Hyun Kim - Academia.edu (original) (raw)

Papers by Hyun Kim

Research paper thumbnail of Fibronectin fragment-induced expression of matrix metalloproteinases is mediated by MyD88-dependent TLR-2 signaling pathway in human chondrocytes

Arthritis research & therapy, 2015

Fibronectin fragments (FN-fs) are increased in the cartilage of patients with osteoarthritis (OA)... more Fibronectin fragments (FN-fs) are increased in the cartilage of patients with osteoarthritis (OA) and have a potent chondrolytic effect. However, little is known about the cellular receptors and signaling mechanisms that are mediated by FN-fs. We investigated whether the 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) regulates cartilage catabolism via the Toll-like receptor (TLR)-2 signaling pathway in human chondrocytes. Small interfering RNA was used to knock down TLR-2 and myeloid differentiation factor 88 (MyD88). TLR-2 was overexpressed in chondrocytes transfected with a TLR-2 expression plasmid. The expression levels of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 were analyzed using quantitative real-time reverse transcription polymerase chain reactions, immunoblotting, or enzyme-linked immunosorbent assay. The effect of TLR-2 on 29-kDa FN-f-mediated signaling pathways was investigated by immunoblotting. TLR-2, TLR-3, TLR-4, and TLR-5 mRNA were significantly ...

Research paper thumbnail of Hepatoma targeting peptide conjugated bio-reducible polymer complexed with oncolytic adenovirus for cancer gene therapy

Journal of controlled release : official journal of the Controlled Release Society, Jan 2, 2015

Despite adenovirus (Ad) vector's numerous advantages for cancer gene therapy, such as high ab... more Despite adenovirus (Ad) vector's numerous advantages for cancer gene therapy, such as high ability of endosomal escape, efficient nuclear entry mechanism, and high transduction, and therapeutic efficacy, tumor specific targeting and antiviral immune response still remain as a critical challenge in clinical setting. To overcome these obstacles and achieve cancer-specific targeting, we constructed tumor targeting bioreducible polymer, an arginine grafted bio-reducible polymer (ABP)-PEG-HCBP1, by conjugating PEGylated ABP with HCBP1 peptides which has high affinity and selectivity towards hepatoma. The ABP-PEG-HCBP1-conjugated replication incompetent GFP-expressing ad, (Ad/GFP)-ABP-PEG-HCBP1, showed a hepatoma cancer specific uptake and transduction compared to either naked Ad/GFP or Ad/GFP-ABP. Competition assays demonstrated that Ad/GFP-ABP-PEG-HCBP1-mediated transduction was specifically inhibited by HCBP1 peptide rather than coxsackie and adenovirus receptor specific antibody. ...

Research paper thumbnail of Rheumatoid arthritis patients fulfilling Korean National Health Insurance reimbursement guidelines for anti-tumor necrosis factor-α treatment and comparison to other guidelines

Rheumatology international, Jan 5, 2015

The aim of this study was to compare anti-tumor necrosis factor-α (TNFα) treatment status in rheu... more The aim of this study was to compare anti-tumor necrosis factor-α (TNFα) treatment status in rheumatoid arthritis (RA) patients with the Korean National Health Insurance (KNHI) reimbursement eligibility criteria and with American College of Rheumatology (ACR) recommendations, Japan College of Rheumatology (JCR) guidelines and British Society for Rheumatology (BSR) guidelines. Between December 2011 and August 2012, outpatients from 17 South Korean general hospitals diagnosed with RA according to the 1987 ACR criteria were enrolled into a noninterventional, cross-sectional, observational study. Of 1700 patients (1414 female (83.2 %), mean age of 56.6 ± 12.0, mean disease duration 97.9 ± 91.8 months), 306 (18.0 %) had used anti-TNFα agents, and 224 (13.2 %) were currently using an anti-TNFα agent. Of 1394 anti-TNFα-naive patients, 32 (2.3 %) met KNHI reimbursement guidelines, 148 (10.6 %) met ACR recommendations, and 127 (9.1 %) and 126 (9.0 %) were considered eligible for anti-TNFα ag...

Research paper thumbnail of Comparison of the disease activity score using the erythrocyte sedimentation rate and C-reactive protein levels in Koreans with rheumatoid arthritis

International journal of rheumatic diseases, Jan 22, 2015

The Disease Activity Score based on 28 joints (DAS28) has been widely used in clinical practice a... more The Disease Activity Score based on 28 joints (DAS28) has been widely used in clinical practice and research studies of rheumatoid arthritis (RA). The objective of this study was to evaluate the discordance in the DAS28 based on the erythrocyte sedimentation rate (ESR) versus C-reactive protein (CRP) levels in Korean patients with RA. From August to December 2011, 540 patients with RA who visited two rheumatology clinics affiliated with Hallym University (Korea) and had at least one DAS28 evaluation were examined. The mean age of the included patients was 53 years, and 82% were female. The mean duration of disease was 32.9 ± 41.2 months. The mean DAS28-ESR was higher than the DAS28-CRP (3.65 vs. 3.44; P < 0.001). In the DAS28-ESR group, 126 patients (23.3%) satisfied the criteria for remission versus 134 (24.8%) in the DAS28-CRP group. High disease activity was determined in 80 (14.8%) patients in the DAS28-ESR group and in 43 (8.0%) in the DAS28-CRP group. A comparison of the tw...

Research paper thumbnail of Prognostic role of copeptin after stroke: A systematic review and meta-analysis of observational studies

Scientific reports, 2015

Copeptin, the C-terminal part of provasopressin, has emerged as a novel prognostic marker after h... more Copeptin, the C-terminal part of provasopressin, has emerged as a novel prognostic marker after hemorrhagic or ischemic stroke. The aim of this study was to quantitatively assess the prognostic significance of plasma copeptin level on functional outcome and mortality in patients with acute stroke using a meta-analysis of the available evidence. Thirteen relevant studies from 2,746 patients were finally included in our study. An elevated plasma copeptin level was associated with an increased risk of unfavorable outcome and mortality after stroke (OR 1.77; 95% CI, 1.44-2.19 and OR 3.90; 95% CI 3.07-4.95, respectively). The result of the pooled measure on standardized mean difference (SMD) was that plasma copeptin levels were found to be significantly higher in patients who died compared to survivors (SMD 1.70; 95% CI, 1.36-2.03). A stratified analysis by study region showed significant differences in SMD of copeptin, and the heterogeneity among studies was significantly decreased. How...

