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1.  Immunomodulatory Effects of High-Protein Diet with Resveratrol Supplementation on Radiation-Induced Acute-Phase Inflammation in Rats 
Journal of Medicinal Food  2014;17(9):963-971.
We hypothesized that a high-protein diet and/or resveratrol supplementation will improve acute inflammatory responses in rats after receiving experimental abdominal radiation treatment (ART). Based on our previous study, the period of 10 days after ART was used as an acute inflammation model. Rats were exposed to a radiation dose of 17.5 Gy and were supplied with a control (C), 30% high-protein diet (HP), resveratrol supplementation (RES), or HP with RES diet ([HP+RES]). At day 10 after ART, we measured profiles of lipids, proteins, and immune cells in blood. The levels of clusters of differentiating 4+ (CD4+) cells and regulatory T cells, serum proinflammatory cytokines, and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in urine were also measured. ART caused significant disturbances of lipid profiles by increasing triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), and decreasing high-density lipoprotein cholesterol. The proinflammatroy cytokine levels were also increased by ART. All the experimental diets (HP, RES, and [HP+RES]) significantly decreased levels of TG, monocytes, proinflammatory cytokines, and 8-OHdG, whereas the platelet counts were increased. In addition, the HP and [HP+RES] diets decreased the concentrations of plasma LDL-C and total cholesterol. Also, the HP and RES diets decreased regulatory T cells compared with those of the control diet in ART group. Further, the HP diet led to a significant recovery of white blood cell counts, as well as increased percentages of lymphocyte and decreased percentages of neutrophils. In summary, RES appeared to be significantly effective in minimizing radiation-induced damage to lipid metabolism and immune responses. Our study also demonstrated the importance of dietary protein intake in recovering from acute inflammation by radiation.
PMCID: PMC4152788  PMID: 25054274
acute-phase inflammation; high-protein diet; radiation; resveratrol
2.  Quantitative analysis of nailfold capillary morphology in patients with fibromyalgia 
Nailfold capillaroscopy (NFC) has been used to examine morphological and functional microcirculation changes in connective tissue diseases. It has been demonstrated that NFC patterns reflect abnormal microvascular dynamics, which may play a role in fibromyalgia (FM) syndrome. The aim of this study was to determine NFC patterns in FM, and their association with clinical features of FM.
A total of 67 patients with FM, and 30 age- and sex-matched healthy controls, were included. Nailfold capillary patterns were quantitatively analyzed using computerized NFC. The parameters of interest were as follows: number of capillaries within the central 3 mm, deletion score, apical limb width, capillary width, and capillary dimension. Capillary dimension was determined by calculating the number of capillaries using the Adobe Photoshop version 7.0.
FM patients had a lower number of capillaries and higher deletion scores on NFC compared to healthy controls (17.3 ± 1.7 vs. 21.8 ± 2.9, p < 0.05; 2.2 ± 0.9 vs. 0.7 ± 0.6, p < 0.05, respectively). Both apical limb width (µm) and capillary width (µm) were significantly decreased in FM patients (1.1 ± 0.2 vs. 3.7 ± 0.6; 5.4 ± 0.5 vs. 7.5 ± 1.4, respectively), indicating that FM patients have abnormally decreased digital capillary diameter and density. Interestingly, there was no difference in capillary dimension between the two groups, suggesting that the length or tortuosity of capillaries in FM patients is increased to compensate for diminished microcirculation.
FM patients had altered capillary density and diameter in the digits. Diminished microcirculation on NFC may alter capillary density and increase tortuosity.
PMCID: PMC4497341  PMID: 26161020
Nailfold capillaroscopy; Fibromyalgia; Capillary dimension
3.  Current Status of Huntington’s Disease in Korea: A Nationwide Survey and National Registry Analysis 
Journal of Movement Disorders  2015;8(1):14-20.
