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1.  Broadband antireflective silicon nanostructures produced by spin-coated Ag nanoparticles 
We report the fabrication of broadband antireflective silicon (Si) nanostructures fabricated using spin-coated silver (Ag) nanoparticles as an etch mask followed by inductively coupled plasma (ICP) etching process. This fabrication technique is a simple, fast, cost-effective, and high-throughput method, making it highly suitable for mass production. Prior to the fabrication of Si nanostructures, theoretical investigations were carried out using a rigorous coupled-wave analysis method in order to determine the effects of variations in the geometrical features of Si nanostructures to obtain antireflection over a broad wavelength range. The Ag ink ratio and ICP etching conditions, which can affect the distribution, distance between the adjacent nanostructures, and height of the resulting Si nanostructures, were carefully adjusted to determine the optimal experimental conditions for obtaining desirable Si nanostructures for practical applications. The Si nanostructures fabricated using the optimal experimental conditions showed a very low average reflectance of 8.3%, which is much lower than that of bulk Si (36.8%), as well as a very low reflectance for a wide range of incident angles and different polarizations over a broad wavelength range of 300 to 1,100 nm. These results indicate that the fabrication technique is highly beneficial to produce antireflective structures for Si-based device applications requiring low light reflection.
PMCID: PMC3917369  PMID: 24484636
Silicon nanostructures; Spin-coated Ag nanoparticles; Antireflection; Rigorous coupled-wave analysis
2.  Relationship between insulin resistance, obesity and serum prostate-specific antigen levels in healthy men 
Asian Journal of Andrology  2010;12(3):400-404.
The purpose of this study was to determine the relationship between insulin resistance, obesity and serum prostate-specific antigen (PSA) levels in healthy men with serum PSA level below 4 ng mL−1. The men included in the study cohort were 11 827 healthy male employees of the Korea Hydro and Nuclear Power Co., LTD who had undergone medical checkups including fasting glucose, fasting insulin and serum PSA between January 2003 and December 2008. Insulin resistance was calculated by homeostasis model assessment (HOMA [fasting glucose × fasting insulin]/22.5) and quantitative insulin sensitivity check index (QUICKI; 1/[log (fasting insulin) + log (fasting glucose)]). Age-adjusted body mass index (BMI) was significantly increased according to increasing quartile of insulin resistance as determined by HOMA and QUICKI, respectively, in analysis of variance (ANOVA) test and Duncan's multiple comparison test (P < 0.001), but age-adjusted serum PSA concentration was significantly decreased according to increasing quartile of insulin resistance as determined by HOMA and QUICKI (P < 0.001). Age, BMI, insulin resistance by HOMA or QUICKI were significantly independent variables to serum PSA level in a multivariate linear regression analysis (P < 0.001). Insulin resistance was a significant independent variable to serum PSA level along with BMI. Insulin resistance and BMI were negatively correlated with serum PSA level in healthy men. Insulin resistance was positively correlated with BMI.
PMCID: PMC3739256  PMID: 20305674
body mass index; insulin resistance; metabolic syndrome X; obesity; prostate-specific antigen
3.  PKA-activated ApAF–ApC/EBP heterodimer is a key downstream effector of ApCREB and is necessary and sufficient for the consolidation of long-term facilitation 
The Journal of Cell Biology  2006;174(6):827-838.
Long-term memory requires transcriptional regulation by a combination of positive and negative transcription factors. Aplysia activating factor (ApAF) is known to be a positive transcription factor that forms heterodimers with ApC/EBP and ApCREB2. How these heterodimers are regulated and how they participate in the consolidation of long-term facilitation (LTF) has not, however, been characterized. We found that the functional activation of ApAF required phosphorylation of ApAF by PKA on Ser-266. In addition, ApAF lowered the threshold of LTF by forming a heterodimer with ApCREB2. Moreover, once activated by PKA, the ApAF–ApC/EBP heterodimer transactivates enhancer response element–containing genes and can induce LTF in the absence of CRE- and CREB-mediated gene expression. Collectively, these results suggest that PKA-activated ApAF–ApC/EBP heterodimer is a core downstream effector of ApCREB in the consolidation of LTF.
PMCID: PMC2064337  PMID: 16966424
4.  Rifabutin-based High-dose Proton-pump Inhibitor and Amoxicillin Triple Regimen as the Rescue treatment for Helicobacter pylori 
Helicobacter  2014;19(6):455-461.
Rifabutin has been known to be effective in multidrug-resistant Helicobacter pylori-harboring patients undergoing treatment failure for H. pylori infection.
To evaluate the efficacy of 7-day treatment regimen consisting rifabutin daily but increasing the dose of amoxicillin and lansoprazole in patients who have failed first and second eradication and to assess the side effect profiles in South Korea.