Research paper thumbnail of PEP-1-FK506BP12 inhibits matrix metalloproteinase expression in human articular chondrocytes and in a mouse carrageenan-induced arthritis model

BMB reports, Jan 18, 2015

The FK506-binding protein 12 kDa (FK506BP12), immunosuppressive drug, modulates T cell activation... more The FK506-binding protein 12 kDa (FK506BP12), immunosuppressive drug, modulates T cell activation via calcineurin inhibition. In this study, we investigated the ability of PEP-1-FK506BP12, consisting of FK506BP12 fused to the protein transduction domain PEP-1 peptide, to suppress catabolic responses in primary human chondrocytes and in a mouse carrageenan-induced paw arthritis model. Western blotting and immunofluorescence analysis showed that PEP-1-FK506BP12 efficiently penetrated chondrocytes and cartilage explants. In interleukin-1β (IL-1β)-treated chondrocytes, PEP-1-FK506BP12 significantly suppressed the expression of catabolic enzymes, including matrix metalloproteinases (MMPs)-1, -3, and -13; and cyclooxygenase-2, at both the mRNA and protein levels, whereas FK506BP12 alone did not. In addition, PEP-1-FK506BP12 decreased IL-1β-induced phosphorylation of the mitogen-activated protein kinase (MAPK) complex (p38, JNK, and ERK) and the inhibitor kappa B alpha. In the mouse model ...

Research paper thumbnail of Low Baseline Interleukin-17A Levels Are Associated with Better Treatment Response at 12 Weeks to Tocilizumab Therapy in Rheumatoid Arthritis Patients

Journal of Immunology Research, 2015

T helper 17-related cytokines have been implicated in rheumatoid arthritis (RA) pathogenesis. The... more T helper 17-related cytokines have been implicated in rheumatoid arthritis (RA) pathogenesis. The study aimed to identify cytokines associated with the treatment response of RA patients to tocilizumab (TCZ), a humanized monoclonal antibody against the interleukin- (IL-) 6 receptor. As an independent substudy of the 24-week, randomized, double-blinded CWP-TCZ301 trial of TCZ in RA patients with an inadequate response to disease-modifying antirheumatic drugs, serum levels of cytokines including tumor necrosis factor-alpha, IL-17A, IL-21, IL-23, IL-6, and soluble IL-6 receptor were measured. Baseline IL-17A levels were significantly lower in RA patients who achieved disease activity score 28 (DAS28) remission at 12 weeks of TCZ treatment, compared to patients not in remission. Patients were stratified into IL-17A low group and IL-17A high group. Significantly more patients in the IL-17A low group achieved remission as compared to the IL-17A high group (47.6 versus 17.4%, P = 0.032). DAS28 improvement was significantly better in the IL-17A low group than in the IL-17A high group at 12 weeks (P = 0.045) and 24 weeks (P = 0.046) after adjustment. Other baseline cytokines were not associated with treatment response to TCZ. The data demonstrate that low baseline IL-17A levels are associated with better clinical response to TCZ treatment in RA patients.

Research paper thumbnail of PEP-1-FK506BP inhibits alkali burn-induced corneal inflammation on the rat model of corneal alkali injury

BMB reports, Jan 30, 2015

FK506 binding protein 12 (FK506BP) is a small peptide with a single FK506BP domain that is involv... more FK506 binding protein 12 (FK506BP) is a small peptide with a single FK506BP domain that is involved in suppression of immune response and reactive oxygen species. FK506BP has emerged as a potential drug target for several inflammatory diseases. Here, we examined the protective effects of directly applied cell permeable FK506BP (PEP-1-FK506BP) on corneal alkali burn injury (CAI). In cornea, there was a significant decrease in the number of cells expressing pro-inflammation, apoptotic, and angiogenic factors such as TNF-α, COX-2, and VEGF. Both corneal opacity and corneal neovascularization (CNV) were significantly decreased in the PEP-1-FK506BP treated group. Our results showed that PEP-1-FK506BP can significantly inhibit alkali burn-induced corneal inflammation, in rats, possibly by accelerating corneal wound healing and by reducing the production of angiogenic factors, and inflammatory cytokines. These results suggest that PEP-1-FK506BP may be a potential therapeutic agent for CAI.

Research paper thumbnail of The Study of Risk Factors for Symptomatic Knee Osteoarthritis in Korea

The Journal of the Korean Rheumatism Association, 2008

＆ ７； ＆＆ ８ ＆ ８６６＞ --124 -1.04∼1.12) and living in rural area (OR=5.39, 05% CI 1.94∼14.96) were ass... more ＆ ７； ＆＆ ８ ＆ ８６６＞ --124 -1.04∼1.12) and living in rural area (OR=5.39, 05% CI 1.94∼14.96) were associated with symptomatic knee OA in men and age (older than 40 years, OR=1.11, 95% CI 1.07∼1.16), living in rural area (OR=2.46, 95% CI 1.17∼5.17), and BMI over 25 kg/m 2 (OR=3.45, 95% CI 1.63∼7.29) in women.

Research paper thumbnail of Correlation between ultrasonographic findings and the response to corticosteroid injection in pes anserinus tendinobursitis syndrome in knee osteoarthritis patients

Journal of Korean medical science, 2005

The objectives of this study were to assess the ultrasonographic (US) findings in patients with k... more The objectives of this study were to assess the ultrasonographic (US) findings in patients with knee osteoarthritis (OA) with pes anserinus tendinitis or bursitis (PATB) syndrome and to determine the correlation between the US findings and the response to local corticosteroid injection. We prospectively studied 26 patients with knee OA with clinically diagnosed PATB syndrome. A linear array 7 MHz transducer was used for US examination of the knee. Seventeen patients were injected locally with tramcinolone acetonide in the anserine bursa area. Response to local corticosteroid injection was evaluated by pain visual analog scale (VAS), Western Ontario and MacMaster (WOMAC) osteoarthritis index and Global patient/physician assessment using Likert scale. On US examination, only 2 patients (8.7%) showed evidence of PATB. Pain VAS, WOMAC pain index and WOMAC physical function index improved significantly after corticosteroid injection. Global patient assessment revealed that 2 patients sho...

