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1.  Abnormal Neural Processing during Emotional Salience Attribution of Affective Asymmetry in Patients with Schizophrenia 
PLoS ONE  2014;9(3):e90792.
Aberrant emotional salience attribution has been reported to be an important clinical feature in patients with schizophrenia. Real life stimuli that incorporate both positive and negative emotional traits lead to affective asymmetry such as negativity bias and positivity offset. In this study, we investigated the neural correlates of emotional salience attribution in patients with schizophrenia when affective asymmetry was processed. Fifteen patients with schizophrenia and 14 healthy controls were scanned using functional magnetic resonance imaging (fMRI) while performing an emotion judgment task in which two pictures were juxtaposed. The task consisted of responding to affective asymmetry condition (ambivalent and neutral) and affective symmetry conditions (positive and negative), and group comparisons were performed for each condition. Significantly higher activity in the medial prefrontal cortex and inferior frontal gyrus was observed for the ambivalent condition than for the other conditions in controls, but not in patients. Compared with controls, patients showed decreased activities in the dorsolateral prefrontal cortex, dorsal anterior cingulate cortex, insula, and putamen for the ambivalent condition, but no changes were observed for the neutral condition. Multiple prefrontal hypoactivities during salience attribution of negativity bias in schizophrenia may underlie deficits in the integrative processing of emotional information. Regional abnormalities in the salience network may be the basis of defective emotional salience attribution in schizophrenia, which is likely involved in symptom formation and social dysfunction.
doi:10.1371/journal.pone.0090792
PMCID: PMC3949688  PMID: 24619004
2.  Reference Values and Determinants of Fractional Concentration of Exhaled Nitric Oxide in Healthy Children 
Purpose
Measurement of the fractional concentration of exhaled nitric oxide (FeNO) is a quantitative, noninvasive, simple, safe method of assessing airway inflammation. While FeNO measurement has been standardized, reference values for elementary school children are scarce. The aim of this study was to establish reference values for FeNO in children.
Methods
FeNO was measured in elementary school children at 6-12 years of age in Seoul, Korea, following American Thoracic Society guidelines and using a chemiluminescence analyzer (NIOX Exhaled Nitric Oxide Monitoring System, Aerocrine, Sweden). A total of 1,252 children completed a modified International Study of Asthma and Allergy in Children (ISAAC) questionnaire; FeNO was measured in 1,063 children according to the protocol and in 808 children defined as healthy controls.
Results
Mean FeNO were 10.32 ppb, 16.58 ppb, and 12.36 ppb in non-atopic, atopic, and all 808 healthy controls, respectively. FeNO was not associated with age and gender. The FeNO reference equations were determined by multiple linear regression analysis, taking into account the variables of age, height, weight, total IgE, eosinophil percent, and bronchial hyper-responsiveness (methacholine PC20). FeNO=0.776+0.003×total IgE+0.340×eosinophil percent; coefficient of determination (R2)=0.084 in the 501 healthy non-atopic controls. FeNO=-18.365+1.536×eosinophil percent, R2=0.183 in the 307 healthy atopic controls; and FeNO=-7.888+0.130×Height+0.004×total IgE+1.233×eosinophil percent, R2=0.209 in the 808 all healthy controls. Eosinophil percent was correlated with FeNO in all healthy controls. FeNO was not associated with BMI.
Conclusion
This study provides reference values for FeNO that can be used to evaluate airway inflammation in elementary school children. Determinants that could most accurately predict FeNO in healthy school-age children were assessed.
doi:10.4168/aair.2014.6.2.169
PMCID: PMC3936047  PMID: 24587955
FeNO; reference value; determinants; healthy; children
3.  EGCG Attenuates Autoimmune Arthritis by Inhibition of STAT3 and HIF-1α with Th17/Treg Control 
PLoS ONE  2014;9(2):e86062.
Epigallocatechin-3-gallate (EGCG) is a green tea polyphenol exerting potent anti-oxidant and anti-inflammatory effects by inhibiting signaling and gene expression. The objective of the study was to evaluate the effect of EGCG on interleukin (IL)-1 receptor antagonist knockout (IL-1RaKO) autoimmune arthritis models. IL-1RaKO arthritis models were injected intraperitoneally with EGCG three times per week after the first immunization. EGCG decreased the arthritis index and showed protective effects against joint destruction in the IL-1RaKO arthritis models. The expression of pro-inflammatory cytokines, oxidative stress proteins, and p-STAT3 (Y705) and p-STAT3 (S727), mTOR and HIF-1α were significantly lower in mice treated with EGCG. EGCG reduced osteoclast markers in vivo and in vitro along with anti-osteoclastic activity was observed in EGCG-treated IL-1RaKO mice. The proportion of Foxp3+ Treg cells increased in the spleens of mice treated with EGCG, whereas the proportion of Th17 cells reduced. In vitro, p-STAT3 (Y705) and p-STAT3 (S727), HIF1α and glycolytic pathway molecules were decreased by EGCG. EGCG suppressed the activation of mTOR and subsequently HIF-1α, which is considered as a metabolic check point of Th17/Treg differentiation supporting the therapeutic potential of EGCG in autoimmune arthritis.
