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      • Combined photothermal-chemotherapy of breast cancer by near infrared light responsive hyaluronic acid-decorated nanostructured lipid carriers

        Zheng, Shaohui,Nguyen, Van Du,Song, Seung Yoon,Han, Jiwon,Park, Jong-Oh IOP 2017 Nanotechnology Vol.28 No.43

        <P>In this study, a novel type of hyaluronic acid (HA)-decorated nanostructured lipid carrier (NLC) was prepared and investigated as a light-triggered drug release and combined photothermal-chemotherapy for cancer treatment. Polyhedral gold nanoparticles (Au NPs) with an average size of 10 nm were synthesized and co-encapsulated with doxorubicin (DOX) in the matrix of NLCs with a high drug loading efficiency (above 80%). HA decoration was achieved by the electrostatic interaction between HA and CTAB on the NLC surface. A remarkable temperature increase was observed by exposing the Au NP-loaded NLCs to an NIR laser, which heated the samples sufficiently (above 40 °C) to kill tumor cells. The entrapped DOX exhibited a sustained, stepwise NIR laser-triggered drug release pattern. The biocompatibility of the NLCs was investigated by MTT assay and the cell viability was maintained above 85%, even at high concentrations. The intracellular uptake of free DOX and entrapped DOX, observed by confocal microscopy, revealed two distinct uptake mechanisms, i.e. passive diffusion and endocytosis, respectively. In particular, internalization of the HA-Au-DOX-NLCs was more extensively enhanced than the Au-DOX-NLCs, which was attributed to HA-CD44 receptor-mediated endocytosis. Meanwhile, the internalized NLCs successfully escaped from the lysosomes, increasing the intracellular DOX. The HA-Au-DOX-NLCs IC<SUB>50</SUB> value decreased from 2.3 to 0.6 <I>μ</I>g ml<SUP>−1</SUP> with NIR irradiation at 72 h, indicating the excellent synergistic antitumor effect of photothermal-chemotherapy. The photothermal ablation was further confirmed by a live/dead cell staining assay. Thus, a combined photothermal-chemotherapy approach has been proposed as a promising strategy for cancer treatment.</P>

      • SCISCIESCOPUS

        Dual tumor-targeted multifunctional magnetic hyaluronic acid micelles for enhanced MR imaging and combined photothermal-chemotherapy

        Zheng, Shaohui,Han, Jiwon,Jin, Zhen,Kim, Chang-Sei,Park, Sukho,Kim, Kyu-pyo,Park, Jong-Oh,Choi, Eunpyo Elsevier 2018 Colloids and Surfaces B Vol.164 No.-

        <P><B>Abstract</B></P> <P>Multifunctional polymeric micelles were developed as a promising dual tumor-targeted drug delivery platform for magnetic resonance (MR) imaging and combined photothermal-chemotherapy. HA-C<SUB>16</SUB> copolymers were synthesized via peptide formation process with subsequent co-encapsulation of therapeutic agent docetaxel (DTX) and superparamagnetic iron oxide nanoparticles (SPIONs) to form the multifunctional micelles. The micelles exhibited uniform nanosize and remarkable colloidal stability in aqueous solution. The sustained drug release behavior from HA micelles was observed over the test period. Moreover, the specific targeting capability based on CD44 recptor-mediated endocytosis and the enhanced targeting efficacy by in presence of external magnetic field were investigated. The clustered SPIONs within micelles exerted excellent contrast effect with high r<SUB>2</SUB> relaxivity in MR phantom test. Furthermore, the multifunctional micelles could readily convert light to heat to hyperthermia temperature upon near infrared light irradition and induce photothermal ablation to breast cancer cells. The combined photothermal therapy with DTX-mediated chemotherapy of the developed multifunctional polymeric micells could generate a synergistic therapeutic effect. Based on these findings, the resulting multifunctional micelles may provide high potential for multimodality theragnosis of cancer.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A novel multifunctional magnetic hyaluronic acid micelle was developed. </LI> <LI> Active tumor targeting was realized through CD44 receptor-mediated endocytosis. </LI> <LI> Active tumor targeting was enhanced by external magnetic field application. </LI> <LI> MRI contrast was enhanced by incorporation of targeting ligands and magnetic field. </LI> <LI> Cancer therapeutic efficacy was improved by chemotherapy and photothermal-therapy. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • KCI등재