From December 2007 to May 2013, 59 H. pylori-infected patients with two previous eradication failures were enrolled for this study prospectively. The eligible patients were randomly assigned to either group A or B. Group A received lansoprazole 30 mg bid, amoxicillin 1.0 g tid and rifabutin 150 mg bid during 7 days, whereas group B received lansoprazole 60 mg bid, amoxicillin 1.0 g tid and rifabutin 150 mg bid during 7 days.
In group A, H. pylori eradication was achieved in 25 (78.1%) of the 32 patients in the ITT analysis and in 25 (80.6%) of the 31 patients in the PP analysis. In group B, H. pylori eradication was achieved in 26 (96.3%) of the 27 patients in the ITT analysis and in 27 (100%) of the 26 patients in the PP analysis. There was statistically significant difference between the two groups in terms of the eradication rates in PP analysis (p = .047), whereas a marginally statistical significance was found in terms of the eradication rates in ITT analysis (p = .051). Reported side effects were mild, and treatment was well tolerated. No major changes in physical examination or in standard laboratory parameters were observed after treatment.
Rifabutin-based high-dose proton-pump inhibitor (PPI)-combined therapy as empirical rescue treatment is more effective than standard dose PPI-combined rifabutin-based therapy, safe and best tolerable in third-line therapy in the Korean population. The key to successful rescue therapy with rifabutin–amoxicillin–PPI regimen may be to increase doses of PPI.
PMCID: PMC4284035  PMID: 25231089
Rifabutin; third-line recue therapy; high-dose proton-pump inhibitor; amoxicillin
5.  PFKFB3 regulates oxidative stress homeostasis via its S-glutathionylation in cancer 
Journal of molecular biology  2013;426(4):830-842.
Whereas moderately increased cellular oxidative stress is supportive for cancerous growth of cells, excessive levels of reactive oxygen species (ROS) is detrimental to their growth and survival. We demonstrated that high ROS levels, via increased oxidized glutathione (GSSG), induce isoform-specific S-glutathionylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) at the residue Cys206, which is located near the entrance to the 6-phosphofructo-2-kinase catalytic pocket. Upon this ROS-dependent, reversible, covalent modification, a marked decrease in its catalytic ability to synthesize the Fructose-2,6-bisphosphate (Fru-2,6-P2), the key glycolysis allosteric activator, was observed. This event was coupled to a decrease in glycolytic flux and an increase in glucose metabolic flux into the pentose phosphate pathway (PPP). This shift, in turn, caused an increase in reduced glutathione (GSH) and, ultimately, resulted in ROS detoxification inside HeLa cells. The ability of PFKFB3 to control the Fru-2,6-P2 levels in an ROS-dependent manner allows the PFKFB3-expressing cancer cells to continue energy metabolism with a reduced risk of excessive oxidative stress and, thereby, to support their cell survival and proliferation. This study provides a new insight into the roles of PFKFB3 as switch that senses and controls redox homeostasis in cancer in addition to its role in cancer glycolysis.
PMCID: PMC3919529  PMID: 24295899
reactive oxygen species; Warburg effect; TCA cycle; glutathione; pentose phosphate pathway
6.  Analysis of Anesthesia-related Medical Disputes in the 2009-2014 Period Using the Korean Society of Anesthesiologists Database 
Journal of Korean Medical Science  2015;30(2):207-213.
Using the Korean Society of Anesthesiologists database of anesthesia-related medical disputes (July 2009-June 2014), causative mechanisms and injury patterns were analyzed. In total, 105 cases were analyzed. Most patients were aged < 60 yr (82.9%) and were classified as American Society of Anesthesiologists physical status ≤ II (90.5%). In 42.9% of all cases, the injuries were determined to be 'avoidable' if the appropriate standard of care had been applied. Sedation was the sec most common type of anesthesia (37.1% of all cases), following by general anesthesia. Most sedation cases (27/39, 69.2%) showed a common lack of vigilance: no pre-procedural testing (82.1%), absence of anesthesia record (89.7%), and non-use of intra-procedural monitoring (15.4%). Most sedation (92.3%) was provided simultaneously by the non-anesthesiologists who performed the procedures. After the resulting injuries were grouped into four categories (temporary, permanent/minor, permanent/major, and death), their causative mechanisms were analyzed in cases with permanent injuries (n=20) and death (n=82). A 'respiratory events' was the leading causative mechanism (56/102, 54.9%). Of these, the most common specific mechanism was hypoxia secondary to airway obstruction or respiratory depression (n=31). The sec most common damaging event was a 'cardiovascular events' (26/102, 25.5%), in which myocardial infarction was the most common specific mechanism (n=12). Our database analysis demonstrated several typical injury profiles (a lack of vigilance in seemingly safe procedures or sedation, non-compliance with the airway management guidelines, and the prevalence of myocardial infarction) and can be helpful to improve patient safety.
