Gachon Medical Research Institute

Incheon, South Korea

Gachon Medical Research Institute

Incheon, South Korea
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Wan Woo K.,Sungkyunkwan University | Wook Kwon O.,Kyung Hee University | Yeou Kim S.,Gachon University | Yeou Kim S.,Gachon Medical Research Institute | And 4 more authors.
Journal of Ethnopharmacology | Year: 2014

Ethnopharmacological relevance Dioscorea nipponica (Dioscoreaceae) have been used as traditional medicines for diabetes, inflammatory and neurodegenerative diseases in Korea. The aim of the study was to isolate the bioactive components from the rhizomes of Dioscorea nipponica and to evaluate their anti-neuroinfalmmatory and neuroprotective activities. Material and methods The phytochemical investigation of 50% EtOH extract of Dioscorea nipponica using successive column chromatography over silica gel, Sephadex LH-20, and preparative high performance liquid chromatography (HPLC) resulted in the isolation and identification of 17 phenolic derivatives, including four new phenolic compounds (1-4). The structural elucidation of these compounds was based on spectroscopic methods, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy techniques, mass spectrometry, and optical rotation. All isolated compounds were evaluated for their effects on nerve growth factor (NGF) secretion in a C6 rat glioma cell line and nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV2 cells. The neurite outgrowth of compound 16 was further evaluated by using mouse neuroblastoma N2a cell lines. Results Three new stilbene derivatives, diosniponol C (1), D (2) and diosniposide A (3) and one new phenanthrene glycoside, diosniposide B (4), together with 13 known compounds were isolated from the rhizomes of Dioscorea nipponica. Of the tested compounds (1-17), phenanthrene, 3,7-dihydroxy-2,4,6-trimethoxy-phenanthrene (16) was the most potent NGF inducer, with 162.35±16.18% stimulation, and strongly reduced NO levels with an IC50 value of 19.56 μM in BV2 microglial cells. Also, it significantly increased neurite outgrowth in N2a cells. Conclusions This study supports the ethnopharmacological use of Dioscorea nipponica rhizomes as traditional medicine. © 2014 Elsevier Ireland Ltd.


Kim K.H.,Sungkyunkwan University | Moon E.,Gachon University | Kim S.Y.,Gachon University | Kim S.Y.,Gachon Medical Research Institute | And 3 more authors.
Journal of Ethnopharmacology | Year: 2014

Ethnopharmacological relevance Raphanus sativus seeds (Brassicaceae) known as Raphani Semen have long been used as anti-cancer and/or anti-inflammatory agents in Korean traditional medicine. This study was designed to isolate the bioactive constituents from the seed extracts of Raphanus sativus and evaluate their anti-inflammatory and antitumor activities. Material and methods Bioassay-guided fractionation and chemical investigation of a methanolic extract of the seeds of Raphanus sativus led to the isolation and identification of seven 4-methylthio-butanyl derivatives. Structural elucidation of the isolated compounds was carried out using 1D and 2D nuclear magnetic resonance (NMR) spectroscopy techniques (1H, 13C, COSY, HMQC and HMBC experiments) and mass spectrometry. Results The isolated compounds were characterized as in the following: three new 4-methylthio-butanyl derivatives, sinapoyl desulfoglucoraphenin (1), (E)-5-(methylsulfinyl)pent-4-enoxylimidic acid methyl ester (2), and (S)-5-((methylsulfinyl)methyl)pyrrolidine-2-thione (3), together with four known compounds, 5-(methylsulfinyl)-4-pentenenitrile (4), 5-(methylsulfinyl)-pentanenitrile (5), sulforaphene (6), and sulforaphane (7). Full NMR data assignments of the three known compounds 4-6 were also reported for the first time. We evaluated the anti-neuroinflammatory effect of 1-7 in lipopolysaccharide-stimulated murine microglia BV2 cells. Compound 1 significantly inhibited nitrite oxide production with IC50 values of 45.36 μM. Moreover, it also reduced the protein expression of inducible nitric oxide synthase. All isolates were also evaluated for their antiproliferative activities against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15), and all of them showed antiproliferative activity against the HCT-15 cell, with IC50 values of 8.49-23.97 μM. Conclusions 4-Methylthio-butanyl derivatives were one of the main compositions of Raphanus sativus seeds, and activities demonstrated by the isolated compounds support the ethnopharmacological use of Raphanus sativus seeds (Brassicaceae) as anti-cancer and/or anti-inflammatory agents. © 2013 Elsevier Ltd. All rights reserved.