Research paper thumbnail of The mechanism of low-concentration sodium nitroprusside-mediated protection of chondrocyte death

Arthritis research & therapy, 2005

Sodium nitroprusside (SNP), a widely used nitric oxide donor, has recently been shown to mediate ... more Sodium nitroprusside (SNP), a widely used nitric oxide donor, has recently been shown to mediate chondrocyte apoptosis by generating reactive oxygen species, whereas more potent nitric oxide donors do not induce chondrocyte apoptosis. The present study was performed to investigate the protective effect of a low concentration of SNP upon the cytotoxicity of chondrocytes to higher concentrations of SNP, and to elucidate the underlying mechanism. Human osteoarthritis chondrocytes were cultured as monolayers, and first-passage cells were used for the experiments. Chondrocyte death induced by 1 mM SNP was completely inhibited by pretreating with 0.1 mM SNP. This protective effect of SNP was replicated by the guanosine-3',5'kappa-cyclic monophosphate analog, DBcGMP. Protection from chondrocyte death conferred by 0.1 mM SNP was mediated by heme oxygenase 1 (HO-1), as was revealed by the increased expression of HO-1 in 0.1 mM SNP pretreated chondrocytes and by the reversal of this p...

Research paper thumbnail of Transduction of Cu, Zn-superoxide dismutase mediated by an HIV-1 Tat protein basic domain into human chondrocytes

Arthritis research & therapy, 2006

This study was performed to investigate the transduction of a full-length superoxide dismutase (S... more This study was performed to investigate the transduction of a full-length superoxide dismutase (SOD) protein fused to transactivator of transcription (Tat) into human chondrocytes, and to determine the regulatory function of transduced Tat-SOD in the inflammatory cytokine induced catabolic pathway. The pTat-SOD expression vector was constructed to express the basic domain of HIV-1 Tat as a fusion protein with Cu, Zn-SOD. We also purified histidine-tagged SOD without an HIV-1 Tat and Tat-GFP as control proteins. Cartilage samples were obtained from patients with osteoarthritis (OA) and chondrocytes were cultured in both a monolayer and an explant. For the transduction of fusion proteins, cells/explants were treated with a variety of concentrations of fusion proteins. The transduced protein was detected by fluorescein labeling, western blotting and SOD activity assay. Effects of transduced Tat-SOD on the regulation of IL-1 induced nitric oxide (NO) production and inducible nitric oxid...

Research paper thumbnail of The Prevalence of Knee Osteoarthritis in Elderly Community Residents in Korea

Journal of Korean Medical Science, 2010

The purpose of this study was to estimate the prevalence of radiographic and symptomatic knee ost... more The purpose of this study was to estimate the prevalence of radiographic and symptomatic knee osteoarthritis (OA) among community residents and to elucidate the relevant risk factors. This prospective, population-based study was conducted on residents over 50 yr of age in Chuncheon. Subjects completed an interview based on a standardized questionnaire and clinical evaluation including standardized weight bearing semiflexed knee A-P radiographs. We defined a subject with the Kellgren and Lawrence grade &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=2 as having radiographic knee OA (ROA). Symptomatic knee OA (SOA) was defined by the presence of both ROA and knee pain. We obtained symptom information and radiographs from 504 subjects. The prevalence of ROA and SOA was 37.3% and 24.2%, respectively. The prevalence of both ROA and SOA was significantly higher among women than among men. Multivariate analysis revealed that the presence of hypertension, and a manual occupation were significantly associated with the presence of ROA and SOA. Lower level of education was significantly associated with the presence of ROA, and female sex with the presence of SOA. In conclusion, both ROA and SOA are common in the aged adult population of Korea, with preponderance for women.

Research paper thumbnail of Clinical and Radiographic Features of Adult-onset Ankylosing Spondylitis in Korean Patients: Comparisons between Males and Females

Journal of Korean Medical Science, 2010

The objective of this study was to investigate clinical and radiographic features and gender diff... more The objective of this study was to investigate clinical and radiographic features and gender differences in Korean patients with adult-onset ankylosing spondylitis. Multicenter cross-sectional studies were conducted in the rheumatology clinics of 13 Korean tertiary referral hospitals. All patients had a confirmed diagnosis of ankylosing spondylitis according to the modified New York criteria. Clinical, laboratory, and radiographic features were evaluated and disease activities were assessed using the Bath ankylosing spondylitis disease activity index. Five hundred and five patients were recruited. The male to female ratio was 6.1:1. Average age at symptom onset was 25.4±8.9 yr and average disease duration was 9.6±6.8 yr. Males manifested symptoms at a significantly earlier age. HLA-B27 was more frequently positive in males. Hips were more commonly affected in males, and knees in females. When spinal mobility was measured using tragus-to-wall distance and the modified Schober's test, females had significantly better results. Radiographic spinal changes, including bamboo spine and syndesmophytes, were more common in males after adjustment of confounding factors. In conclusion, we observed significant gender differences in radiographic spinal involvement as well as other clinical manifestations among Korea patients with adult-onset ankylosing spondylitis. These findings may influence the timing of the diagnosis and the choice of treatment.

Research paper thumbnail of A Case of Ankylosing Spondylitis in a Patient with Henoch-Schönlein Purpura

The Journal of the Korean Rheumatism Association, 2008

＜접수일：2007년 11월 19일, 심사통과일：2008년 9월 1일＞ ※통신저자：김 수 진 경기도 안양시 동안구 평안동 한림대학교 성심병원 내과 Tel：031) 380-150... more ＜접수일：2007년 11월 19일, 심사통과일：2008년 9월 1일＞ ※통신저자：김 수 진 경기도 안양시 동안구 평안동 한림대학교 성심병원 내과 Tel：031) 380-1500, Fax：031) 380-4111, E-mail：being97@hallym.or.kr ... A Case of Ankylosing Spondylitis in a Patient with ...

