Hyun Ju Lee

MEDIPOST Biomedical Research Institute, Sŏul, Seoul, South Korea

Are you Hyun Ju Lee?

Claim your profile

Publications (231)582.89 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Dry eye syndrome (DES) is one of the most common ocular diseases affecting nearly 10% of the U.S. population. Most of the currently-available treatments are palliative, and few therapeutic agents target biological pathway of DES. Although DES is a multifactorial disease, it is well-known that inflammation in the ocular surface plays an important role in the pathogenesis of DES. Mesenchymal stem/stromal cells (MSCs) have been shown to repair tissues by modulating excessive immune responses in various diseases. Therefore, we here investigated the therapeutic potential of MSCs in a murine model of an inflammation-mediated dry eye that was induced by an intraorbital injection of concanavalin A. We found that a periorbital administration of MSCs reduced the infiltration of CD4(+) T cells and the levels of inflammatory cytokines in the intraorbital gland and ocular surface. Also, MSCs significantly increased aqueous tear production and the number of conjunctival goblet cells. Subsequently, corneal epithelial integrity was well-preserved by MSCs. Together, the results demonstrate that MSCs protect the ocular surface by suppressing inflammation in DES, and suggest that MSCs may offer a therapy for a number of ocular surface diseases where inflammation plays a key role.Molecular Therapy (2014); doi:10.1038/mt.2014.159.
    Molecular therapy : the journal of the American Society of Gene Therapy. 08/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: To investigate the effect of an anti-inflammatory protein, TNF-α stimulated gene/protein (TSG)-6 and an anti-apoptotic protein, stanniocalcin (STC)-1 on corneal endothelium in rabbits with transcorneal cryoinjury. Methods: Transcorneal freezing (-80°C) was applied to rabbit corneas for 30 sec. Immediately post-injury, either TSG-6 (10 μg/100 μl), STC-1 (10 μg/100 μl), or the same volume of balanced salt solution (BSS) was injected into the anterior chamber. Each eye was examined for corneal opacity, corneal thickness, endothelial cell density, and endothelial hexagonality every 2 to 6 h for 48 h post-injury. The concentrations of myeloperoxidase (MPO) and IL-1β were measured in the aqueous humor every 6 h. At 48 h post-injury, each cornea was assayed for TNF-α, IL-1β, IL-6, and MPO, and histologically evaluated with alizarin red-trypan blue staining, hematoxylin-eosin staining, and immunostaining for neutrophils. Results: TSG-6 significantly decreased the development of corneal opacity and edema after cryoinjury compared to STC-1 or BSS. The corneal endothelial cell density and hexagonality were markedly preserved by TSG-6. The mRNA levels of TNF-α, IL-1β, and IL-6 in the cornea and the protein levels of MPO and IL-1β in the aqueous humor and cornea were significantly lower in TSG-6-treated eyes than BSS-treated controls. Similarly, the expression of fibroblast growth factor-2 was reduced by TSG-6 treatment. Histologic evaluation demonstrated that neutrophil infiltration of the cornea was decreased in TSG-6-treated eyes. Conclusions: TSG-6 protected corneal endothelial cells from transcorneal cryoinjury through suppression of inflammation.
    Investigative ophthalmology & visual science. 07/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Alteration of retinal angiogenesis during development leads to retinopathy of prematurity (ROP) in preterm infants, which is a leading cause of visual impairment in children. A number of clinical studies have reported higher rates of ROP in infants who had perinatal infections or inflammation, suggesting that exposure of the developing retina to inflammation may disturb retinal vessel development. Thus, we investigated the effects of systemic inflammation on retinal vessel development and retinal inflammation in neonatal rats.