Cong V.T.,Gachon University | Cong V.T.,Gachon Medical Research Institute | Ganbold E.-O.,Soongsil University | Saha J.K.,Pusan National University | And 9 more authors.
Journal of the American Chemical Society | Year: 2014

A subnanometer gap-separated linear chain gold nanoparticle (AuNP) silica nanotube peapod (SNTP) was fabricated by self-assembly. The geometrical configurations of the AuNPs inside the SNTPs were managed in order to pose either a single-line or a double-line nanostructure by controlling the diameters of the AuNPs and the orifice in the silica nanotubes (SNTs). The AuNPs were internalized and self-assembled linearly inside the SNTs by capillary force using a repeated wet-dry process on a rocking plate. Transmission electron microscopy (TEM) images clearly indicated that numerous nanogap junctions with sub-1-nm distances were formed among AuNPs inside SNTs. Finite-dimension time domain (FDTD) calculations were performed to estimate the electric field enhancements. Polarization-dependent surface-enhanced Raman scattering (SERS) spectra of bifunctional aromatic linker p-mercaptobenzoic acid (p-MBA)-coated AuNP-embedded SNTs supported the linearly aligned nanogaps. We could demonstrate a silica wall-protected nanopeapod sensor with single nanotube sensitivity. SNTPs have potential application to intracellular pH sensors after endocytosis in mammalian cells for practical purposes. The TEM images indicated that the nanogaps were preserved inside the cellular constituents. SNTPs exhibited superior quality SERS spectra in vivo due to well-sustained nanogap junctions inside the SNTs, when compared to simply using AuNPs without any silica encapsulation. By using these SNTPs, a robust intracellular optical pH sensor could be developed with the advantage of the sustained nanogaps, due to silica wall-protection. © 2014 American Chemical Society.


Lee N.Y.,Gachon University | Lee N.Y.,Gachon Medical Research Institute
Colloids and Surfaces B: Biointerfaces | Year: 2013

In this study, a simple and facile scheme for selectively hydrophobizing microwell-patterned hydrophilic polymer substrate is demonstrated, and applied for a targeted adhesion. Microwell-patterned polymer substrate was replicated from a silicon mold using a photocurable prepolymer under ultraviolet (UV) light for 30. min. While the surface of the replica was partially cured, it was contact printed with a flat, hydrophobic poly(dimethylsiloxane) (PDMS) elastomer, and the assembly was further cured under UV light for approximately 3. h and detached. In this manner, the PDMS molecules were transferred selectively onto the protruding regions of the partially cured microwell-patterned substrate, while the inner walls of the microwells remained hydrophilic. The surface hydrophobization was characterized by contact angle measurement and X-ray photoelectron spectroscopy (XPS). In addition, time-dependent contact angle variations were investigated to verify the robustness and durability of the coating of the PDMS functional group. As a proof-of-concept experiment, functionalized polymer beads were targeted and successfully guided selectively into arrays of microwells without being adsorbed onto the protruding regions of the microwell-patterned substrate, which could further be applied for the targeted immobilization of biomolecules with high selectivity in a relatively simple and facile manner. © 2013 Elsevier B.V.


Devadhasan J.P.,Gachon University | Kim S.,Gachon University | Kim S.,Gachon Medical Research Institute
Biochip Journal | Year: 2013

We report on the use of a complementary metal oxide semiconductor (CMOS) image sensor in an immunodiagnostic system for detecting the human immunodeficiency virus (HIV). It is based on photon counting and the interaction of the HIV antigen (Ag) with respective antibodies, which are deposited in various thicknesses on indium nanoparticles (InNPs) substrate. The sensor measures the number of photons that depends on the concentration of HIV Ag and converts them into digital numbers. Photons are refracted on the protein adsorbed InNP substrate and hit the CMOS image sensor surface based on the Ag concentration. Topographical studies such as field emission scanning electron microscopy (FE-SEM) and fluorescence microscopy images are demonstrated the reliability of this scheme. Also, the UV-spectral studies proved the efficiency of the analysis with InNP substrate. The sensor is simple, compact, highly specific and accurate. Also, it can detect HIV at levels as low as 10 fg mL-1. Therefore, the sophisticated system of the CMOS image sensor based immunodetection now requires point-of-care (POC) diagnosis. © 2013 The Korean BioChip Society and Springer-Verlag Berlin Heidelberg.


Devadhasan J.P.,Gachon University | Kim S.,Gachon University | Kim S.,Gachon Medical Research Institute | Choi C.S.,Gachon University
Analyst | Year: 2013

Complementary metal oxide semiconductor (CMOS) image sensors have been used previously in the analysis of biological samples. In the present study, a CMOS image sensor was used to monitor the concentration of oxidized mouse plasma glucose (86-322 mg dL-1) based on photon count variation. Measurement of the concentration of oxidized glucose was dependent on changes in color intensity; color intensity increased with increasing glucose concentration. The high color density of glucose highly prevented photons from passing through the polydimethylsiloxane (PDMS) chip, which suggests that the photon count was altered by color intensity. Photons were detected by a photodiode in the CMOS image sensor and converted to digital numbers by an analog to digital converter (ADC). Additionally, UV-spectral analysis and time-dependent photon analysis proved the efficiency of the detection system. This simple, effective, and consistent method for glucose measurement shows that CMOS image sensors are efficient devices for monitoring glucose in point-of-care applications. This journal is © The Royal Society of Chemistry.


