Hyung-Seok Kim

Chonnam National University, Gwangju, Gwangju, South Korea

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Publications (61)182.78 Total impact

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    ABSTRACT: The antioxidant properties of alpha-lipoic acid (aLA) correlate with its ability to promote neuroproliferation. However, there have been no comprehensive studies examining the neurorestorative effects of aLA administration after the onset of ischemia. The middle cerebral artery (MCA) of adult rats was occluded for 2 hours and then reperfused. aLA (20 mg/kg) was administered in 71 animals (aLA group) through the left external jugular vein immediately after reperfusion. An equivalent volume of vehicle was administered to 71 animals (control group). Functional outcome, levels of endogenous neural precursors with neurogenesis, glial cell activation, and brain metabolism were evaluated. Immediate aLA administration after reperfusion resulted in significantly reduced mortality, infarct size, and neurological deficit score (NDS) in the test group compared to the control group. Long-term functional outcomes, measured by the rotarod test, were markedly improved by aLA treatment. There was a significant increase in the number of cells expressing nestin and GFAP in the boundary zone and infarct core regions after aLA treatment. Furthermore, significantly more BrdU/GFAP, BrdU/DCX, and BrdU/NeuN double-labeled cells were observed along the boundary zone of the aLA group on days 7, 14, and 28 days, respectively. And brain metabolism using 18F-FDG microPET imaging was markedly improved in aLA group. The effects of aLA was blocked by insulin receptor inhibitor, HNMPA (AM)3. These results indicate that immediate treatment with aLA after ischemic injury may have significant neurorestorative effects mediated at least partially via insulin receptor activation. Thus, aLA may be useful for the treatment of acute ischemic stroke.
    Molecular Brain 12/2015; 8(1). DOI:10.1186/s13041-015-0101-6 · 4.35 Impact Factor
  • SeonYoung Yu, Joo-Young Na, Young-Jik Lee, Kyung-Tae Kim, Jong-Tae Park, Hyung-Seok Kim
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    ABSTRACT: Forensic research using microRNA has been used so far only for the identification of body fluids, but its use in understanding biological processes in post-mortem pathology has not been studied before. Therefore, we performed experiments in mice to compare between freshwater and saltwater drowning models, and miRNA expression was analyzed in the brain through a forward bioinformatics screening approach. In this study, we identified eight specific microRNAs whose expression increased in freshwater and decreased in saltwater. Among them, miR-706 - targeting HCN1 - was identified as a potent biomarker for the drowning pattern identification. A higher expression of miR-706 was detected in the freshwater drowning compared to the control and saltwater drowning group (p<0.05, and p<0.01, respectively). HCN1 mRNA expression, a suggested candidate target for miR-706, was lower in the freshwater (p<0.01) than in the saltwater drowning group, and showed statistical difference between freshwater and saltwater drowning (p<0.01). miR-706 was specifically expressed in the hippocampal neurons as detected by in situ hybridization. Our data suggest that a specific microRNA may provide clues to understanding some crime scene investigations and pathobiological processes in the dead body. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Forensic science international 06/2015; DOI:10.1016/j.forsciint.2015.06.011 · 2.12 Impact Factor
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    ABSTRACT: Inflammation and fibrosis are implicated in the pathogenesis of hypertensive kidney damage. We previously demonstrated that a nonspecific histone deacetylase (HDAC) inhibitor attenuates cardiac fibrosis in deoxycorticosterone acetate-salt hypertensive rats, which induces HDAC6 protein and enzymatic activity. However, the HDAC inhibitor's effect and mechanism have not yet been demonstrated. We sought to determine whether an HDAC6-selective inhibitor could treat hypertension and kidney damage in angiotensin II-infused mice. Hypertension was induced by infusion of ANG in mice. Tubastatin A, an HDAC6 selective inhibitor, did not regulate blood pressure. Hypertensive stimuli enhanced the expression of HDAC6 in vivo and in vitro. We showed that the inhibition of HDAC6 prevents fibrosis and inflammation as determined by quantitative real-time PCR, western blot, and immunohistochemistry. Small interfering RNA (siRNA) against HDAC6 or Smad3 attenuated hypertensive stimuli-induced fibrosis and inflammation, whereas Smad2 siRNA failed to inhibit fibrosis. Interestingly, the combination of the HDAC6 inhibitor and Smad3 knockdown synergistically blocked transforming growth factor β (TGF-β) or ANG-induced fibrosis. We also demonstrated for the first time, to our knowledge, that acetylation of collagen type I can be regulated by HDAC6/p300 acetyltransferase. The chromatin immunoprecipitation assay revealed that the HDAC6 inhibitor suppressed TGF-β-induced acetylated histone H4 or phospho-Smad2/3 to Smad3 binding elements in the fibrosis-associated gene promoters including collagen type I. These results suggest that HDAC6 may be a valuable therapeutic target for the treatment of hypertension-induced kidney fibrosis and inflammation. Copyright © 2015. Published by Elsevier Inc.