Research paper thumbnail of Tat-biliverdin reductase A inhibits inflammatory response by regulation of MAPK and NF-κB pathways in Raw 264.7 cells and edema mouse model

Molecular immunology, 2015

Reactive oxygen species (ROS) accumulation induces oxidative stress and cell damage, which then a... more Reactive oxygen species (ROS) accumulation induces oxidative stress and cell damage, which then activates several signaling pathways and triggers inflammatory response. Biliverdin is a natural product of heme metabolism which is converted to bilirubin by the enzyme biliverdin reductase A (BLVRA) which also plays a role in antioxidant activity via the ROS scavenging activity of bilirubin. In this study, we examined the anti-inflammatory and anti-apoptotic effects of Tat-BLVRA protein on lipopolysaccharide (LPS)-induced inflammation in Raw 264.7 macrophage cells. Transduction of Tat-BLVRA protein into Raw 264.7 cells and mice ear tissue was tested by Western blot analysis and immunohistochemical analysis. Tat-BLVRA protein was effective in inhibiting mitogen activated protein kinases (MAPKs), Akt and NF-κB activation, intracellular ROS production and DNA fragmentation. Also, Tat-BLVRA protein significantly inhibited the expression of cytokines, COX-2, and iNOS. In a 12-O-tetradecanoyl...

Research paper thumbnail of The development of herbicide-resistant maize: stable Agrobacterium-mediated transformation of maize using explants of type II embryogenic calli

Plant Biotechnology Reports, 2009

One of the limitations to conducting maize Agrobacterium-mediated transformation using explants o... more One of the limitations to conducting maize Agrobacterium-mediated transformation using explants of immature zygotic embryos routinely is the availability of the explants. To produce immature embryos routinely and continuously requires a well-equipped greenhouse and laborious artificial pollination. To overcome this limitation, an Agrobacterium-mediated transformation system using explants of type II embryogenic calli was developed. Once the type II embryogenic calli

Research paper thumbnail of Expression, purification and characterization of TAT-high mobility group box-1A peptide as a carrier of nucleic acids

Biotechnology Letters, 2008

High mobility group box 1 (HMGB1) is an abundant nuclear protein that binds to double-stranded DN... more High mobility group box 1 (HMGB1) is an abundant nuclear protein that binds to double-stranded DNA. HMGB1 is composed of high mobility (HMG) box A, box B, and C-terminal acidic regions. In this study, a recombinant TAT linked HMGB1 box A (rTAT-HMGB1A) peptide was expressed, purified, and characterized as a carrier of nucleic acids. The HMGB1A cDNA was amplified by

Research paper thumbnail of Genomic Changes in the Striatum of Unilateral 6-hydroxydopamine Lesioned Parkinson Rat Model

B a c k g r o u n d : Parkinson' s disease is the primary degenerative disease characterized... more B a c k g r o u n d : Parkinson' s disease is the primary degenerative disease characterized by rigidity, bradykinesia and resting tremor. Even though dopaminergic cell loss of the substantia nigra compacta is a main pathogenesis of the Parkinson' s disease, the striatal dysfuntion is major pathophysiology of pakinsonian symptoms. Methods : Since gene expression profile can explain the symptomatic varieties of Parkinson ' s disease, gene expression was investigated in the striatum of rat brain after lesioning of unilateral substantia nigra compacta with 6-hydroxydopamine using cDNA microarray technique for the first time. The expression patterns of 5,200 rat brain cDNAs were screened and clustered according to the function of gene. The expression patterns of enkephaline and substance-P mRNA were also studied for validation of animal preparation. Results : Various genes involved in apoptosis, cytokines. cytoskeletal molecules, neu - rotrophic factors, receptors, intrac...

Research paper thumbnail of Role of the Oxygen-Dependent Degradation Domain in a Hypoxia-Inducible Gene Expression System in Vascular Endothelial Growth Factor Gene Therapy

Spine, 2009

STUDY DESIGN.: An in vitro neural hypoxia model and rat spinal cord injury (SCI) model were used ... more STUDY DESIGN.: An in vitro neural hypoxia model and rat spinal cord injury (SCI) model were used to assess the regulation effect of a reporter or therapeutic gene expression by an oxygen-dependent degradation (ODD) domain in a hypoxia-inducible gene expression system with or without the erythropoietin (EPO) enhancer. OBJECTIVE.: To increase vascular endothelial growth factor (VEGF) gene expression in SCI lesions but avoid unwanted overexpression of VEGF in normal sites, we developed a hypoxia-inducible gene expression system consisting of the EPO enhancer upstream of the SV promoter and an ODD domain C-terminally fused to VEGF. SUMMARY OF BACKGROUND DATA.: ODD domain plays a major role in the degradation of hypoxia-inducible factor 1alpha and has been used in a hypoxia-specific gene expression system as a post-translational regulatory factor. METHODS.: The hypoxia-inducible luciferase or VEGF plasmid was constructed using the EPO enhancer combined with or without the ODD domain. The constructed plasmid was transfected into mouse Neuro 2a (N2a) neuroblastoma cells by Lipofectamine 2000, followed by a 24-hour incubation in hypoxia or normoxia. For in vivo analysis, the naked plasmid DNA was directly injected into the injured rat spinal cord. The gene expression was evaluated by luciferase activity assay, enzyme-linked immunosorbent assay, reverse transcriptase-polymerase chain reaction, and immunofluorescence staining. RESULTS.: The EPO enhancer/ODD domain-combined hypoxia-inducible gene expression system clearly increased the expression of the reporter luciferase gene and therapeutic VEGF gene specifically under hypoxic conditions and SCI, and quickly downregulated protein expression to a very low level after reoxygenation. CONCLUSION.: These results strongly suggest the potential applicability of this EPO enhancer/ODD domain-based hypoxia-inducible gene expression system in the development of a safer and more effective VEGF gene therapy for SCI.