        The Risk of Gastrointestinal Cancer on Daily Intake of Low-Dose BaP in C57BL/6 for 60 Days

        Zheng Zhi,Park Jung Kuk,Kwon Oh Wook,Ahn Sung Hoon,Kwon Young Joo,Jiang Linjuan,Zhu Shaohui,Park Byoung Hee 대한의학회 2022 Journal of Korean medical science Vol.37 No.30

        Background: Benzo(a)pyrene (BaP) is a carcinogenic compound in contaminated foodstuffs. The effect of oral intake of the environmental carcinogen BaP under low doses and frequent exposure on a digestive system has not been thoroughly verified. Methods: In this regard, this study was conducted to prove the toxicity effects of BaP on the stomach and colon tissue after exposure to C57BL/6 mouse (3 and 6 µg/kg) following daily oral administration for 60 days. This study investigated acute gastric mucosal injury, severe gastric edema, cell infiltration, and mononuclear cells, multifocal cells, and tumoral inflammatory cells. Results: The results of ELISA showed that the expression of serum interleukin (IL)-6 and tumor necrosis factor-α in the BaP exposure group were significantly increased, and a high level of DNA adduct distribution in their stomach and colon. Moreover, this study has confirmed the expression of early carcinogenesis markers: nuclear factor (NF)-κB, p53, IL-6, superoxide dismutase 1 (SOD1), mucin (MUC1 and MUC2), and β-catenin in the stomach and colon, and showed that there was a significant increase in IL-6, NF-κB, SOD1, β-catenin, and MUC1 (P < 0.05). At the same time, there was a significant decrease in MUC2 and p53 (P < 0.05). Thus, even in low doses, oral intake of BaP can induce DNA damage, increasing the potential risk of gastrointestinal cancer. Conclusion: This study will provide a scientific basis for researching environmental contaminated food and intestinal health following daily oral administration of BaP.

      • SCIESCOPUSKCI등재

        The differences between copper sulfate and tribasic copper chloride on growth performance, redox status, deposition in tissues of pigs, and excretion in feces

        Zheng, Ping,Pu, Bei,Yu, Bing,He, Jun,Yu, Jie,Mao, Xiangbing,Luo, Yuheng,Luo, Junqiu,Huang, Zhiqing,Luo, Chenggui,Wang, Shaohui,Chen, Daiwen Asian Australasian Association of Animal Productio 2018 Animal Bioscience Vol.31 No.6

        Objective: The objective of this experiment was to compare the effects of adding 130 mg/kg Cu from either copper sulfate (CS) or tribasic copper chloride (TBCC) on growth performance, mineral deposition in tissues, and the excretion in feces of pigs as well as changes in the mineral contents in tissues and feces when the supplemental Cu level was decreased from 130 mg/kg to 10 mg/kg. Methods: A total of 72 pigs ($32.6{\pm}1.2kg$) were randomly assigned to a CS diet or a TBCC diet with 6 pens per treatment. The trial lasted 102 d and included 3 phases (phase 1, 1 to 30 d; phase 2, 31 to 81 d; and phase 3, 82 to 102 d). The supplemental levels of Cu in the 2 treatments were 130 mg/kg in phase 1 and 2 and 10 mg/kg in phase 3. Results: The results showed that pigs fed the CS diet tended to have higher average daily gain than pigs fed the TBCC diet during d 1 to 81 (p<0.10). Compared with CS, TBCC increased the activities of aspartate transaminase (AST), ceruloplasmin, and superoxide dismutase in serum on d 30 (p<0.05). The TBCC decreased the Cu level in the liver on d 81 (p<0.05) and increased the Mn level in the liver on d 102 (p<0.05). The concentration of Cu in feces sharply decreased when the supplemental Cu level in diet changed from 130 mg/kg to 10 mg/kg in both diets (p<0.05). Conclusion: The result suggested that TBCC and CS had no significant difference on growth performance but TBCC had higher activities of AST and antioxidant enzymes and lower liver Cu than CS when pigs fed diets with 130 mg Cu /kg diet.

