Jeon-Soo Shin

Yonsei University Hospital, Sŏul, Seoul, South Korea

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Publications (45)226.77 Total impact

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    ABSTRACT: High mobility group nucleosomal binding domain 2 (HMGN2) is a small and unique non-histone protein that has many functions in a variety of cellular processes, including regulation of chromatin structure, transcription, and DNA repair. In addition, it may have other roles in antimicrobial activity, cell homing, and regulating cytokine release. Although the biochemical properties of HMGN2 protein are regulated by acetylation and phosphorylation, it is not yet known whether HMGN2 activity can also be regulated by SUMOylation. In this study, we demonstrated for the first time that HMGN2 is modified by covalent attachment of small ubiquitin-related modifier 1 (SUMO1) by pro-inflammatory signal and identified the major SUMOylated lysine residues that localize to the HMGN2 nucleosome-binding domain at K17 and K35. SENP1 can deSUMOylate SUMOylated HMGN2, and PIAS1 is the E3 ligase responsible for SUMOylation of HMGN2. Finally, using SUMO1-conjugated HMGN2 purified from a basal SUMOylation system in E. coli, we demonstrated that SUMOylated HMGN2 has decreased the binding affinity to nucleosome core particles in comparison to unSUMOylated HMGN2. These observations potentially provide new perspectives for understanding the functions of HMGN2 in inflammatory reaction.
    The Journal of biological chemistry. 05/2014;
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    ABSTRACT: The capsular polysaccharide (PS) of Neisseria meningitidis serogroup B (NMGB) is α(2-8)-linked N-acetylneuraminic acid (Neu5Ac), which is almost identical to the O-acetylated colominic acid (CA) of Escherichia coli K1 Although E. coli K1 has long been known to elicit cross-protective antibodies against NMGB, limited information on these highly cross-reactive antibodies is available. In the present study, six new monoclonal antibodies (mAbs) specific to both E. coli K1 CA and NMGB PS were produced by immunizing Balb/c mice with E. coli K1, and their serological and molecular properties were characterized, together with 12 previously reported hybridoma mAbs. Among the bactericidal mAbs against NMGB, both HmenB5 and HmenB18, which are genetically identical though of different mouse origins, were able to kill serogroup C and Y meningococci. Based on SPR sensograms, the binding affinity of HmenB18 for PS was suggested to be associated with at least two different binding forces: the polyanionicity of Neu5Ac and an interaction with the O-acetyl groups of Neu5Ac. Molecular analysis showed that similar to most mAbs presenting a few restricted V region germline genes, the V region genes of HmenB18 were 979% and 986% identical to the closest IGHV1-1401 and IGLV15-10301 germline gene alleles, respectively, and V-D-J editing in this mAb generated an unusually long VH-CDR3 sequence (17 amino acid residues), containing one basic arginine, two hydrophobic isoleucine residues and a 'YAMDY' motif. Models of the mAb combining sites demonstrate that most of the mAbs exhibited a wide, shallow groove with a high overall positive charge, as seen in mAb735, which is specific for a polyanionic helical epitope. In contrast, the combining site of HmenB18 was shown to be wide but to present a relatively weak positive charge, consistent with the extensive recognition by HmenB18 of the various structural epitopes formed with the Neu5Ac residue and its O-acetylation.
    Molecular Immunology 03/2014; 59(2):142-153. · 2.65 Impact Factor
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    ABSTRACT: To investigate the possibility of treating multidrug-resistant tumors with targeted chemo-photothermal treatment, we conducted in vitro and in vivo studies using a doxorubicin (DOX)-resistant DLD-1 cell line (DLD-1/DOX) and nude mice with human xenograft tumors, respectively. The chemo-photothermal treatment consisted of DOX-loaded-poly(lactic-co-glycolic acid)-Au half-shell nanoparticles with targeting moieties of anti-death receptor-4 monoclonal antibody conjugated to the Au surface. The cells or xenografted tumors treated with nanoparticles were exposed to near infrared light for 10 min, which caused an increase in temperature to 45 °C. Chemo-photothermal treatment resulted in a large reduction in the rate of tumor xenograft growth on DLD-1/DOX tumor-bearing mice with a much smaller dose of DOX than conventional DOX chemotherapy. These results demonstrate that targeted chemo-photothermal treatment can provide high therapeutic efficacy and low toxicity in the treatment of multidrug-resistant tumors.