PMCID: PMC4310949  PMID: 25653494
Adverse Effects; Injuries; Legislation; Malpractice
7.  Delayed redo pyeloplasty fails to recover lost renal function after failed pyeloplasty: Early sonographic changes that correlate with a loss of differential renal function 
Korean Journal of Urology  2015;56(2):157-163.
To evaluate changes in differential renal function (DRF), as a functional outcome, in children who underwent redo pyeloplasty for management of failed pyeloplasty and to examine the factors that affect functional outcomes.
Materials and Methods
Between January 2002 and November 2010, a total of 18 patients who underwent redo pyeloplasty for persistent ureteropelvic junction obstruction after failed pyeloplasty were enrolled in this study. We assessed perioperative factors and evaluated changes in renal cortical thickness (RCT), renal function, and hydronephrosis by use of serial ultrasound and diuretic renography.
The mean follow-up period was 44.83±28.86 months. After redo pyeloplasty, prevention of further functional deterioration was observed in only 12 of the 18 patients. After dividing the patients according to this observation, we discovered significant differences in both change in DRF (dDRF) and change in RCT (dRCT) (difference between before and after initial pyeloplasty) between the two groups (p<0.001). Additionally, we noted a significant positive correlation between dRCT and dDRF. All patients showed improvements in hydronephrosis grade and relief of symptoms compared with before redo pyeloplasty.
Redo pyeloplasty should be considered in cases of failed pyeloplasty to preserve renal function and obtain relief from symptoms. If patients show severe deterioration of DRF or a decrease in RCT after initial pyeloplasty, preservation of DRF in these patients after redo pyeloplasty could be difficult. Therefore, redo pyeloplasty should be performed before severe deterioration of DRF or decrease in RCT.
PMCID: PMC4325121
Hydronephrosis; Radioisotope renography; Treatment failure
8.  Clinical Relationship between Steatocholecystitis and Gallbladder Contractility Measured by Cholescintigraphy 
Objective. Contractility of gallbladder is known to be decreased in fatty gallbladder diseases. However, clinical estimation data about this relationship is still lacking. The aim of this study was to investigate the association between steatocholecystitis and contractility of gallbladder. Methods. Patients with cholecystitis (steatocholecystitis versus nonsteatocholecystitis) who underwent cholescintigraphy before cholecystectomy were retrospectively evaluated in a single teaching hospital of Korea. The association of steatocholecystitis with contractility of gallbladder, measured by preoperative cholescintigraphy, was assessed by univariable and multivariable analysis. Results. A total of 432 patients were finally enrolled (steatocholecystitis versus nonsteatocholecystitis; 75 versus 357, calculous versus acalculous cholecystitis; 316 versus 116). In the multivariable analysis, age (OR: 0.94, 95% CI: 0.90–0.99, P = 0.01) and total serum cholesterol (OR: 1.02, 95% CI: 1.01–1.04, P = 0.04) were related to steatocholecystitis in patients with acalculous cholecystitis. Only age (OR: 0.97, 95% CI: 0.94–0.99, P = 0.004) was significantly related to steatocholecystitis in patients with calculous cholecystitis. However, ejection fraction of gallbladder reflecting contractility measured by cholescintigraphy was not related to steatocholecystitis irrespective of presence of gallbladder stone in patients with cholecystitis. Conclusion. Ejection fraction of gallbladder measured by cholescintigraphy cannot be used for the detection or confirmation of steatocholecystitis.
PMCID: PMC4326214
9.  Whole Brain Radiation-Induced Vascular Cognitive Impairment: Mechanisms and Implications 
Journal of vascular research  2013;50(6):445-457.
Mild cognitive impairment is a well-documented consequence of whole brain radiation therapy (WBRT) that affects 40-50% of long-term brain tumor survivors. The exact mechanisms for the decline in cognitive function post-WBRT remain elusive and no treatment or preventative measures are available for use in the clinic. Here, we review recent findings indicating how changes in the neurovascular unit may contribute to the impairments of learning and memory. In addition to affecting neuronal development, WBRT induces profound capillary rarefaction within the hippocampus-a region of the brain important for learning and memory. Therapeutic strategies such as hypoxia, which restore the capillary density, result in the rescue of cognitive function. In addition to decreasing vascular density, WBRT impairs vasculogenesis and/or angiogenesis, which may also contribute to radiation-induced cognitive decline. Further studies aimed at uncovering the specific mechanisms underlying these WBRT-induced changes in the cerebrovasculature are essential for developing therapies to mitigate the deleterious effects of WBRT on cognitive function.
PMCID: PMC4309372  PMID: 24107797
angiogenesis; cerebrovasculature; cognitive impairment; neurogenesis; vasculogenesis
10.  Acute Toxicity Comparison of Single-Walled Carbon Nanotubes in Various Freshwater Organisms 
BioMed Research International  2015;2015:323090.