Research paper thumbnail of Fibronectin fragment-induced expression of matrix metalloproteinases is mediated by MyD88-dependent TLR-2 signaling pathway in human chondrocytes

Arthritis research & therapy, 2015

Fibronectin fragments (FN-fs) are increased in the cartilage of patients with osteoarthritis (OA)... more Fibronectin fragments (FN-fs) are increased in the cartilage of patients with osteoarthritis (OA) and have a potent chondrolytic effect. However, little is known about the cellular receptors and signaling mechanisms that are mediated by FN-fs. We investigated whether the 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) regulates cartilage catabolism via the Toll-like receptor (TLR)-2 signaling pathway in human chondrocytes. Small interfering RNA was used to knock down TLR-2 and myeloid differentiation factor 88 (MyD88). TLR-2 was overexpressed in chondrocytes transfected with a TLR-2 expression plasmid. The expression levels of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 were analyzed using quantitative real-time reverse transcription polymerase chain reactions, immunoblotting, or enzyme-linked immunosorbent assay. The effect of TLR-2 on 29-kDa FN-f-mediated signaling pathways was investigated by immunoblotting. TLR-2, TLR-3, TLR-4, and TLR-5 mRNA were significantly ...

Research paper thumbnail of Hepatoma targeting peptide conjugated bio-reducible polymer complexed with oncolytic adenovirus for cancer gene therapy

Journal of controlled release : official journal of the Controlled Release Society, Jan 2, 2015

Despite adenovirus (Ad) vector's numerous advantages for cancer gene therapy, such as high ab... more Despite adenovirus (Ad) vector's numerous advantages for cancer gene therapy, such as high ability of endosomal escape, efficient nuclear entry mechanism, and high transduction, and therapeutic efficacy, tumor specific targeting and antiviral immune response still remain as a critical challenge in clinical setting. To overcome these obstacles and achieve cancer-specific targeting, we constructed tumor targeting bioreducible polymer, an arginine grafted bio-reducible polymer (ABP)-PEG-HCBP1, by conjugating PEGylated ABP with HCBP1 peptides which has high affinity and selectivity towards hepatoma. The ABP-PEG-HCBP1-conjugated replication incompetent GFP-expressing ad, (Ad/GFP)-ABP-PEG-HCBP1, showed a hepatoma cancer specific uptake and transduction compared to either naked Ad/GFP or Ad/GFP-ABP. Competition assays demonstrated that Ad/GFP-ABP-PEG-HCBP1-mediated transduction was specifically inhibited by HCBP1 peptide rather than coxsackie and adenovirus receptor specific antibody. ...

Research paper thumbnail of Rheumatoid arthritis patients fulfilling Korean National Health Insurance reimbursement guidelines for anti-tumor necrosis factor-α treatment and comparison to other guidelines

Rheumatology international, Jan 5, 2015

The aim of this study was to compare anti-tumor necrosis factor-α (TNFα) treatment status in rheu... more The aim of this study was to compare anti-tumor necrosis factor-α (TNFα) treatment status in rheumatoid arthritis (RA) patients with the Korean National Health Insurance (KNHI) reimbursement eligibility criteria and with American College of Rheumatology (ACR) recommendations, Japan College of Rheumatology (JCR) guidelines and British Society for Rheumatology (BSR) guidelines. Between December 2011 and August 2012, outpatients from 17 South Korean general hospitals diagnosed with RA according to the 1987 ACR criteria were enrolled into a noninterventional, cross-sectional, observational study. Of 1700 patients (1414 female (83.2 %), mean age of 56.6 ± 12.0, mean disease duration 97.9 ± 91.8 months), 306 (18.0 %) had used anti-TNFα agents, and 224 (13.2 %) were currently using an anti-TNFα agent. Of 1394 anti-TNFα-naive patients, 32 (2.3 %) met KNHI reimbursement guidelines, 148 (10.6 %) met ACR recommendations, and 127 (9.1 %) and 126 (9.0 %) were considered eligible for anti-TNFα ag...

Research paper thumbnail of Comparison of the disease activity score using the erythrocyte sedimentation rate and C-reactive protein levels in Koreans with rheumatoid arthritis

International journal of rheumatic diseases, Jan 22, 2015

The Disease Activity Score based on 28 joints (DAS28) has been widely used in clinical practice a... more The Disease Activity Score based on 28 joints (DAS28) has been widely used in clinical practice and research studies of rheumatoid arthritis (RA). The objective of this study was to evaluate the discordance in the DAS28 based on the erythrocyte sedimentation rate (ESR) versus C-reactive protein (CRP) levels in Korean patients with RA. From August to December 2011, 540 patients with RA who visited two rheumatology clinics affiliated with Hallym University (Korea) and had at least one DAS28 evaluation were examined. The mean age of the included patients was 53 years, and 82% were female. The mean duration of disease was 32.9 ± 41.2 months. The mean DAS28-ESR was higher than the DAS28-CRP (3.65 vs. 3.44; P < 0.001). In the DAS28-ESR group, 126 patients (23.3%) satisfied the criteria for remission versus 134 (24.8%) in the DAS28-CRP group. High disease activity was determined in 80 (14.8%) patients in the DAS28-ESR group and in 43 (8.0%) in the DAS28-CRP group. A comparison of the tw...

Research paper thumbnail of Prognostic role of copeptin after stroke: A systematic review and meta-analysis of observational studies

Scientific reports, 2015

Copeptin, the C-terminal part of provasopressin, has emerged as a novel prognostic marker after h... more Copeptin, the C-terminal part of provasopressin, has emerged as a novel prognostic marker after hemorrhagic or ischemic stroke. The aim of this study was to quantitatively assess the prognostic significance of plasma copeptin level on functional outcome and mortality in patients with acute stroke using a meta-analysis of the available evidence. Thirteen relevant studies from 2,746 patients were finally included in our study. An elevated plasma copeptin level was associated with an increased risk of unfavorable outcome and mortality after stroke (OR 1.77; 95% CI, 1.44-2.19 and OR 3.90; 95% CI 3.07-4.95, respectively). The result of the pooled measure on standardized mean difference (SMD) was that plasma copeptin levels were found to be significantly higher in patients who died compared to survivors (SMD 1.70; 95% CI, 1.36-2.03). A stratified analysis by study region showed significant differences in SMD of copeptin, and the heterogeneity among studies was significantly decreased. How...

