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1.  Full-Genome Sequences of Severe Fever with Thrombocytopenia Syndrome Virus, Isolated from South Korea in 2014 
Genome Announcements  2015;3(2):e00181-15.
Here, we present the full-length genome sequencing of severe fever with thrombocytopenia syndrome (SFTS) virus, isolated from South Korea in 2014. The five Korean strains were compared by phylogenetic analysis with full SFTS genome sequences of two neighboring nations, China and Japan.
PMCID: PMC4400419  PMID: 25883276
2.  Indian hedgehog signaling triggers Nkx3.2 protein degradation during chondrocyte maturation 
The Biochemical journal  2012;443(3):789-798.
The Indian hedgehog (Ihh) pathway plays an essential role in facilitating chondrocyte hypertrophy and bone formation during skeletal development. Nkx3.2 is initially induced in chondrocyte precursor cells, maintained in early-stage chondrocytes, and down-regulated in terminal-stage chondrocytes. Consistent with these expression patterns, Nkx3.2 has been shown to enhance chondrocyte differentiation and cell survival, while inhibiting chondrocyte hypertrophy and apoptosis. Thus, in this work, we investigate whether Nkx3.2, an early stage chondrogenic factor, can be regulated by Ihh, a key regulator for chondrocyte hypertrophy. Here, we show that Ihh signaling can induce proteasomal degradation of Nkx3.2. In addition, we found that Ihh can suppress levels of Lrp (Wnt co-receptor) and Sfrp (Wnt antagonist) expression, which, in turn, may selectively enhance Lrp-independent non-canonical Wnt pathways in chondrocyte. In agreement with these findings, Ihh-induced Nkx3.2 degradation requires Wnt5a, which is capable of triggering Nkx3.2 degradation. Finally, we found that Nkx3.2 protein levels in chondrocytes are remarkably elevated in mice defective in Ihh signaling by deletion of either Ihh or Smoothened. Thus, these results suggest that Ihh/Wnt5a signaling may play a role in negative regulation of Nkx3.2 for appropriate progression of chondrocyte hypertrophy during chondrogenesis.
PMCID: PMC4334119  PMID: 22507129
3.  Genome-wide identification of antimicrobial peptides in the liver fluke, Clonorchis sinensis 
Bioinformation  2015;11(1):17-20.
The increase in prevalence of antimicrobial resistance makes the search for new antibiotic agents imperative. Antimicrobial peptides (AMPs) from natural resources have been recognized as suitable tools to combat antibiotic-resistant bacteria. The liver fluke Clonorchis sinensis living in germ-filled environments could be a good source of antimicrobials. Here, we report the use of a rational protocol that combines AMP predictions based on their physicochemical properties and their in vivo stability to discover AMP candidates from the entire genome of C. sinensis. To screen AMP candidates, in silico analyses based on the physicochemical properties of known AMPs, such as length, charge, isoelectric point, and in vitro and in vivo aggregation values were performed. To enhance their in vivo stability, proteins having proteolytic cleavage sites were excluded. As a consequence, four high-activity, highstability peptides were identified. These peptides could be potential starting materials for the development of new AMPs via structural modification and optimization. Thus, this study proposes a refined computational method to develop new AMPs and identifies four AMP candidates, which could serve as templates for further development of peptide antibiotics.
PMCID: PMC4349934  PMID: 25780275
Antibiotics; Infection; Antibacterial agent; Bioinformatics; Rational drug design
4.  Optimal Time to Start Peripheral Blood Stem Cell Collection in Children with High-Risk Solid Tumors 
Journal of Korean Medical Science  2013;29(1):110-116.
In order to clarify the optimal timing for peripheral blood stem cell (PBSC) collection, PBSC collection records of 323 children who were scheduled to undergo autologous stem cell transplantation from two study periods differing in the timing of PBSC collection were analyzed. In the early study period (March 1998 to August 2007, n=198), PBSC collection was initiated when the peripheral WBC count exceeded 1,000/µL during recovery from chemotherapy. Findings in this study period indicated that initiation of PBSC collection at a higher WBC count might result in a greater CD34+ cell yield. Therefore, during the late study period (September 2007 to December 2012, n=125), PBSC collection was initiated when the WBC count exceeded 4,000/µL. Results in the late study period validated our conclusion from the early study period. Collection of a higher number of CD34+ cells was associated with a faster hematologic recovery after transplant in the late study period. Initiation of PBSC collection at WBC count > 4,000/µL was an independent factor for a greater CD34+ cell yield. In conclusion, PBSC collection at a higher WBC count is associated with a greater CD34+ cell yield, and consequently a faster hematologic recovery after transplant.