Huntington’s disease (HD) is a rare neurological disorder, and its current status in Korea is not well investigated. This study aims to determine the prevalence and incidence of HD and to investigate the clinical features of HD patients in Korea.
We estimated the crude prevalence and annual incidence of HD based on the databases of the Rare Diseases Registry (RDR) and the National Health Insurance (NHI). The clinical data of genetically confirmed HD patients was collected from 10 referral hospitals and analyzed.
The mean calculated annual incidence was 0.06 cases per 100,000 persons, and the mean calculated prevalence was 0.38 based on the NHI database. The estimated crude prevalence based on the RDR was 0.41. Of the sixty-eight HD patients recruited, the mean age of onset was 44.16 ± 14.08 years and chorea was most frequently reported as the initial symptom and chief complaint. The mean CAG repeat number of the expanded allele was 44.7 ± 4.8 and correlated inversely with the age of onset (p < 0.001). About two-thirds of the patients have a positive family history, and HD patients without positive family history showed a delay in onset of initial symptoms, a prolonged interval between initial symptom onset and genetic diagnosis and a delay in the age of genetic diagnosis.
To the best of our knowledge, this is the first study to estimate the prevalence and incidence of HD in Korea and the largest HD series in the Asian population. Our analyses might be useful for further studies and large-scale investigations in HD patients.
PMCID: PMC4298714  PMID: 25614781
Huntington’s disease; Phenotype; Database; Prevalence; Incidence
4.  Effects of High-Protein Diet and/or Resveratrol Supplementation on the Immune Response of Irradiated Rats 
We investigated the effects of a high-protein diet and resveratrol supplementation on immune cells changes induced by abdominal irradiation in rats. Female Wistar rats were divided into 5 groups: 1) control diet, 2) control diet with irradiation 3) 30% high-protein diet with irradiation, 4) normal diet with resveratrol supplementation and irradiation, and 5) 30% high-protein diet with resveratrol supplementation and irradiation. We measured blood protein and albumin concentrations, lipid profiles, white blood cell (WBC) counts, proinflammatory cytokine production, and splenocyte proliferation in rats that had been treated with a 17.5 Gy dose of radiation 30 days prior. A high-protein diet affected plasma total cholesterol and very low density lipoprotein-cholesterol levels, which were increased by the radiation treatment. In addition, the lymphocyte percentage and immunoglobulin M (IgM) concentration were increased, and the neutrophil percentage was decreased in rats fed a high-protein diet. Resveratrol supplementation decreased the triglyceride (TG) level, but increased the IgM concentration and splenocyte proliferation. Proinflammatory cytokine production was lower in rats fed a high-protein diet supplemented with resveratrol than in rats fed a control diet. The results of the present study indicate that high-protein diets, with or without resveratrol supplementation, might assist with recovery from radiation-induced inflammation by modulating immune cell percentages and cytokine production.
PMCID: PMC4195620  PMID: 25320712
radiation treatment; high-protein diet; resveratrol; immune function; inflammation
5.  Carpal tunnel syndrome caused by tophaceous gout 
PMCID: PMC4101606  PMID: 25045307
6.  Unusual cause of back pain in a 13-year-old boy: a thoracic osteoblastoma 
PMCID: PMC4028536  PMID: 24851081
7.  Can natural products serve as potential treatments for osteoarthritis? 
PMCID: PMC3956986  PMID: 24648799
8.  Erratum: Funding Acknowledgment 
PMCID: PMC3506880
9.  Effect of quercetin on impaired immune function in mice exposed to irradiation 
Nutrition Research and Practice  2012;6(4):301-307.