    Biomaterials 12/2013; · 8.31 Impact Factor
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    ABSTRACT: Due to its unique non-diffracting and self-reconstructing nature, Bessel beams have been successfully adopted to trap multiple particles along the beam's axial direction. However, prior bulk-optic based Bessel beams have a fundamental form-factor limitation for in situ, in-vitro, and in-vivo applications. Here we present a novel implementation of Fourier optics along a single strand of hybrid optical fiber in a monolithic manner that can generate pseudo Bessel beam arrays in two-dimensional space. We successfully demonstrate unique optofluidic transport of the trapped dielectric particles along a curvilinear optical route by multiplexing the fiber optic pseudo Bessel beams. The proposed technique can form a new building block to realize reconfigurable optofluidic transportation of particulates that can break the limitations of both prior bulk-optic Bessel beam generation techniques and conventional microfluidic channels.
    Optics Express 10/2013; 21(20):23021-23029. · 3.55 Impact Factor
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    ABSTRACT: We describe a rapid, sensitive, and label-free method to detect interferon-gamma (IFN-γ), a biomarker of latent tuberculosis infection (LTBI). IFN-γ is detected by measuring the capacitance change caused by its binding to an anti-IFN-γ antibody. The antibody is immobilized on the surface of an anodized aluminum oxide (AAO)-based capacitive sensor. With this technique, IFN-γ can be detected in the range of ~0.1pg/ml to ~10ng/ml, with a detection limit of 0.2pg/ml. We have also measured the concentration of IFN-γ in clinical samples using the AAO-based capacitive sensor and compared this concentration with the results of the commercial QuantiFERON-TB Gold (QFT-G) ELISA kit to determine whether the two sets of data are consistent. Comparable results were obtained with the two measurement strategies, demonstrating the applicability of the AAO-based capacitive sensor to the diagnosis of LTBI.
    Biosensors & bioelectronics 08/2013; 51C:366-370. · 5.43 Impact Factor
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    ABSTRACT: High-mobility group box 1 protein (HMGB1), which mainly exists in the nucleus, has recently been shown to function as a sentinel molecule for viral nucleic acid sensing and an autophagy regulator in the cytoplasm. In this study, we studied the chaperone-like activity of HMGB1 and found that HMGB1 inhibited the chemically induced aggregation of insulin and lysozyme, as well as the heat-induced aggregation of citrate synthase. HMGB1 also restored the heat-induced suppression of cytoplasmic luciferase activity as a reporter protein in hamster lung fibroblast O23 cells with expression of HMGB1. Next, we demonstrated that HMGB1 inhibited the formation of aggregates and toxicity caused by expanded polyglutamine (polyQ), one of the main causes of Huntington disease. HMGB1 directly interacted with polyQ on immunofluorescence and coimmunoprecipitation assay, whereas the overexpression of HMGB1 or exogenous administration of recombinant HMGB1 protein remarkably reduced polyQ aggregates in SHSY5Y cells and hmgb1(-/-) mouse embryonic fibroblasts upon filter trap and immunofluorescence assay. Finally, overexpressed HMGB1 proteins in mouse embryonic primary striatal neurons also bound to polyQ and decreased the formation of polyQ aggregates. To this end, we have demonstrated that HMGB1 exhibits chaperone-like activity and a possible therapeutic candidate in polyQ disease.