    Vascular Pharmacology 04/2015; DOI:10.1016/j.vph.2015.04.006 · 4.62 Impact Factor
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    ABSTRACT: This study aimed to assess the expression of vasohibin-2 (VASH2) in pancreatic ductal adenocarcinoma (PDAC) as a marker of tumor aggressiveness and its impact on tumor angiogenesis, proliferation, and clinical outcome. We examined the expression of the VASH2 gene in human pancreatic cell lines PANC-1 and MiaPaCa-2 by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunocytochemistry. Fifty samples from patients with PDAC were immunostained with VASH2, CD34, and Ki-67 antibodies. Further, the immunoreactivity of VASH2 correlated with the pathological features, including microvessel density (MVD), tumor cell proliferation (Ki-67 labeling index), and survival. Forty-seven of the 50 samples from PDAC patients showed immunoreactivity for VASH2 along the tumor cell cytoplasm. Among the VASH2-positive samples, 22 were categorized as high VASH2 expression group, and this group had statistical significance with pN stage (p = 0.006), UICC stage (p = 0.033), tumor proliferation (p < 0.001), and MVD (p = 0.017). Moreover, patients with high VASH2 expression showed worse prognosis compared to those showing low VASH2 expression (overall logrank p = 0.003). Thus, our results suggested that overexpression of VASH2 accelerated the pace of tumor development toward a more serious malignant phenotype and was associated with a poor clinical outcome. VASH2 may be an important novel target for the management of PDAC after surgery.
    Hepato-gastroenterology 03/2015; 62(138):251-6. DOI:10.5754/hge141015 · 0.91 Impact Factor
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    ABSTRACT: Cerebral venous thrombosis is an uncommon cause of cerebral infarction. A 31-year-old man complained of headache, weakness, and numbness of the left leg a day before being admitted to the hospital. After admission, brain computed tomography and brain magnetic resonance imaging revealed superior sagittal sinus thrombosis with cerebral infarction in the right hemisphere. He had no significant medical history. On the fourth hospital day, he suddenly collapsed and died. Medicolegal autopsy was performed 3 days later; medical malpractice was suspected. External examination revealed a few conjunctival petechiae. Internal examination revealed thrombi in the superior sagittal sinus and superficial cortical veins. Thrombi were noted in the pulmonary trunk and both pulmonary arteries. Upon dissection of the left leg, we found thrombi in the posterior tibial vein. A microscopic examination revealed vasculitis of the same cortical veins, and we therefore assumed that vasculitis of the cortical veins gave rise to thrombosis. In typical autopsy practice, an examination of the dura mater is often overlooked, but careful examination of this region should be performed in cases of cerebral infarction in young adults, such as this one.