Radiation used in cancer treatment may cause side effects such as inflammation. Quercetin is a polyphenol that reduces inflammation. This study evaluated the recovery efficacy of quercetin on impaired immune function in irradiation-induced inflammatory mice. Quercetin administered at two concentrations of 10 and 40 mg/kg body weight was initiated 2 weeks before irradiation and was continued 30 days after irradiation. The animals exposed/not exposed to radiation were sacrificed on radiation days 10 and 30. Splenocyte proliferation, which was diminished after irradiation, was enhanced significantly by quercetin supplementation after 30 days of irradiation. Cytokine secretion increased in the radiation group compared to that in the non-radiation control group. After 30 days of radiation, interleukin (IL)-1β and IL-6 secretion decreased significantly in the radiation-quercetin groups. When quercetin was administered for 44 days, it showed a possible protective effect against irradiation-induced inflammation in mice. Quercetin could be beneficial in the recovery of irradiation-induced increases in cytokine secretion.
PMCID: PMC3439573  PMID: 22977683
Quercetin; irradiation; cytokines; anti-inflammatory; mice
10.  Comparison of anti-oxidant activities of seventy herbs that have been used in Korean traditional medicine 
Nutrition Research and Practice  2008;2(3):143-151.
Many herbs have been used as therapeutics in Korean traditional medicine. In view of their clinical indications, anti-oxidant activity may contribute to their pharmacological effects. However, anti-oxidant information on these plants has not been available. In this study, seventy herbs which have been used in Korean traditional medicine were selected and screened for anti-oxidant activity using their water extracts. The anti-oxidant activity was assessed by their ability to inhibit three oxidation reactions; luminol/Fenton reagent, 2, 7-dichlorodihydrofluorescein (DCHF)/Fenton reagent and DCHF/peroxynitrite. In each assay, 70 herbs were divided into two groups; anti-oxidant group which inhibited the respective oxidation reaction and was majority (about 60 herbs), and pro-oxidant group which enhanced the oxidation reaction but was minority (more or less 10 herbs). When the herbs were listed in the order of their anti-oxidant strength, the orders obtained from each assay were found to be quite similar. The upper top rankers (more or less 10 herbs) in each assay showed strong activity compared to the others. The uppermost rankers in each assay were Rubus coreanus Miquel/ Rubus schizostylus, Schisandra chinensis Baillon/ Schizandra chinensis and Terminalia chebula Retzius/ Terminalia chebula. Of the pro-oxidant herbs, about 4-5 herbs were strongly pro-oxidant, which enhanced the control oxidation reactions to 150-300%. But the meaning of this observation is not known since few of them in one assay were also anti-oxidant in other assays. The results obtained in the present study may serve as information for understanding pharmacological effects of these herbs and developing new drugs from them.
PMCID: PMC2814189  PMID: 20126599
Anti-oxidants; herbs; chemiluminescence; peroxynitrite; Fenton reagent
11.  Tracheal calcification 
PMCID: PMC2474880  PMID: 18663210
12.  Myoepitheliomas of the Soft Palate: Helical CT Findings in Two Patients 
Korean Journal of Radiology  2007;8(6):552-555.
We describe the enhancement patterns of myoepithelioma in two patients with a soft palate mass. In the first case, helical CT revealed a faintly enhancing mass. Histologically, the tumor was composed of plasmacytoid cells in a background of rich myxoid stroma. Immunostaining for CD34 showed scanty blood vessels. In the second case, helical CT revealed an intensely enhancing mass. Histologically, the mass was a cellular tumor with fibrous stroma. Immunostaining for CD34 also showed frequent blood vessels.
PMCID: PMC2627460  PMID: 18071288
Myoepithelioma; Soft palate; Minor salivary gland; Computed tomography (CT)
13.  Complete Separation of the Vertebral Body Associated with a Schmorl's Node Accompanying Severe Osteoporosis 
A Schmorl's node is defined as a simple endplate intravertebral herniation resulting from trauma or idiopathic causes. Although Schmorl's nodes have been considered clinically insignificant, they might indicate an active symptomatic process or cause serious complications. In this study, we report an interesting case of complete separation of a vertebral body caused by an untreated Schmorl's node accompanying severe osteoporosis. To our knowledge, this is the first clinical report in the published literature to evaluate the complete separation of a vertebral body associated with a Schmorl's node.