    The Journal of Immunology 01/2013; · 5.52 Impact Factor
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    ABSTRACT: The regulation of cellular activities in a controlled manner is one of the most challenging issues in fields ranging from cell biology to biomedicine. Nanoparticles have the potential of becoming useful tools for controlling cell signalling pathways in a space and time selective fashion. Here, we have developed magnetic nanoparticles that turn on apoptosis cell signalling by using a magnetic field in a remote and non-invasive manner. The magnetic switch consists of zinc-doped iron oxide magnetic nanoparticles (Zn(0.4)Fe(2.6)O(4)), conjugated with a targeting antibody for death receptor 4 (DR4) of DLD-1 colon cancer cells. The magnetic switch, in its On mode when a magnetic field is applied to aggregate magnetic nanoparticle-bound DR4s, promotes apoptosis signalling pathways. We have also demonstrated that the magnetic switch is operable at the micrometre scale and that it can be applied in an in vivo system where apoptotic morphological changes of zebrafish are successfully induced.
    Nature Material 10/2012; · 35.75 Impact Factor
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    ABSTRACT: High mobility group box-1 (HMGB1), a nuclear protein, is overexpressed and secreted in cancer cells. Phosphorylation on two different nuclear localization signal regions are known to be important for the nuclear-to-cytoplasmic transport and secretion of HMGB1. However, little is known about the biochemical mechanism of HMGB1 modifications and its subsequent secretion from cancer cells. To identify the specific enzyme and important sites for HMGB1 phosphorylation, we screened the protein kinase C (PKC) family in a colon cancer cell line (HCT116) for HMGB1 binding by pull-down experiments using a 3XFLAG-HMGB1 construct. Strong interactions between atypical PKCs (PKC-ζ, λ, and ι) and cytoplasmic HMGB1 were observed in HCT116 cells. We further identified the most critical PKC isotype that regulates HMGB1 secretion is PKC-ζ by using PKC inhibitors and siRNA experiments. The serine residues at S39, S53 and S181 of HMGB1 were related to enhancing HMGB1 secretion. We also demonstrated overexpression and activation of PKC-ζ in colon cancer tissues. Our findings suggest that PKC-ζ is involved in the phosphorylation of HMGB1, and the phosphorylation of specific serine residues in the nuclear localization signal regions is related to enhanced HMGB1 secretion in colon cancer cells.
    Biochemical and Biophysical Research Communications 06/2012; 424(2):321-6. · 2.41 Impact Factor
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    ABSTRACT: With the aim of controlling nanoscale magnetism, we demonstrate an approach encompassing concepts of surface and exchange anisotropy while reflecting size, shape, and structural hybridization of nanoparticles. We visualize that cube has higher magnetization value than sphere with highest coercivity at 60 nm. Its hybridization into core-shell (CS) structure brings about a 14-fold increase in the coercivity with an exceptional energy conversion of magnetic field into thermal energy of 10600 W/g, the largest reported to date. Such capability of the CS-cube is highly effective for drug resistant cancer cell treatment.
    Nano Letters 06/2012; 12(7):3716-21. · 13.03 Impact Factor
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    ABSTRACT: Label-free cell-based assays have emerged as a promising means for high-throughput screening. Most label-free sensors are based on impedance measurements that reflect the passive electrical properties of cells. Here we introduce a capacitance-based assay that measures the dielectric constant (capacitance) of biological cells, and demonstrate the feasibility of analyzing endocytosis and screening chemotherapeutic agents with this assay. Endocytosis induces a change in the zeta potential, leading to a change in the dielectric constant which enables real-time endocytosis monitoring using the capacitance sensor. Additionally, since the dielectric constant is proportional to cell radius and cell volume, cell viability can be estimated from the change in capacitance. Therefore, the capacitance sensor array can also be used for cytotoxicity testing for large-scale chemotherapeutic screening.