    01/2015; 39(1). DOI:10.7580/kjlm.2015.39.1.22
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    ABSTRACT: Astrocytes become reactive after central nervous system injury, re-expressing glial fibrillary acidic protein (GFAP), vascular endothelial growth factor (VEGF), and nestin. Hypoxia-inducible transcription factor alpha (HIF-1α) is an important transcription factor for several genes including the VEGF and nestin genes, the expression of which generate reactive astrocytes and cause gliosis after cerebral ischemia. To evaluate the role of HIF-1α in reactive astrocyte formation, we applied the potent HIF-1α inhibitor YC-1 to a focal cerebral ischemia model and analyzed the expression of HIF-1α, VEGF, nestin, and GFAP. Quantitative real-time reverse transcription polymerase chain reaction and western blot analyses demonstrated that the expression of HIF-1α and its downstream genes (VEGF and nestin) were markedly attenuated in the YC-1-treated group versus the control group (HIF-1α, VEGF: p < 0.01; nestin: p < 0.05). GFAP expression was also effectively inhibited in the YC-1-treated group (p < 0.05). Immunohistochemical evaluations showed that GFAP-positive (GFAP+) cells in the YC-1-treated group were sparse in the peri-infarct area, while an immunofluorescence assay revealed that the number of VEGF+/GFAP+ and nestin+/GFAP+ reactive astrocytes were decreased in the YC-1-treated group (p < 0.05). These results demonstrate that HIF-1α suppression decreases the formation of reactive astrocytes and gliosis that occur following focal ischemia.
    American Journal of Translational Research 01/2015; 7(4):751-60. · 3.23 Impact Factor
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    ABSTRACT: Vibrio vulnificus infection can lead to the rapid expansion of cellulitis or sepsis and can be lethal. Vibrio vulnificus is transmitted through seawater or ingestion of raw or undercooked shellfish. We experienced an uncommon case of death due to Vibrio sepsis, which was confirmed by autopsy. A 56-year-old man who was a sailor was found dead in a fishing boat. Autopsy was performed 3 days later. External examination revealed a few blisters and erythematous lesions on both legs. Internal examination revealed a fatty liver and edema of the legs. The skin lesions on the legs showed blisters that extended from the epidermis to the dermis, accompanied by massive acute inflammation in the dermis and subcutaneous tissue with multinuclear giant cells, as noted on the histologic examination. Vibrio vulnificus was isolated from postmortem blood and subcutaneous tissue of the leg. To the best of our knowledge, this is the first autopsy case in Korea in which Vibrio vulnificus was isolated from postmortem blood. Herein, we present a case of sepsis due to Vibrio vulnificus which was confirmed by autopsy, pathological findings, and postmortem microbiological culture.
    01/2015; 39(2). DOI:10.7580/kjlm.2015.39.2.45
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    ABSTRACT: Pineal cysts are usually asymptomatic; however, they may rarely cause symptoms such as chronic headache, paroxysmal headache with gaze paresis, postural syncope, loss of consciousness, and sudden death. A 30-year-old woman with no specific medical history except chronic headache was found collapsed in a public toilet per se. Postmortem examination revealed no external injuries or internal diseases except a cystic lesion of the pineal gland. Histologic examination showed an internal cyst surrounded by glial tissues and pineal parenchyma that was diagnosed as a glial cyst of the pineal gland. Although the pineal cyst cannot be confirmed as the cause of death, it was considered, as no other cause was evident. Herein, we report a pineal cyst considered as an assumed cause of death.
    American Journal of Forensic Medicine & Pathology 07/2014; 35(3). DOI:10.1097/PAF.0000000000000107 · 0.62 Impact Factor
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    ABSTRACT: Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9 play an important role in secondary inflammatory reaction and blood-central nervous system (CNS) barrier disruption after spinal cord injury (SCI). Theoretically, it is expected that early blockade of activation of MMPs can provide neuro-protective effects from secondary tissue damage and improve functional neurological outcomes. The aim of this study was to investigate the expression and the activity of MMP-2 and MMP-9, and to determine the regulatory effect of melatonin on MMP expression and activity after photochemically induced SCI in rats.
    Acta Neurochirurgica 05/2014; 156(11). DOI:10.1007/s00701-014-2119-4 · 1.79 Impact Factor
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    ABSTRACT: Polymer-free drug-eluting stents (DES) may overcome the shortcomings of polymer-based DES. The aim of this study was to examine the effect of the polymer-free TiO2 film-coated stent with abciximab or alpha lipoic acid in a porcine coronary overstretch restenosis model.