doi:10.1371/journal.pone.0086062
PMCID: PMC3928092  PMID: 24558360
4.  Recent advance in brown adipose physiology and its therapeutic potential 
Brown adipose tissue (BAT) is a specialized thermoregulatory organ that has a critical role in the regulation of energy metabolism. Specifically, energy expenditure can be enhanced by the activation of BAT function and the induction of a BAT-like catabolic phenotype in white adipose tissue (WAT). Since the recent recognition of metabolically active BAT in adult humans, BAT has been extensively studied as one of the most promising targets identified for treating obesity and its related disorders. In this review, we summarize information on the developmental origin of BAT and the progenitors of brown adipocytes in WAT. We explore the transcriptional control of brown adipocyte differentiation during classical BAT development and in WAT browning. We also discuss the neuronal control of BAT activity and summarize the recently identified non-canonical stimulators of BAT that can act independently of β-adrenergic stimulation. Finally, we review new findings on the beneficial effects of BAT activation and development with respect to improving metabolic profiles. We highlight the therapeutic potential of BAT and its future prospects, including pharmacological intervention and cell-based therapies designed to enhance BAT activity and development.
doi:10.1038/emm.2013.163
PMCID: PMC3944445  PMID: 24556827
brown adipose tissue (BAT); obesity; progenitors; white adipose tissue (WAT)
5.  Effect of Discontinuation of Anticoagulation in Patients with Intracranial Hemorrhage at High Thromboembolic Risk 
Objective
There was no abundance of data on the use of anticoagulant in patients with previous high risk of thromboembolic conditions under a newly developed intracranial hemorrhage in Korean society. The purpose of this study was to evaluate the safety of discontinuance and suggest the proper time period for discontinuance of anticoagulant among these patients.
Methods
We reviewed the medical records of 19 patients who took anticoagulant because of thromboembolic problems and were admitted to our department with newly developed anticoagulation associated intracranial hemorrhage (AAICH), and stopped taking medicine due to concern of rebleeding from January 2008 to December 2012. Analysis of the incidence of thromboembolic complications and proper withdrawal time of anticoagulant was performed using the Kaplan-Meier method.
Results
Our patients showed high risk for thromboembolic complication. The CHA2DS2-VASc score ranged from two to five. Thromboembolic complication occurred in eight (42.1%) out of 19 patients without restarting anticoagulant since the initial hemorrhage. Among them, three patients (37.5%) died from direct thromboembolic complications. Mean time to outbreak of thromboembolic complication was 21.38±14.89 days (range, 8-56 days). The probability of thromboembolic complications at 7, 14, and 30 days since cessation of anticoagulation was 0.00, 10.53, and 38.49%, respectively.
Conclusion
Short term discontinuance of anticoagulant within seven days in patients with AAICH who are at high embolic risk (CHA2DS2-VASc score >2) appears to be relatively safe in Korean people. However, prolonged cessation (more than seven days) may result in increased incidence of catastrophic thromboembolic complications.
doi:10.3340/jkns.2014.55.2.69
PMCID: PMC3958575  PMID: 24653798
Anticoagulation; Intracerebral hemorrhage; Thromboembolic complication
6.  A Novel Synthetic Mycolic Acid Inhibits Bronchial Hyperresponsiveness and Allergic Inflammation in a Mouse Model of Asthma 
Purpose
Recognition of microbes is important to trigger the innate immune system. Mycolic acid (MA) is a component of the cell walls of mycobacteria such as Mycobacterium bovis Bacillus Calmette-Guerin. MA has immunogenic properties, which may modulate the innate and adaptive immune response. This study aimed to investigate whether a novel synthetic MA (sMA) inhibits allergic inflammatory responses in a mouse model of asthma.
Methods
BALB/c mice were injected intraperitoneally with sMA followed by sensitization and challenge with ovalbumin (OVA). Mice were examined for bronchial hyperresponsiveness (BHR), the influx of inflammatory cells into the lung tissues, histopathological changes in the lungs and CD4+CD25+Foxp3+ T cells in the spleen, and examined the response after the depleting regulatory T cells (Tregs) with an anti-CD25mAb.
Results
Treatment of mice with sMA suppressed the asthmatic response, including BHR, bronchoalveolar inflammation, and pulmonary eosinophilic inflammation. Anti-CD25mAb treatment abrogated the suppressive effects of sMA in this mouse model of asthma and totally depleted CD4+CD25+Foxp3+ T cells in the spleen.
Conclusions
sMA attenuated allergic inflammation in a mouse model of asthma, which might be related with CD4+CD25+Foxp3+ T cell.
doi:10.4168/aair.2014.6.1.83
PMCID: PMC3881406  PMID: 24404398
Mycolic acid; asthma; allergic inflammation; regulatory T cells; mice
7.  Mortality and Real Cause of Death from the Nonlesional Intracerebral Hemorrhage 
Objective
The case fatality rate of nonlesional intracerebral hemorrhage (n-ICH) was high and not changed. Knowing the causes is important to their prevention; however, the reasons have not been studied. The aims of this study were to determine the cause of death, to improve the clinical outcomes.