      • KCI등재

        Beneficial Effects of Fermentation of Red Chili Pepper Using Lactococcus lactis subs. Cremoris RPG-HL-0136 in High-Fat Diet-Induced Obese Mice

        Zhi Zheng,Jung Kuk Park,Linjuan Jiang,Shaohui Zhu,권오욱,이병천,이혜민,노연진,강재현,박병희 한국식품영양과학회 2023 Journal of medicinal food Vol.26 No.2

        Red chili pepper is a beneficial natural spicy food that has antiobesity and antitype II diabetes effects, but it is not conducive to in-depth research as a dietary strategy to treat obesity. This study aims to investigate the beneficial effects of red chili pepper, fermented with a novel Lactococcus lactis subs. cremoris RPG-HL-0136. LC-MS/MS analysis is conducted to detect the content of capsaicin and dihydrocapsaicin, and no significant difference is observed between the nonfermented red chili pepper (NFP) (W/W) and the prepared L. lactis subs. cremoris RPG-HL-0136-fermented chili mixture (LFP). After establishing a high-fat diet-induced obese type II diabetic mouse model, the effects on weight gain, weight loss of liver and testicular fat, total cholesterol, triglyceride, fasting glucose, insulin, and homeostatic model assessment for insulin resistance in LFP were evaluated to be better than those in NFP following 10 weeks of interventions. All animal experiments were approved by the Institutional Animal Care and Use Committee of Xinxiang medical university. NFP and LFP could increase the expression of transient receptor potential vanilloid subfamily 1, peroxisome proliferator-activated receptor-alpha and caspase-2 in the high-fat mice. Compared with unfermented red chili pepper, the fermented red chili pepper complex significantly reduced LPS, tumor necrosis factor-alpha, and interleukin-6 in serum (P < .05). Intake of LFP significantly increased the expression of claudin-1 and occludin in the colon of the high-fat mice (P < .05), and there was no damage to the stomach and colon. This study provides scientific evidence that red chili pepper, fermented with L. lactis subs. cremoris RPG-HL-0136, may be beneficial for future treatment of obesity and accompanying diabetes. (IACUC.No.XYLL-20200019).

      • SCISCIESCOPUS

        Nanohybrid magnetic liposome functionalized with hyaluronic acid for enhanced cellular uptake and near-infrared-triggered drug release

        Nguyen, Van Du,Zheng, Shaohui,Han, Jiwon,Le, Viet Ha,Park, Jong-Oh,Park, Sukho Elsevier 2017 Colloids and Surfaces B Vol.154 No.-

        <P><B>Abstract</B></P> <P>The aim of this work is to prepare and evaluate a novel lipid-polymer hybrid liposomal nanoplatform (hyaluronic acid-magnetic nanoparticle-liposomes, HA-MNP-LPs) as a vehicle for targeted delivery and triggered release of an anticancer drug (docetaxel, DTX) in human breast cancer cells. We first synthesize an amphiphilic hyaluronic acid hexadecylamine polymer (HA-C<SUB>16</SUB>) to enhance the targeting ability of the hybrid liposome. Next, HA-MNP-LPs are constructed to achieve an average size of 189.93±2.74nm in diameter. In addition, citric acid-coated magnetic nanoparticles (MNPs) are prepared and embedded in the aqueous cores while DTX is encapsulated in the hydrophobic bilayers of the liposomes. Experiments with coumarin 6 loaded hybrid liposomes (C6/HA-MNP-LPs) show that the hybrid liposomes have superior cellular uptake in comparison with the conventional non-targeting liposomes (C6/MNP-LPs), and the result is further confirmed by Prussian blue staining. Under near-infrared laser irradiation (NIR, 808nm), the HA-MNP-LPs aqueous solution can reach 46.7°C in 10min, and the hybrid liposomes released over 20% more drug than the non-irradiated liposomes. Using a combination of photothermal irradiation and chemotherapy, the DTX-loaded hybrid liposomes (DTX/HA-MNP-LPs) significantly enhance therapeutic efficacy, with the IC<SUB>50</SUB> value of 0.69±0.10μg/mL, which is much lower than the values for DTX monotherapy. Consequently, the prepared hybrid nanoplatform may offer a promising drug delivery vehicle with selective targeting and enhanced drug release in treating CD44-overexpressing cancers.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Novel polymer-lipid nanohybrid liposomes for active tumor targeting are synthesized. </LI> <LI> Magnetic nanoparticles and drug are encapsulated for photothermal-chemotherapy. </LI> <LI> Nanohybrid liposomes significantly enhance cellular uptake to breast cancer cells. </LI> <LI> Near-infrared light can trigger drug release from the nanohybrid liposomes. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • SCISCIESCOPUS

