be continuously released and absorbed to play a positive role in protecting the intestinal barrier and anti-inflammatory activity.
研究领域:
食品科学
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营养学
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药理学
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细胞生物学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
Nutrients
·
2026
·Vol. 18
·期 9
·1389
·
IF 5.8
Fan Wu,Nan Chen,Yu Peng,Mo Li,Yuanying Ni,Tong Li,Ruihai Liu,Xin Wen
Background/Objectives: Zeaxanthin and lutein, which are essential dietary xanthophylls existing abundantly in free and esterified forms, require efficient intestinal absorption due to their insufficient synthesis in humans. However, limited knowledge on intestinal uptake and transport of xanthophyll esters is available. Methods: This study investigated the cellular uptake and transport mechanism of free and esterified xanthophylls using human Caco-2 cell monolayer, with lutein, zeaxanthin and their dipalmitates as representatives. Results: The results showed that free xanthophylls were uptaken without cellular re-esterification. Esterified xanthophylls were predominantly uptaken in free forms, as evidenced by Caco-2 cells incubated with zeaxanthin and lutein dipalmitates containing 80.8% and 89.4% of zeaxanthin and lutein, along with minor amounts of monoesters and diesters, respectively. Subsequent basolateral detection of both free xanthophylls and monoesters also confirmed intact ester uptake. Additionally, time- and concentration-dependent uptake patterns were observed, with all xanthophylls showing moderate permeability. Mechanistically, SR-BI and NPC1L1 were involved in the uptake of both free and esterified xanthophylls. At the expression level, free and esterified xanthophylls differentially affected ABCG5, with significant upregulation observed only in response to free xanthophylls. Tight junction integrity remained unaffected, excluding paracellular transport. Uptake of free and esterified xanthophyll micelles also involved clathrin- and caveolae-dependent endocytosis, whereas macropinocytosis was excluded. Conclusions: These findings provide insight into the uptake behavior of free and esterified xanthophylls and the transporter- and endocytosis-related processes involved.
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Ritian Jin,Jiaqi Shang,Xiangyu Teng,Ligang Zhang,Minhe Liao,Jiaxin Kang,Ran Meng,Dangfeng Wang,Haowei Ren,Ning Liu
Here, we characterize the activities of two depeptidyl peptidase-IV (DPP-IV) inhibitory peptides, VLATSGPG and LDKVFER, using the Caco-2 monolayer model for the intestine. VLATSGPG and LDKVFR inhibited the DPP-IV in the cells via a mixed-type inhibition mode, with in situ IC50 values of 207.3 and 148.5 μM, respectively. Furthermore, VLATSGPG and LDKVFR were transported intact across the cells, with Papp values of 2.41 ± 0.16 and 4.23 ± 0.29 × 10–7 cm/s, respectively. Fragmented peptides were identified in the basolateral side of the membrane. Two of these, GPG and VLA, exhibited high inhibitory activities of 83.6 ± 3.3 and 58.5 ± 2.5%, respectively, at 100 μM concentration. Although 3 mM VLATSGPG and LDKVFR were transported across the epithelium in a concentration-dependent manner, their transport did not damage the tight junction proteins, ZO-1 and occludin. This study demonstrates that the two peptides potentially regulate DPP-IV activity in the intestine.