While the commercialization of single-walled carbon nanotubes (SWCNTs) is rapidly expanding, the environmental impact of this nanomaterial is not well understood. Therefore, the present study evaluates the acute aquatic toxicity of SWCNTs towards two freshwater microalgae (Raphidocelis subcapitata and Chlorella vulgaris), a microcrustacean (Daphnia magna), and a fish (Oryzias latipes) based on OECD test guidelines (201, 202, and 203). According to the results, the SWCNTs inhibited the growth of the algae R. subcapitata and C. vulgaris with a median effective concentration (EC50) of 29.99 and 30.96 mg/L, respectively, representing “acute category 3” in the Globally Harmonized System (GHS) of classification and labeling of chemicals. Meanwhile, the acute toxicity test using O. latipes and D. magna did not show any mortality/immobilizing effects up to a concentration of 100.00 mg/L SWCNTs, indicating no hazard category in the GHS classification. In conclusion, SWCNTs were found to induce acute ecotoxicity in freshwater microalgae, yet not in D. magna and medaka fish.
PMCID: PMC4310303  PMID: 25654094
11.  Beyond Burst Pressure: Initial Evaluation of the Natural History of the Biaxial Mechanical Properties of Tissue-Engineered Vascular Grafts in the Venous Circulation Using a Murine Model 
Tissue Engineering. Part A  2013;20(1-2):346-355.
We previously developed and validated a murine model for investigating neotissue formation in tissue-engineered vascular grafts (TEVGs). Herein, we present the first longitudinal assessment of both the microstructural composition and the mechanical properties of a TEVG through the process of neovessel formation (total scaffold degradation). We show that when (poly)glycolic acid-based biodegradable scaffolds were used as inferior vena cava interposition grafts in mice, the evolving neovessel developed biaxial properties that approached those of the native vein within 24 weeks of implantation. Further, we found that these changes in biaxial properties related temporally to extracellular matrix production and remodeling, including deposition of collagen (types I and III), elastic fibers (elastin and fibrillin-1), and glycosaminoglycans in addition to changes in matrix metalloproteinase (MMP)-2 and -9 activity. Improving our understanding of the mechanobiological principles underlying vascular neotissue formation in TEVGs holds great promise for improving the design of TEVGs and enabling us to continue the translation of this technology from the bench to the clinic.
PMCID: PMC3875183  PMID: 23957852
12.  Opinion: Assessing the Barriers to Image Guided Drug Delivery 
Imaging has become a cornerstone for medical diagnosis and the guidance of patient management. A new field called Image Guided Drug Delivery (IGDD) now combines the vast potential of the radiological sciences with the delivery of treatment and promises to fulfill the vision of personalized medicine. Whether imaging is used to deliver focused energy to drug-laden particles for enhanced, local drug release around tumors, or it is invoked in the context of nanoparticle-based agents to quantify distinctive biomarkers that could risk-stratify patients for improved targeted drug delivery efficiency, the overarching goal of IGDD is to use imaging to maximize effective therapy in diseased tissues and to minimize systemic drug exposure in order to reduce toxicities. Over the last several years innumerable reports and reviews covering the gamut of IGDD technologies have been published, but inadequate attention has been directed towards identifying and addressing the barriers limiting clinical translation. In this consensus opinion, the opportunities and challenges impacting the clinical realization of IGDD-based personalized medicine were discussed as a panel and recommendations were proffered to accelerate the field forward.
PMCID: PMC3967549  PMID: 24339356
13.  Loss of β2-spectrin prevents cardiomyocyte differentiation and heart development 
Cardiovascular Research  2013;101(1):39-47.
β2-Spectrin is an actin-binding protein that plays an important role in membrane integrity and the transforming growth factor (TGF)-β signalling pathway as an adaptor for Smads. Loss of β2-spectrin in mice (Spnb2−/−) results in embryonic lethality with gastrointestinal, liver, neural, and heart abnormalities that are similar to those in Smad2+/−Smad3+/− mice. However, to date, the role of β2-spectrin in embryogenesis, particularly in heart development, has been poorly delineated. Here, we demonstrated that β2-spectrin is required for the survival and differentiation of cardiomyocytes, and its loss resulted in defects in heart development with failure of ventricular wall thickening.
Methods and results
Disruption of β2-spectrin in primary muscle cells not only inhibited TGF-β/Smad signalling, but also reduced the expression of the cardiomyocyte differentiation markers Nkx2.5, dystrophin, and α-smooth muscle actin (α-SMA). Furthermore, cytoskeletal networks of dystrophin, F-actin, and α-SMA in cardiomyocytes were disorganized upon loss of β2-spectrin. In addition, deletion of β2-spectrin in mice (Spnb2tm1a/tm1a) prevented proper development of the heart in association with disintegration of dystrophin structure and markedly reduced survival.