Research paper thumbnail of PEP-1-FK506BP12 inhibits matrix metalloproteinase expression in human articular chondrocytes and in a mouse carrageenan-induced arthritis model

BMB reports, Jan 18, 2015

The FK506-binding protein 12 kDa (FK506BP12), immunosuppressive drug, modulates T cell activation... more The FK506-binding protein 12 kDa (FK506BP12), immunosuppressive drug, modulates T cell activation via calcineurin inhibition. In this study, we investigated the ability of PEP-1-FK506BP12, consisting of FK506BP12 fused to the protein transduction domain PEP-1 peptide, to suppress catabolic responses in primary human chondrocytes and in a mouse carrageenan-induced paw arthritis model. Western blotting and immunofluorescence analysis showed that PEP-1-FK506BP12 efficiently penetrated chondrocytes and cartilage explants. In interleukin-1β (IL-1β)-treated chondrocytes, PEP-1-FK506BP12 significantly suppressed the expression of catabolic enzymes, including matrix metalloproteinases (MMPs)-1, -3, and -13; and cyclooxygenase-2, at both the mRNA and protein levels, whereas FK506BP12 alone did not. In addition, PEP-1-FK506BP12 decreased IL-1β-induced phosphorylation of the mitogen-activated protein kinase (MAPK) complex (p38, JNK, and ERK) and the inhibitor kappa B alpha. In the mouse model ...

Research paper thumbnail of Low Baseline Interleukin-17A Levels Are Associated with Better Treatment Response at 12 Weeks to Tocilizumab Therapy in Rheumatoid Arthritis Patients

Journal of Immunology Research, 2015

T helper 17-related cytokines have been implicated in rheumatoid arthritis (RA) pathogenesis. The... more T helper 17-related cytokines have been implicated in rheumatoid arthritis (RA) pathogenesis. The study aimed to identify cytokines associated with the treatment response of RA patients to tocilizumab (TCZ), a humanized monoclonal antibody against the interleukin- (IL-) 6 receptor. As an independent substudy of the 24-week, randomized, double-blinded CWP-TCZ301 trial of TCZ in RA patients with an inadequate response to disease-modifying antirheumatic drugs, serum levels of cytokines including tumor necrosis factor-alpha, IL-17A, IL-21, IL-23, IL-6, and soluble IL-6 receptor were measured. Baseline IL-17A levels were significantly lower in RA patients who achieved disease activity score 28 (DAS28) remission at 12 weeks of TCZ treatment, compared to patients not in remission. Patients were stratified into IL-17A low group and IL-17A high group. Significantly more patients in the IL-17A low group achieved remission as compared to the IL-17A high group (47.6 versus 17.4%, P = 0.032). DAS28 improvement was significantly better in the IL-17A low group than in the IL-17A high group at 12 weeks (P = 0.045) and 24 weeks (P = 0.046) after adjustment. Other baseline cytokines were not associated with treatment response to TCZ. The data demonstrate that low baseline IL-17A levels are associated with better clinical response to TCZ treatment in RA patients.

Research paper thumbnail of PEP-1-FK506BP inhibits alkali burn-induced corneal inflammation on the rat model of corneal alkali injury

BMB reports, Jan 30, 2015

FK506 binding protein 12 (FK506BP) is a small peptide with a single FK506BP domain that is involv... more FK506 binding protein 12 (FK506BP) is a small peptide with a single FK506BP domain that is involved in suppression of immune response and reactive oxygen species. FK506BP has emerged as a potential drug target for several inflammatory diseases. Here, we examined the protective effects of directly applied cell permeable FK506BP (PEP-1-FK506BP) on corneal alkali burn injury (CAI). In cornea, there was a significant decrease in the number of cells expressing pro-inflammation, apoptotic, and angiogenic factors such as TNF-α, COX-2, and VEGF. Both corneal opacity and corneal neovascularization (CNV) were significantly decreased in the PEP-1-FK506BP treated group. Our results showed that PEP-1-FK506BP can significantly inhibit alkali burn-induced corneal inflammation, in rats, possibly by accelerating corneal wound healing and by reducing the production of angiogenic factors, and inflammatory cytokines. These results suggest that PEP-1-FK506BP may be a potential therapeutic agent for CAI.

Research paper thumbnail of The Study of Risk Factors for Symptomatic Knee Osteoarthritis in Korea

The Journal of the Korean Rheumatism Association, 2008

＆ ７； ＆＆ ８ ＆ ８６６＞ --124 -1.04∼1.12) and living in rural area (OR=5.39, 05% CI 1.94∼14.96) were ass... more ＆ ７； ＆＆ ８ ＆ ８６６＞ --124 -1.04∼1.12) and living in rural area (OR=5.39, 05% CI 1.94∼14.96) were associated with symptomatic knee OA in men and age (older than 40 years, OR=1.11, 95% CI 1.07∼1.16), living in rural area (OR=2.46, 95% CI 1.17∼5.17), and BMI over 25 kg/m 2 (OR=3.45, 95% CI 1.63∼7.29) in women.

Research paper thumbnail of Correlation between ultrasonographic findings and the response to corticosteroid injection in pes anserinus tendinobursitis syndrome in knee osteoarthritis patients

Journal of Korean medical science, 2005

The objectives of this study were to assess the ultrasonographic (US) findings in patients with k... more The objectives of this study were to assess the ultrasonographic (US) findings in patients with knee osteoarthritis (OA) with pes anserinus tendinitis or bursitis (PATB) syndrome and to determine the correlation between the US findings and the response to local corticosteroid injection. We prospectively studied 26 patients with knee OA with clinically diagnosed PATB syndrome. A linear array 7 MHz transducer was used for US examination of the knee. Seventeen patients were injected locally with tramcinolone acetonide in the anserine bursa area. Response to local corticosteroid injection was evaluated by pain visual analog scale (VAS), Western Ontario and MacMaster (WOMAC) osteoarthritis index and Global patient/physician assessment using Likert scale. On US examination, only 2 patients (8.7%) showed evidence of PATB. Pain VAS, WOMAC pain index and WOMAC physical function index improved significantly after corticosteroid injection. Global patient assessment revealed that 2 patients sho...