PMCID: PMC3890460  PMID: 24431914
High-Dose Chemotherapy; Autologous Stem Cell Transplantation; Peripheral Blood Stem Cell Collection
5.  Applied and Translational Genomics for Human Genetics and Clinical Science 
PMCID: PMC4126438
computational genomics; translational bioinformatics; systems biology for human genetics; next-generation sequencing (NGS); personalized medicine
6.  Ophthalmic Artery Occlusion After Carotid Revascularization 
Distal embolization resulting from carotid angioplasty and stenting (CAS) occurs mainly in the cerebral hemisphere. We report a case of ophthalmic artery occlusion after carotid revascularization. A 75-year old man received emergency CAS for cervical internal carotid artery occlusion. Two months later, the patient was readmitted for decreased visual acuity. We found ophthalmic artery occlusion that was not noticed soon after CAS. Although ophthalmic artery occlusion after CAS is rare, endovascular neurosurgeons should be aware of this potential complication.
PMCID: PMC3983535  PMID: 24729961
Carotid angioplasty and stenting; Embolization; Ophthalmic artery occlusion
7.  Sensitization to Multiple Rh Antigens by Transfusion of Random Donor Platelet Concentrates in a -D- Phenotype Patient 
Annals of Laboratory Medicine  2012;32(6):429-432.
The -D- phenotype is a rare Rh phenotype that strongly expresses D antigen without C, c, E, or e antigens. In -D- phenotype individuals, anti-Rh17 (Hro) is commonly found if there is a history of pregnancy or transfusion with red blood cells (RBCs) that express C, c, E, or e antigens. We report the first case of a -D- phenotype patient with multiple Rh antibodies including anti-Rh17 who had a history of two occasions of transfusion with eight random donor platelet concentrates two and six years ago. We found that a trivial amount of RBCs in the platelet components was able to trigger sensitization to RBC antigens, especially the highly immunogenic and clinically significant Rh antigens, including C, c, E, e or CcEe polypeptides. To avoid unnecessary sensitization and to minimize the risk of hemolytic transfusion reactions in patients with this rare Rh phenotype, a modified strategy for pretransfusion screenings needs to be discussed in the field of transfusion medicine.
PMCID: PMC3486938  PMID: 23130343
Rh-Hr blood group system; Rh isoimmunization; Platelet transfusion
8.  Clinical and Angiographic Outcomes of Wingspan Stent Placement for Treatment of Symptomatic Intracranial Stenosis: Single Center Experience with 19 Cases 
The limitations of medical management of symptomatic intracranial arterial stenosis (ICS) have prompted development of new strategies, including endovascular treatment. However, stenting of symptomatic ICS remains investigational. Here, we have reported and analyzed a series of 19 endovascular procedures involving placement of a Wingspan stent.
We conducted a retrospective review of a series of ICS in which patients were treated with percutaneous transarterial balloon angioplasty and stent placement (PTAS). Patients included in the study were diagnosed as symptomatic ICS between May 2010 and September 2011.
Nineteen patients (median age, 65 years; 12 males, seven women) were treated with the Wingspan stent system for symptomatic ICS ranging from 50% to 99%. The technical success rate was 100%. The location of ICS included the internal carotid (n = 5; 1 petrous, 3 cavernous, and 1 clinoid segments), vertebral (n = 1; V4 segment), basilar (n = 1), and middle cerebral (n = 12; 9 M1, 3 M2) arteries. There was no occurrence of procedure-related mortality. Periprocedural morbidity occurred in two cases (10.5%), including carotid-cavernous fistula (n = 1) and subarachnoid hemorrhage (n = 1). No ipsilateral stroke was recorded beyond 30 days during a mean follow-up period of 13.2 months (range 9-19 months). Restenosis (> 50%) was observed in one patient (6.3%), who was asymptomatic, on follow-up imaging.
Wingspan stent for symptomatic ICS can be performed with a high rate of technical success and acceptable periprocedural morbidity rates. Our initial experience indicates that this procedure represents a viable treatment option for this patient population.