Methods
We retrospectively analyzed consecutive cases of nonlesional intracerebral hemorrhage in a prospective stroke registry from January 2010 to December 2010.
Results
Among 174 patients (61.83±13.36, 28-90 years), 29 patients (16.7%) died during hospitalization. Most common cause of death was initial neurological damage (41.4%, 12/29). Seventeen patients who survived the initial damage may then develop various potentially fatal complications. Except for death due to the initial neurological sequelae, death associated with immobilization (such as pneumonia or thromboembolic complication) was the most common in eight cases (8/17, 47.1%). However, death due to early rebleeding was not common and occurred in only 2 cases (2/17, 11.8%). Age, initial Glasgow Coma Scale, and diabetes mellitus were statistically significant factors influencing mortality (p<0.05).
Conclusion
Mortality of n-ICH is still high. Initial neurological damage is the most important factor; however, non-neurological medical complications are a large part of case fatality. Most cases of death of patients who survived from the first bleeding were due to complications of immobilization. These findings have implications for clinical practice and planning of clinical trials. In addition, future conduct of a randomized study will be necessary in order to evaluate the benefits of early mobilization for prevention of immobilization related complications.
doi:10.3340/jkns.2014.55.1.1
PMCID: PMC3928341  PMID: 24570810
Intracerebral hemorrhage; Cause of death
8.  Prognostic Factors of Neurocognitive and Functional Outcomes in Junior and Senior Elderly Patients with Traumatic Brain Injury Undergoing Disability Evaluation or Appointed Disability Evaluation 
Objective
This study explored the relationships among demographic (DVs) and clinical variables (CVs), neurocognitive (NOs) and functional outcome (FO) that could be used as prognostic factors for old aged patients with traumatic brain injury (TBI) undergoing or appointed disability evaluation (DE) after treatment.
Methods
A total of 162 subjects with TBI above the age of 55 years undergoing DE or appointed to do so after treatments were selected. The patients were divided into two subgroups according to age : a junior elderly group 55 to 64 years old and a senior elderly group over the age of 65. NOs and FO were evaluated using the Seoul Neuropsychological Screening Battery and Clinical Dementia Rating scale.
Results
Gender, age, and education level were shown to significantly impact the recovery of NOs after TBI. Other DVs and CVs such as area of residency, occupation, type of injury, or loss of consciousness were not found to significantly affect the recovery of NOs after TBI. Analysis of the relationships among DVs, CVs and NOs demonstrated that gender, age, and education level contributed to the variance of NOs. In FO, loss of consciousness (LOC) was included to prognostic factor.
Conclusion
Gender, age and education level significantly influence the NOs of elderly patients with TBI. LOC may also serve as a meaningful prognostic factor in FO. Unlike younger adult patients with TBI, old aged patients with TBI did not show global faking-bad or malingering attitudes to DE for compensation, but assume that they could faking their performance in a test set available visual feedback.
doi:10.3340/jkns.2014.55.1.18
PMCID: PMC3928343  PMID: 24570813
Advanced age; Traumatic brain injury; Prognosis; Gender; Education
9.  Helicobacter pylori and interleukin-8 in gastric cancer 
Helicobacter pylori (H. pylori) is a major etiological factor in the development of gastric cancer. Large-scale epidemiological studies have confirmed the strong association between H. pylori infection and both cancer development and progression. Interleukin-8 (IL-8) is overexpressed in gastric mucosa exposed to H. pylori. The expression of IL-8 directly correlates with a poor prognosis in gastric cancer. IL-8 is multifunctional. In addition to its potent chemotactic activity, it can induce proliferation and migration of cancer cells. In this review, we focus on recent insights into the mechanisms of IL-8 signaling associated with gastric cancer. The relationship between IL-8 and H. pylori is discussed. We also summarize the current therapeutics against IL-8 in gastric cancer.
doi:10.3748/wjg.v19.i45.8192
PMCID: PMC3857441  PMID: 24363509
Helicobacter pylori; Interleukin-8; Signals; Gastric cancer; Therapeutics
10.  Posterior Cruciate Ligament: Focus on Conflicting Issues 
Clinics in Orthopedic Surgery  2013;5(4):256-262.
There is little consensus on how to optimally reconstruct the posterior cruciate ligament (PCL) and the natural history of injured PCL is also unclear. The graft material (autograft vs. allograft), the type of tibial fixation (tibial inlay vs. transtibial tunnel), the femoral tunnel position within the femoral footprint (isometric, central, or eccentric), and the number of bundles in the reconstruction (1 bundle vs. 2 bundles) are among the many decisions that a surgeon must make in a PCL reconstruction. In addition, there is a paucity of information on rehabilitation after reconstruction of the PCL and posterolateral structures. This article focused on the conflicting issues regarding the PCL, and the scientific rationales behind some critical points are discussed.
doi:10.4055/cios.2013.5.4.256
PMCID: PMC3858094  PMID: 24340144
Knee; Posterior cruciate ligament; Biomechanics; Outcome; Rehabilitation
11.  Remnant Preservation is Helpful to Obtain Good Clinical Results in Posterior Cruciate Ligament Reconstruction: Comparison of Clinical Results of Three Techniques 
Clinics in Orthopedic Surgery  2013;5(4):278-286.