    Journal of Neuroinflammation 05/2014; 11(1):87. · 4.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To estimate the incidence of, and identify risk factors for, spontaneous expulsion of the levonorgestrel-releasing intrauterine system (LNG-IUS). Pre-insertion characteristics for 481 women who received the LNG-IUS at a single institution in the Republic of Korea between 2003 and 2011 were analyzed retrospectively. The median duration of follow-up was 13.4months. Kaplan-Meier plots were constructed to estimate the time to occurrence of spontaneous expulsion in multiple subgroups. The overall crude incidence of spontaneous LNG-IUS expulsion was 9.6%. The cumulative incidence was 7.9%, 9.1%, and 9.6% at 1, 2, and 3years, respectively. It was significantly higher in women with adenomyosis (9.1%, 10.6%, and 11.1%) or uterine leiomyoma (14.5%, 15.8%, and 15.8%) than in those with a normal uterus (3.6%, 4.1%, and 4.6%) (P=0.008). Women with heavy menstrual bleeding (11.0%, 12.7%, and 13.4%), dysmenorrhea (8.1%, 9.0%, and 10.0%), or pre-insertion receipt of gonadotropin-releasing hormone agonists (13.3%, 16.0%, and 17.3%) also had higher cumulative incidences than those without these conditions (P<0.05). Most (84.5%) women with a spontaneous expulsion chose to discontinue the device. Clinicians need to be aware of the risk factors for spontaneous LNG-IUS expulsion because this can lead to a discontinuation of its use.
    International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 04/2014; · 1.41 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Various phenol derivatives (III) synthesized by a one-pot reaction of Morita—Baylis—Hillman acetates and sodium diethyl oxalacetate via a [4 + 2]-cyclization.
    ChemInform 03/2014; 45(9).
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pulmonary artery tumor embolism (PATE) is a rare disease without an established diagnostic method. In an autopsy series, however, the incidence of PATE was relatively high, between 3% and 26% in patients with a solid tumor. Here we report a case of a patient with a massive PATE from hepatocellular carcinoma diagnosed safely and promptly by endobronchial ultrasound-guided transbronchial needle aspiration.
    Thoracic Cancer. 03/2014; 5(2).
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Purpose: To investigate the effects of intravenous (IV) infusion of human mesenchymal stem/stromal cells (hMSCs) on activation and migration of CCR7(+) antigen presenting cells (APCs) in allogeneic corneal transplantation. Materials and Methods: We first analyzed the cellular and molecular profiles of draining lymph nodes (DLNs) in early and late phases after syngeneic or allogeneic corneal transplantation in mice, and then investigated the effects of hMSCs on APCs expressing CCR7, a key molecule implicated in APC migration to DLNs. Results: After early transplantation, the numbers of MHC class II(+)CD11b(+)CD11c(-), MHC class II(+)CD11b(-)CD11c(+), and MHC II(+)CD11b(+)CD11c(+) cells as well as the levels of APC-derived cytokines (IL-12a and IL-12b) driving the Th1 response were increased in both syngeneic and allogeneic transplants indicating activation of APCs. In late phase, the numbers of CD3(+)CD4(+)CD8(-) and CD3(+)CD4(-)CD8(+) cells and the levels of T cell-derived cytokines were increased in allogeneic transplants, but not in syngeneic transplants indicating immune rejection. The peri-transplant infusion of IV hMSCs significantly reduced the numbers of CCR7(+)CD11b(+) or CCR7(+)CD11c(+) cells in DLNs and the cornea in the early phase. Also, the expression of CCR7 and its ligands, CCL19, CCL21, and CXC3R as well as IL-12 were markedly decreased by hMSCs in the cornea and DLNs. Conclusions: IV hMSCs reduced the activation and migration of CCR7(+) APCs in the cornea and DLNs in allogeneic corneal transplantation.
    Current eye research 02/2014; · 1.51 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 3-Alkylideneoxindoles have been prepared in excellent yields from oxindole and carbonyl compounds via an in situ generated titanium enolate of oxindole. (Z)-3-Alkylideneoxindoles could be synthesized selectively as major products from unsymmetrical ketones.
