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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2020 · IF 5.162

Chondroitin sulfate and its nanocomposites with protamine or chitosan stabilize and deliver available nanosized iron

Guangxin Feng,Shuwei Tang,Yuxin Gang,Mingyong Zeng,Haohao Wu

Nanostructured iron (III) compounds are promising candidates for iron fortification applications due to their good solubility, bioavailability, and redox inertia. The current study synthesized ferric oxyhydroxide nanoparticles (FeONPs) based on chondroitin sulfate (ChS) and its nanocomposites with protamine sulfate (PS) or chitosan (CS) in neutral aqueous solution under ambient conditions, and evaluated their iron availability to polarized human intestinal epithelial (Caco-2) cells. Ultraviolet-visible spectroscopy, dynamic light scattering, transmission electron microscopy and energy-dispersive X-ray spectroscopy showed that ChS-FeONPs were wave-like anionic particles where FeONPs attached on the polysaccharide chains and PS/ChS-FeONPs and CS/ChS-FeONPs were irregular anionic nanoparticles where FeONPs scattered across the entire region. The calcein-fluorescence-quenching assay in polarized Caco-2 cells showed good iron uptake from ChS-FeONPs, PS/ChS-FeONPs and CS/ChS-FeONPs mainly via endocytosis, with the latter two exhibiting better iron absorption. Overall, our study provides a more facile and greener alternative route to synthesize the bioavailable nano-sized iron.

CAS / MDL: 10025-77-1
研究领域: 营养学 · 材料科学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Evidence-based Complementary and Alternative Medicine · 2022 · IF 2.65

Study on the Absorption of Arsenic Species in Realgar Based on the Form and Valence

Mingyi Sun,Yaolei Li,Ying Wang,Huimin Wu,Jing Liu,Longtai You,HuLinyue Peng,Huating Huang,Hongyu Jin,Xiaoxu Dong,Changhai Qu,Xingbin Yin,Jian Ni

At present, several experiments have been carried out to study the changes in total arsenic content of realgar and its prescription, but few researches on its form and valence. We evaluated the change in arsenic species concentration in realgar from the perspective of absorption by using an in vitro dissolution study, an in vivo unidirectional intestinal perfusion study, transmembrane transport in Caco-2 cells, and a pharmacokinetic study in rats. In the gastrointestinal tract, arsenic species are mainly present inorganic forms of AsIII and AsV. The cumulative dissolution rates of soluble arsenic in 4 h artificial gastric fluid and 8 h artificial intestinal fluid were 21.99% and 59.20%, respectively. The values of soluble arsenic in realgar in the duodenum, jejunum, and ileum of rats were 5.4 × 10−3, 6.1 × 10−3 and 5.8 × 10−3 cm/min, respectively. In the process of small intestine perfusion, the AsIII of realgar was partially converted into AsV in the duodenum and jejunum. As the transport time increased, the transmembrane transport rate and value of soluble arsenic in realgar were increased in Caco-2 cells, and it also suggested that arsenic species may be passively transported across the Caco-2 cell monolayer. The Cmax and AUC (0-24) of AsIII, AsV, and DMA in plasma of realgar were 41.26 ng L−1/343.977 ng h mL−1, 21.626 ng L−1/47.310 ng h mL−1, and 2.372 ng L−1/30.429 ng h mL−1, respectively. Tmax and MRT (0-∞) of AsIII, AsV, and DMA were 2.571 h/9.649 h, 0.393 h/2.790 h, and 3.143 h/23.145 h, respectively. It is hoped to provide a basis for clarifying the arsenic species in realgar.

CAS / MDL: 7697-37-2
研究领域: 药学 · 毒理学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Antioxidants · 2025 ·Vol. 14 ·期 6 ·737 · IF 6.6

Inactivated Cells and Metabolites of Saccharomyces boulardii Alleviate Inflammation Damage in Caco-2 Monolayer Cells and Mice with Ulcerative Colitis