    Lab on a Chip 04/2012; 12(13):2377-84. · 5.70 Impact Factor
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    ABSTRACT: Highly efficient Bessel-like beam generation was achieved based on a new all-fiber method that implements Fourier transformation of a micro annular aperture along a concatenated composite optical fiber. The beam showed unique characteristics of tilted washboard optical potential in the transverse plane and sustained a nondiffracting length over 400 μm along the axial direction. Optical trapping of multiple dielectric particles and living Jurkat cells were successfully demonstrated along the axial direction of the beam in the water.
    Optics Letters 02/2012; 37(4):623-5. · 3.39 Impact Factor
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    ABSTRACT: All-fiber Bessel-like beam generator achieved optical trapping and displacement control of micron particles. A pair of generators being compatible with lab on a chip system can be good tools for manipulation and analysis of bio-sample.
    Photonics Conference (IPC), 2012 IEEE; 01/2012
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    ABSTRACT: Since CKD-712 has been developed as an anti-inflammatory agent, we examined the effect of CKD-712 during TLR4 signaling. Using HEK293 cells expressing TLR4, CKD-712 was pre-treated 1 hr before LPS stimulation. Activation of NF-κB was assessed by promoter assay. The activation of ERK, JNK, p38, IRF3 and Akt was measured by western blotting. CKD-712 inhibited the NF-κB signaling triggered by LPS. The activation of ERK, JNK, p38 or IRF3 was not inhibited by CKD-712. On the contrary the activation of these molecules was augmented slightly. The activation of Akt with stimulation of LPS was also enhanced with CKD-712 pre-treatment at lower concentration, but was inhibited at higher concentration. We suggest that during TLR4 signaling CKD-712 inhibits NF-κB activation. However, CKD-712 augmented the activation of Akt as well as Map kinases. Therefore, we suggest that CKD-712 might have a role as an immunomodulator.
    Immune Network 12/2011; 11(6):420-3.
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    ABSTRACT: We present a novel implementation of Fourier optics along a single strand of hybrid optical fiber in a monolithic manner that can generate a highly efficient pseudo-Bessel beam. The incident fundamental mode of an optical fiber is adiabatically transformed to multiple ring modes by interference within a coreless silica fiber, which serves as a micro annulus apertures. A micro polymer lens was formed at the end face to complete the Fourier-transform providing a pseudo-Bessel beam at the output. Efficient multiple particle trapping experiments for both polystyrene beads were realized over 1 mm distance along the pseudo-Bessel beam. Furthermore all-optical transport of the trapped particles along a three dimensional optical route was demonstrated by spatially multiplexing pseudo-Bessel beams via multi mode interference (MMI) type Bessel beam generators. 1x3 pseudo-Bessel beam multiplexer was installed in the water based solution with 10mm(micro meter?) polystyrene beads. After a polystyrene particle was trapped by pseudo-Bessel beam, the initial acceleration was observed as 150mum/s2. The final velocity of the trapped particle maintained about 300mum/s with 40mum/s undulation due to pseudo-Bessel beam crossing points. The spatial multiplexing of fiber optic pseudo- Bessel beam arrays could make a new building block to realize reconfigurable all-optical transportation of particles.
    Proc SPIE 09/2011;
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    ABSTRACT: Optical lining of multiple dielectric beads was experimentally demonstrated using two counter- propagating Bessel-like beam generated by multimode interference in optical fibers embedded in polydimethylsiloxane (PDMS) channel. All Fiber Bessel-like beam (AFB) generator was composed of a single mode fiber concatenated with a segment of coreless silica fiber of 1600 mum length and a fiberized focusing lens. A Bessel-like beam was achieved by multimode interference along the coreless silica fiber, and it maintained an average center beam diameter of 3.7 mum over an axial length of 300 mum, having a nearly uniform output power within a variation of +/-0.11%. AFB generator was designed to be compatible with a continuous wave Yb-doped fiber laser oscillating at the wavelength of 1084nm in order to provide all-fiber solution. A micro-fluidic system of cross-channel was fabricated using PDMS to embed two counter-propagating fiber probes, which provided an accurate beam alignment and stable delivery of sample. One dimensional optical potential well was generated along the counter propagating beams, where samples were trapped, and then self-optical line of them was formed along longitudinal axis. This results from self-reconstruction, which is property of Bessel beam and it was confirmed in not only dielectric particles but also biological sample. This AFB generator paves the way for novel integration of microfluidic system as optical filter or chromatography.