    Tetrahedron Letters 01/2014; 55(6):1183–1187. · 2.40 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective : To estimate the incidence of, and identify risk factors for, spontaneous expulsion of the levonorgestrel-releasing intrauterine system (LNG-IUS). Methods : Pre-insertion characteristics for 481 women who received the LNG-IUS at a single institution in the Republic of Korea between 2003 and 2011 were analyzed retrospectively. The median duration of follow-up was 13.4 months. Kaplan–Meier plots were constructed to estimate the time to occurrence of spontaneous expulsion in multiple subgroups. Results : The overall crude incidence of spontaneous LNG-IUS expulsion was 9.6%. The cumulative incidence was 7.9%, 9.1%, and 9.6% at 1, 2, and 3 years, respectively. It was significantly higher in women with adenomyosis (9.1%, 10.6%, and 11.1%) or uterine leiomyoma (14.5%, 15.8%, and 15.8%) than in those with a normal uterus (3.6%, 4.1%, and 4.6%) (P = 0.008). Women with heavy menstrual bleeding (11.0%, 12.7%, and 13.4%), dysmenorrhea (8.1%, 9.0%, and 10.0%), or pre-insertion receipt of gonadotropin-releasing hormone agonists (13.3%, 16.0%, and 17.3%) also had higher cumulative incidences than those without these conditions (P < 0.05). Most (84.5%) women with a spontaneous expulsion chose to discontinue the device. Conclusion : Clinicians need to be aware of the risk factors for spontaneous LNG-IUS expulsion because this can lead to a discontinuation of its use.
    International Journal of Gynecology & Obstetrics. 01/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: We tested whether rosiglitazone (RGZ), a peroxisome proliferator-activated receptor-γ agonist, can restore alveolar development and vascular growth in a rat model of bronchopulmonary dysplasia (BPD). Materials and Methods: A rat model of BPD was induced through intra-amniotic delivery of lipopolysaccharide (LPS) and postnatal hyperoxia (80% for 7 days). RGZ (3 mg/kg/d, i.p.) or vehicle was given daily to rat pups for 14 days. This model included four experimental groups: No BPD+vehicle (V), No BPD+RGZ, BPD+V, and BPD+RGZ. On D14, alveolarization, lung vascular density, and right ventricular hypertrophy (RVH) were evaluated. Results: Morphometric analysis revealed that the BPD+RGZ group had significantly smaller and more complex airspaces and larger alveolar surface area than the BPD+V group. The BPD+RGZ group had significantly greater pulmonary vascular density than the BPD+V group. Western blot analysis revealed that significantly decreased levels of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 by the combined exposure to intra-amniotic LPS and postnatal hyperoxia were restored by the RGZ treatment. RVH was significantly lesser in the BPD+RGZ group than in the BPD+V group. Conclusion: These results suggest that RGZ can restore alveolar and pulmonary vascular development and lessen pulmonary hypertension in a rat model of BPD.
    Yonsei medical journal 01/2014; 55(1):99-106. · 0.77 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Autoimmune uveitis is one of the leading causes of blindness. We here investigated whether intraperitoneal administration of human mesenchymal stem/stromal cells (hMSCs) might prevent development of experimental autoimmune uveitis (EAU) in mice. Time course study showed that the number of IFN-γ- or IL-17-expressing CD4(+) T cells was increased in draining lymph nodes (DLNs) on the postimmunization day 7 and decreased thereafter. The retinal structure was severely disrupted on day 21. An intraperitoneal injection of hMSCs at the time of immunization protected the retina from damage and suppressed the levels of proinflammatory cytokines in the eye. Analysis of DLNs on day 7 showed that hMSCs decreased the number of Th1 and Th17 cells. The hMSCs did not reduce the levels of IL-1β, IL-6, IL-12, and IL-23 which are the cytokines that drive Th1/Th17 differentiation. Also, hMSCs did not induce CD4(+)CD25(+)Foxp3(+) cells. However, hMSCs increased the level of an immunoregulatory cytokine IL-10 and the population of IL-10-expressing B220(+)CD19(+) cells. Together, data demonstrate that hMSCs attenuate EAU by suppressing Th1/Th17 cells and induce IL-10-expressing B220(+)CD19(+) cells. Our results support suggestions that hMSCs may offer a therapy for autoimmune diseases mediated by Th1/Th17 responses.