    Journal of Cardiology 05/2014; DOI:10.1016/j.jjcc.2014.02.015 · 2.57 Impact Factor
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    ABSTRACT: BackgroundTo compare the different resorption patterns between resorbable membrane barrier and periosteum after iliac block bone grafting radiographically and histologically.MethodsEighteen mature male rabbits weighing from 2.0 to 2.5 kg were used. The recipient site was the rabbit skull, and autogenous iliac bone was used as the grafting material. The harvested iliac block bones were divided in the following groups: autogenous iliac block bone with preservation of the periosteum (the periosteum group), autogenous iliac block bone covered with a resorbable collagen membrane (Biomesh®, Samyang Co, Korea) after removing the periosteum (the collagen membrane group), and autogenous iliac block bones with removal of the periosteum (the control group). In each experimental group, periosteum or resorbable collagen membrane of the donor site was fixed directed to the periosteum of the recipient site. The specimens were examined macroscopically, radiographically, histologically, and histomorphometrically at every 2, 4, and 8 weeks.ResultsAll groups presented excellent bone graft healing state without inflammation, dehiscence, or displacement. The radiolucency increased from mild to moderate in all groups over the experiment. The mean thickness of the upper end of the cortical iliac bone graft was statistically significantly different between the control group and the periosteum group, between the four-week and eight-week control group, and between the four- week and eight-week periosteum group (p & 0.05).ConclusionThis study suggests that both the periosteum and the resorbable collagen membrane may help to prevent soft tissue infiltration into the bone graft and to reduce bone graft resorption compared to block graft alone.
    Head & Face Medicine 05/2014; 10(1):15. DOI:10.1186/1746-160X-10-15 · 0.87 Impact Factor
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    ABSTRACT: Endogenous neural stem cells become "activated" after neuronal injury, but the activation sequence and fate of endogenous neural stem cells in focal cerebral ischemia model are little known. We evaluated the relationships between neural stem cells and hypoxia-inducible factor-1α and vascular endothelial growth factor expression in a photothromobotic rat stroke model using immunohistochemistry and western blot analysis. We also evaluated the chronological changes of neural stem cells by 5-bromo-2'-deoxyuridine (BrdU) incorporation. Hypoxia-inducible factor-1α expression was initially increased from 1 hour after ischemic injury, followed by vascular endothelial growth factor expression. Hypoxia-inducible factor-1α immunoreactivity was detected in the ipsilateral cortical neurons of the infarct core and peri-infarct area. Vascular endothelial growth factor immunoreactivity was detected in bilateral cortex, but ipsilateral cortex staining intensity and numbers were greater than the contralateral cortex. Vascular endothelial growth factor immunoreactive cells were easily found along the peri-infarct area 12 hours after focal cerebral ischemia. The expression of nestin increased throughout the microvasculature in the ischemic core and the peri-infarct area in all experimental rats after 24 hours of ischemic injury. Nestin immunoreactivity increased in the subventricular zone during 12 hours to 3 days, and prominently increased in the ipsilateral cortex between 3-7 days. Nestin-labeled cells showed dual differentiation with microvessels near the infarct core and reactive astrocytes in the peri-infarct area. BrdU-labeled cells were increased gradually from day 1 in the ipsilateral subventricular zone and cortex, and numerous BrdU-labeled cells were observed in the peri-infarct area and non-lesioned cortex at 3 days. BrdU-labeled cells rather than neurons, were mainly co-labeled with nestin and GFAP. Early expressions of hypoxia-inducible factor-1α and vascular endothelial growth factor after ischemia made up the microenvironment to increase the neuronal plasticity of activated endogenous neural stem cells. Moreover, neural precursor cells after large-scale cortical injury could be recruited from the cortex nearby infarct core and subventricular zone.