Background
The purpose of the present study was to compare the clinical results of 3 posterior cruciate ligament reconstruction techniques according to the time from injury to surgery and remnant PCL status and to evaluate the efficiency of each technique.
Methods
The records of 89 patients who underwent primary PCL reconstructions with a posterolateral corner sling were analyzed retrospectively. Thirty-four patients were treated by anterolateral bundle (ALB) reconstruction with preservation of the remnant PCL using a transtibial tunnel technique in the acute and subacute stages of injury (group 1). Forty patients were treated with remnant PCL tensioning and an ALB reconstruction using the modified inlay technique in the chronic stage (group 2), and fifteen patients were treated with double-bundle reconstruction using the modified inlay technique (group 3). The double-bundle reconstruction was performed if there was a very weak or no PCL remnant.
Results
The mean side-to-side differences in posterior tibial translation on the stress radiographs were reduced from 10.1 ± 2.5 mm in group 1, 10.6 ± 2.4 mm in group 2, and 12.8 ± 3.2 mm in group 3 preoperatively to 2.3 ± 1.4 mm in group 1, 2.3 ± 1.5 mm in group 2, and 4.0 ± 2.5 mm in group 3 at the last follow-up (p < 0.001, p < 0.001, and p < 0.001, respectively). Statistical analyses revealed that group 1 and group 2 were similar in terms of side-to-side difference changes in posterior tibial translation on the stress radiographs; however, group 3 was inferior to group 1 and group 2 at the last follow-up (p = 0.022). The clinical results were not significantly different among the three groups.
Conclusions
Excellent posterior stability and good clinical results were achieved with ALB reconstruction preserving the injured remnant PCL in the acute and subacute stages and remnant PCL tensioning with ALB reconstruction in the chronic stage. The PCL injuries could be surgically corrected with different techniques depending on both the remnant PCL status and the interval between the knee trauma and operation.
doi:10.4055/cios.2013.5.4.278
PMCID: PMC3858099  PMID: 24340147
Posterior cruciate ligament; Posterolateral corner reconstruction; Modified inlay; Transtibial tunnel; Double-bundle
12.  Phenolic Composition, Antioxidant Activity and Anti-Adipogenic Effect of Hot Water Extract from Safflower (Carthamus tinctorius L.) Seed 
Nutrients  2013;5(12):4894-4907.
This study was to evaluate the phenolic content and composition of Carthamus tinctorius L. seed extract (CSE) and to further assess its antioxidant and anti-adipogenic activities using various radical scavenging systems and 3T3-L1 cells. Our results show that the total phenolic and flavonoid contents of CSE were 126.0 ± 2.4 mg GAE/g and 62.2 ± 1.9 mg QE/g, respectively. The major phenolic compounds in CSE was (−)-epigallocatechin (109.62 mg/g), with a 4-hydroxy benzhydrazide derivative and gallocatechin present at 18.28 mg/g and 17.02 mg/g, respectively. CSE exhibited remarkable radical scavenging activities, FRAP (ferric reducing antioxidant power) and reducing power in a dose-dependent manner. Moreover, the oxygen radical absorbance capacity (ORAC) value of CSE (0.1 mg/mL) was 62.9 ± 4.7 μM TE (trolox equivalent)/g. During adipogenesis, CSE significantly inhibited fat accumulation in 3T3-L1 cells compared with control cells. Overall, these results indicate that CSE might be a valuable source of bioactive compounds that impart functional food and natural antioxidant properties.
doi:10.3390/nu5124894
PMCID: PMC3875912  PMID: 24288028
antioxidant activity; phenolic compound; Carthamus tinctorius L. seed; 3T3-L1 adipocyte; hot-water extract
13.  Precautionary effects of Red Liriope platyphylla on NGF secretion and Aβ42 deposition under the preclinical stage of Alzheimer's disease in Tg2576 mice 
Laboratory Animal Research  2013;29(4):212-220.
Red Liriope platyphylla (RLP) has been manufactured from Liriope platyphylla (L. platyphylla, LP) roots using steaming process and investigated as a curative agent for treatment of diabetes, obesity and neurodegenerative disorders. To examine the precautionary effects of aqueous extract RLP (AEtRLP) on the preclinical stages of Alzheimer's Disease (AD), alterations of the key factors influencing AD were investigated in Tg2576 mice after AEtRLP7 treatment for 4 months. Aβ-42 peptides level was significantly decreased in the brain of AEtRLP7-treated Tg2576 mice compared to vehicle-treated Tg2576 mice, although significant differences on improving behavioral defects were not observed in the same group. The concentration of nerve growth factor (NGF) in serum was also higher in AEtRLP7-treated Tg2576 mice than vehicle-treated Tg2576 mice. However, the phosphorylation of TrkA and Erk among the downstream effectors of the high affinity NGF receptor was significantly lower in AEtRLP7-treated Tg2576 mice. A similar pattern was observed in the expression level of downstream effectors within low affinity NGF receptor. Overall, these results suggest that AEtRLP7 can contribute to preventing the production and deposition of Aβ-42 peptides during the early progression stage of AD in the brain of Tg2576 mice through increased NGF secretion.