    Proc SPIE 09/2011;
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    ABSTRACT: Lipopolysaccharide (LPS) triggers deleterious systemic inflammatory responses when released into the circulation. LPS-binding protein (LBP) in the serum plays an important role in modifying LPS toxicity by facilitating its interaction with LPS signaling receptors, which are expressed on the surface of LPS-responsive cells. We have previously demonstrated that high mobility group box 1 (HMGB1) can bind to and transfer LPS, consequently increasing LPS-induced TNF-α production in human peripheral blood mononuclear cells (PBMCs). We report here on the identification of two LPS-binding domains within HMGB1. Furthermore, using 12 synthetic HMGB1 peptides, we define the LPS-binding regions within each domain. Among them, synthetic peptides HPep1 and HPep6, which are located in the A and B box domains of HMGB1, bind to the polysaccharide and lipid A moieties of LPS respectively. Both HPep1 and HPep6 peptides inhibited binding of LPS to LBP and HMGB1, LBP-mediated LPS transfer to CD14, and cellular uptake of LPS in RAW264.7 cells. These peptides also inhibited LPS-induced TNF-α release in human PBMCs and induced lower levels of TNF-α in the serum in a subclinical endotoxemia mouse model. These results indicate that HMGB1 has two LPS-binding peptide regions that can be utilized to design anti-sepsis or LPS-neutralizing therapeutics.
    European Journal of Immunology 06/2011; 41(9):2753-62. · 4.97 Impact Factor
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    ABSTRACT: CKD712, (S)-1-(α-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, was considered as a new effective drug candidate to sepsis, based on its anti-inflammatory activity. It was reported that CKD712 inhibited various signal pathways which play a key role in production of proinflammatory cytokines. Here, we examined the effect of CKD712 on the secretion of high mobility group box 1 (HMGB1), which is one of the proinflammatory cytokines. CKD712 can reduce Gram-negative lipopolysaccharide (LPS)- and Gram-positive lipoteichoic acid (LTA)-stimulated HMGB1 secretion in RAW264.7 and human peripheral blood monocytes (PBMo), and also reduce LPS-induced nucleocytoplasmic translocation of HMGB1 1h before or after LPS treatment. CKD712 could dose-dependently inhibit the activation of PI3K and PI3K-dependent kinase 1 (PDK1), which are involved in HMGB1 secretion signaling pathway. In addition, CKD712 inhibited classical protein kinase C (cPKC), the effective kinase for phosphorylation of HMGB1 for secretion, however, had no effect on histone acetyl-transferase activity, which is another mechanism known for HMGB1 secretion. Thus, we suggest that CKD712 could inhibit LPS- and LTA-stimulated HMGB1 secretion through the inhibition of HMGB1 phosphorylation by inhibiting PI3K-PKC signaling pathway.