PMCID: PMC4564749  PMID: 26361533
Schmorl's node; Osteoporosis; Fracture
14.  Effects of Korean Red Ginseng extract on busulfan-induced dysfunction of the male reproductive system 
Journal of Ginseng Research  2015;39(3):243-249.
Anticancer agents induce a variety of adverse effects when administered to cancer patients. Busulfan is a known antileukemia agent. When administered for treatment of leukemia in young patients, busulfan could cause damage to the male reproductive system as one of its adverse effects, resulting in sterility.
We investigated the effects of Korean Red Ginseng extract (KRGE) on busulfan-induced damage and/or dysfunction of the male reproductive system.
We found that administration of busulfan to mice: decreased testis weight; caused testicular histological damage; reduced the total number of sperm, sperm motility, serum testosterone concentration; and eventually, litter size. Preadministration of KRGE partially attenuated various busulfan-induced damages to the male reproductive system. These results indicate that KRGE has a protective effect against busulfan-induced damage to the male reproduction system.
The present study shows a possibility that KRGE could be applied as a useful agent to prevent or protect the male reproductive system from the adverse side effects induced by administration of anticancer agents such as busulfan.
PMCID: PMC4506375  PMID: 26199556
adverse effects; anticancer; busulfan; Panax ginseng; reproductive systems
15.  Clinical Analysis of Acute Radiculopathy after Osteoporotic Lumbar Compression Fracture 
The purpose of this study was to analyze the relationship between fracture pattern and the development of acute radiculopathy after osteoporotic lumbar compression fracture.
This study included 59 patients who underwent bone cement augmentation for osteoporotic compression fracture below the L2 level, which can lead to radiculopathic radiating pain. The patients were divided into two groups according to the presence of radiculopathy (group A : back pain only; group B : back pain with newly developed radiating pain). We categorized compression fractures into three types by the position of the fracture line. The incidence of newly developed radiculopathy was examined retrospectively for each compression fracture type.
The overall incidence of newly developed leg pain (group B) was 25%, and the frequency increased with descending spinal levels (L2 : 0%, L3 : 22%, L4 : 43%, and L5 : 63%). The back pain-only group (group A) had mostly superior-type fractures. On the other hand, the back pain with radiculopathy group (group B) had mostly inferior-type fractures. Most patients in group B showed significant relief of leg pain as well as back pain after bone cement augmentation.
The incidence of a newly developed, radiating pain after osteoporotic compression fractures increased gradually from the L3 to L5 levels. Most of these fractures were of the inferior type, and the bone cement augmentation procedures seemed to be sufficient for relief of both back and radiating pain.
PMCID: PMC4323502  PMID: 25674341
Fracture; Osteoporosis; Radiculopathy
16.  Impact of Framingham Risk Score, Flow-Mediated Dilation, Pulse Wave Velocity, and Biomarkers for Cardiovascular Events in Stable Angina 
Journal of Korean Medical Science  2014;29(10):1391-1397.
Although the age-adjusted Framingham risk score (AFRS), flow-mediated dilation (FMD), brachial-ankle pulse wave velocity (baPWV), high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and free fatty acid (FFA) can predict future cardiovascular events (CVEs), a comparison of these risk assessments for patients with stable angina has not been reported. We enrolled 203 patients with stable angina who had been scheduled for coronary angiography (CAG). After CAG, 134 patients showed significant coronary artery disease. During 4.2 yr follow-up, 36 patients (18%) showed CVEs, including myocardial infarction, de-novo coronary artery revascularization, in-stent restenosis, stroke, and cardiovascular death. ROC analysis showed that AFRS, FMD, baPWV, and hsCRP could predict CVEs (with AUC values of 0.752, 0.707, 0.659, and 0.702, respectively, all P<0.001 except baPWV P=0.003). A Cox proportional hazard analysis showed that AFRS and FMD were independent predictors of CVEs (HR, 2.945; 95% CI, 1.572-5.522; P=0.001 and HR, 0.914; 95% CI, 0.826-0.989; P=0.008, respectively). However, there was no difference in predictive power between combining AFRS plus FMD and AFRS alone (AUC 0.752 vs. 0.763; z=1.358, P=0.175). In patients with stable angina, AFRS and FMD are independent predictors of CVEs. However, there is no additive value of FMD on the AFRS in predicting CVEs.