Yuxin Jin,Zehui Niu,Menglin Feng,Huilian Che,Zhihong Liang

Saccharomyces boulardii(S. boulardii) has attracted widespread attention due to its antimicrobial and anti-inflammatory properties. In this study, we prepared postbiotics from the heat-inactivated cells (HIC) and cell-free supernatant (CFS) ofS. boulardii, with the important component L-arginine (Arg) from the metabolic products included as one of the experimental groups. The results showed that in LPS-stimulated Caco-2 cells, HIC, CFS, and Arg protect intestinal epithelial barrier integrity by inhibiting the expression of TNF-α, IL-1β, and IL-6 while enhancing the expression of occludin and ZO-1 proteins. In dextran sulfate sodium (DSS)-induced colitis mice, HIC, CFS, and Arg alleviate symptoms such as weight loss and colonic damage while suppressing the upregulation of pro-inflammatory factors and the downregulation of tight junction proteins. Moreover, these postbiotics help restore the gut microbiota composition and functionality in colitis mice, with potentially superior regulatory effects compared to sulfasalazine (SASP). Overall, HIC and CFS protect the intestinal barrier function and improve DSS-induced colitis, supporting the development of functional food supplements.

CAS / MDL: 74-79-3
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF FOOD COMPOSITION AND ANALYSIS · 2024 · IF 4

Application of green tea residue-derived carbon dots in the detection of Fe3+ ions and imaging of Caco-2 cells

Yu He,Suqing Liu,Feng Xie,Yan Zhou,Xiaosheng Yang

In this study, we successfully synthesized green luminescent carbon dots by using green tea residue as the precursor of carbon source. Based on the internal filter effect (IFE), the fluorescence emission intensity of the probe decreased significantly with the increase of Fe 3 + concentration. Based on this, a linear relationship between Fe 3 + concentration and the fluorescence emission intensity of the probe was established to semi-quantitatively detect Fe 3 + . The results showed that the linear range was 1–400 μM, and the detection limit was 3.58 μM. In addition, the probe was further applied to actual samples, and it was found that the recovery rate was between 97.75% and 104.59%, and the relative standard deviation was below 1.81%. These findings underscore the considerable potential of the carbon dots for practical Fe 3+ detection applications. In a further application, the fluorescent carbon dots were diluted and directly employed to stain Caco-2 cells. Remarkably, even after 10 and 20-fold dilutions, the Caco-2 cells displayed vivid fluorescence at the green excitation wavelength. This outcome suggests a promising avenue for the application of fluorescent carbon dots in the field of biology.

CAS / MDL: 6119-70-6
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Drug Metabolism and Pharmacokinetics · 2013 · IF 2.071

Involvement of AP-1 and NF-κB in the Up-regulation of P-gp in Vinblastine Resistant Caco-2 Cells

Qiuxia Chen,Yicong Bian,Su Zeng

Caco-2 is a widely used cell model in drug absorption and P-glycoprotein (P-gp,MDR1) substrate identification. Long term vinblastine treatment of Caco-2 cells could increase the expression of P-gp, thus, the vinblastine resistant Caco-2 (Caco-2 vbl) cells can be used as a rapid and sensitive alternative model in identifying P-gp substrates. The mechanism of P-gp induction in this model is not clear, this study was therefore intended to clarify the possible factors involved in P-gp up- regulation in Caco-2 vbl cells. Since vinblastine is the inducer of both activator protein-1 (AP-1) and nuclear factor kappa B(NF-κB), we investigated the role of AP-1 and NF-κB in regulation of MDR1 gene expression. Our results indicated that the AP-1 and NF-κB luciferase activity was higher in Caco-2 vbl cells than that in Caco-2 cells by reporter gene assay. The mRNA expression of AP-1 subunit c-Jun and NF-κB was increased in Caco-2 vbl cells. The c-Jun inhibitor SP600125 and NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) suppressed the expression of MDR1 mRNA in Caco-2 vbl cells. In conclusion, this study provides the evidence that AP-1 and NF-κB are involved in the P-gp induction in Caco-2 vbl cells.

研究领域: 药理学 · 细胞生物学 · 分子生物学 · 癌症研究
✓ 已验证 DOI PubMed 高影响因子
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CELLULAR AND MOLECULAR BIOLOGY · 2023 ·Vol. 69 ·期 7 · IF 1.6

LncRNA-CBR3-AS1 promotes and enhances the malignancy of ulcerative colitis via targeting miRNA-145-5p/FN1