    Neural Regeneration Research 05/2014; 9(9):912-8. DOI:10.4103/1673-5374.133136 · 0.23 Impact Factor
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    ABSTRACT: In response to microbial infection, expression of the defensin-like peptide hepcidin (encoded by Hamp) is induced in hepatocytes to decrease iron release from macrophages. To elucidate the mechanism by which Salmonella enterica var. Typhimurium (S. typhimurium), an intramacrophage bacterium, alters host iron metabolism for its own survival, we examined the role of nuclear receptor family members belonging to the NR3B subfamily in mouse hepatocytes. Here, we report that estrogen-related receptor γ (ERRγ, encoded by Esrrg) modulates the intramacrophage proliferation of S. typhimurium by altering host iron homeostasis, and we demonstrate an antimicrobial effect of an ERRγ inverse agonist. Hepatic ERRγ expression was induced by S. typhimurium-stimulated interleukin-6 signaling, resulting in an induction of hepcidin and eventual hypoferremia in mice. Conversely, ablation of ERRγ mRNA expression in liver attenuated the S. typhimurium-mediated induction of hepcidin and normalized the hypoferremia caused by S. typhimurium infection. An inverse agonist of ERRγ ameliorated S. typhimurium-mediated hypoferremia through reduction of ERRγ-mediated hepcidin mRNA expression and exerted a potent antimicrobial effect on the S. typhimurium infection, thereby improving host survival. Taken together, these findings suggest an alternative approach to control multidrug-resistant intracellular bacteria by modulating host iron homeostasis.
    Nature medicine 03/2014; DOI:10.1038/nm.3483 · 28.05 Impact Factor
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    ABSTRACT: A 69-year-old man was admitted to the hospital because of flu-like symptoms and fatigue for 2 weeks. Computed tomography revealed ground glass opacity and consolidation in both the lungs as well as pleural effusion. The patient was diagnosed with pneumonia and was hospitalized. At the time of hospitalization, he complained of shortness of breath and coughed-up blood-tinged sputum. Two days after admission, he died suddenly. An autopsy was performed; cardiomegaly was noted, and further examination revealed that the aortic valve had been destroyed by multiple, irregular vegetations. Herein, we report an autopsy case of infective endocarditis with a review of the relevant literatures.
    01/2014; 38(2):78. DOI:10.7580/kjlm.2014.38.2.78
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    ABSTRACT: MicroRNAs (miRNAs) are endogenous non-coding 21–23 nucleotide RNAs that are involved in post-transcriptional regulation. They control various cellular processes, one of which is tumorigenesis. miRNAs have been implicated in the pathogenesis of hepatocellular carcinoma (HCC), the most common primary liver cancer. To find yet-to-be-identified miRNAs associated with HCC tumorigenesis, we resected HCC and adjacent non-tumor liver tissues from patients and excluded liver tissues harboring fibrosis from further analysis. We then carried out miRNA microarray analysis with miRNAs extracted from the tissues. Sixteen miRNAs displayed a significant change in expression levels between non-tumor and HCC liver tissues. To validate the microarray findings, we transfected HEK293 cells with miR-128 alone or miR-128 and plasmid encoding luciferase fused to the 3′ untranslated region (UTR) of E2F3, a predicted target of miR-128. As expected, miR-128 downregulated luciferase activities of E2F3 3′UTR fused to luciferase, confirming that E2F3 is a target gene of miR-128. Identification of miRNAs dysregulated in non-cirrhotic HCC will further the understanding of the pathogenesis of non-cirrhotic HCC.