doi:10.5625/lar.2013.29.4.212
PMCID: PMC3879340  PMID: 24396386
Red Liriope platyphylla; NGF; NGF signaling pathway; Aβ-42
14.  Effects of Color Temperature and Brightness on Electroencephalogram Alpha Activity in a Polychromatic Light-emitting Diode 
Objective
It has been reported that working and learning efficiency might be increased through artificially controlling the color temperature and brightness of light. However, the neurological bases of these outcomes are not well established. Our study was designed to observe whether electroencephalogram (EEG) alpha frequency, as a candidate biological marker, demonstrates significant changes in response to alterations of specific light parameters.
Methods
Thirty-two healthy subjects performed cognitive tasks under four different polychromatic light conditions: a combination of two different levels of color temperature (2766K vs. 5918K) and brightness (300 lux vs. 600 lux). Spectrum analyses were performed on alpha frequency.
Results
Subjects reported that they felt more pleasant in bright conditions and more relaxed in warm color temperature conditions. Our findings indicate that alpha power increases in warm, low-light and cool, high-light conditions, and there is a significant interaction between color temperature and brightness.
Conclusion
EEGs might serve as a useful biological marker for further research related to the effects of polychromatic light on cognitive function.
doi:10.9758/cpn.2013.11.3.126
PMCID: PMC3897760  PMID: 24465248
Polychromatic light; Color temperature; Brightness; Electroencephalogram; Alpha frequency
15.  Aqueous Extract of Bambusae Caulis in Taeniam Inhibits PMA-Induced Tumor Cell Invasion and Pulmonary Metastasis: Suppression of NF-κB Activation through ROS Signaling 
PLoS ONE  2013;8(10):e78061.
Bamboo shavings (Bambusae Caulis in Taeniam, BCT) are widely used as a traditional Chinese medicine to control hypertension and cardiovascular disease, and to alleviate fever, vomiting, and diarrhea. It has been demonstrated that BCT reduces ovalbumin-induced airway inflammation by regulating pro-inflammatory cytokines, and decreases tumor growth in tumor-bearing mice. However, the effects of BCT on the metastatic potential of malignant cancer cells and the detailed mechanism of its anti-metastatic activity have not been examined previously. In this study, we investigated whether an aqueous extract of BCT (AE-BCT) reduces the metastatic potential of HT1080 cells, and elucidated the underlying anti-metastatic mechanism. In addition, we examined whether AE-BCT administration inhibits pulmonary metastasis of intravenously injected B16F10 cells in C57BL/6J mice. AE-BCT (50–250 µg/ml) dose-dependently suppressed colony-forming activity under anchorage-dependent and -independent growth conditions. Pretreatment with AE-BCT efficiently inhibited cell migration, invasion, and adhesion. AE-BCT also dramatically suppressed PMA-induced MMP-9 activity and expression by blocking NF-κB activation and ERK phosphorylation. Production of intracellular ROS, a key regulator of NF-κB-induced MMP-9 activity, was almost completely blocked by pretreatment with AE-BCT. Furthermore, daily oral administration of AE-BCT at doses of 50 and 100 mg/kg efficiently inhibited lung metastasis of B16F10 cells injected into the tail veins of C57BL/6J mice with no systemic toxicity. These results demonstrate that AE-BCT significantly reduced the metastatic activity of highly malignant cancer cells by suppressing MMP-9 activity via inhibition of ROS-mediated NF-κB activation. These results indicate that AE-BCT may be a safe natural product for treatment of metastatic cancer.
doi:10.1371/journal.pone.0078061
PMCID: PMC3810142  PMID: 24205091
16.  Effect of Rosemarinus officinalis L. on MMP-9, MCP-1 Levels, and Cell Migration in RAW 264.7 and Smooth Muscle Cells 
Journal of Medicinal Food  2012;15(10):879-886.