    Mediators of Inflammation 01/2014; 2014:624640. · 3.88 Impact Factor
  • Tetrahedron Letters 01/2014; · 2.40 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study is to investigate cross-reactivity between hypertonic saline-treated decellularized porcine corneal lamellae for corneal xenobridging and subsequent corneal allotransplants. Five Chinese rhesus macaques, which had undergone anterior partial thickness corneal transplantation using hypertonic saline-treated decellularized porcine corneal lamellae in preceding experiments, were used as recipients for subsequent full-thickness corneal allografts. To determine whether sensitization of recipients to xenoantigens leads to cross-reactivity against alloantigens, we compared; (i) allogeneic one-way mixed lymphocyte reaction (MLR) of peripheral blood mononuclear cells (PBMCs) from xeno-sensitized recipients with that of PBMCs from naïve rhesus macaques, and (ii) amounts of IgG antibodies that bound to the PBMCs of a rhesus panel (five monkeys) before and after xeno-sensitization. Graft survival and immunologic profiles including memory T-cell subsets and donor rhesus-specific antibodies were also evaluated. No hyperacute or acute rejection was observed within a month of subsequent allotransplantation in any recipient. Alloreactivity by MLR was not different between xeno-sensitized rhesus recipients and naïve rhesus monkeys. Panel-reactive IgG antibodies were unchanged after xeno-sensitization, and no change in donor rhesus-specific antibodies was observed in any recipient. No significant changes in memory T-cell subsets were observed during the early post-operative period in any recipient. Decellularized porcine corneal lamellae may not increase cross-reactivity to alloantigens, and thus, porcine corneal lamellae may be used as a bridge to subsequent corneal allografting.
    Xenotransplantation 12/2013; · 2.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mesenchymal stem/stromal cells (MSCs) control excessive inflammatory responses by modulating a variety of immune cells including monocytes/macrophages. However, the mechanisms by which MSCs regulate monocytes/macrophages are unclear. Inflammasomes in macrophages are activated upon cellular 'danger' signals, and initiate inflammatory responses through the maturation and secretion of pro-inflammatory cytokines such as interleukin 1β. Here we demonstrate that human MSCs (hMSCs) negatively regulate NLRP3 inflammasome activation in human or mouse macrophages stimulated with LPS and ATP. Caspase-1 activation and subsequent IL-1β release were decreased in macrophages by direct or transwell co-culture with hMSCs. Addition of hMSCs to macrophages either at a LPS priming or at a subsequent ATP step similarly inhibited the inflammasome activation. The hMSCs had no effect on NLRP3 and IL-1β expression at mRNA levels during LPS priming. However, MSCs markedly suppressed the generation of mitochondrial reactive oxygen species (ROS) in macrophages. Further analysis showed that NLRP3-activated macrophages stimulated hMSCs to increase the expression and secretion of stanniocalcin (STC)-1, an anti-apoptotic protein. Addition of recombinant protein STC-1 reproduced the effects of hMSCs in inhibiting NLRP3 inflammasome activation and ROS production in macrophages. Conversely, the effects of hMSCs on macrophages were largely abrogated by an siRNA knockdown of STC-1. Together, our results reveal that hMSCs inhibit NLRP3 inflammasome activation in macrophages primarily by secreting STC-1 in response to activated macrophages and thus by decreasing mitochondrial ROS. Stem Cells 2013.