    Genes & genomics 12/2013; 35(6). DOI:10.1007/s13258-013-0126-0 · 0.57 Impact Factor
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    ABSTRACT: Posterolateral fusion (PLF) with an autogenous iliac bone graft is the most common procedure for treating various lumbar spinal diseases. However, the limited success and associated morbidity from an iliac crest graft demands new biologically competent graft enhancers or substitutes. To investigate the feasibility of tubular mesh container made of bioabsorbable sutures (poly-1,4-dioxane-2-one, PDO) for spinal fusion. Experimental animal study. A biodegradable PDO tubular mesh container was used to contain small pieces of bone grafts. Twenty Sprague-Dawley male rats underwent PLF between L4 and L5 transverse processes with bilateral iliac grafts. Experimental animals were assigned into two different groups: autograft-only group (N=10) that underwent PLF with autograft-only or mesh container group (N=10) that underwent PLF with tubular mesh container filled with autogenous bone grafts. The rats were sacrificed at 8 weeks postoperatively, and the lumbar spines were removed. Spinal fusion was evaluated by manual palpation, microcomputed tomography, three-point bending test, and histological examination. Solid fusion was achieved in all cases of the mesh container group, whereas the autograft-only group showed 60% of solid fusion. New bone mass was higher and more solidly fused in the mesh container group than the autograft-only group (p<.01). Volume of fusion mass and density of bone were significantly higher in the mesh container group (p<.05). In all cases, inflammatory response was minimal. This study demonstrated that a tubular mesh container made of bioabsorbable suture is useful to hold small pieces of bone grafts and to enhance spinal fusion.
    The spine journal: official journal of the North American Spine Society 11/2013; DOI:10.1016/j.spinee.2013.08.038 · 2.80 Impact Factor
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    ABSTRACT: A number of recent reports have demonstrated that attenuated Salmonella typhimurium are capable of targeting both primary and metastatic tumors. The use of bacteria as a vehicle for the delivery of anti-cancer drugs requires a mechanism that precisely regulates and visualizes gene expression to ensure the appropriate timing and location of drug production. To integrate these functions into bacteria, we used a repressor-regulated tetracycline efflux system, in which the expression of a therapeutic gene and an imaging reporter gene were controlled by divergent promoters (tetAP and tetRP) in response to extracellular tetracycline.Attenuated S.typhimurium was transformed with the expression plasmids encoding cytolysin A, a therapeutic gene, and renilla luciferase variant 8, an imaging reporter gene, and administered intravenously to tumor-bearing mice. The engineered Salmonella successfully localized to tumor tissue and gene expression was dependent on the concentration of inducer, indicating the feasibility of peripheral control of bacterial gene expression. The bioluminescence signal permitted the localization of gene expression from the bacteria. The engineered bacteria significantly suppressed both primary and metastatic tumors and prolonged survival in mice. Thus, engineered bacteria that carry a therapeutic and an imaging reporter gene for targeted anti-cancer therapy can be designed as a theranostic agent.Molecular Therapy (2013); doi:10.1038/mt.2013.183.
    Molecular Therapy 08/2013; 21(11). DOI:10.1038/mt.2013.183 · 6.43 Impact Factor
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    ABSTRACT: Bone tissue regeneration is orchestrated by the surrounding supporting tissues and involves the build up of osteogenic cells, which orchestrate remodeling/healing through the expression of numerous mediators and signaling molecules. Periodontal regeneration models have proven to be a useful approach to studying the interaction and communication between alveolar bone and supporting soft tissue. We applied a quantitative proteomic approach to analyze and compare the proteins whose expression was altered in gingival soft tissue and alveolar bone following tooth extraction. For target identification and validation, hard and soft tissue were extracted from mini-pigs at the indicated times after tooth extraction. From triplicate experiments, 56 proteins in soft tissue and 27 proteins in alveolar bone were found to be differentially expressed before and after tooth extraction. Expression of 21 of those proteins was altered in both soft tissue and bone. Comparison of the activated networks in soft tissue and alveolar bone highlighted their distinct responsibilities in bone and tissue healing. Moreover, we found that there is crosstalk between identified proteins in soft tissue and alveolar bone with respect to cellular assembly, organization and communication. Among these proteins, we examined in detail the expression patterns and associated networks of ATP5B and FN1. ATP5B is involved in nucleic acid metabolism, small molecule biochemistry and neurological disease, while fibronectin 1 is involved in cellular assembly and organization and cellular maintenance. Collectively, our findings indicate that bone regeneration is accompanied by a profound interaction among networks regulating cellular resources, and provide novel insight into the molecular mechanisms involved in healing of periodontal tissue after tooth extraction.