Graphical Abstract
PMCID: PMC4214940  PMID: 25368493
Framingham Risk Score; Flow-Mediated Dilation; Cardiovascular Event
17.  Ginseng Gintonin Activates the Human Cardiac Delayed Rectifier K+ Channel: Involvement of Ca2+/Calmodulin Binding Sites 
Molecules and Cells  2014;37(9):656-663.
Gintonin, a novel, ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand, elicits [Ca2+]i transients in neuronal and non-neuronal cells via pertussis toxin-sensitive and pertussis toxin-insensitive G proteins. The slowly activating delayed rectifier K+ (IKs) channel is a cardiac K+ channel composed of KCNQ1 and KCNE1 subunits. The C terminus of the KCNQ1 channel protein has two calmodulin-binding sites that are involved in regulating IKs channels. In this study, we investigated the molecular mechanisms of gintonin-mediated activation of human IKs channel activity by expressing human IKs channels in Xenopus oocytes. We found that gintonin enhances IKs channel currents in concentration- and voltage-dependent manners. The EC50 for the IKs channel was 0.05 ± 0.01 μg/ml. Gintonin-mediated activation of the IKs channels was blocked by an LPA1/3 receptor antagonist, an active phospholipase C inhibitor, an IP3 receptor antagonist, and the calcium chelator BAPTA. Gintonin-mediated activation of both the IKs channel was also blocked by the calmodulin (CaM) blocker calmidazolium. Mutations in the KCNQ1 [Ca2+]i/CaM-binding IQ motif sites (S373P, W392R, or R539W)blocked the action of gintonin on IKs channel. However, gintonin had no effect on hERG K+ channel activity. These results show that gintonin-mediated enhancement of IKs channel currents is achieved through binding of the [Ca2+]i/CaM complex to the C terminus of KCNQ1 subunit.
PMCID: PMC4179134  PMID: 25234465
ginseng; gintonin; heart; IKs channel; LPA receptor
18.  Microarray-based DNA methylation study of Ewing’s sarcoma of the bone 
Oncology Letters  2014;8(4):1613-1617.
Alterations in DNA methylation patterns are a hallmark of malignancy. However, the majority of epigenetic studies of Ewing’s sarcoma have focused on the analysis of only a few candidate genes. Comprehensive studies are thus lacking and are required. The aim of the present study was to identify novel methylation markers in Ewing’s sarcoma using microarray analysis. The current study reports the microarray-based DNA methylation study of 1,505 CpG sites of 807 cancer-related genes from 69 Ewing’s sarcoma samples. The Illumina GoldenGate Methylation Cancer Panel I microarray was used, and with the appropriate controls (n=14), a total of 92 hypermethylated genes were identified in the Ewing’s sarcoma samples. The majority of the hypermethylated genes were associated with cell adhesion, cell regulation, development and signal transduction. The overall methylation mean values were compared between patients who survived and those that did not. The overall methylation mean was significantly higher in the patients who did not survive (0.25±0.03) than in those who did (0.22±0.05) (P=0.0322). However, the overall methylation mean was not found to significantly correlate with age, gender or tumor location. GDF10, OSM, APC and HOXA11 were the most significant differentially-methylated genes, however, their methylation levels were not found to significantly correlate with the survival rate. The DNA methylation profile of Ewing’s sarcoma was characterized and 92 genes that were significantly hypermethylated were detected. A trend towards a more aggressive behavior was identified in the methylated group. The results of this study indicated that methylation may be significant in the development of Ewing’s sarcoma.