PMCID: PMC3491208  PMID: 23210041
Intracranial stenosis; Angioplasty; Stent implantation; Wingspan stent
9.  Concomitant Dual Origin and Fenestration of the Left Vertebral Artery Resembling Dissection 
Dual origin and fenestration of the vertebral artery (VA) are very rare anomalies. Understanding of these variations, however, is important because they can be misdiagnosed as a VA dissection. A 42-year-old woman presented with motor weakness and sensory disturbance of the right upper extremity. Radiologic evaluations showed ectatic change in the right VA and an arteriovenous fistula between the right VA and the vertebral vein. We decided on endovascular occlusion of the proximal right VA and its fistulous portion. During the endovascular procedure, we had misunderstood the dual origin and fenestration of the VA as a dissection. Thus, failure to recognize these anomalies might result in unnecessary anticoagulation or therapeutic intervention. Clinicians should be alert to such VA variations when making a diagnosis and when planning any intervention or surgery involving the proximal VA.
PMCID: PMC2796360  PMID: 20041064
Dissection; Dual origin; Fenestration; Vertebral artery
10.  In Situ Floating Resin Cranioplasty for Cerebral Decompression 
The purpose of this report is to describe our surgical experiences in the treatment of cerebral decompression with in situ floating resin cranioplasty. We included in this retrospective study 7 patients who underwent in situ floating resin cranioplasty for cerebral decompression between December 2006 and March 2008. Of these patients, 3 patients had traumatic brain injury, 3 cerebral infarction, and one subarachnoid hemorrhage due to aneurysmal rupture. In situ floating resin cranioplasty for cerebral decompression can reduce complications related to the absence of a bone flap and allow reconstruction by secondary cranioplasty without difficulty. Furthermore, it provides cerebral protection and selectively eliminates the need for secondary cranioplasty in elderly patients or patients who have experienced unfavorable outcome.
PMCID: PMC2773405  PMID: 19893737
Decompressive craniectomy; Floating; Resin cranioplasty
11.  Antioxidant effects of Dendropanax morbifera Léveille extract in the hippocampus of mercury-exposed rats 
Dendropanax morbifera Léveille has been employed for the treatment of infectious diseases using folk medicine. In this study, we evaluated the antioxidant effects of a leaf extract of Dendropanax morbifera Léveille in the hippocampus of mercury-exposed rats.
Seven-week-old Sprague–Dawley rats received a daily intraperitoneal injection of 5 μg/kg dimethylmercury and/or oral Dendropanax morbifera Léveille leaf extract (100 mg/kg) for 4 weeks. Animals were sacrificed 2 h after the last dimethylmercury and/or leaf extract treatment. Mercury levels were measured in homogenates of hippocampal tissue, a brain region that is vulnerable to mercury toxicity. In addition, we measured reactive oxygen species production, lipid peroxidation levels, and antioxidant levels in these hippocampal homogenates.
Treatment with Dendropanax morbifera Léveille leaf extract significantly reduced mercury levels in hippocampal homogenates and attenuated the dimethylmercury-induced increase in the production of reactive oxygen species and formation of malondialdehyde. In addition, this leaf extract treatment significantly reversed the dimethylmercury-induced reduction in the hippocampal activities of Cu, Zn-superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase.
These results suggest that a leaf extract of Dendropanax morbifera Léveille had strong antioxidant effects in the hippocampus of mercury-exposed rats.
PMCID: PMC4511420  PMID: 26201852
Dendropanax morbifera extract; Mercury; Hippocampus; Reactive oxygen species; Protein modification
12.  Tat-antioxidant 1 protects against stress-induced hippocampal HT-22 cells death and attenuate ischaemic insult in animal model 
Oxidative stress-induced reactive oxygen species (ROS) are responsible for various neuronal diseases. Antioxidant 1 (Atox1) regulates copper homoeostasis and promotes cellular antioxidant defence against toxins generated by ROS. The roles of Atox1 protein in ischaemia, however, remain unclear. In this study, we generated a protein transduction domain fused Tat-Atox1 and examined the roles of Tat-Atox1 in oxidative stress-induced hippocampal HT-22 cell death and an ischaemic injury animal model. Tat-Atox1 effectively transduced into HT-22 cells and it protected cells against the effects of hydrogen peroxide (H2O2)-induced toxicity including increasing of ROS levels and DNA fragmentation. At the same time, Tat-Atox1 regulated cellular survival signalling such as p53, Bad/Bcl-2, Akt and mitogen-activate protein kinases (MAPKs). In the animal ischaemia model, transduced Tat-Atox1 protected against neuronal cell death in the hippocampal CA1 region. In addition, Tat-Atox1 significantly decreased the activation of astrocytes and microglia as well as lipid peroxidation in the CA1 region after ischaemic insult. Taken together, these results indicate that transduced Tat-Atox1 protects against oxidative stress-induced HT-22 cell death and against neuronal damage in animal ischaemia model. Therefore, we suggest that Tat-Atox1 has potential as a therapeutic agent for the treatment of oxidative stress-induced ischaemic damage.