研究领域:
生物化学
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药理学
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产品关联
DOI
PubMed
高影响因子
Water
·
2022
·Vol. 14
·期 20
·3288
·
IF 3.53
Fangfang Ding,Qianqian Zhao,Luchen Wang,Juan Ma,Lingmin Song,Danfei Huang
As two environmental pollutants of great concern, polystyrene microplastics (PS-MPs) and nonylphenol (NP) often coexist in the environment and cause combined pollution. Batch adsorption experiments were carried out by varying parameters such as pH, the particle sizes of the PS-MPs, the initial concentration of NP, and metal ion content. The results showed that the particle size of the PS-MPs in the range tested (0.1, 1, 10, 50, and 100 μm) had a significant effect on their NP adsorption capacity. The NP adsorption process of the PS-MPs was best described by the pseudo-second-order kinetic model and the Langmuir isotherm model, while the intraparticle diffusion and Bangham models were also involved in determining the NP adsorption process of 0.1 μm PS-MPs. Both PS-MPs and NP significantly affected cell proliferation, which had been confirmed by reduced cell viability, a blocked cell cycle G1 phase, and elevated apoptosis by affecting the basic cell functions. Furthermore, the negative effects of 0.1 μm PS-MPs on cell proliferation and function were aggravated after the adsorption of NP. Further research on the potential health risks of PS-MPs combined with NP or other environmental contaminants is needed.Keywords:microplastics;nonylphenol;adsorption;desorption;cytotoxicity
研究领域:
环境科学
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毒理学
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细胞生物学
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产品关联
DOI
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 12
·3669
·
IF 4.927
Yi Wang,Xiangli Zhang,Wenya Zhuang,Yanlei Yu,Xuanrong Sun,Hong Wang,Fengzhi Li,Qingyong Li
Irinotecan and Topotecan are two Camptothecin derivatives (CPTs) whose resistance is associated with the high expression of breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp). To reverse this resistance, two novel CPTs, FL77-28 (7-(3-Fluoro-4-methylphenyl)-10,11-methylenedioxy-20(S)-CPT) and FL77-29 (7-(4-Fluoro-3-methylphenyl)-10,11-methylenedioxy-20(S)-CPT), were synthesized by our group. In this study, the anti-tumor activities of FL77-28, FL77-29, and their parent, FL118 (10,11-methylenedioxy-20(S)-CPT), were evaluated and the results showed that FL77-28 and FL77-29 had stronger anti-tumor activities than FL118. The transport and uptake of FL118, FL77-28, and FL77-29 were investigated in Caco-2 cells for the preliminary prediction of intestinal absorption. The apparent permeability coefficient from apical to basolateral (Papp AP-BL) values of FL77-28 and FL77-29 were (2.32 ± 0.04) × 10−6cm/s and (2.48 ± 0.18) × 10−6cm/s, respectively, suggesting that the compounds had moderate absorption. Since the transport property of FL77-28 was passive diffusion and the efflux ratio (ER) was less than 2, two chemical inhibitors were added to further confirm the involvement of efflux proteins. The results showed that FL77-28 was not a substrate of P-gp or BCRP, but FL77-29 was mediated by P-gp. In conclusion, FL77-28 might be a promising candidate to overcome drug resistance induced by multiple efflux proteins.Keywords:Camptothecin derivatives;cytotoxicity;bioavailability;Caco-2 cells model;drug resistance
研究领域:
药理学
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肿瘤学
·
药物递送系统
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DOI
PubMed
高影响因子
Foods
·
2026
·Vol. 15
·期 4
·642
·
IF 6
Simin Zhao,Jiao Zhang,Yuting Huang,Yanan Yuan,Ting Wu,Siyi Pan,Xiaoyun Xu
Caffeoylquinic acids (CQAs) are polyphenolic compounds widely present in daily diets, but their bioactivities are limited by poor intestinal absorption, the mechanisms of which remain incompletely understood for various isomers. This study investigated the transepithelial transport of three mono-CQAs and three di-CQAs using Caco-2 monolayers. Concurrently, the potential of five dietary flavonoids to enhance intestinal absorption by modulating efflux transporters was evaluated. Results suggest that CQAs were mainly transported via passive paracellular diffusion. The apparent permeability coefficients (Papp) of mono-CQAs were (1.49 ± 0.22) × 10−6, (1.49 ± 0.25) × 10−6, and (2.15 ± 0.57) × 10−6cm/s, which were significantly higher than those of di-CQAs. And the efflux of 5-CQA, 3,4-diCQA, and 3,5-diCQA was primarily mediated by P-gp. Among the five dietary flavonoids tested for their potential to inhibit this efflux, quercetin and kaempferol exhibited the most potent enhancing CQA uptake. They increased thePappof 5-CQA from (2.15 ± 0.21) × 10−6to (3.05 ± 0.08) × 10−6cm/s and (2.57 ± 0.17) × 10−6cm/s, respectively. Similar promoting trends were observed for 3,4-diCQA and 3,5-diCQAs. Molecular docking revealed that CQAs and these effective flavonoids share common binding residues within the P-gp pocket, providing a structural basis for the inhibition of efflux. These findings provide insights into the intestinal transport of structurally diverse CQAs and highlight the potential of dietary flavonoids to improve the oral bioavailability of CQAs.