PMCID: PMC4156184  PMID: 25202378
microarray; DNA methylation; Ewing’s sarcoma
19.  Monitoring the Differentiation and Migration Patterns of Neural Cells Derived from Human Embryonic Stem Cells Using a Microfluidic Culture System 
Molecules and Cells  2014;37(6):497-502.
Microfluidics can provide unique experimental tools to visualize the development of neural structures within a microscale device, which is followed by guidance of neurite growth in the axonal isolation compartment. We utilized microfluidics technology to monitor the differentiation and migration of neural cells derived from human embryonic stem cells (hESCs). We co-cultured hESCs with PA6 stromal cells, and isolated neural rosette-like structures, which subsequently formed neurospheres in suspension culture. Tuj1-positive neural cells, but not nestin-positive neural precursor cells (NPCs), were able to enter the microfluidics grooves (microchannels), suggesting that neural cell-migratory capacity was dependent upon neuronal differentiation stage. We also showed that bundles of axons formed and extended into the microchannels. Taken together, these results demonstrated that microfluidics technology can provide useful tools to study neurite outgrowth and axon guidance of neural cells, which are derived from human embryonic stem cells.
PMCID: PMC4086344  PMID: 24938227
axons; human embryonic stem cells; microfluidics; migration; neural differentiation
20.  In Vivo Roles of a Patient-Derived Induced Pluripotent Stem Cell Line (HD72-iPSC) in the YAC128 Model of Huntington’s Disease 
Induced pluripotent stem cells (iPSCs) generated from somatic cells of patients can provide immense opportunities to model human diseases, which may lead to develop novel therapeutics. Huntington’s disease (HD) is a devastating neurodegenerative genetic disease, with no available therapeutic options at the moment. We recently reported the characteristics of a HD patient-derived iPSC carrying 72 CAG repeats (HD72-iPSC). In this study, we investigated the in vivo roles of HD72-iPSC in the YAC128 transgenic mice, a commonly used HD mouse model carrying 128 CAG repeats. To do this, we transplanted HD72-iPSC-derived neural precursors into the striatum of YAC128 mice bilaterally and observed a significant behavioral improvement in the grafted mice. Interestingly, the transplanted HD72-iPSC-derived neural precursors formed GABAeric neurons efficiently, but no EM48-positive protein aggregates were detected at 12 weeks after transplantation. Taken together, these results indicate no HD pathology was developed from the grafted cells, or no transmission of HD pathology from the host to the graft occurred at 12 weeks post-transplantation.
PMCID: PMC4049731  PMID: 24921027
Huntington’s disease (HD); Induced pluripotent stem cells (iPSCs); YAC128 transgenic mice; GABAergic neurons; Aggregate formation
21.  The Effect of Imiquimod on Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Malignant Melanoma Cell Invasion 
Annals of Dermatology  2014;26(3):363-373.
A number of reports have been published regarding the use of imiquimod for the treatment of melanoma in situ and metastatic melanoma. Essential steps in the process of melanoma invasion and metastasis include degradation of basement membranes and remodeling of the extracellular matrix by proteolytic enzymes, including matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs).
To evaluate the antiinvasive effect of imiquimod in human malignant melanoma cell lines, SK-MEL-2 and SK-MEL-24, in vitro, and to investigate imiquimod-induced changes in the expression of MMPs and TIMPs.
Invasiveness of melanoma cell lines following imiquimod treatment was evaluated by invasion assays. In order to investigate the mechanism of the anti-invasive effect of imiquimod, mRNA and protein levels of MMP-2, -9, membrane type 1 (MT1)-MMP, TIMP-1, and -2 were assessed by real-time reverse transcription-polymerase chain reaction, gelatin zymography, and western blotting.