Abstract
Atherosclerosis is a chronic and progressive inflammatory disease. Novel anti-inflammatory therapies may have promise as treatment strategies for cardiovascular risk reduction. Rosemary (Rosemarinus officinalis L.) has been used in folk medicine to treat headaches, epilepsy, poor circulation, and many other ailments. It was found that rosemary could act as a stimulant and mild analgesic and could reduce inflammation. However, the mechanisms underlying the anti-inflammatory and antiatherosclerotic effects of rosemary need more study. This study investigated effects of the rosemary components, carnosic acid (CA), and carnosol (CAR), on cell migration. Monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) were determined by Western blot and gelatin zymography, respectively, in RAW 264.7 macrophages and vascular smooth muscle cells (VSMCs). VSMC migration was assessed by a Matrigel migration assay. Active compounds of rosemary extracts were also analyzed using a reversed-phase high-performance liquid chromatography. MMP-9 and MCP-1 activities were markedly diminished with methanol extract (RM), n-hexane fraction (RH), and CA in RAW 264.7 cells. RM, RH, CA, and CAR suppressed tumor necrosis factor-alpha–induced VSMC migration by inhibiting MMP-9 expression. Chromatograms of RM- and RH-containing CA and CAR revealed higher CA contents of RM (9.4%, 93.85 μg/mg dry wt.) and, especially, RH (18.4%, 184.00 μg/mg dry wt.), which were appreciably elevated compared with the similar CAR content in RM and RH (3.7%, 37.30 μg/mg dry wt.; and 2.5%, 25.05 μg/mg dry wt., respectively). Rosemary, especially its CA component, has potential antiatherosclerosis effects related to cell migration.
doi:10.1089/jmf.2012.2162
PMCID: PMC3466913  PMID: 22985398
Rosemarinus officinalis L.; rosemary; matrix metalloproteinase-9 (MMP-9); monocyte chemoattractant protein-1 (MCP-1); migration; RAW 264.7 macrophages; vascular smooth muscle cell
17.  Association between cord blood 25-hydroxyvitamin D concentrations and respiratory tract infections in the first 6 months of age in a Korean population: a birth cohort study (COCOA) 
Korean Journal of Pediatrics  2013;56(10):439-445.
Purpose
Previous studies suggest that the concentration of 25-hydroxyvitamin D [25(OH)D] in cord blood may show an inverse association with respiratory tract infections (RTI) during childhood. The aim of the present study was to examine the influence of 25(OH)D concentrations in cord blood on infant RTI in a Korean birth cohort.
Methods
The levels of 25(OH)D in cord blood obtained from 525 Korean newborns in the prospective COhort for Childhood Origin of Asthma and allergic diseases were examined. The primary outcome variable of interest was the prevalence of RTI at 6-month follow-up, as diagnosed by pediatricians and pediatric allergy and pulmonology specialists. RTI included acute nasopharyngitis, rhinosinusitis, otitis media, croup, tracheobronchitis, bronchiolitis, and pneumonia.
Results
The median concentration of 25(OH)D in cord blood was 32.0 nmol/L (interquartile range, 21.4 to 53.2). One hundred and eighty neonates (34.3%) showed 25(OH)D concentrations less than 25.0 nmol/L, 292 (55.6%) showed 25(OH)D concentrations of 25.0-74.9 nmol/L, and 53 (10.1%) showed concentrations of ≥75.0 nmol/L. Adjusting for the season of birth, multivitamin intake during pregnancy, and exposure to passive smoking during pregnancy, 25(OH)D concentrations showed an inverse association with the risk of acquiring acute nasopharyngitis by 6 months of age (P for trend=0.0004).
Conclusion
The results show that 89.9% of healthy newborns in Korea are born with vitamin D insufficiency or deficiency (55.6% and 34.3%, respectively). Cord blood vitamin D insufficiency or deficiency in healthy neonates is associated with an increased risk of acute nasopharyngitis by 6 months of age. More time spent outdoors and more intensified vitamin D supplementation for pregnant women may be needed to prevent the onset of acute nasopharyngitis in infants.
doi:10.3345/kjp.2013.56.10.439
PMCID: PMC3827492  PMID: 24244212
Cohort studies; Infant; Respiratory tract infections; Umbilical cord blood; Vitamin D
18.  Cediranib Inhibits both the Intraosseous Growth of PDGF D-Positive Prostate Cancer Cells and the Associated Bone Reaction 
The Prostate  2011;72(12):1328-1338.
BACKGROUND
The major cause of death in prostate cancer (PCa) cases is due to distant metastatic lesions, with the bone being the most prevalent site for secondary colonization. Utilization of small molecule inhibitors to treat bone metastatic PCa have had limited success either as monotherapies or in combination with other chemotherapeutics due to intolerable toxicities. In the current study, we developed a clinically relevant in vivo intraosseous tumor model overexpressing the platelet-derived growth factor D (PDGF D) to test the efficacy of a newly characterized VEGFR/PDGFR inhibitor, cediranib (also called AZD2171).
METHODS
An intratibial-injection model was established utilizing DU145 cells without or with increased platelet-derived growth factor D (PDGF D) expression. Tumor-bearing mice were treated by daily gavage administration of cediranib and/or weekly i.p. injection of docetaxel for 7 weeks. Tibiae were monitored by in vivo/ex vivo x-rays and histomorphometry analysis was performed to estimate tumor volume and tumor-associated trabecular bone growth.
RESULTS
Cediranib reduced intraosseous growth of prostate tumors as well as tumor-associated bone responses. When compared to the standard chemotherapeutic agent docetaxel, cediranib exhibited a stronger inhibition of tumor-associated bone response. The efficacy of cediranib was further enhanced when the drug was co-administered with docetaxel. Importantly, the therapeutic benefits of cediranib and docetaxel are more prominent in intraosseous prostate tumors overexpressing PDGF D.