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2025
·
IF 3.5
Lijun Su,Zhipeng Yu,Wenzhu Zhao
BACKGROUND This study aimed to elucidate the transport mechanism of lycopene-loaded nanomicelles to improve intestinal absorption of lycopene. The interactive mechanism between lycopene and nanomicelles was investigated through isothermal titration calorimetry (ITC). The cytotoxicity, cellular uptake, endocytosis, and intracellular transport pathways of lycopene-loaded nanomicelles were investigated using the Caco-2 cell model. RESULTS The ITC results demonstrated that nanomicelles/lycopene binding was an entropy-driven spontaneous exothermic reaction, and hydrophobic interactions were the main driving force. Lycopene-loaded nanomicelles were not cytotoxic, and uptake of lycopene by Caco-2 cells increased 2.20-fold after nanoencapsulation. The results of intracellular transport of lycopene-loaded nanomicelles indicated that the endoplasmic reticulum, Golgi apparatus, and lysosomes play key roles in this process. The intracellular transport results showed that the endoplasmic reticulum, Golgi apparatus, and lysosomes were important organelles for intracellular transport of lycopene-loaded nanomicelles. CONCLUSION Nanomicelles effectively enhance the cellular uptake of lycopene and are promising carriers for its delivery. This study contributes to the understanding of the transport mechanism of nanomicelles through intestinal epithelial cells. © 2025 Society of Chemical Industry.
研究领域:
营养学
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生物化学
·
药剂学
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DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2025
·
IF 4.2
Yuxin Shao,Yipu Li,Shuxian Xie,Bo Zhang,Jing Li,Yalei Wang,Yusheng Gao,Jianyuan Ma,Tenghe Ma,Zheng Wang
This study aimed to evaluate the effects of 4-hydroxyphenylacetic acid ( 4-HPAA ), a phenolic acid compound from Yucca schidigera extract, in Caco-2 cells and artificial rearing of pigeons. In vitro experiments showed that 4-HPAA at different levels exhibited higher cell viability than shikimic acid and 3,4-dihydroxybenzoic acid, and with the highest viability observed at 600 μM. Additionally, 600 μM 4-HPAA alleviated LPS-induced upregulation of IL-1β and CASPASE1 expressions ( P < 0.05) . In vivo results demonstrated that supplemental 4-HPAA at 500, 1000, and 2000 mg/kg levels did not affect the body weight of 25-day-old pigeons ( P > 0.05), but all levels increased immunoglobulin G ( IgG ) and IgM levels ( P < 0.05). Compared with control, 2000 mg/kg 4-HPAA significantly reduced serum L-lactic acid, D-lactic acid and lactate dehydrogenase ( LDH ) activity ( P < 0.05); increased spleen and bursa of Fabricius indices and intestinal total antioxidant capacity activity of 25-day-old pigeons ( P < 0.05); and elevated ileal barrier-related genes ( OCCLUDIN, CLAUDIN1 and MUC2) in 7-day-old pigeons, as well as jejunal MUC2 and ileal OCCLUDIN in 25-day-old meat pigeons ( P < 0.05). It also inhibited glycolytic gene hexokinase 2 expression, while upregulating the signaling pathway genes CAMK2G and MKNK1 ( P < 0.05). Supplemental 500 and 1000 mg/kg 4-HPAA significantly increased serum total cholesterol levels ( P < 0.05). Notably, 500 mg/kg 4-HPAA had an adverse effect on intestinal integrity, as indicated by the highest serum diamine oxidase content, and increased glycolytic gene LDH-B expression; However, it enhanced microbial richness and diversity in the intestines of 7-day-old pigeon ( P < 0.05). Besides, 1000 mg/kg 4-HPAA impaired intestinal morphology, as evidenced by a lower ileal villus height-to-crypt depth ratio ( P < 0.05), but resulted in the highest abundance of Lactococcus in 25-day-old pigeons. In conclusion, 600 μM 4-HPAA exhibits anti-inflammatory activity in Caco-2 cells, and 2000 mg/kg 4-HPAA promotes immune function and intestinal barrier integrity while inhibiting glycolytic gene expression and the production of related serum metabolites in meat pigeons.