Imiquimod treatment decreased in vitro viability of melanoma cells in a concentration-dependent manner. Imiquimod also elicited a concentration-dependent suppression of invasion in both melanoma cell lines. A concentration-dependent decrease in MMP-2 and MT1-MMP protein levels and a concentration-dependent increase in TIMP-1 and -2 protein levels by imiquimod was observed in both melanoma cell lines. However, expression of MMP-9 protein was increased in SK-MEL-2 but decreased in SK-MEL-24 with increasing imiquimod concentrations. Imiquimod elicited alterations in MMPs and TIMPs mRNA levels that parallel the observed changes in protein levels.
Imiquimod may elicit an anti-invasive effect on human melanoma cells by regulating MMPs and TIMPs.
PMCID: PMC4069648  PMID: 24966637
Imiquimod; Invasion; Melanoma; Matrix metalloproteinase; Tissue inhibitor of metalloproteinase
22.  Crystallization and preliminary X-ray crystallographic analysis of the methionine sulfoxide reductase A domain of MsrAB from Haemophilus influenzae  
The MsrA domain of MsrAB from H. influenzae was crystallized. X-ray diffraction data were collected to 1.6 Å resolution.
Methionine sulfoxide reductase (Msr) is a repair enzyme that reduces oxidized methionine to methionine. The Msr enzyme is divided into MsrA and MsrB, which reduce the S and R configurations of the substrate, respectively. In some pathogenic bacteria MsrA and MsrB exist in a fusion-protein form, MsrAB. In this study, the recombinant MsrA part of MsrAB from Haemophilus influenzae (HIMsrA) was overexpressed, purified and crystallized using the hanging-drop vapour-diffusion method. A diffraction data set was collected to 1.6 Å resolution. The crystal of HIMsrA was found to belong to space group P41212, with unit-cell parameters a = b = 57.29, c = 186.28 Å, a calculated Matthews coefficient of 1.82 Å3 Da−1 and two molecules per asymmetric unit. A preliminary solution was determined by molecular replacement. Refinement of the structure is currently in progress.
PMCID: PMC3374512  PMID: 22691787
reductases; reactive oxygen species; MsrAB; Haemophilus influenzae
23.  Contralaterally transplanted human embryonic stem cell-derived neural precursor cells (ENStem-A) migrate and improve brain functions in stroke-damaged rats 
The transplantation of neural precursor cells (NPCs) is known to be a promising approach to ameliorating behavioral deficits after stroke in a rodent model of middle cerebral artery occlusion (MCAo). Previous studies have shown that transplanted NPCs migrate toward the infarct region, survive and differentiate into mature neurons to some extent. However, the spatiotemporal dynamics of NPC migration following transplantation into stroke animals have yet to be elucidated. In this study, we investigated the fates of human embryonic stem cell (hESC)-derived NPCs (ENStem-A) for 8 weeks following transplantation into the side contralateral to the infarct region using 7.0T animal magnetic resonance imaging (MRI). T2- and T2*-weighted MRI analyses indicated that the migrating cells were clearly detectable at the infarct boundary zone by 1 week, and the intensity of the MRI signals robustly increased within 4 weeks after transplantation. Afterwards, the signals were slightly increased or unchanged. At 8 weeks, we performed Prussian blue staining and immunohistochemical staining using human-specific markers, and found that high percentages of transplanted cells migrated to the infarct boundary. Most of these cells were CXCR4-positive. We also observed that the migrating cells expressed markers for various stages of neural differentiation, including Nestin, Tuj1, NeuN, TH, DARPP-32 and SV38, indicating that the transplanted cells may partially contribute to the reconstruction of the damaged neural tissues after stroke. Interestingly, we found that the extent of gliosis (glial fibrillary acidic protein-positive cells) and apoptosis (TUNEL-positive cells) were significantly decreased in the cell-transplanted group, suggesting that hESC-NPCs have a positive role in reducing glia scar formation and cell death after stroke. No tumors formed in our study. We also performed various behavioral tests, including rotarod, stepping and modified neurological severity score tests, and found that the transplanted animals exhibited significant improvements in sensorimotor functions during the 8 weeks after transplantation. Taken together, these results strongly suggest that hESC-NPCs have the capacity to migrate to the infarct region, form neural tissues efficiently and contribute to behavioral recovery in a rodent model of ischemic stroke.