CONCLUSION
These novel findings support the utilization of cediranib, either alone or in combination with docetaxel, to treat bone metastatic prostate cancer exhibiting PDGF D expression.
doi:10.1002/pros.22481
PMCID: PMC3369116  PMID: 22213159
PDGF D; Prostate Cancer; AZD2171; Metastasis; Markers
19.  The Anatomy of the Superficial Temporal Artery in Adult Koreans Using 3-Dimensional Computed Tomographic Angiogram: Clinical Research 
Objective
The increased use of bypass surgery in the treatment of ischemic cerebrovascular diseases requires a better understanding of the superficial temporal artery (STA) anatomy. This study is to describe the gross anatomy of STA in adult Korean population with respect to cranial surgery and to provide basic anatomic data for bypass surgery.
Methods
The study evaluated retrospectively 35 patients who visited the neurosurgery department at a single institution. For each patient, both the left and right STA (70 vessels) were evaluated by a 3-dimensional computed tomographic angiogramfor diameter and anatomic relationships to external landmarks.
Results
Of 70 STAs, 69 had a bifurcation. Among these, 57 (82.6%) were above the superior margin of the zygomatic arch. The STA bifurcation was 53.2 ± 5.9 mm posterior to the keyhole, 9.5 ± 5.3 mm anterior to the posterior margin of condylar process of the mandible, and 21.7 ± 15.8 mm superior to the superior margin of the zygomatic arch. The inner diameter of the STA was 1.8 ± 0.5 mm at the superior margin of the zygomatic arch, and 1.4 ± 0.4 mm and 1.4 ± 0.5 mm for frontal and parietal branches, respectively. The 75.7% of frontal and 66.7% of parietal branches were suitable for microvascular anastomosis.
Conclusion
This present study demonstrated the STA in Korean adults, which may benefit the clinician in dealing with the surgical procedures related to this STA.
doi:10.7461/jcen.2013.15.3.145
PMCID: PMC3804650  PMID: 24167792
Carotid artery; External; Temporal arteries
20.  Intraosseous Arteriovenous Malformation of the Sphenoid Bone Presenting with Orbital Symptoms Mimicking Cavernous Sinus Dural Arteriovenous Fistula: A Case Report 
Intraosseous arteriovenous malformation (AVM) in the craniofacial region is rare. When it occurs, it is predominantly located in the mandible and maxilla. We encountered a 43-year-old woman with Klippel-Trenaunay syndrome affecting the right lower extremity who presented with a left orbital chemosis and proptosis mimicking the cavernous sinus dural arteriovenous fistula. Computed tomography angiography revealed an intraosseous AVM of the sphenoid bone. The patient's symptoms were completely relieved after embolization with Onyx. We report an extremely rare case of intraosseous AVM involving the sphenoid bone, associated with Klippel-Trenaunay syndrome.
doi:10.7461/jcen.2013.15.3.251
PMCID: PMC3804667  PMID: 24167809
Arteriovenous malformations; Hemangioma; Primary intraosseous vascular malformation; Klippel-Trenaunay-Weber syndrome
21.  Incidental Superior Hypophygeal Artery Aneurysm Embedded within Pituitary Adenoma 
Intra-cranial aneurysm can be incidental findings in patients with pituitary adenomas, and are usually located outside the pituitary region. However, the coexistence of intrasellar (not intracranial) aneurysms with pituitary adenomas is extremely rare. We report a patient with an incidental superior hypophygeal aneurysm embedded within a non-functional pituitary adenoma which was treated by transsphenoidal surgery after endovascular coil embolization.
doi:10.3340/jkns.2013.54.3.250
PMCID: PMC3836936  PMID: 24278658
Pituitary adenoma; Aneurysm; Therapeutic embolization; Surgical procedure
22.  Disruption of Orbitofronto-Striatal Functional Connectivity Underlies Maladaptive Persistent Behaviors in Alcohol-Dependent Patients 
Psychiatry Investigation  2013;10(3):266-272.
Objective
Alcohol dependence is characterized by persistent alcohol-seeking despite negative consequences. Previous studies suggest that maladaptive persistent behaviors reflect alcohol-induced brain changes that cause alterations in the cortico-striatal-limbic circuit.
Methods
Twenty one alcohol dependent patients and 24 age-matched healthy controls performed a decision-making task during functional MRI. We defined the medial orbitofrontal cortex (mOFC) as a region-of-interest and performed seed-based functional connectivity analysis.
Results
Healthy controls were more flexible in adapting an alternative behavioral strategy, which correlated with stronger mOFC-dorsal striatum functional connectivity. In contrast, alcohol dependent patients persisted to the first established behavioral strategy. The mOFC-dorsal striatum functional connectivity was impaired in the alcohol-dependent patients, but increased in correlation with the duration of abstinence.
Conclusion
Our findings support that the disruption of the mOFC-striatal circuitry contribute to the maldaptive persistent behaviors in alcohol dependent patients.
doi:10.4306/pi.2013.10.3.266
PMCID: PMC3843019  PMID: 24302950
Alcohol; Medial orbitofrontal cortex; Dorsal striatum; Decision-making; fMRI
23.  Ovarian metastasis from pulmonary adenocarcinoma 
Obstetrics & Gynecology Science  2013;56(5):341-344.