Jingmei Cao,Qing Zhao,Qing Jia,Yiming Li

Growing evidence suggested that long non-coding RNA (lncRNA) played a crucial role in the progression of ulcerative colitis (UC). Therefore, the purpose of this study is to understand how the lncRNA CBR3-AS1, which has been found to be up-regulated in UC, contributes to the bio-progression of the disease. To determine the concentration and relationship of the lncRNA CBR3-AS1, miRNA-145-5p, and FN1 in the LPS-induced Caco-2 model cells, qRT-PCR was employed in this study.  Starbase was used to predict the target sites of the lncRNA CBR3-AS1 and the miRNA-145-5p, and Targetscan was used to predict the probable linking points of the FN1 and the miRNA-145-5p, which was confirmed by a twofold luciferase reporter test. The vitality of Caco-2 cells was determined using the CCK-8 and FCM tests. Using the ELISA kit, TNF, IFN, IL-6, and IL-17 were identified. The results of the experiment show that in Caco-2 cells treated with 10 ng/mL LPS, LncRNA CBR3-AS1 was up-regulated. Additionally, Caco-2 cells' LPS-induced apoptosis and inflammatory response were inhibited by lncRNA CBR3-AS1 inhibition. Dual-luciferase reporter experiments demonstrated that miRNA-145-5p and lncRNA CBR3-AS1 might connect. Moreover, miRNA-145-5p, which was shown to be poorly expressed in UC, was found to suppress inflammatory and apoptotic responses in Caco-2 cells activated by LPS. It's significant that FN1 was confirmed to be miRNA-145-5p's downstream target. Sh-CBR3-AS1's inhibitory effects were reversed by miRNA-145-5p knockdown, and the effects of the miRNA-145-5p inhibitor were reversed by sh-FN1. In conclusion, LncRNA CBR3-AS1 may offer a unique method for treating UC by suppressing the function of miRNA-145-5p, which is implicated in the development of UC.

研究领域: 分子生物学 · 胃肠病学 · 免疫学
✓ 已验证 DOI PubMed 高影响因子
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PeerJ · 2022 · IF 3.061

Microfluidics-assisted electrospinning of aligned nanofibers for modeling intestine barriers

Wentao Su,Miao Zhang,Wenbo Wei,Haitao Wang,Wei Zhang,Zhongyu Li,Mingqian Tan,Zongzheng Chen

During electrospinning, the fibers deposited on the collector are usually randomly oriented in a disordered form. Researchers hope to generate periodic structures to expand the application of electrospinning, including improving the sensing properties of electronic and photonic devices, improving the mechanical properties of solid polymer composites and directional growth of human tissues. Here, we propose a technique to control the preparation of aligned foodborne nanofibers by placing dielectric polymers on microfluidic devices, which does not require the use of metal collectors. This study was conducted by introduced PEDOT:PSS polymer as a ground collector to prepare aligned foodborne nanofibers directly on the microfluidic platform. The fluidity of the electrolytic polymer collector makes it possible to shape the grounding collector according to the shape of the microcavity, thus forming a space adjustable nanofiber membrane with a controllable body. The simplicity of dismantling the collector also enables it extremely simple to obtain a complete electrospun fiber membrane without any additional steps. In addition, nanofibers can be easily stacked into a multi-layer structure with controllable hierarchical structures. The Caco-2 cells that grow on the device formed a compact intestinal epithelial layer that continuously expresses the tightly bound protein ZO-1. This intestinal barrier, which selectively filters small molecules, has a higher level of TEER, reproducing intestinal filtration functions similar to those of in vivo models. This method provides new opportunities for the design and manufacture of various tissue scaffolds, photonic and electronic sensors.

研究领域: 材料科学 · 生物医学工程 · 组织工程 · 纳米技术
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BMC GASTROENTEROLOGY · 2023 ·Vol. 23 ·期 1 ·1-10 · IF 2.4