    International immunopharmacology 03/2011; 11(9):1160-5. · 2.21 Impact Factor
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    ABSTRACT: The cell lytic activity and toxicity against lepidopteran larvae of 13 venom peptides (4 OdVPs and 9 EpVPs) from two solitary hunting wasps, Orancistrocerus drewseni and Eumenes pomiformis, were examined with mastoparan as a reference peptide. Of the 13 peptides, 7 were predicted to have α-helical structures that exhibit the typical character of amphipathic α-helical antimicrobial peptides. The remaining peptides exhibited coil structures; among these, EpVP5 possesses two Cys residues that form an internal disulfide bridge. All the helical peptides including mastoparan showed antimicrobial and insect cell lytic activities, whereas only two of them were hemolytic against human erythrocytes. The helical peptides induced a feeding disorder when injected into the vicinity of the head and thorax of Spodoptera exigua larvae, perhaps because their non-specific neurotoxic or myotoxic action induced cell lysis. At low concentrations, however, these helical peptides increased cell permeability without inducing cell lysis. These findings suggest that the helical venom peptides may function as non-specific neurotoxins or myotoxins and venom-spreading factors at low concentrations, as well as preservatives for long-term storage of the prey via antimicrobial, particularly antifungal, activities.
    Peptides 03/2011; 32(3):568-72. · 2.52 Impact Factor
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    Jieun Choi, Hyun Jin Min, Jeon-Soo Shin
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    ABSTRACT: Febrile seizures are the most common form of childhood seizures. Fever is induced by pro-inflammatory cytokines during infection, and pro-inflammatory cytokines may trigger the development of febrile seizures. In order to determine whether active inflammation, including high mobility group box-1 (HMGB1) and pro-inflammatory cytokines, occurs in children with febrile seizures or epilepsy, we analyzed cytokine profiles of patients with febrile seizures or epilepsy. Forty-one febrile seizure patients who visited the emergency department of Seoul National University Boramae Hospital from June 2008 to May 2009 were included in this study. Blood was obtained from the febrile seizure child patients within 30 minutes of the time of the seizure; subsequently, serum cytokine assays were performed. Control samples were collected from children with febrile illness without convulsion (N = 41) and similarly analyzed. Serum samples from afebrile status epilepticus attacks in intractable epilepsy children (N = 12), afebrile seizure attacks in generalized epilepsy with febrile seizure plus (GEFSP) children (N = 6), and afebrile non-epileptic controls (N = 7) were also analyzed. Serum HMGB1 and IL-1β levels were significantly higher in febrile seizure patients than in fever only controls (p < 0.05). Serum IL-6 levels were significantly higher in typical febrile seizures than in fever only controls (p < 0.05). Serum IL-1β levels were significantly higher in status epilepticus attacks in intractable epilepsy patients than in fever only controls (p < 0.05). Serum levels of IL-1β were significantly correlated with levels of HMGB1, IL-6, and TNF-α (p < 0.05). HMGB1 and pro-inflammatory cytokines were significantly higher in febrile seizure children. Although it is not possible to infer causality from descriptive human studies, our data suggest that HMGB1 and the cytokine network may contribute to the generation of febrile seizures in children. There may be a potential role for anti-inflammatory therapy targeting cytokines and HMGB1 in preventing or limiting febrile seizures or subsequent epileptogenesis in the vulnerable, developing nervous system of children.
    Journal of Neuroinflammation 01/2011; 8:135. · 4.35 Impact Factor
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    ABSTRACT: Mesoporous silica nanoparticles are useful nanomaterials that have demonstrated the ability to contain and release cargos with mediation by gatekeepers. Magnetic nanocrystals have the ability to exhibit hyperthermic effects when placed in an oscillating magnetic field. In a system combining these two materials and a thermally sensitive gatekeeper, a unique drug delivery system can be produced. A novel material that incorporates zinc-doped iron oxide nanocrystals within a mesoporous silica framework that has been surface-modified with pseudorotaxanes is described. Upon application of an AC magnetic field, the nanocrystals generate local internal heating, causing the molecular machines to disassemble and allowing the cargos (drugs) to be released. When breast cancer cells (MDA-MB-231) were treated with doxorubicin-loaded particles and exposed to an AC field, cell death occurred. This material promises to be a noninvasive, externally controlled drug delivery system with cancer-killing properties.
    Journal of the American Chemical Society 08/2010; 132(31):10623-5. · 10.68 Impact Factor