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      • KCI등재

        Evaluation of epithelial transport and oxidative stress protection of nanoengineered curcumin derivative-cyclodextrin formulation for ocular delivery

        Pooja Maharjan,Minki Jin,Daseul Kim,JaeWook Yang,Anjila Maharjan,Meong Cheol Shin,Kwan Hyung Cho,김만수,Kyoung Ah Min 대한약학회 2019 Archives of Pharmacal Research Vol.42 No.10

        Ocular drug delivery has been a well-knownroute for the drug administration for the treatment of oculardiseases. However, numerous anatomical and physiologicalbarriers prevailing in the eye itself create considerablechallenges for achieving the necessitated therapeutic efficacyalong with ocular bioavailability. However, recentadvances in nanoengineered strategies hold definite promisesin terms of devising improved ophthalmic medicinesfor the effective drug delivery to target the sites withenhanced ocular bioavailability. Curcumin, a hydrophobicpolyphenol yellow colored compound, and its metabolicreduced product, tetrahydrocurcumin (THC), have beenknown for their beneficial pharmacological functions, suchas anti-inflammatory or anti-oxidant activities at varioustissue sites. However, the low aqueous solubility of thesecompounds results in their poor bioavailability, therebylimiting their widespread application. Therefore, in thepresent study, we investigated the changes in drug solubilityby forming inclusion complexes with differentderivatives of hydroxypropyl (HP)-cyclodextrins (CD). To this end, the spray drying technique was used for nanoengineeringcurcumin or THC-loaded formulations toimprove the stability of formulations during the storage. The formulations were characterized in terms of physicochemicalproperties and cellular permeability. The resultsdemonstrated that the encapsulation of curcumin (or THC)into the HP-CDs significantly increased the drug solubilityand enhanced the corneal and retinal epithelial permeability. Curcumin or THC complexes in HP-CDs withimproved bioavailability also induced anti-oxidant activity(SOD1, CAT1, and HMOX1) in higher levels in the ocularepithelial cells and showed oxidative protection effects inrabbit cornea tissues that will boost up their application inocular medicine.

      • SCISCIESCOPUS
      • Microstrip Bandpass Filters Using Window Hairpin Resonator and T-Feeder Coupling Lines

        Maharjan, R. K.,Kim, N. Y. KING FAHD UNIVERSITY OF PETROLEUM MINERALS 2014 Arabian journal for science and engineering: AJSE Vol.39 No.5

        A new structure of planar window hairpin-based bandpass filters with symmetrical T-shaped feeder coupling line resonators is introduced. With varying different width in X axis and length in Y axis of the window of the hairpin resonator configuration, correspondingly the changes can be observed in the resonant frequency and useable bandwidth. By these methods, frequency tuning can be easily achieved by adjusting hairpin window dimension of the structure. Both filters were designed for 5.205 GHz resonant frequency. The geometrical window hairpin structure areas of both type filters are quite similar and both filters are resonated at almost the same frequency. The measurement results show that return loss (S-11) for both filters is higher than 23.0 dB and insertion loss (S-21) is measured less than -1.4 dB at resonant frequency of 5.13 GHz. The S-parameter responses of the fabricated filter nearly match with the electromagnetic simulated results; therefore, the feasibility of practical application of the proposed filters can be expected.

      • SCISCIESCOPUS

        Systemic administration of RANKL overcomes the bottleneck of oral vaccine delivery through microfold cells in ileum

        Maharjan, Sushila,Singh, Bijay,Jiang, Tao,Yoon, So-Yeon,Li, Hui-Shan,Kim, Girak,Gu, Min Jeong,Kim, Soo Ji,Park, Ok-Jin,Han, Seung Hyun,Kang, Sang-Kee,Yun, Cheol-Heui,Choi, Yun-Jaie,Cho, Chong-Su Elsevier 2016 Biomaterials Vol.84 No.-