    Stem Cells 12/2013; · 7.70 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: To investigate the phenotype of macrophages infiltrating rejected corneal allografts. Methods: We performed allogeneic or syngeneic corneal transplantation in mice, and sacrificed animals at day 28 during allograft rejection when 60% of corneal allografts were rejected. We divided allografts into two groups: grafts with rejection as rejectors and grafts without rejection as non-rejectors, and analyzed for macrophage infiltration and their phenotype using immunohistochemistry. In addition, we investigated the time course of pro-inflammatory cytokines and chemokines by analyzing corneal grafts at days 7, 28, and 42 using real-time RT-PCR. Also, we assayed human corneal allografts with chronic graft failure. Results: We found that a large number of CD11b+, F4/80+, or iNOS+ cells infiltrated corneal allografts during rejection in mice, while the cells were rarely found in syngeneic or allogeneic grafts that were not rejected. There were rare CD11c+ cells both in rejectors and non-rejectors. Many MRC (mannose receptor)+ cells were present in non-rejectors, but not in rejectors. The levels of Th1 cytokines, IFN-γ and IL-2 were highly increased in rejectors at day 28 indicating immune rejection. Also, the levels of IL-12a, IL-1β, TNF-α, CCL3, and iNOS that are produced by activated macrophages were markedly increased in rejectors at day 28 compared to syngeneic grafts or non-rejectors. Similarly, human corneal allografts with chronic graft failure had higher levels of IL-12a, IL-1β, CCL3, and iNOS than controls. Conclusions: Increased numbers of macrophages in rejected corneal allografts implicate that these cells might contribute to the immunopathogenesis of corneal graft rejection.
    Investigative ophthalmology & visual science 10/2013; · 3.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Aim: To determine the clinical characteristics and safety of kangaroo mother care (KMC) according to the gestational age (GA) or postmenstrual age (PMA). Methods: We conducted a prospective clinical study in 31 infants between 25 and 32 weeks' GA. The subjects were categorized into two groups (25-28 weeks' and 29-32 weeks' GA groups) to compare the clinical characteristics associated with KMC. Heart rate, respiratory rate, oxygen saturation, blood pressure and body temperature (BT) were longitudinally assessed for 60 min with respect to the PMA group (29-32 weeks' and 33-36 weeks' PMA groups). Results: The authors analyzed 70 sessions with 31 infants (25-32 weeks' GA, birth weight 760-1740 g, 29-36 weeks' PMA). All infants had statistically significant higher temperatures during KMC than before KMC within clinically acceptable limits (P<0.001). We found a significantly lower variation of BT in the 25-28 weeks' GA group compared with the 29-32 weeks' GA group at 33-36 weeks' PMA, suggesting accelerated skin maturation in more premature infants (P<0.001). Conclusion: Our intermittent KMC was a safe and feasible method for preterm infants. Notably, at the same PMA, preterm infants in the lower at-birth GA group showed an advanced maturation of thermoregulation compared with those in the higher GA group.
    Journal of Perinatal Medicine 10/2013; · 1.95 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The bromides (I) are synthesized by literature-known procedures from Morita—Baylis—Hillman-alcohols by treatment with HBr or PBr3.
    ChemInform 10/2013; 44(40).
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Aim: We investigated the combined effects of intra-amniotic lipopolysaccharide (LPS) and maternal betamethasone (BMZ) on alveolarization using a newborn rat model. Methods: LPS (1.0 μg/sac) or vehicle was injected into the amniotic sacs of pregnant rats and BMZ (170 μg/kg) or vehicle was injected intramuscularly into the pregnant rats twice at 8-h intervals on gestation day 20. The rat pups were delivered spontaneously after 2-2.5 days and raised until the measurements were taken. Bronchoalveolar lavage was performed on days 2 and 5, and morphometric analyses of the lungs were performed on days 5 and 14. Results: Intra-amniotic LPS significantly increased the neutrophils in the bronchoalveolar lavage fluid (BALF) on day 2, but double exposure to LPS and BMZ significantly alleviated the neutrophil increase in the BALF. On day 5, while the neutrophils in the BALF decreased in the animals exposed to LPS alone, the neutrophil numbers in the BALF were steady in the animals exposed to both LPS and BMZ. Morphometric analyses on days 5 and 14 revealed a significant disruption of alveolarization only in the animals exposed to both LPS and BMZ. Conclusions: Our results suggested that double exposure to maternal BMZ and intra-amniotic LPS induces sustained increase of neutrophils in the lungs and disrupts alveolarization.