Metastatic ovarian cancer is not an uncommon finding. Such tumors almost always originate from female genital tract, colon, stomach, or breast. Lung cancer is not a common origin of ovarian metastases. Of all metastatic ovarian tumors, approximately 0.3% arise from lung cancer. Ovarian torsion is not an uncommon finding, but ovarian torsion with cancer is rare. Here, we report a 44-year-old woman who was previously diagnosed with advanced stage lung cancer and who emergently visited our hospital for abdominal pain. An imaging work-up revealed, ovarian torsion and exploratory laparotomy was performed. Pathological examination led to the diagnosis ovarian metastasis from lung cancer. This is the first case of ovarian metastasis from lung cancer, ovarian torsion.
doi:10.5468/ogs.2013.56.5.341
PMCID: PMC3784134  PMID: 24328026
Lung cancer; Metastatic ovarian cancer; Ovarian torsion
24.  Ssanghwa-tang, an oriental herbal cocktail, exerts anti-melanogenic activity by suppression of the p38 MAPK and PKA signaling pathways in B16F10 cells 
Background
Ssanghwa-tang (SHT) is a widely used medication for the treatment of fatigue, pain, inflammation, hypothermia, erectile dysfunction, cancer, and osteoporosis in Asia, however, role of SHT on the melanin synthesis has not been checked previously. Thus, the present study was designed to determine the effect of SHT on α-melanocyte stimulating hormone (α-MSH)-induced melanogensis and its mechanisms of action in murine B16F10 melanoma cells.
Method
Cellular melanin content and tyrosinase activity in murine B16F10 melanoma cells were determined after α-MSH stimulation with or without pre-treatment of SHT at the concentration of 250 and 500 μg/ml. Expression level of tyrosinase, tyrosinase-related protein 1 (TRP-1), TRP-2, microphthalmia-associated transcription factor (MITF), and activation of c-AMP-dependent protein kinase (PKA), c-AMP-related element binding protein (CREB), and mitogen-activated protein kinases (MAPKs) were examined by Western blot analysis.
Results
SHT significantly inhibited α-MSH-induced melanin synthesis and tyrosinase activity, and also decreased α-MSH-induced expression of MITF, tyrosinase, and TRP-1. In addition, SHT remarkably suppressed tyrosinase, CRE, and MITF luciferase reporter activity in a resting state as well as in α-MSH-stimulating condition. Phosphorylation of p38 MAPK by α-MSH stimulation was efficiently blocked by SHT pre-treatment. Moreover, SHT as an herbal cocktail showed synergistic anti-melanogenic effect compared with that of each single constituent herb.
Conclusion
SHT efficiently inhibited c-AMP-induced melanin synthesis in B16F10 cells via suppression of PKA and p38 MAPK signaling pathways and subsequently decreased the level of CREB phosphorylation, MITF, and melanogenic enzymes. These results indicate that SHT may be useful as herbal medicine for treating hyperpigmentation and cosmetics as a skin-whitening agent.
doi:10.1186/1472-6882-13-214
PMCID: PMC3765811  PMID: 23981281
Ssanghwa-tang; Melanogenesis; p38 MAPK; PKA; MITF; Tyrosinase; B16F10 cells
25.  The Impact of Inosine Triphosphatase Variants on Hemoglobin Level and Sustained Virologic Response of Chronic Hepatitis C in Korean 
Journal of Korean Medical Science  2013;28(8):1213-1219.
Two variants of the inosine triphosphatase (ITPA: rs1127354, rs7270101) gene cause ITPA deficiency and protect against the hemolytic toxicity of ribavirin. We investigated the clinical significance of ITPA variants in Korean patients treated with pegylated interferon (PEG-IFN) plus ribavirin. Of the 133 patients, 108 were CC and 25 were non-CC at rs1127354 (groups A and B, respectively). On the other hand, at rs7270101 all 133 were AA. The mean values of Hemoglobin (Hgb) after 4, 8, and 12 weeks of treatment in groups A and B were 12.2 and 14.0, 11.8 and 13.2, and 11.5 and 12.9, respectively (P=0.001, 0.036, 0.036). Sustained virologic response (SVR) was achieved in 67.8% (40/59) of genotype 1 patients and in 75% (27/36) of non-genotype 1 patients. Regarding ITPA variants, SVR was achieved by 66% and 80% of genotype 1 (P=0.282), and by 78% and 71% (P=0.726) of non-genotype 1. SVR was not significantly different in groups A and B. In conclusion, non-CC at rs1127354 without involvement of rs7270101 is strongly associated with protection from ribavirin-induced anemia, however, ITPA genotype is not associated with SVR.
doi:10.3346/jkms.2013.28.8.1213
PMCID: PMC3744711  PMID: 23960450
Hepatitis C, Chronic; Ribavirin; Anemia; ITPA; IL28B

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