        <P><B>Abstract</B></P> <P>A successful delivery of antigen through oral route requires to overcome several barriers, such as enzymatic barrier of gastrointestinal tract and epithelial barrier that constitutes of microfold cells (M cells) for antigen uptake. Although each barrier represents a critical step in determining the final efficiency of antigen delivery, the transcytosis of antigen by M cells in the follicle-associated epithelium (FAE) to Peyer's patches appears to be a major bottleneck. Considering the systemic administration of receptor activator of nuclear factor (NF)-ĸB ligand (RANKL) induces differentiation of receptor activator of nuclear factor (NF)-ĸB (RANK)-expressing enterocytes into M cells, here, we illustrated a promising approach of antigen delivery using full length transmembrane RANKL (mRANKL). The results showed that the intraperitoneal injection of mRANKL increased the population of dendritic cells and macrophages in mesenteric lymph nodes and spleen. Subsequently, systemic administration of mRANKL resulted in significantly higher number of functional GP2<SUP>+</SUP> M cells leading higher transcytosis of fluorescent beads through them. To corroborate the effect of mRANKL in antigen delivery through M cells, we orally delivered microparticulate antigen to mice treated with mRANKL. Oral immunization induced strong protective IgA and systemic IgG antibody responses against orally delivered antigen in mRANKL-treated mice. The higher antibody responses are attributed to the higher transcytosis of antigens through M cells. Ultimately, the higher memory B cells and effector memory CD4 T cells after oral immunization in RANKL-treated mice confirmed potency of RANKL-mediated antigen delivery. To the best of our knowledge, this is the first study to demonstrate significant induction of mucosal and humoral immune responses to M cell targeted oral vaccines after the systemic administration of RANKL.</P>

      • A human locomotion inspired hybrid nanogenerator for wrist-wearable electronic device and sensor applications

        Maharjan, P.,Toyabur, R.M.,Park, J.Y. Elsevier 2018 Nano energy Vol.46 No.-

        <P><B>Abstract</B></P> <P>The availability of realistic, wearable efficient energy harvesters for powering body-worn IoT devices and health monitoring sensors is essential, in order to reduce the dependence of these wearable electronic devices, on batteries. Herein, we demonstrate a novel curve-shaped wearable hybridized electromagnetic-triboelectric nanogenerator (WHEM-TENG), operating as a fully-enclosed light-weight low-frequency energy harvester, driven by human motion. The WHEM-TENG incorporates the swinging behavior of a human arm during locomotion, and the freestanding rolling mode of a magnetic ball. Simulations of the magnetic flux density and the triboelectric surface potential assisted in improving the design and performance of the nanogenerator. The harvester device was manufactured using a 3D-printing method, which makes the fabrication process faster, easier, and more cost-effective than traditional methods. The 3D-printing material was used as triboelectric material for the nanogenerator. Experiments illustrate that at the low input frequencies characteristic of walking and running, the electromagnetic generator (EMG) and triboelectric nanogenerator (TENG) deliver peak power densities of 5.14 mW/cm<SUP>3</SUP> and 0.22 µW/cm<SUP>3</SUP>, across load resistances of 49.2 Ω and 13.9 MΩ, respectively. Moreover, we also demonstrate that the WHEM-TENG can drive a commercially available electric wrist-watch continuously for 410 s from the power generated by just 5 s of running activity. Also, we demonstrate a self-powered heart-rate sensor driven by the nanogenerator. The electrical output of this distinctively structured device is promising for optimization of similar hybrid wearable energy harvesters, and for practical applications, towards the development of self-powered wearable smart bands/watches and fitness/health monitoring sensors.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Human locomotion inspired novel curve-shape design is introduced as nanogenerator. </LI> <LI> Low frequency driven, light weight, fully enclosed and wrist-wearable generator. </LI> <LI> The 3d-printing method and material were used for fabrication of the nanogenerator. </LI> <LI> Converting human arm-motion energy into electrical energy to power wearable devices. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • SCIESCOPUS
      • In-situ synthesis of AgNPs in the natural/synthetic hybrid nanofibrous scaffolds: Fabrication, characterization and antimicrobial activities

        Maharjan, Bikendra,Joshi, Mahesh Kumar,Tiwari, Arjun Prasad,Park, Chan Hee,Kim, Cheol Sang Elsevier 2017 Journal of the mechanical behavior of biomedical m Vol.65 No.-