Devadhasan J.P.,Gachon University | Kim S.,Gachon University | Kim S.,Gachon Medical Research Institute
Analytica Chimica Acta | Year: 2015

CMOS sensors are becoming a powerful tool in the biological and chemical field. In this work, we introduce a new approach on quantifying various pH solutions with a CMOS image sensor. The CMOS image sensor based pH measurement produces high-accuracy analysis, making it a truly portable and user friendly system. pH indicator blended hydrogel matrix was fabricated as a thin film to the accurate color development. A distinct color change of red, green and blue (RGB) develops in the hydrogel film by applying various pH solutions (pH 1-14). The semi-quantitative pH evolution was acquired by visual read out. Further, CMOS image sensor absorbs the RGB color intensity of the film and hue value converted into digital numbers with the aid of an analog-to-digital converter (ADC) to determine the pH ranges of solutions. Chromaticity diagram and Euclidean distance represent the RGB color space and differentiation of pH ranges, respectively. This technique is applicable to sense the various toxic chemicals and chemical vapors by situ sensing. Ultimately, the entire approach can be integrated into smartphone and operable with the user friendly manner. © 2014 Elsevier B.V.


Wu W.,Gachon University | Trinh K.T.L.,Gachon University | Lee N.Y.,Gachon University | Lee N.Y.,Gachon Medical Research Institute
Analyst | Year: 2015

We introduce a new strategy for fabricating a seamless three-dimensional (3D) helical microreactor utilizing a silicone tube and a paraffin mold. With this method, various shapes and sizes of 3D helical microreactors were fabricated, and a complicated and laborious photolithographic process, or 3D printing, was eliminated. With dramatically enhanced portability at a significantly reduced fabrication cost, such a device can be considered to be the simplest microreactor, developed to date, for performing the flow-through polymerase chain reaction (PCR). This journal is © The Royal Society of Chemistry.


Jang M.,Gachon University | Park C.K.,Gachon University | Lee N.Y.,Gachon University | Lee N.Y.,Gachon Medical Research Institute
Sensors and Actuators, B: Chemical | Year: 2014

In this paper, we introduce a simple strategy for modifying the surface of polycarbonate (PC) to make it either hydrophilic or hydrophobic. The aminosilane, bis[3-(trimethoxysilyl)propyl]amine (bis-TPA), was used to produce the hydrophilic surface via aminolysis of the carbonate backbone to form strong urethane linkages, leaving alkoxysilane parts exposed on the surface. To obtain the hydrophobic surface, PC coated with bis-TPA was further reacted with (tridecafluoro-1,1,2,2-tetrahydrooctyl)-triethoxysilane (FTES), where inorganic moieties of both silanes condensed to realize siloxane (Si-O-Si) bonds. In this way, fluorinated groups were left exposed on the terminal surface of the PC, rendering it hydrophobic. In-depth surface characterizations were performed, including water contact angle measurement and X-ray photoelectron spectroscopy (XPS) analysis, in order to identify the optimum conditions for achieving surface modification without sacrificing substrate transparency. To extend the use of these PC surface treatments to microfluidic applications, the hydrophilic coating was further adopted for use in bonding two PC substrates by forming Si-O-Si bonds at the interface. Using the hydrophilic treatment of PC, we obtained microchannels, which were resistant to organic solvents. Furthermore, by employing subsequent hydrophobic treatment, multiple liquids were successfully injected into microchannels sequentially in a valve-free manner © 2013 Elsevier B.V.


Trinh K.T.L.,Gachon University | Wu W.,Gachon University | Lee N.Y.,Gachon University | Lee N.Y.,Gachon Medical Research Institute
Sensors and Actuators, B: Chemical | Year: 2014

In this study, we fabricate a hybrid planar microdevice to perform an on-chip flow-through polymerase chain reaction (PCR) constructed by assembling glass and poly(dimethylsiloxane) (PDMS) on which a serpentine microchannel is engraved. The proposed system employs a metal alloy slab, called Invar, which is basically a nickel iron alloy, sandwiched between the microdevice and a heater. Owing to the high thermal conductivity (10 W K-1 m-1) but notably low thermal expansion coefficient (1.6 × 10-6 K -1) of Invar, a stable temperature gradient was established on its surface. The Invar was placed on the heater in such a way that they made partial contact, with the rest of the Invar exposed to the air. A uniformly distributed temperature gradient, which ranged in temperatures from 57 C to 95 C, was first established on the Invar sheet, and a planar microdevice was directly placed atop the Invar sheet. The proposed system was successfully applied to amplify three targets: a 230 bp gene fragment from a plasmid vector, the first 282 bp of the interferon-beta (IFN-β) promoter from human genomic DNA, and a 409 bp long gene fragment in thyroid transcription factor-1 (TTF-1), which is used effectively as a marker for diagnosing lung and thyroid carcinomas, from human genomic DNA. All of the targets were amplified within less than 30 min. One microdevice was utilized repeatedly for multiple target amplifications by fine tuning the relative position of the Invar sheet on the heater. © 2013 Elsevier B.V. All rights reserved.

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