PMCID: PMC4459847  PMID: 25781353
Tat-Atox1; ischaemic injury; oxidative stress; protein transduction domain; protein therapy
13.  Prolonged survival of a patient with metastatic leptomeningeal melanoma treated with BRAF inhibition-based therapy: a case report 
BMC Cancer  2015;15:400.
Leptomeningeal metastasis of melanoma is a devastating complication with a grave prognosis, and there are no known effective standard treatments. Although selective BRAF inhibitors have demonstrated a significant clinical activity in patients with metastatic melanoma harboring a BRAF mutation, the clinical benefit of BRAF inhibitor-based therapy in leptomeningeal disease is not clear.
Case presentation
We present a case of prolonged survival of a patient with BRAF V600E-mutant leptomeningeal disease who was treated with vemurafenib followed by whole brain radiation and a combination of dabrafenib and trametinib. Both vemurafenib and the sequential treatment of radiation and dabrafenib/trametinib led to regression of the leptomeningeal disease, and the patient survived for 19 months after the diagnosis of the leptomeningeal disease.
This case suggests a possible clinically meaningful benefit of BRAF inhibitor-based therapy and a need for close investigation of this therapeutic approach in patients with this devastating disease.
PMCID: PMC4440312  PMID: 25962795
Metastatic melanoma; Leptomeningeal disease; BRAF inhibitors
14.  Results of a Randomized Phase I Gene Therapy Clinical Trial of Nononcolytic Fowlpox Viruses Encoding T Cell Costimulatory Molecules 
Human Gene Therapy  2014;25(5):452-460.
Oncolytic viruses have shown promise as gene delivery vehicles in the treatment of cancer; however, their efficacy may be inhibited by the induction of anti-viral antibody titers. Fowlpox virus is a nonreplicating and nononcolytic vector that has been associated with lesser humoral but greater cell-mediated immunity in animal tumor models. To test whether fowlpox virus gene therapy is safe and can elicit immune responses in patients with cancer, we conducted a randomized phase I clinical trial of two recombinant fowlpox viruses encoding human B7.1 or a triad of costimulatory molecules (B7.1, ICAM-1, and LFA-3; TRICOM). Twelve patients (10 with melanoma and 2 with colon adenocarcinoma) enrolled in the trial and were randomized to rF-B7.1 or rF-TRICOM administered in a dose escalation manner (∼3.7×107 or ∼3.7×108 plaque-forming units) by intralesional injection every 4 weeks. The therapy was well tolerated, with only four patients experiencing grade 1 fever or injection site pain, and there were no serious adverse events. All patients developed anti-viral antibody titers after vector delivery, and posttreatment anti-carcinoembryonic antigen antibody titers were detected in the two patients with colon cancer. All patients developed CD8+ T cell responses against fowlpox virus, but few responses against defined tumor-associated antigens were observed. This is the first clinical trial of direct (intratumoral) gene therapy with a nononcolytic fowlpox virus. Treatment was well tolerated in patients with metastatic cancer; all subjects exhibited anti-viral antibody responses, but limited tumor-specific T cell responses were detected. Nononcolytic fowlpox viruses are safe and induce limited T cell responses in patients with cancer. Further development may include prime–boost strategies using oncolytic viruses for initial priming.
PMCID: PMC4027985  PMID: 24484178
15.  Complete Genome Sequences of Human Respiratory Syncytial Virus Genotype A and B Isolates from South Korea 
Genome Announcements  2015;3(2):e00332-15.
There is a paucity of complete genome sequence information for human respiratory syncytial virus (HRSV). To this end, we sequenced the complete genome sequences of HRSV genotype A (HRSV-A/IC688/12) and genotype B (HRSV-B/GW0047/14 and HRSV-B/IC0027/14). This information will increase the understanding of HRSV genetic diversity, evolution, pathogenicity, antigenicity, and transmissibility.