These data suggest that β2-spectrin deficiency leads to inactivation of TGF-β/Smad signalling and contributes to dysregulation of the cell cycle, proliferation, differentiation, and the cytoskeletal network, and it leads to defective heart development. Our data demonstrate that β2-spectrin is required for proper development of the heart and that disruption of β2-spectrin is a potential underlying cause of congenital heart defects.
PMCID: PMC4229887  PMID: 24064296
β2-Spectrin; TGF-β; Cytoskeleton; Cardiogenesis
14.  Overcoming the Limitations of Fine Needle Aspiration Biopsy: Detection of Lateral Neck Node Metastasis in Papillary Thyroid Carcinoma 
Yonsei Medical Journal  2014;56(1):182-188.
Ultrasound (US) and US-guided fine needle aspiration biopsies (FNAB) are considered the modalities of choice for assessing lymph nodes suspected of containing metastases, but the sensitivity of FNAB varies and is specific to the operator. We analyzed the risk of FNAB providing false negative results of lateral neck node metastasis, and evaluated diagnostic accuracy of FNAB, in patients with papillary thyroid cancer.
Materials and Methods
FNAB was performed in 242 patients suspected of having lateral neck node metastasis on preoperative imaging. Thyroglobulin in the fine-needle aspirate washout (FNA wash-out Tg) and computed tomography enhancement (Hounsfield units) were measured. Patients with negative results on FNAB were examined by intraoperative frozen section. The false negative and true negative groups were compared.
Of the 242 patients, 130 were confirmed as having lateral neck node metastases. In 74 patients, the metastasis was identified by FNAB. False positive results were observed in 2 patients (0.8%) and false negatives in 58 (44.6%). Risk analysis showed that patient age <45 years (p=0.006), tumor size >1 cm (p=0.008) and elevated FNA wash-out Tg (p=0.004) were significantly associated with false negative results on FNAB. The accuracy of FNAB increased significantly when combined with FNA wash-out Tg (p=0.003).
To reduce the false negative rate of FNAB, patient age (<45 years), tumor size (>1 cm) and FNA wash-out Tg (>34.8 ng/mL) should be considered in preoperative planning. Accuracy may be improved by combining the results of FNAB and FNA wash-out Tg.
PMCID: PMC4276754  PMID: 25510763
Papillary thyroid carcinoma; metastasis
15.  Second-Look Endoscopy after Gastric Endoscopic Submucosal Dissection for Reducing Delayed Postoperative Bleeding 
Gut and Liver  2015;9(1):43-51.
This stuy evaluated the role of a second-look endoscopy after gastric endoscopic submucosal dissection in patients without signs of bleeding.
Between March 2011 and March 2012, 407 patients with gastric neoplasms who underwent endoscopic submucosal dissection for 445 lesions were retrospectively reviewed. After the patients had undergone endoscopic submucosal dissection, they were allocated to two groups (with or without second-look endoscopy) according to the following endoscopy. The postoperative bleeding risk of the lesions was not considered when allocating the patients.
The delayed postoperative bleeding rates did not differ between the two groups (with vs without second-look endoscopy, 3.0% vs 2.1%; p=0.546). However, a tumor in the upper-third of the stomach (odds ratio [OR], 5.353; 95% confidence interval [CI], 1.075 to 26.650) and specimen size greater than 40 mm (OR, 4.794; 95% CI, 1.307 to 17.588) were both independent risk factors for delayed postoperative bleeding. Additionally, second-look endoscopy was not related to reduced delayed postoperative bleeding. However, delayed postoperative bleeding in the patients who did not undergo a second-look endoscopy occurred significantly earlier than that in patients who underwent a second-look endoscopy (4.5 and 14.0 days, respectively, p=0.022).
A routine second-look endoscopy after gastric endoscopic submucosal dissection is not necessary for all patients.
PMCID: PMC4282856  PMID: 25170062
Second-look endoscopy; Endoscopic submucosal dissection; Bleeding; Delayed bleeding; Hemostasis
16.  Clinical Efficacy of Endoscopic Treatment for Benign Colorectal Stricture: Balloon Dilatation versus Stenting 
Gut and Liver  2015;9(1):73-79.
There has been a lack of research comparing balloon dilatation and self-expandable metal stent (SEMS) placement to determine which is better for long-term clinical outcomes in patients with benign colorectal strictures. We aimed to compare the clinical efficacy and complication rates of balloon dilatation and SEMS placement for benign colorectal strictures from a variety of causes.
Between January 1999 and January 2012, a total of 43 consecutive patients who underwent endoscopic treatment for benign colorectal stricture (balloon only in 29 patients, SEMS only in seven patients, and both procedures in seven patients) were retrospectively reviewed.