    Journal of Perinatal Medicine 08/2013; · 1.95 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Sustainability and environmental initiatives continue to receive an increasing amount of attention, both within the corporate, consumer, and individual domains of behavior. As individuals act on their environmental interests, or lack thereof, it is incumbent upon researchers to continue delineating factors that may influence the commitment and behaviors that take place. To this end, this research effort capitalizes on the long history of cultural orientation, examining the influence of individualism and collectivism as antecedents to perceived consumer effectiveness (PCE), environmental attitude, and environmental commitment. Utilizing cross-cultural data drawn from South Korea and the United States, the empirical results provide support for horizontal collectivism and vertical individualism as important influencers of perceived consumer effectiveness. In turn, PCE positively affects environmental attitude which results in pro-environmental commitment manifested in specific behavioral intentions.
    Journal of Business Research. 08/2013; 66(8):1052–1059.
  • [Show abstract] [Hide abstract]
    ABSTRACT: N-Bromoallyl-N-tosyl compounds of type (I) - readily derived from Morita—Baylis—Hillman adducts - undergo Pd-catalyzed domino 5-exo/3-exo carbapalladation, ring-expansion rearrangement, and aromatization to give pyridines (III) in fair yields.
    Advanced Synthesis & Catalysis 07/2013; 355(10). · 5.54 Impact Factor

Publication Stats

2k Citations
582.89 Total Impact Points

Institutions

  • 2014
    • MEDIPOST Biomedical Research Institute
      Sŏul, Seoul, South Korea
  • 2002–2014
    • Chonnam National University
      • • Department of Chemistry
      • • Hormone Research Center
      Gwangju, Gwangju, South Korea
    • Seoul National University Hospital
      • • Department of Obstetrics and Gynecology
      • • Department of Ophthalmology
      • • Department of Internal Medicine
      • • Department of Radiology
      Sŏul, Seoul, South Korea
    • University of Oslo
      • Institute of Theoretical Astrophysics
      Kristiania (historical), Oslo County, Norway
  • 2013
    • Sungkyunkwan University
      Sŏul, Seoul, South Korea
  • 2011–2013
    • Ewha Womans University
      • Department of Pediatrics
      Sŏul, Seoul, South Korea
    • Daegu Gyeongbuk Institute of Science and Technology
      Daikyū, Daegu, South Korea
  • 2008–2013
    • Seoul National University Bundang Hospital
      • • Department of Pathology
      • • Department of Radiology
      Seoul, Seoul, South Korea
  • 2006–2013
    • Seoul National University
      • • Cancer Research Institute
      • • Inter-University Semiconductor Research Center
      • • Department of Materials Science and Engineering
      Sŏul, Seoul, South Korea
  • 2012
    • Soonchunhyang University
      Onyang, South Chungcheong, South Korea
  • 2011–2012
    • Chonnam National University Hospital
      Sŏul, Seoul, South Korea
  • 2010–2012
    • Chung-Ang University
      • School of Chemical Engineering and Materials Science
      Seoul, Seoul, South Korea
    • Kyungpook National University
      Daikyū, Daegu, South Korea
  • 2008–2011
    • Pai Chai University
      • Department of Biology and Medicinal Sciences
      Sŏul, Seoul, South Korea
  • 2008–2010
    • Pusan National University
      • Division of Materials Science and Engineering
      Pusan, Busan, South Korea
  • 2007
    • Yonsei University Hospital
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
    • University of Seoul
      Sŏul, Seoul, South Korea
  • 2003–2007
    • Asan Medical Center
      • Department of Gastroenterology
      Seoul, Seoul, South Korea
    • Chungbuk National University
      • Department of Computer Science
      Tyundyu, North Chungcheong, South Korea
  • 1993
    • Sogang University
      • Department of Chemistry
      Sŏul, Seoul, South Korea