研究领域:
兽医学
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营养学
·
分子生物学
·
动物科学
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产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2014
·Vol. 14
·期 6
·842-852
·
IF 3.65
Yan Zhang,Xuli Du,Yu Zhang,Guofei Li,Cuifang Cai,Jinghua Xu,Xing Tang
This work deals with the synthesis of insulin loaded nanoparticles (NPs) composed of thiolated Eudragit L100 (Eul-cys) and reduced glutathione (GSH) as potential nanocarriers for oral delivery of insulin. Perfectly spherical NPs with an average particle size of nearly 200–300 nm are prepared. The insulin release from Eul-cys/GSH and Eul-cys NPs in PBS (pH 7.4) shows that GSH can slightly decrease the release rate of insulin. Eul-cys in combination with GSH or sodium caprate (SC) is evaluated for its permeation enhancing effect of FITC-insulin using the Caco-2 monolayer and Caco-2/HT29-MTX co-cultured cells models. SC results in greater permeation enhancement compared to GSH. However, GSH proves to be less toxic. Paracellular transport of insulin represents the main mechanism by which the NPs facilitate insulin permeation through the intestinal epithelium, whereas a number of NPs are also taken up by the cells and release insulin within the cells.
研究领域:
药剂学
·
生物医学工程
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Cardiovascular Medicine
·
2024
·
IF 2.8
Wang Aiping,Ning Jie,Zhao Lu,Xu Renjie
Introduction: The incidence of metabolic disorders during pregnancy is increasing year by year, with diseases including hypertension and hyperlipidemia. Statins are the primary drugs for treating hyperlipidemia or atherosclerosis, yet some patients remain unresponsive to them, and pregnant women are prohibited from taking statins. Curculigoside is the major biologically active natural product present in Curculigo orchioides.Methods: In this study, A high-fat mice model was developed to study the lipid-lowering effect of curculigoside. Using intestinal Caco-2 cell monolayer, the curculigoside transport properties at two temperatures and possible transporters were systemically studied.Results: Curculigoside at concentrations used during the experiments have no toxic effect to Caco-2 cells. The curculigoside transfer from the apical to the basolateral side was strongly influenced by temperature. P-glycoprotein, breast cancer resistance protein, and efflux transporters are crucial components of the human intestinal cell line Caco-2. The curculigoside can significantly affect the contents of total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol in mice.Discussion: The transport properties and potential mechanism of curculigoside offer valuable insights for the design of development of hypolipidemic drugs like anti-atherosclerotic drugs and also be helpful to the further study of the pharmacological activity of curculigoside.
研究领域:
药理学
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生物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Foods
·
2021
·Vol. 10
·期 10
·2357
·
IF 4.35
Fei Li,Solju Pak,Jing Zhao,Yunlu Wei,Yuyu Zhang,Quanhong Li
A neutral pumpkin polysaccharide (NPPc) was extracted fromCucurbia moschataand its structural characterization is performed. Moreover, uptake behaviors of an NPPC were investigated at the cellular level. The results showed that NPPc, an average molecular weight (Mw) of 9.023 kDa, was linear (1→4)-α-D-Glcpresidues in the backbone, which branched point atO-6 position of (1→4,6)-α-D-Glcp. The side chain contained (1→6)-α-D-Glcpand terminal glucose. The cellular uptake kinetics results showed that the uptake of fluorescent-labeled NPPc was in time- and dose-dependent manners in Caco-2 cells. For subcellular localization of NPPc, it was accumulated in endoplasmic reticulum and mitochondrion. This study illustrates the characteristics on the uptake of NPPc and provides a rational basis for the exploration of polysaccharides absorption in intestinal epithelium.Keywords:Cucurbia moschata;polysaccharide;structural characterization;uptake characteristic
研究领域:
食品科学
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营养学
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药理学
✓ 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）