Thirty-six patients underwent endoscopic balloon dilatation, representing 65 individual sessions, and 14 patients received a total of 17 SEMS placements. The initial clinical success rates were similar in both groups (balloon vs SEMS, 89.1% vs 87.5%). Although the reobstruction rates were similar in both groups (balloon vs SEMS, 54.4% vs. 57.1%), the duration of patency was significantly longer in the balloon dilatation group compared with the SEMS group (65.5±13.3 months vs. 2.0±0.6 months, p=0.031).
Endoscopic balloon dilatation is safe and effective as an initial treatment for benign colorectal stricture and as an alternative treatment for recurrent strictures.
PMCID: PMC4282860  PMID: 25170060
Benign stricture; Colorectal stricture; Balloon dilatation; Self-expandable metal stent
17.  Protective Effect of Liriodendrin Isolated from Kalopanax pictus against Gastric Injury 
Biomolecules & Therapeutics  2015;23(1):53-59.
In this study, we investigated the inhibitory activities on gastritis and gastric ulcer using liriodendrin which is a constituent isolated from Kalopanax pictus. To elucidate its abilities to prevent gastric injury, we measured the quantity of prostaglandin E2 (PGE2) as the protective factor, and we assessed inhibition of activities related to excessive gastric acid be notorious for aggressive factor and inhibition of Helicobacter pylori (H. pylori) colonization known as a cause of chronic gastritis, gastric ulcer, and gastric cancer. Liriodendrin exhibited higher PGE2 level than rebamipide used as a positive control group at the dose of 500 μM. It was also exhibited acid-neutralizing capacity (10.3%) and H+/K+-ATPase inhibition of 42.6% (500 μM). In pylorus-ligated rats, liriodendrin showed lower volume of gastric juice (4.38 ± 2.14 ml), slightly higher pH (1.53 ± 0.41), and smaller total acid output (0.47 ± 0.3 mEq/4 hrs) than the control group. Furthermore liriodendrin inhibited colonization of H. pylori effectively. In vivo test, liriodendrin significantly inhibited both of HCl/EtOH-induced gastritis (46.9 %) and indomethacin-induced gastric ulcer (46.1%). From these results, we suggest that liriodendrin could be utilized for the treatment and/or protection of gastritis and gastric ulcer.
PMCID: PMC4286750  PMID: 25593644
Liriodendrin; Prostaglandin E2; H+/K+-ATPase; Gastritis; Gastric ulcer
18.  MicroRNA-1 Participates in Nitric Oxide-Induced Apoptotic Insults to MC3T3-E1 Cells by Targeting Heat-Shock Protein-70 
Our previous studies showed that nitric oxide (NO) could induce osteoblast apoptosis. MicroRNA-1 (miR-1), a skeletal- and cardiac muscle-specific small non-coding RNA, contributes to the regulation of multiple cell activities. In this study, we evaluated the roles of miR-1 in NO-induced insults to osteoblasts and the possible mechanisms. Exposure of mouse MC3T3-E1 cells to sodium nitroprusside (SNP) increased amounts of cellular NO and intracellular reactive oxygen species. Sequentially, SNP decreased cell survival but induced caspase-3 activation, DNA fragmentation, and cell apoptosis. In parallel, treatment with SNP induced miR-1 expression in a time-dependent manner. Application of miR-1 antisense inhibitors to osteoblasts caused significant inhibition of SNP-induced miR-1 expression. Knocking down miR-1 concurrently attenuated SNP-induced alterations in cell morphology and survival. Consecutively, SNP time-dependently inhibited heat-shock protein (HSP)-70 messenger (m)RNA and protein expressions. A bioinformatic search predicted the existence of miR-1-specific binding elements in the 3'-untranslational region of HSP-70 mRNA. Downregulation of miR-1 expression simultaneously lessened SNP-induced inhibition of HSP-70 mRNA and protein expressions. Consequently, SNP-induced modifications in the mitochondrial membrane potential, caspase-3 activation, DNA fragmentation, and apoptotic insults were significantly alleviated by miR-1 antisense inhibitors. Therefore, this study showed that miR-1 participates in NO-induced apoptotic insults through targeting HSP-70 gene expression.
PMCID: PMC4323364
Nitric oxide; MicroRNA-1; Apoptosis; HSP-70; Mitochondria
19.  Sub-acute toxicity study in female ICR mice following repetitive intramuscular injection of cervical cancer vaccines 
The sub-acute toxic effects following repetitive intramuscular injection of two cervical cancer vaccines newly developed against human papillomaviruse (HPV)16/58/18 and HPV16 were investigated in female ICR (CrljOri: CD1) mice, and the no-observedadverse- effect-level (NOAEL) of the cervical cancer vaccines was estimated.