Protective role of circRNA CCND1 in ulcerative colitis via miR-142-5p/NCOA3 axis

Xiang Ping,Ge Tingrui,Zhou Jingyi,Zhang Yonggang

Background Increasing research indicates that circular RNAs (circRNAs) play critical roles in the development of ulcerative colitis (UC). This study aimed to determine the role of circRNA CCND1 in UC bio-progression, which has been shown to be downregulated in UC tissues. Methods Reverse transcription quantitative polymerase chain reaction was used to determine the levels of circRNA CCND1 , miR-142-5p, and nuclear receptor coactivator-3 ( NCOA3 ) in UC tissues and in lipopolysaccharide (LPS)-induced Caco-2 cells. Target sites of circRNA CCND1 and miR-142-5p were predicted using StarBase, and TargetScan to forecast potential linkage points of NCOA3 and miR-142-5p, which were confirmed by a double luciferase reporter-gene assay. Cell Counting Kit 8 and flow cytometry assays were performed to assess Caco-2 cell viability and apoptosis. TNF-α, IL-1β, IL-6, and IL-8 were detected using Enzyme-Linked Immunosorbent Assay kits. Results CircRNA CCND1 was downregulated in UC clinical samples and LPS-induced Caco-2 cells. In addition, circRNA CCND1 overexpression suppressed LPS-induced apoptosis and inflammatory responses in Caco-2 cells. Dual-luciferase reporter-gene assays showed that miR-142-5p could be linked to circRNA CCND1 . Moreover, miR-142-5p was found to be highly expressed in UC, and its silencing inhibited LPS-stimulated Caco-2 cell apoptosis and inflammatory responses. Importantly, NCOA3 was found downstream of miR-142-5p. Overexpression of miR-142-5p reversed the inhibitory effect of circRNA CCND1 -plasmid on LPS-stimulated Caco-2 cells, and the effects of miR-142-5p inhibitor were reversed by si- NCOA3 . Conclusion CircRNA CCND1 is involved in UC development by dampening miR-142-5p function, and may represent a novel approach for treating UC patients.

研究领域: 分子生物学 · 胃肠病学 · 免疫学 · 细胞生物学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2026 · IF 6.2

Galangin Mitigates Alcohol-Induced Intestinal Damage by Suppressing Ferroptosis via the SESN2/KEAP1/NRF2 Pathway in Mice and Caco-2 Cells

Yanan Zhao,Rui Wang,Ziyang Huang,Siting Ju,Binghua Dong,Hui Teng,Lei Chen

The gut is often referred to as the “second brain” and is highly vulnerable to alcohol exposure. Galangin, a flavonoid extracted from traditional medicinal herbs, Alpinia officinarum Hance, has manifested auspicious clinical application potential. This study aims to explore the regulatory effect of galangin on ferroptosis in an alcohol-related intestinal injury model and its underlying mechanism. In vivo, we confirmed that galangin administration could alleviate alcohol-induced iron metabolism dysfunction and ferroptosis and activate the SESN2/KEAP1/NRF2 signaling pathway in mice colon. In vitro, alcohol-caused disruption of iron homeostasis and ferroptosis could also be significantly reduced by galangin. Using specific small interfering RNA targeting SESN2 (Si-SESN2) or the NRF2 inhibitor ML385 significantly abrogated the protective effect of galangin. Molecular docking and Co-IP results further revealed that galangin activates NRF2 nuclear translocation by promoting KEAP1/SESN2 formation as well as KEAP1/NRF2 dissociation. Collectively, galangin suppressed ferroptosis by activating the SESN2/KEAP1/NRF2 pathway in mice and Caco-2 cells.

CAS / MDL: 548-83-4
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2026 · IF 6

Nanosized genistein solid dispersion with superior mucus-penetrating ability significantly boosts intestinal absorption: A combined SPIP and Caco-2 cell study

Yu Zhang,Na Zhang,Yingsai Fan,Yanling Sun,Xin He,Xinghua Zhao

A food-grade nanosized genistein solid dispersion with superior mucus-penetrating property was successfully fabricated. • GEN-SD improves intestinal absorption via paracellular diffusion, clathrin-mediated endocytosis and low BCRP efflux. • The integrated SPIP–mucus–Caco-2 model provides a universal strategy for poorly soluble nutraceuticals. Genistein (GEN) is a typical soy-derived nutraceutical ingredient with multiple health-promoting bioactivities, but its application is severely limited by poor solubility and low oral bioavailability. In this study, the intestinal absorption behavior, transport pathways, and underlying mechanisms of GEN, its physical mixture (GEN-PM) and genistein solid dispersion (GEN-SD) were systematically investigated using a combined strategy including rat in situ single-pass intestinal perfusion (SPIP), mucus penetration evaluation and Caco-2 cell monolayer model. The prepared GEN-SD presented a particle size of only 100.11 nm and a BET specific surface area of 8.46 m 2 /g, which was 59.7% smaller and 130.5% larger than raw GEN respectively. SPIP results showed that GEN-SD exhibited significantly higher effective permeability coefficient ( P eff ) and absorption rate constant ( K a ) in the duodenum at pH 7.4 and 10 μg/mL ( P  < 0.05). Removal of the intestinal mucus layer markedly reduced the absorption advantage of GEN-SD ( P  < 0.05), and in vitro Transwell assay verified its superior mucus-penetrating ability, with the 240 min cumulative transport quantity of GEN-SD increased by 26.04% and its Papp value elevated by 24.15% compared with pure GEN. In Caco-2 monolayers, GEN-SD displayed significantly enhanced time-dependent bidirectional transport and apparent permeability ( P app ) ( P  < 0.05), and CLSM confirmed stronger intracellular uptake. Inhibitor studies in both SPIP and Caco-2 models demonstrated that the absorption of GEN-SD was prominently inhibited by EDTA and chlorpromazine hydrochloride ( P  < 0.05), indicating involvement of paracellular diffusion and clathrin-mediated endocytosis, while reserpine showed no significant effect, suggesting minimal BCRP-mediated efflux. The superior absorption of GEN-SD was attributed to the synergistic effects of amorphization, nanoscale particle size, enlarged specific surface area, improved mucus penetration, enhanced paracellular diffusion and clathrin-mediated endocytosis. This study provides a mechanistic basis for developing oral delivery systems with improved bioavailability for genistein. Download: Download high-res image (163KB) Download: Download full-size image