Research paper thumbnail of The mechanism of low-concentration sodium nitroprusside-mediated protection of chondrocyte death

Arthritis research & therapy, 2005

Sodium nitroprusside (SNP), a widely used nitric oxide donor, has recently been shown to mediate ... more Sodium nitroprusside (SNP), a widely used nitric oxide donor, has recently been shown to mediate chondrocyte apoptosis by generating reactive oxygen species, whereas more potent nitric oxide donors do not induce chondrocyte apoptosis. The present study was performed to investigate the protective effect of a low concentration of SNP upon the cytotoxicity of chondrocytes to higher concentrations of SNP, and to elucidate the underlying mechanism. Human osteoarthritis chondrocytes were cultured as monolayers, and first-passage cells were used for the experiments. Chondrocyte death induced by 1 mM SNP was completely inhibited by pretreating with 0.1 mM SNP. This protective effect of SNP was replicated by the guanosine-3',5'kappa-cyclic monophosphate analog, DBcGMP. Protection from chondrocyte death conferred by 0.1 mM SNP was mediated by heme oxygenase 1 (HO-1), as was revealed by the increased expression of HO-1 in 0.1 mM SNP pretreated chondrocytes and by the reversal of this p...

Research paper thumbnail of Transduction of Cu, Zn-superoxide dismutase mediated by an HIV-1 Tat protein basic domain into human chondrocytes

Arthritis research & therapy, 2006

This study was performed to investigate the transduction of a full-length superoxide dismutase (S... more This study was performed to investigate the transduction of a full-length superoxide dismutase (SOD) protein fused to transactivator of transcription (Tat) into human chondrocytes, and to determine the regulatory function of transduced Tat-SOD in the inflammatory cytokine induced catabolic pathway. The pTat-SOD expression vector was constructed to express the basic domain of HIV-1 Tat as a fusion protein with Cu, Zn-SOD. We also purified histidine-tagged SOD without an HIV-1 Tat and Tat-GFP as control proteins. Cartilage samples were obtained from patients with osteoarthritis (OA) and chondrocytes were cultured in both a monolayer and an explant. For the transduction of fusion proteins, cells/explants were treated with a variety of concentrations of fusion proteins. The transduced protein was detected by fluorescein labeling, western blotting and SOD activity assay. Effects of transduced Tat-SOD on the regulation of IL-1 induced nitric oxide (NO) production and inducible nitric oxid...

Research paper thumbnail of The Prevalence of Knee Osteoarthritis in Elderly Community Residents in Korea

Journal of Korean Medical Science, 2010

The purpose of this study was to estimate the prevalence of radiographic and symptomatic knee ost... more The purpose of this study was to estimate the prevalence of radiographic and symptomatic knee osteoarthritis (OA) among community residents and to elucidate the relevant risk factors. This prospective, population-based study was conducted on residents over 50 yr of age in Chuncheon. Subjects completed an interview based on a standardized questionnaire and clinical evaluation including standardized weight bearing semiflexed knee A-P radiographs. We defined a subject with the Kellgren and Lawrence grade &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=2 as having radiographic knee OA (ROA). Symptomatic knee OA (SOA) was defined by the presence of both ROA and knee pain. We obtained symptom information and radiographs from 504 subjects. The prevalence of ROA and SOA was 37.3% and 24.2%, respectively. The prevalence of both ROA and SOA was significantly higher among women than among men. Multivariate analysis revealed that the presence of hypertension, and a manual occupation were significantly associated with the presence of ROA and SOA. Lower level of education was significantly associated with the presence of ROA, and female sex with the presence of SOA. In conclusion, both ROA and SOA are common in the aged adult population of Korea, with preponderance for women.

Research paper thumbnail of Clinical and Radiographic Features of Adult-onset Ankylosing Spondylitis in Korean Patients: Comparisons between Males and Females

Journal of Korean Medical Science, 2010

The objective of this study was to investigate clinical and radiographic features and gender diff... more The objective of this study was to investigate clinical and radiographic features and gender differences in Korean patients with adult-onset ankylosing spondylitis. Multicenter cross-sectional studies were conducted in the rheumatology clinics of 13 Korean tertiary referral hospitals. All patients had a confirmed diagnosis of ankylosing spondylitis according to the modified New York criteria. Clinical, laboratory, and radiographic features were evaluated and disease activities were assessed using the Bath ankylosing spondylitis disease activity index. Five hundred and five patients were recruited. The male to female ratio was 6.1:1. Average age at symptom onset was 25.4±8.9 yr and average disease duration was 9.6±6.8 yr. Males manifested symptoms at a significantly earlier age. HLA-B27 was more frequently positive in males. Hips were more commonly affected in males, and knees in females. When spinal mobility was measured using tragus-to-wall distance and the modified Schober's test, females had significantly better results. Radiographic spinal changes, including bamboo spine and syndesmophytes, were more common in males after adjustment of confounding factors. In conclusion, we observed significant gender differences in radiographic spinal involvement as well as other clinical manifestations among Korea patients with adult-onset ankylosing spondylitis. These findings may influence the timing of the diagnosis and the choice of treatment.

Research paper thumbnail of A Case of Ankylosing Spondylitis in a Patient with Henoch-Schönlein Purpura

The Journal of the Korean Rheumatism Association, 2008

＜접수일：2007년 11월 19일, 심사통과일：2008년 9월 1일＞ ※통신저자：김 수 진 경기도 안양시 동안구 평안동 한림대학교 성심병원 내과 Tel：031) 380-150... more ＜접수일：2007년 11월 19일, 심사통과일：2008년 9월 1일＞ ※통신저자：김 수 진 경기도 안양시 동안구 평안동 한림대학교 성심병원 내과 Tel：031) 380-1500, Fax：031) 380-4111, E-mail：being97@hallym.or.kr ... A Case of Ankylosing Spondylitis in a Patient with ...