Female ICR mice (n=15 in each group) were exposed to a 1:1 mixture of two cervical cancer vaccines by repetitive intramuscular injection (once a week, 5 times) for 5 weeks. Mortality, body weight, organ weight, hematological/biochemical parameters, and histopathological effects were examined at different concentrations (0, 1×108, 5×108, and 2.5×109 copies/animal) of the cervical cancer vaccines.
The cervical cancer vaccines did not show toxic responses for body weight, absolute/ relative organ weight, hematological/biochemical parameters, or histopathological parameters.
Female ICR mice exposed to vaccines for cervical cancer did not show any toxic response. We suggest that a NOAEL of the vaccine following repetitive intramuscular injection for 5 weeks is >2.5×109 copies/animal.
PMCID: PMC4313933  PMID: 25622643
Cervical cancer vaccine; Female ICR mice; Repetitive intramuscular injection
20.  Scrub Typhus Meningitis or Meningoencephalitis 
Orientia tsutsugamushi induces vasculitis leading to symptoms of systemic organ invasion including meningitis and meningoencephalitis. We conducted a retrospective case-control study of scrub typhus patients to investigate the clinical and laboratory features of patients with scrub typhus meningitis or meningoencephalitis, and the therapeutic outcomes, and to determine the predictor factors. Cases were 22 patients with scrub typhus meningitis or meningoencephalitis, and controls were 303 patients without meningitis or meningoencephalitis. Multivariate analysis showed that the presence of pneumonitis was associated with the occurrence of scrub typhus meningitis and meningoencephalitis (odds ratio [OR] 8.9; P < 0.001; confidence interval [CI] 2.9–27.2). Although appropriate antimicrobials such as doxycycline agents were administered at an early stage, meningitis or meningoencephalitis still occurred in some cases. Physicians should be aware that meningitis or meningoencephalitis may develop during appropriate drug therapy such as doxycycline. Close observation and great care are essential for patients with risk factors, particularly pneumonitis.
PMCID: PMC3854902  PMID: 24166036
21.  Differential effects of Best disease causing missense mutations on bestrophin-1 trafficking 
Human Molecular Genetics  2013;22(23):4688-4697.
Mutations in bestrophin-1 (Best1) cause Best vitelliform macular dystrophy (BVMD), a dominantly inherited retinal degenerative disease. Best1 is a homo-oligomeric anion channel localized to the basolateral surface of retinal pigment epithelial (RPE) cells. A number of Best1 mutants mislocalize in Madin–Darby canine kidney (MDCK) cells. However, many proteins traffic differently in MDCK and RPE cells, and MDCK cells do not express endogenous Best1. Thus, effects of Best1 mutations on localization in MDCK cells may not translate to RPE cells. To determine whether BVMD causing mutations affect Best1 localization, we compared localization and oligomerization of Best1 with Best1 mutants V9M, W93C, and R218C. In MDCK cells, Best1 and Best1R218C were basolaterally localized. Best1W93C and Best1V9M accumulated in cells. In cultured fetal human retinal pigment epithelium cells (fhRPE) expressing endogenous Best1, Best1R218C and Best1W93C were basolateral. Best1V9M was intracellular. All three mutants exhibited similar fluorescence resonance energy transfer (FRET) efficiencies to, and co-immunoprecipitated with Best1, indicating unimpaired oligomerization. When human Best1 was expressed in RPE in mouse eyes it was basolaterally localized. However, Best1V9M accumulated in intracellular compartments in mouse RPE. Co-expression of Best1 and Best1W93C in MDCK cells resulted in basolateral localization of both Best1 and Best1W93C, but co-expression of Best1 with Best1V9M resulted in mislocalization of both proteins. We conclude that different mutations in Best1 cause differential effects on its localization and that this effect varies with the presence or absence of wild-type (WT) Best1. Furthermore, MDCK cells can substitute for RPE when examining the effects of BVMD causing mutations on Best1 localization if co-expressed with WT Best1.
PMCID: PMC3820130  PMID: 23825107
22.  Epigenetic regulation by long noncoding RNAs in plants 
Many eukaryotes, including plants, produce a large number of long noncoding RNAs (lncRNAs). Growing number of lncRNAs are being reported to have regulatory roles in various developmental processes. Emerging mechanisms underlying the function of lncRNAs indicate that lncRNAs are versatile regulatory molecules. They function as potent cis- and trans-regulators of gene expression, including the formation of modular scaffolds that recruit chromatin-modifying complexes to target chromatin. LncRNAs have also been reported in plants. Here, we describe our current understanding on potential roles of lncRNA in plants.