PMCID: PMC4408341  PMID: 25908140
16.  The effects of PEP-1-FK506BP on dry eye disease in a rat model 
BMB Reports  2015;48(3):153-158.
As FK506 binding proteins (FK506BPs) are known to play an important role in the regulation of a variety of biological processes related to cell survival, this study was designed to examined the protective effects of FK506 binding protein 12 (FK506BP) on low humidity air flow induced dry eye in a rat model using transduced PEP-1-FK506BP. After the topical application of PEP-1-FK506BP, tear volumes were markedly increased and significant prevention of cornea damage was observed compared with dry eye rats. Further, immunohistochemical analysis demonstrated that PEP-1-FK506BP markedly prevented damage to the cornea, the bulbar conjunctiva, and the palpebral conjunctiva epithelial lining compared with dry eye rats. In addition, caspase-3 and PARP expression levels were found to be decreased. These results demonstrated that topical application of PEP-1-FK506BP significantly ameliorates dry eye injury in an animal model. Thus, we suggest that PEP-1-FK506BP can be developed as a new ophthalmic drop to treat dry eye diseases. [BMB Reports 2015; 48(3): 153-158]
PMCID: PMC4453030  PMID: 24998262
Dry eye disease; FK506BP; Tear volume; Protein therapy; Protein transduction
17.  Whole-Genome Sequence of Borrelia garinii Strain 935T Isolated from Ixodes persulcatus in South Korea 
Genome Announcements  2014;2(6):e01298-14.
We report here the genome sequence of Borrelia garinii strain 935T isolated from Ixodes persulcatus in South Korea. The 1,176,739 bp (G+C content, 27.73%) genome consists of 1,194 coding regions, 4 rRNA genes, and 33 aminoacyl-tRNA synthetase genes. This is the first whole-genome report of a Korean Borrelia species isolate.
PMCID: PMC4276819  PMID: 25540341
18.  Changes in the expression of DNA-binding/differentiation protein inhibitors in neurons and glial cells of the gerbil hippocampus following transient global cerebral ischemia 
Molecular Medicine Reports  2014;11(4):2477-2485.
Inhibitors of DNA-binding/differentiation (ID) proteins bind to basic helix-loop-helix (bHLH) transcription factors, including those that regulate differentiation and cell-cycle progression during development, and regulate gene transcription. However, little is known about the role of ID proteins in the brain under transient cerebral ischemic conditions. In the present study, we examined the effects of ischemia-reperfusion (I-R) injury on the immunoreactivity and protein levels of IDs 1–4 in the gerbil hippocampus proper Cornu Ammonis regions CA1–3 following 5 min of transient cerebral ischemia. Strong ID1 immunoreactivity was detected in the nuclei of pyramidal neurons in the hippocampal CA1–3 regions; immunoreactivity was significantly changed following I-R in the CA1 region, but not in the CA2/3 region. Five days following I-R, ID1 immunoreactivity was not detected in the CA1 pyramidal neurons. ID1 immunoreactivity was detected only in GABAergic interneurons in the ischemic CA1 region. Weak ID4 immunoreactivity was detected in non-pyramidal cells, and immunoreactivity was again only changed in the ischemic CA1 region. Five days following I-R, strong ID4 immunoreactivity was detected in non-pyramidal cells, which were identified as microglia, and not astrocytes, in the ischemic CA1 region. Furthermore, changes in the protein levels of ID1 and ID4 in the ischemic CA1 region studied by western blot were consistent with patterns of immunoreactivity. In summary, these results indicate that immunoreactivity and protein levels of ID1 and ID4 are distinctively altered following transient cerebral ischemia only in the CA1 region, and that the changes in ID1 and ID4 expression may relate to the ischemia-induced delayed neuronal death.
PMCID: PMC4337738  PMID: 25503067
inhibitors of DNA binding proteins; ischemic damage; hippocampus; pyramidal neurons; delayed neuronal death; glial cells
19.  PEP-1-HO-1 prevents MPTP-induced degeneration of dopaminergic neurons in a Parkinson’s disease mouse model 
BMB Reports  2014;47(10):569-574.