        <P><B>Abstract</B></P> <P>Silver nanoparticles embedded within a nanofibrous polymer matrix have significant attention in recent years as an antimicrobial wound dressing materials. Herein, we have fabricated a novel Ag-polyurethane-zein hybrid nanofibrous scaffold for wound dressing applications. AgNPs were synthesized in-situ via reduction of silver nitrate in electrospinning solution. Varying mass composition of the components showed the pronounced effect on the morphology and physicochemical properties of the composite fibers. Field-Emission Scanning Electron Microscopy (FESEM) images revealed that PU and zein with mass ratio 2:1 produced the bead-free continuous and uniformly distributed nanofibers. Fourier-transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD) and Thermogravimetric Analysis (TGA) confirmed the well interaction between component polymers. Compared to the pristine PU nanofibers, composite fibers showed enhanced tensile strength, young׳s modulus and surface wettability. The antibacterial capacity of the nanofibrous membrane was evaluated against gram-positive (<I>Staphylococcus aureus</I>) and gram-negative (<I>Escherichia coli</I>) bacterial strains via a zone of inhibition test, and the results showed high antibacterial performance for Ag incorporated composite mat. Experimental results of cell viability assay and microscopic imaging revealed that as-fabricated scaffolds have an excellent ability for fibroblast cell adhesion, proliferation and growth. Overall, as-fabricated antibacterial natural/synthetic composite scaffold can be a promising substrate for repairing skin defects.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A novel antibacterial natural/synthetic hybrid nanofibrous scaffold. </LI> <LI> Synthetization of AgNPs by in-situ reduction of silver nitrate in solution. </LI> <LI> Wettability and bioactivity of PU fiber improved by blending with biopolymer zein. </LI> <LI> Composite fibers showed enhanced tensile strength and young’s modulus. </LI> <LI> As-fabricated composite scaffold can be promising substrate for skin repairing. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • SCISCIESCOPUS

        Autophagy alteration prevents primary cilium disassembly in RPE1 cells

        Maharjan, Yunash,Lee, Joon No,Kwak, SeongAe,Lim, Hyewon,Dutta, Raghbendra Kumar,Liu, Zhi-qiang,So, Hong-Seob,Park, Raekil Elsevier 2018 Biochemical and biophysical research communication Vol.500 No.2

        <P><B>Abstract</B></P> <P>Primary cilium is a microtubule structure that emanates from the surface of most human cells. Primary cilia assemble during the resting stage (G<SUB>0</SUB> phase) and disassemble with cell cycle progression. Defects associated with the control of the assembly or disassembly of the primary cilium have been implicated in various human diseases, including ciliopathy and cancer. Although studies have suggested the interplay between activation of autophagy and ciliogenesis, any direct mechanism between autophagy abatement and disassembly of primary cilium remains elusive. In this study, we found that the gradual abatement in autophagy during serum-restimulation was a dynamic process and significantly correlated with the disassembly of primary cilium in human retinal pigmented epithelial (RPE1) cells. Although autophagy activity was gradually decreased during serum-restimulation, the alteration in autophagy under the same condition prevented the disassembly of the primary cilium. Autophagy inhibitors such as chloroquine, U18666A and 3-methyladenine (3-MA) retained both the number of ciliated cells and cilium length. In contrast, rapamycin treatment during serum-restimulation maintained the number of ciliated cells with shortened cilia. Taken together, alteration in autophagy during serum-restimulation prevent the disassembly of the primary cilium, and autophagy modulators may serve as useful compounds for studying mechanistic details related to the disassembly of the primary cilium and ciliopathy.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Autophagy abatement and cilia disassembly is correlated during serum-restimulation. </LI> <LI> Both activation and inhibition of autophagy flux during serum-restimulation prevents disassembly of primary cilium. </LI> <LI> Inhibition of autophagy maintains cilium length during serum-restimulation. </LI> <LI> Rapamycin-induced autophagy results in shortened cilium length during serum-restimulation. </LI> </UL> </P>

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