PMCID: PMC4049567  PMID: 24233054
Long noncoding RNA (lncRNA); Chromatin modification; RNA-seq; Gene silencing; Gene activation
23.  Association between long working hours and serum gamma-glutamyltransferase levels in female workers: data from the fifth Korean National Health and Nutrition Examination Survey (2010-2011) 
The present study investigated the association between long working hours and serum gamma-glutamyltransferase (GGT) levels, a factor influencing the incidence of cardiovascular disease.
Data from the fifth Korean National Health and Nutrition Examination Survey (2010–2011) were used to analyze 1,809 women. Subjects were divided into three groups based on the number of weekly working hours: ≤29, 30–51, and ≥52 hours per week. Complex samples logistic regression was performed after adjusting for general and occupational factors to determine the association between long working hours and high serum GGT levels.
The prevalence of high serum GGT levels in groups with ≤29, 30–51, and ≥52 working hours per week was 22.0%, 16.9%, and 26.6%, respectively. Even after adjusting for general and occupational factors, those working 30–51 hours per week had the lowest prevalence of high serum GGT levels. Compared to those working 30–51 hours per week, the odds ratios (OR) of having high serum GGT levels in the groups with ≥52 and ≤29 working hours per week were 1.56 (95% confidence interval [CI], 1.10–2.23) and 1.53 (95% CI, 1.05–2.24), respectively.
Long working hours were significantly associated with high serum GGT levels in Korean women.
PMCID: PMC4248444  PMID: 25452851
Long working hours; Gamma-glutamyltransferase; Cardiovascular disease
24.  Impact of Postthyroidectomy Scar on the Quality of Life of Thyroid Cancer Patients 
Annals of Dermatology  2014;26(6):693-699.
Surgical scars are crucial cosmetic problem, especially when in exposed areas such as the anterior neck following thyroidectomy.
To evaluate the impact of post-thyroidectomy scars on quality of life (QoL) of thyroid cancer patients and identify the relationship between scar characteristics and QoL.
Patients with post-thyroidectomy scars on the neck were recruited. QoL was measured using the Dermatology Life Quality Index (DLQI). Scar characteristics were graded according to Vancouver scar scale (VSS) score.
Ninety-seven patients completed a battery of questions at the time of enrollment. Post-thyroidectomy scars were classified according to morphology as linear flat scars, linear bulging scars, hypertrophic scars or adhesive scars. There were 32 patients (33.0%), 9 patients (9.3%), 41 patients (42.3%) and 15 patients (15.5%), respectively, in each group. The mean total DLQI score was 9.02. Domain 2 (daily activities, 2.87 points), which includes questions about clothing, was the most greatly impacted among patients. The total DLQI scores of patients who have experienced scar-related symptoms were significantly higher than those of patients without symptoms (p<0.05). The VSS scores were 3.09 for linear flat scars, 6.89 for linear bulging scars, 6.29 for hypertrophic scars and 5.60 for adhesive scars. However, the DLQI scores did not significantly differ among scar types or VSS scores.
Post-thyroidectomy scars on the neck affect the QoL of thyroid cancer patients regardless of scar type. Therefore, clinicians should pay attention to the psychological effects of scars on patients and take care to minimize post-thyroidectomy scar.
PMCID: PMC4252665  PMID: 25473220
Dermatology life quality index; Post-surgical scar; Quality of life; Scar; Thyroidectomy
25.  Transcriptome Analysis of Early Responsive Genes in Rice during Magnaporthe oryzae Infection 
The Plant Pathology Journal  2014;30(4):343-354.
Rice blast disease caused by Magnaporthe oryzae is one of the most serious diseases of cultivated rice (Oryza sativa L.) in most rice-growing regions of the world. In order to investigate early response genes in rice, we utilized the transcriptome analysis approach using a 300 K tilling microarray to rice leaves infected with compatible and incompatible M. oryzae strains. Prior to the microarray experiment, total RNA was validated by measuring the differential expression of rice defense-related marker genes (chitinase 2, barwin, PBZ1, and PR-10) by RT-PCR, and phytoalexins (sakuranetin and momilactone A) with HPLC. Microarray analysis revealed that 231 genes were up-regulated (>2 fold change, p < 0.05) in the incompatible interaction compared to the compatible one. Highly expressed genes were functionally characterized into metabolic processes and oxidation-reduction categories. The oxidative stress response was induced in both early and later infection stages. Biotic stress overview from MapMan analysis revealed that the phytohormone ethylene as well as signaling molecules jasmonic acid and salicylic acid is important for defense gene regulation. WRKY and Myb transcription factors were also involved in signal transduction processes. Additionally, receptor-like kinases were more likely associated with the defense response, and their expression patterns were validated by RT-PCR. Our results suggest that candidate genes, including receptor-like protein kinases, may play a key role in disease resistance against M. oryzae attack.
PMCID: PMC4262287  PMID: 25506299
defense response; Magnaporthe oryzae; MapMan analysis; rice; transcriptomics

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