Heme oxygenase-1 (HO-1) degrades heme to carbon dioxide, biliverdin, and Fe2+, which play important roles in various biochemical processes. In this study, we examined the protective function of HO-1 against oxidative stress in SH-SY5Y cells and in a Parkinson’s disease mouse model. Western blot and fluorescence microscopy analysis demonstrated that PEP-1-HO-1, fused with a PEP-1 peptide can cross the cellular membranes of human neuroblastoma SH-SY5Y cells. In addition, the transduced PEP-1-HO-1 inhibited generation of reactive oxygen species (ROS) and cell death caused by 1-methyl-4-phenylpyridinium ion (MPP+). In contrast, HO-1, which has no ability to transduce into SH-SY5Y cells, failed to reduce MPP+-induced cellular toxicity and ROS production. Furthermore, intraperitoneal injected PEP-1-HO-1 crossed the blood-brain barrier in mouse brains. In a PD mouse model, PEP-1-HO-1 significantly protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity and dopaminergic neuronal death. Therefore, PEP-1-HO-1 could be a useful agent in treating oxidative stress induced ailments including PD. [BMB Reports 2014; 47(10): 569-574]
PMCID: PMC4261515  PMID: 24499676
Dopaminergic neuron; Heme oxygenase-1; MPTP; Parkinson’s disease; Protein transduction domain
20.  Physical exercise ameliorates the reduction of neural stem cell, cell proliferation and neuroblast differentiation in senescent mice induced by D-galactose 
BMC Neuroscience  2014;15:116.
Aging negatively affects adult hippocampal neurogenesis, and exercise attenuates the age-related reduction in adult hippocampal neurogenesis. In the present study, we used senescent mice induced by D-galactose to examine neural stem cells, cell proliferation, and neuronal differentiation with or without exercise treatment. D-galactose (100 mg/kg) was injected to six-week-old C57BL/6 J mice for 6 weeks to induce the senescent model. During these periods, the animals were placed on a treadmill and acclimated to exercise for 1 week. Then treadmill running was conducted for 1 h/day for 5 consecutive days at 10-12 m/min for 5 weeks.
Body weight and food intake did not change significantly after D-galactose administration with/without treadmill exercise, although body weight and food intake was highest after treadmill exercise in adult animals and lowest after treadmill exercise in D-galactose-induced senescent model animals. D-galactose treatment significantly decreased the number of nestin (a neural stem cell marker), Ki67 (a cell proliferation marker), and doublecortin (DCX, a differentiating neuroblast marker) positive cells compared to those in the control group. In contrast, treadmill exercise significantly increased Ki67- and DCX-positive cell numbers in both the vehicle- and D-galactose treated groups. In addition, phosphorylated cAMP-response element binding protein (pCREB) and brain derived neurotrophic factor (BDNF) was significantly decreased in the D-galactose treated group, whereas exercise increased their expression in the subgranular zone of the dentate gyrus in both the vehicle- and D-galactose-treated groups.
These results suggest that treadmill exercise attenuates the D-galactose-induced reduction in neural stem cells, cell proliferation, and neuronal differentiation by enhancing the expression of pCREB and BDNF in the dentate gyrus of the hippocampus.
Electronic supplementary material
The online version of this article (doi:10.1186/s12868-014-0116-4) contains supplementary material, which is available to authorized users.
PMCID: PMC4219098  PMID: 25359614
D-galactose; Treadmill exercise; Hippocampus; Adult neurogenesis; Phosphorylated cAMP-response element binding protein; Brain derived neurotrophic factor; Mice
21.  Dendropanax morbifera Léveille extract facilitates cadmium excretion and prevents oxidative damage in the hippocampus by increasing antioxidant levels in cadmium-exposed rats 
Dendropanax morbifera Léveille is used in herbal medicine as a cancer treatment. In this study, we investigated the effects of Dendropanax morbifera stem extract (DMS) on cadmium (Cd) excretion from the blood and kidney and brain tissues of rats exposed to cadmium, as well as the effects of DMS on oxidative stress and antioxidant levels in the hippocampus after Cd exposure.
Seven-week-old Sprague-Dawley rats were exposed to 2 mg/kg of cadmium by intragastric gavage and were orally administered 100 mg/kg of DMS for 4 weeks. Animals were sacrificed and Cd determination was performed using inductively coupled plasma mass spectrometry. In addition, the effects of Cd and/or DMS on oxidative stress were assayed by measuring reactive oxygen species production, protein carbonyl modification, lipid peroxidation levels, and antioxidant levels in hippocampal homogenates.
