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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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DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY · 2016 · IF 2.429

Efficacy, safety and mechanism of HP-β-CD-PEI polymers as absorption enhancers on the intestinal absorption of poorly absorbable drugs in rats

Hailong Zhang,Xiaoyan Huang,Yongjing Zhang,Yang Gao

Context: Oral bioavailability of some hydrophilic therapeutic macromolecules was very poor, thus leading to their limited application in clinic.Objective: To investigate the efficacy, safety and mechanism of HP-β-CD-PEI polymers on the intestinal absorption of some poorly absorbable drugs in rats.Methods: Effects of HP-β-CD-PEI polymers on the intestinal absorptions of drugs were investigated by an in situ closed loop method in rats. The safety of HP-β-CD-PEI polymer was evaluated by measurement of lactate dehydrogenase (LDH) activity and amount of protein released from rat intestinal perfusate. The absorption enhancing mechanisms were explored by the measurement of zeta potential, transepithelial electrical resistance (TEER) and in vitro transport of FD4 (a paracellular marker) across rat intestinal membranes, respectively.Results: HP-β-CD-PEI polymers, especially HP-β-CD-PEI1800, demonstrated excellent absorption enhancing effects on drug absorption in a concentration-dependent manner and the enhancing effect was more efficient in the small intestine than that in the large intestine. Five percent (w/v) HP-β-CD-PEI1800 obviously decreased the TEER, accompanied with increase in the intestinal transport of FD4, indicating that absorption enhancing actions of HP-β-CD-PEI polymers were possibly performed by loosening tight junctions of intestinal epithelium cells, thereby increasing drug permeation via a paracellular pathway. A good liner relationship between absorption enhancing effects of HP-β-CD-PEI polymers and their zeta potentials suggested the contribution of positive charge on the surface of these polymers to their absorption enhancing effects.Conclusion: HP-β-CD-PEI polymers might be potential and safe absorption enhancers for improving oral delivery of poorly absorbable macromolecules including peptides and proteins.

CAS / MDL: 47931-85-1 11061-68-0
研究领域: 药剂学 · 药物递送 · 药理学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Comparison of extraction processes, characterization and intestinal protection activity of Bletilla striata polysaccharides

Junjie Qiu,Xiao Xu,Jingyan Guo,Zhenyu Wang,Jinjin Wu,Huiqin Ding,Yuchen Xu,Yili Wu,Qianyi Ying,Jiawei Qiu,Suxiang Wu,Senlin Shi

We optimized the extraction process of Bletilla striata polysaccharides using orthogonal design, Box-Behnken design (BBD), and genetic algorithm-back propagation (GA-BP), then compared and evaluated them to confirm that the combination of BBD and GA-BP neural networks was capable of increasing polysaccharide yields and antioxidant activity. The optimal extraction parameters were as follows: liquid-to-solid ratio of 15 mL/g, extraction power of 450 W, and extraction time of 34 min. Under these conditions, the polysaccharide yield and antioxidant activity were 8.29 ± 0.50 % and 26.20 ± 0.28 (mM FE/mg). Subsequently, the polysaccharide was purified to obtain purified Bletilla striata polysaccharides 1 (pBSP1) with a Mw of 255.172 kDa. Scanning electron microscope (SEM), ultraviolet-visible detector (UV), fourier transform infrared spectrometer (FTIR), high performance liquid chromatography (HPLC), X-ray diffraction (XRD), nuclear magnetic resonance (NMR) and periodate oxidation were used to analyze the structure of pBSP1. The results showed pBSP1 had a smooth surface and a rough interior, with a composition of α-D conformation glucose (18.23 %) and β-D conformation mannose (53.77 %), and an amorphous crystal structure. According to the results of thermogravimetric and rheological tests, pBSP1 exhibits good thermal stability and viscoelastic behavior. Furthermore, pBSP1 protected lipopolysaccharide (LPS)-induced GES − 1 and Caco2 cells, the results showed pBSP1(400 μg/mL) lowered TEER synthesis in Caco2 cells as well as apoptosis and reactive oxygen species (ROS) production in both cells, indicating that pBSP1 may have an intestine protective effect.

CAS / MDL: 7758-02-3
研究领域: 药理学 · 生物化学 · 食品科学 · 生物技术
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF THROMBOSIS AND THROMBOLYSIS · 2024 · IF 2.3

Ghrelin may protect against vascular endothelial injury in Acute traumatic coagulopathy by mediating the RhoA/ROCK/MLC2 pathway

He Chengjian,Song Xiaojing,Zhu Zigui,Xiao Yan,Chen Jiacheng,Yao Hongyi,Xie Rongjun

Ghrelin exerts widespread effects in several diseases, but its role and mechanism in Acute Traumatic Coagulopathy (ATC) are largely unknown. The effect of ghrelin on cell proliferation was examined using three assays: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), Lactate Dehydrogenase (LDH), and flow cytometry. The barrier function of the endothelial cells was evaluated using the Trans-Endothelial Electrical Resistance (TEER) and the endothelial permeability assay. An ATC mouse model was established to evaluate the in vivo effects of ghrelin. The Ras homolog family member A (RhoA) overexpression plasmid or adenovirus was used to examine the molecular mechanism of ghrelin. Ghrelin enhanced Human Umbilical Vein Endothelial Cells (HUVEC) proliferation and endothelial cell barrier function and inhibited HUVEC permeability damage in vitro. Additionally, ghrelin decreased the activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT) in mice blood samples in the ATC mouse model. Ghrelin also improved the pathological alterations in postcava. Mechanistically, ghrelin acts through the RhoA/ Rho-associated Coiled-coil Containing Kinases (ROCK)/ Myosin Light Chain 2 (MLC2) pathway. Furthermore, the protective effects of ghrelin, both in vitro and in vivo, were reversed by RhoA overexpression. Our findings demonstrate that ghrelin may reduce vascular endothelial cell damage and endothelial barrier dysfunction by blocking the RhoA pathway, suggesting that ghrelin may serve as a potential therapeutic target for ATC treatment. Graphical Abstract We explored the effects of ghrelin on coagulopathy and vascular endothelial injury in vivo by establishing an ATC mouse model, and investigated the effects of ghrelin on LPS-induced HUVECs cell damage in vitro. The RhoA overexpression plasmid or adenovirus was used to examine the molecular mechanism. Abbreviations : ATC =acute traumatic coagulopathy; HUVECs =Human Umbilical Vein Endothelial Cells; LPS =lipopolysaccharide; RhoA =The Ras homolog family member A; aPTT =activated partial thromboplastin time; PT =prothrombin time; TEER =trans-endothelial electrical resistance

CAS / MDL: 258338-12-4
研究领域: 血液学 · 血管生物学 · 药理学 · 分子生物学
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