PMCID: PMC3849578  PMID: 24232252
behavioral recovery; human embryonic stem cell-derived neural precursor cells (hESC-NPCs, ENStem-A); magnetic resonance imaging (MRI); migration; stroke
24.  The effect of rhinovirus on airway inflammation in a murine asthma model 
Korean Journal of Pediatrics  2013;56(11):482-489.
The aim of the present study was to investigate the differences in lower airway inflammatory immune responses, including cellular responses and responses in terms of inflammatory mediators in bronchoalveolar lavage fluid (BALF) and the airway, to rhinovirus (RV) infection on asthma exacerbation by comparing a control and a murine asthma model, with or without RV infection.
BALB/c mice were intraperitoneally injected with a crude extract of Dermatophagoides farinae (Df) or phosphate buffered saline (PBS) and were subsequently intranasally treated with a crude extract of Df or PBS. Airway responsiveness and cell infiltration, differential cell counts in BALF, and cytokine and chemokine concentrations in BALF were measured 24 hours after intranasal RV1B infection.
RV infection increased the enhanced pause (Penh) in both the Df sensitized and challenged mice (Df mice) and PBS-treated mice (PBS mice) (P<0.05). Airway eosinophil infiltration increased in Df mice after RV infection (P<0.05). The levels of interleukin (IL) 13, tumor necrosis factor alpha, and regulated on activation, normal T cells expressed and secreted (RANTES) increased in response to RV infection in Df mice, but not in PBS mice (P<0.05). The level of IL-10 significantly decreased following RV infection in Df mice (P<0.05).
Our findings suggest that the augmented induction of proinflammatory cytokines, Th2 cytokines, and chemokines that mediate an eosinophil response and the decreased induction of regulatory cytokines after RV infection may be important manifestations leading to airway inflammation with eosinophil infiltration and changes in airway responsiveness in the asthma model.
PMCID: PMC3859881  PMID: 24348661
Immune response; Rhinovirus; Asthma; Exacerbation
25.  Plasma Total Homocysteine Level Is Associated with the Pulsatility Index of Cerebral Arteries in Lacunar Infarction 
Yonsei Medical Journal  2013;54(4):819-824.
The pulsatility index (PI), measured by transcranial Doppler (TCD), is a surrogate marker for distal vascular resistance in cerebral arteries, and elevated plasma total homocysteine (tHcyt) is regarded as a cause of ischemic stroke, including lacunar infarction. We investigated the relationship between the PI of cerebral arteries and plasma tHcyt in patients with lacunar infarction.
Materials and Methods
Plasma tHcyt level and TCD examination were performed in 94 patients with lacunar infarction. Mean flow velocity (MFV) and PI were assessed at the ipsilateral middle cerebral artery (MCA) and contralateral MCA, relative to the infarction, and the basilar artery (BA). Multivariate regression analysis was conducted between log-transformed tHcyt levels (logHcyt) and the PI of individual arteries.
There was a significant correlation between logHcyt and the PI in all tested arteries (ipsilateral MCA: r=0.21, p=0.03; contralateral MCA: r=0.21, p=0.04; BA: r=0.35, p=0.01). In multivariate regression analysis, this significance remained unchanged after adjusting for vascular risk factors, creatinine, hematocrit and platelet count (ipsilateral MCA: β=0.26, p=0.01; contralateral MCA: β=0.21, p=0.04; BA: β=0.39, p=0.001). There was no significant association between logHcyt and MFV of individual arteries.
A significant association between plasma tHcyt and the PI of cerebral arteries indicates that homocysteine plays a role in the increase of distal arterial resistance in lacunar infarction.
PMCID: PMC3663237  PMID: 23709413
Homocysteine; pulsatility index; lacunar infarction

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