        High-fidelity bioelectronic muscular actuator based on porous carboxylate bacterial cellulose membrane

        Wang, Fan,Jin, Zhen,Zheng, Shaohui,Li, Hao,Cho, Sunghoon,Kim, Hyeon Joe,Kim, Seong-Jun,Choi, Eunpyo,Park, Jong-Oh,Park, Sukho Elsevier 2017 Sensors and actuators. B Chemical Vol.250 No.-

        <P><B>Abstract</B></P> <P>Human-friendly electronic products, such as smart mobile phones, soft haptic devices, wearable electronics, and implantable or disposal biomedical devices, will require the use of high-performance durable soft electroactive actuators with eco-friendly, biocompatible, and biodegradable functionalities. Here, we report a high-fidelity bioelectronic muscular actuator based on porous carboxylate bacterial cellulose (CBC) membranes fabricated using the facile zinc oxide (ZnO) particulate leaching (PL) method. The proposed CZ-PL muscular actuator exhibits large deformation, low actuation voltage, fast response, and high-durability in open air environment. In particular, the CZ-PL membrane shows a dramatic increase in the ionic liquid uptake ratio, ionic exchange capacity, and ionic conductivity of up to 70.63%, 22.50%, and 18.2%, respectively, for CBC, resulting in a 5.8 times larger bending deformation than that of the pure CBC actuator. The developed high-performance CZ-PL muscular actuator can be a promising candidate for meeting the tight requirements of human-friendly electronic devices such as wearable devices, biomimetic robots, and biomedical active devices.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We developed a novel dry-type muscular actuator based on porous carboxylate bacterial cellulose (CBC) membrane. </LI> <LI> The porous CBC membrane was prepared by ZnO particulate leaching method. </LI> <LI> The proposed actuator showed better actuation performance than that of the pure CBC actuator. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • A Magnetically Actuated Microscaffold Containing Mesenchymal Stem Cells for Articular Cartilage Repair

        Go, Gwangjun,Han, Jiwon,Zhen, Jin,Zheng, Shaohui,Yoo, Ami,Jeon, Mi-Jeong,Park, Jong-Oh,Park, Sukho Wiley (John WileySons) 2017 Advanced Healthcare Materials Vol.6 No.13

        <P>This study proposes a magnetically actuated microscaffold with the capability of targeted mesenchymal stem cell (MSC) delivery for articular cartilage regeneration. The microscaffold, as a 3D porous microbead, is divided into body and surface portions according to its materials and fabrication methods. The microscaffold body, which consists of poly(lactic-co-glycolic acid) (PLGA), is formed through water-in-oil-in-water emulsion templating, and its surface is coated with amine functionalized magnetic nanoparticles (MNPs) via amino bond formation. The porous PLGA structure of the microscaffold can assist in cell adhesion and migration, and the MNPs on the microscaffold can make it possible to steer using an electromagnetic actuation system that provides external magnetic fields for the 3D locomotion of the microscaffold. As a fundamental test of the magnetic response of the microscaffold, it is characterized in terms of the magnetization curve, velocity, and 3D locomotion of a single microscaffold. In addition, its function with a cargo of MSCs for cartilage regeneration is demonstrated from the proliferation, viability, and chondrogenic differentiation of D1 mouse MSCs that are cultured on the microscaffold. For the feasibility tests for cartilage repair, 2D/3D targeting of multiple microscaffolds with the MSCs is performed to demonstrate targeted stem cell delivery using the microscaffolds and their swarm motion.</P>

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