Exposure to Cd significantly increased Cd content in the blood, kidneys, and hippocampi. DMS treatment significantly reduced Cd content in the blood and kidneys, but not in the hippocampi. Exposure to Cd significantly increased reactive oxygen species production, protein carbonyl modification, lipid peroxidation, total sulfhydryl content, reduced glutathione content, and glutathione reductase activity. In contrast, Cu, Zn-superoxide dismutase (SOD1), catalase (CAT), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) activity in the hippocampus were significantly decreased after exposure to Cd, and administration of DMS significantly inhibited these Cd-induced changes.
These results indicate that DMS facilitates cadmium excretion from the kidneys, reduces cadmium-induced oxidative stress in the hippocampus, and modulates SOD1, CAT, GPx, and glutathione-S-transferase activities.
PMCID: PMC4228155  PMID: 25362479
Dendropanax morbifera extract; Cadmium; Hippocampus; Oxidative stress; Antioxidants
22.  Native Pig and Chicken Breed Database: NPCDB 
Indigenous (native) breeds of livestock have higher disease resistance and adaptation to the environment due to high genetic diversity. Even though their extinction rate is accelerated due to the increase of commercial breeds, natural disaster, and civil war, there is a lack of well-established databases for the native breeds. Thus, we constructed the native pig and chicken breed database (NPCDB) which integrates available information on the breeds from around the world. It is a nonprofit public database aimed to provide information on the genetic resources of indigenous pig and chicken breeds for their conservation. The NPCDB ( provides the phenotypic information and population size of each breed as well as its specific habitat. In addition, it provides information on the distribution of genetic resources across the country. The database will contribute to understanding of the breed’s characteristics such as disease resistance and adaptation to environmental changes as well as the conservation of indigenous genetic resources.
PMCID: PMC4150170  PMID: 25178289
Indigenous (Native) Breeds; Database; Pig; Chicken; Conservation
23.  Profile of selumetinib and its potential in the treatment of melanoma 
OncoTargets and therapy  2014;7:1631-1639.
The mitogen-activated protein kinase (MAPK) pathway is a critical oncogenic driver signal in a number of malignancies. The discovery of activating mutations in the MAPK pathway has led to the development of MAPK pathway inhibitors. Selumetinib is a potent and selective inhibitor of MEK1 and MEK2, which are essential downstream molecules in the MAPK pathway. Several preclinical and clinical studies have demonstrated the promising antitumor activity of selumetinib. In this review, we discuss the MAPK pathway in melanoma and summarized data from preclinical and clinical studies of selumetinib for advanced melanoma.
PMCID: PMC4179759  PMID: 25278770
selumetinib; MEK inhibitor; melanoma; uveal melanoma
24.  Transcriptome sequencing and analysis of the zoonotic parasite Spirometra erinacei spargana (plerocercoids) 
Parasites & Vectors  2014;7:368.
Although spargana, which are the plerocercoids of Spirometra erinacei, are of biological and clinical importance, expressed sequence tags (ESTs) from this parasite have not been explored. To understand molecular and biological features of this parasite, sparganum ESTs were examined by large-scale EST sequencing and multiple bioinformatics tools.
Total RNA was isolated from spargana and then ESTs were generated, assembled and sequenced. Many biological aspects of spargana were investigated using multi-step bioinformatics tools.
A total of 5,634 ESTs were collected from spargana. After clustering and assembly, the functions of 1,794 Sparganum Assembled ESTs (SpAEs) including 934 contigs and 860 singletons were analyzed. A total of 1,351 (75%) SpAEs were annotated using a hybrid of BLASTX and InterProScan. Of these genes, 1,041 (58%) SpAEs had high similarity to tapeworms. In the context of the biology of sparganum, our analyses reveal: (i) a highly expressed fibronectin 1, a ubiquitous and abundant glycoprotein; (ii) up-regulation of enzymes related with glycolysis pathway; (iii) most frequent domains of protein kinase and RNA recognition motif domain; (iv) a set of helminth-parasitic and spargana-specific genes that may offer a number of antigen candidates.
Our transcriptomic analysis of S. erinacei spargana demonstrates biological aspects of a parasite that invades and travels through subcutaneous tissue in intermediate hosts. Future studies should include comparative analyses using combinations of transcriptome and proteome data collected from the entire life cycle of S. erinacei.
Electronic supplementary material
The online version of this article (doi:10.1186/1756-3305-7-368) contains supplementary material, which is available to authorized users.
PMCID: PMC4262225  PMID: 25128015
Spirometra erinacei; Sparganum; Plerocercoids; Transcriptome; Sequencing

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