CAS / MDL: 69-09-0
✓ 已验证 产品关联 DOI PubMed 高影响因子
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RSC Advances · 2019 ·Vol. 9 ·期 59 ·34607-34616 · IF 3.049

Impact of deoxynivalenol and kaempferol on expression of tight junction proteins at different stages of Caco-2 cell proliferation and differentiation

Xiaojie Wang,Li Li,Genyi Zhang

The barrier function of intestinal tract is essential to gut health, and the expression of tight junction (TJ) proteins in human epithelial colorectal adenocarcinoma (Caco-2) cells, mimicking the intestinal stem cell proliferation and differentiation, was investigated after treatment by the mycotoxin of deoxynivalenol (DON) and phenolic compound of kaempferol (KAM). The results showed that DON (5 μM) significantly reduced the expression of claudin-4 while kaempferol (100 μM) increased the expression of claudin-3 during Caco-2 cell proliferation. After being cultured for 11 days, the DON treatment, unexpectedly, augmented the expression of claudin-4 with an increased TEER. For differentiated Caco-2 cells after a 21 day culture, both the TEER and claudin-4 levels were significantly reduced by DON while KAM pretreatment alleviated the damage caused by DON accompanying an increase of TEER, claudin-3, and ZO-1. Thus, kaempferol and DON differentially affected the expression of tight junction proteins at different stages of Caco-2 cell proliferation and differentiation, and an increase of the integrity of TJ after KAM pretreatment indicates KAM has the potential to protect the integrity of the barrier function of the intestinal epithelium for improved health.

研究领域: 毒理学 · 药理学 · 细胞生物学 · 胃肠病学
✓ 已验证 DOI PubMed 高影响因子
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MOLECULES · 2024 ·Vol. 29 ·期 8 ·1769 · IF 4.2

The Increased Dissolution and Oral Absorption of Itraconazole by Nanocrystals with an Endogenous Small-Molecule Surfactant as a Stabilizer

Sheng Chang,Qiang Yang,Jiahuan Liu,Li Yin,Jihong Han,Lanlan Zong,Xiaohui Pu

The aim of this study was to develop cholic-acid-stabilized itraconazole nanosuspensions (ITZ-Nanos) with the objective of enhancing drug dissolution and oral absorption. A laboratory-scale microprecipitation–high-pressure homogenization method was employed for the preparation of the ITZ-Nanos, while dynamic light scattering, transmission electron microscope analysis, X-ray diffraction, differential scanning calorimetry, and high-performance liquid chromatography analysis were utilized to evaluate their physicochemical properties. The absorption and bioavailability of the ITZ-Nanos were assessed using Caco-2 cells and rats, with Sporanox®pellets as a comparison. Prior to lyophilization, the particle size of the ITZ-Nanos measured approximately 225.7 nm. Both X-ray diffraction and differential scanning calorimetry confirmed that the ITZ remained crystalline within the nanocrystals. Compared to the pellets, the ITZ-Nanos exhibited significantly higher levels of supersaturation dissolution and demonstrated enhanced drug uptake by the Caco-2 cells. The AUC(0–t) value for the ITZ-Nanos in rats was 1.33-fold higher than that observed for the pellets. These findings suggest that cholic acid holds promise as a stabilizer for ITZ nanocrystals, as well as potentially other nanocrystals.

CAS / MDL: 81-25-4 71119-23-8
研究领域: 药学 · 纳米技术 · 药物递送系统 · 药代动力学
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