Research paper thumbnail of Tat-biliverdin reductase A inhibits inflammatory response by regulation of MAPK and NF-κB pathways in Raw 264.7 cells and edema mouse model

Molecular immunology, 2015

Reactive oxygen species (ROS) accumulation induces oxidative stress and cell damage, which then a... more Reactive oxygen species (ROS) accumulation induces oxidative stress and cell damage, which then activates several signaling pathways and triggers inflammatory response. Biliverdin is a natural product of heme metabolism which is converted to bilirubin by the enzyme biliverdin reductase A (BLVRA) which also plays a role in antioxidant activity via the ROS scavenging activity of bilirubin. In this study, we examined the anti-inflammatory and anti-apoptotic effects of Tat-BLVRA protein on lipopolysaccharide (LPS)-induced inflammation in Raw 264.7 macrophage cells. Transduction of Tat-BLVRA protein into Raw 264.7 cells and mice ear tissue was tested by Western blot analysis and immunohistochemical analysis. Tat-BLVRA protein was effective in inhibiting mitogen activated protein kinases (MAPKs), Akt and NF-κB activation, intracellular ROS production and DNA fragmentation. Also, Tat-BLVRA protein significantly inhibited the expression of cytokines, COX-2, and iNOS. In a 12-O-tetradecanoyl...

Research paper thumbnail of The development of herbicide-resistant maize: stable Agrobacterium-mediated transformation of maize using explants of type II embryogenic calli

Plant Biotechnology Reports, 2009

One of the limitations to conducting maize Agrobacterium-mediated transformation using explants o... more One of the limitations to conducting maize Agrobacterium-mediated transformation using explants of immature zygotic embryos routinely is the availability of the explants. To produce immature embryos routinely and continuously requires a well-equipped greenhouse and laborious artificial pollination. To overcome this limitation, an Agrobacterium-mediated transformation system using explants of type II embryogenic calli was developed. Once the type II embryogenic calli

Research paper thumbnail of Expression, purification and characterization of TAT-high mobility group box-1A peptide as a carrier of nucleic acids

Biotechnology Letters, 2008

High mobility group box 1 (HMGB1) is an abundant nuclear protein that binds to double-stranded DN... more High mobility group box 1 (HMGB1) is an abundant nuclear protein that binds to double-stranded DNA. HMGB1 is composed of high mobility (HMG) box A, box B, and C-terminal acidic regions. In this study, a recombinant TAT linked HMGB1 box A (rTAT-HMGB1A) peptide was expressed, purified, and characterized as a carrier of nucleic acids. The HMGB1A cDNA was amplified by

Research paper thumbnail of Genomic Changes in the Striatum of Unilateral 6-hydroxydopamine Lesioned Parkinson Rat Model

B a c k g r o u n d : Parkinson' s disease is the primary degenerative disease characterized... more B a c k g r o u n d : Parkinson' s disease is the primary degenerative disease characterized by rigidity, bradykinesia and resting tremor. Even though dopaminergic cell loss of the substantia nigra compacta is a main pathogenesis of the Parkinson' s disease, the striatal dysfuntion is major pathophysiology of pakinsonian symptoms. Methods : Since gene expression profile can explain the symptomatic varieties of Parkinson ' s disease, gene expression was investigated in the striatum of rat brain after lesioning of unilateral substantia nigra compacta with 6-hydroxydopamine using cDNA microarray technique for the first time. The expression patterns of 5,200 rat brain cDNAs were screened and clustered according to the function of gene. The expression patterns of enkephaline and substance-P mRNA were also studied for validation of animal preparation. Results : Various genes involved in apoptosis, cytokines. cytoskeletal molecules, neu - rotrophic factors, receptors, intrac...

Research paper thumbnail of Role of the Oxygen-Dependent Degradation Domain in a Hypoxia-Inducible Gene Expression System in Vascular Endothelial Growth Factor Gene Therapy

Spine, 2009

STUDY DESIGN.: An in vitro neural hypoxia model and rat spinal cord injury (SCI) model were used ... more STUDY DESIGN.: An in vitro neural hypoxia model and rat spinal cord injury (SCI) model were used to assess the regulation effect of a reporter or therapeutic gene expression by an oxygen-dependent degradation (ODD) domain in a hypoxia-inducible gene expression system with or without the erythropoietin (EPO) enhancer. OBJECTIVE.: To increase vascular endothelial growth factor (VEGF) gene expression in SCI lesions but avoid unwanted overexpression of VEGF in normal sites, we developed a hypoxia-inducible gene expression system consisting of the EPO enhancer upstream of the SV promoter and an ODD domain C-terminally fused to VEGF. SUMMARY OF BACKGROUND DATA.: ODD domain plays a major role in the degradation of hypoxia-inducible factor 1alpha and has been used in a hypoxia-specific gene expression system as a post-translational regulatory factor. METHODS.: The hypoxia-inducible luciferase or VEGF plasmid was constructed using the EPO enhancer combined with or without the ODD domain. The constructed plasmid was transfected into mouse Neuro 2a (N2a) neuroblastoma cells by Lipofectamine 2000, followed by a 24-hour incubation in hypoxia or normoxia. For in vivo analysis, the naked plasmid DNA was directly injected into the injured rat spinal cord. The gene expression was evaluated by luciferase activity assay, enzyme-linked immunosorbent assay, reverse transcriptase-polymerase chain reaction, and immunofluorescence staining. RESULTS.: The EPO enhancer/ODD domain-combined hypoxia-inducible gene expression system clearly increased the expression of the reporter luciferase gene and therapeutic VEGF gene specifically under hypoxic conditions and SCI, and quickly downregulated protein expression to a very low level after reoxygenation. CONCLUSION.: These results strongly suggest the potential applicability of this EPO enhancer/ODD domain-based hypoxia-inducible gene expression system in the development of a safer and more effective VEGF gene therapy for SCI.