    Molecular &amp Cellular Proteomics 07/2013; 12(10). DOI:10.1074/mcp.M112.026740 · 7.25 Impact Factor
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    ABSTRACT: The aim of this study was the immunological characterization of glioblastoma cells. Glioblastoma cell lines were cultured in serum and serum-free neurobasal (NBE) medium conditions. These cell lines were characterized by flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR), western blot and natural killer (NK) cell-cytotoxicity assays. A previously described NK cell expansion method that uses K562 cells expressing interleukin (IL)-15 and 4-1 BB Ligand (BBL) (K562-mb15-41BBL) was used. RT-PCR and western blots for the expression of tumor-associated antigens (TAAs), were carried out in 32 glioblastoma and seven normal brain tissues. U87 and U343 tumor cell lines showed increased expression for major histocompatibility complex (MHC)-I and -II molecules. No significant differences in the levels of CD133, MHC class I/II, MHC class I-related chain A (MICA), MICB, UL16 binding protein 1-3 (ULBP 1-3) expression in these cell lines and in NK cell cytotoxicity were observed between serum and NBE conditions. Regardless of culture conditions, U87 and U343 cell lines were sensitive to expanded NK cells, with median cytotoxicities at 4:1 effector/target ratio of 43.2% and 46.5%, respectively. In RT-PCR, U343 and U87 showed the expression of most TAAs at a high ratio compared with U251. Western blots demonstrated positive expression for BIRC5, CD99 and ERBB2 in U251, U87 and U343 cell lines and tissues. These highly-expressed TAAs such as BIRC5, CD99 and ERBB2 in glioblastoma tissue could be the targets for immunotherapy. U87 and U343 cell lines could be useful for studying the efficacy of immunotherapy related to various TAAs and NK cell immunotherapy.
    Anticancer research 06/2013; 33(6):2525-33. · 1.87 Impact Factor
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    ABSTRACT: BACKGROUND: The accumulation of toxic free radicals plays a pivotal role in the early molecular cascades of blood-brain barrier (BBB) disruption mediated by matrix metalloproteinases (MMPs) activation in ischemic stroke. Theoretically, it is expected that early blockade of activation of MMPs may provide protective effects from secondary neural tissue damage. The present study was designed to determine the ability of melatonin to influence MMP-9 activity and BBB disruption, in a focal ischemia rat model induced by photothrombosis. METHODS: Adult, male, 8-week Sprague-Dawley rats weighing 230-300g received focal cerebral ischemia by photothrombosis using Rose Bengal (RB). The injured animals were divided into two groups. One group received 50mg/kg of melatonin intraperitoneally, starting 1h after injury and at 12h intervals for 3days. The control group received weight-adjusted doses of saline vehicle. In each group, MMP-9 expression and activity were assessed by Western blot and gelatin zymography, respectively, at various times. The effects of melatonin on BBB disruption and brain edema were also determined. RESULTS: MMP-9 activity and expression were significantly elevated at 24h in the ischemic cortex, which remained up-regulated at least until 72h after injury. Melatonin treatment significantly attenuated MMP-9 activity and expression at 24, 48, and 72h after ischemic injury. Relative to control group, BBB permeability was significantly reduced in the melatonin-treated group. The water content was decreased by melatonin treatment, although there was no statistically significant difference. CONCLUSIONS: Melatonin treatment starting 1h after injury attenuated BBB disruption during focal ischemia, which is at least partly due to inhibition of MMP-9 activity. Melatonin might have a potential role in clinical trials aimed to improve the outcome of patients suffering cerebral ischemia.
    Journal of the neurological sciences 10/2012; 323(1-2). DOI:10.1016/j.jns.2012.09.021 · 2.26 Impact Factor

Publication Stats

511 Citations
182.78 Total Impact Points


  • 2006–2015
    • Chonnam National University
      • • Department of Anatomy
      • • Department of Cardiology
      • • Department of Forensic Medicine
      • • Department of Pathology
      Gwangju, Gwangju, South Korea
  • 2007–2014
    • Chonnam National University Hospital
      Sŏul, Seoul, South Korea
  • 2002–2006
    • Seonam University
      Onyang, South Chungcheong, South Korea