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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.  Petasites japonicus Stimulates the Proliferation of Mouse Spermatogonial Stem Cells 
PLoS ONE  2015;10(7):e0133077.
Oriental natural plants have been used as medical herbs for the treatment of various diseases for over 2,000 years. In this study, we evaluated the effect of several natural plants on the preservation of male fertility by assessing the ability of plant extracts to stimulate spermatogonial stem cell (SSC) proliferation by using a serum-free culture method. In vitro assays showed that Petasites japonicus extracts, especially the butanol fraction, have a significant effect on germ cells proliferation including SSCs. The activity of SSCs cultured in the presence of the Petasites japonicus butanol fraction was confirmed by normal colony formation and spermatogenesis following germ cell transplantation of the treated SSCs. Our findings could lead to the discovery of novel factors that activate SSCs and could be useful for the development of technologies for the prevention of male infertility.
PMCID: PMC4514868  PMID: 26207817
6.  Roles of DPY30 in the Proliferation and Motility of Gastric Cancer Cells 
PLoS ONE  2015;10(7):e0131863.
Various types of histone methylation have been associated with cancer progression. Depending on the methylation site in histone proteins, its effects on transcription are different. DPY30 is a common member of SET1/MLL histone H3K4 methyltransferase complexes. However, its expression and roles in gastric cancer have been poorly characterized. To determine whether DPY30 has pathophysiological roles in gastric cancer, its expression and roles were examined. Immunohistochemistry and real time PCR showed up-regulation of DPY30 expression in some gastric cancer cell lines and patients’ tissues. Its knockdown by siRNA decreased the proliferation, migration, and invasion of gastric cancer cells, whereas its overexpression showed the opposite effects. These results indicate that DPY30 has critical roles in the proliferation, migration, and invasion of gastric cancer cells, and suggest DPY30 might be a therapeutic target in gastric cancer.
PMCID: PMC4493084  PMID: 26147337
7.  Systematic characterization of the peroxidase gene family provides new insights into fungal pathogenicity in Magnaporthe oryzae 
Scientific Reports  2015;5:11831.
Fungal pathogens have evolved antioxidant defense against reactive oxygen species produced as a part of host innate immunity. Recent studies proposed peroxidases as components of antioxidant defense system. However, the role of fungal peroxidases during interaction with host plants has not been explored at the genomic level. Here, we systematically identified peroxidase genes and analyzed their impact on fungal pathogenesis in a model plant pathogenic fungus, Magnaporthe oryzae. Phylogeny reconstruction placed 27 putative peroxidase genes into 15 clades. Expression profiles showed that majority of them are responsive to in planta condition and in vitro H2O2. Our analysis of individual deletion mutants for seven selected genes including MoPRX1 revealed that these genes contribute to fungal development and/or pathogenesis. We identified significant and positive correlations among sensitivity to H2O2, peroxidase activity and fungal pathogenicity. In-depth analysis of MoPRX1 demonstrated that it is a functional ortholog of thioredoxin peroxidase in Saccharomyces cerevisiae and is required for detoxification of the oxidative burst within host cells. Transcriptional profiling of other peroxidases in ΔMoprx1 suggested interwoven nature of the peroxidase-mediated antioxidant defense system. The results from this study provide insight into the infection strategy built on evolutionarily conserved peroxidases in the rice blast fungus.
PMCID: PMC4488832  PMID: 26134974
8.  CXCR2 Inhibition Enhances Sulindac-Mediated Suppression of Colon Cancer Development 
Small chemical compound sulindac has been approved as a preventive approach against colon cancer for its effectiveness in treatment of precancerous adenoma. Due to its severe toxicities in the cardiovascular, gastrointestinal and renal systems, however, a combination of low-dose sulindac with other chemopreventive agents has been sought after as an alternative therapeutic strategy that could increase its effectiveness, while minimizing its adverse effects. In order to identify the promising alternative approach, we investigated the therapeutic potential of targeting the Interleukin (IL)-8/CXCR2 pathway in colon cancer treatment using both loss-of-function (CXCR2 knockout) and gain-of-function (IL-8 overexpression) mouse models, as the IL-8/CXCR2 pathway has been shown to be activated in intestinal tumors of both human and experimental animals. We found that deletion of CXCR2 gene and ectopic expression of IL-8 suppresses and enhances, respectively, intestinal tumor development caused by a mutation in the APC gene. Moreover, a single copy deletion of CXCR2 gene resulted in abrogation of COX-2 and Gro-α upregulation in intestinal tumors caused by the APC mutation. Moreover, a single copy (heterozygote) deletion of CXCR2 gene was sufficient to synergize with a low-dose sulindac treatment in suppressing APCmin-induced intestinal polyposis. Together, our study provides a therapeutic justification of combined inhibition of CXCR2 and sulindac treatment in colon cancer prevention.
PMCID: PMC4166491  PMID: 24338666
Interleukin-8; CXCR2; adenomatous polyposis coli; colon cancer; sulindac
9.  The dietary ingredient, genistein, stimulates cathelicidin antimicrobial peptide expression through a novel S1P-dependent mechanism 
We recently discovered that a signaling lipid, sphingosine-1-phosphate (S1P), generated by sphingosine kinase 1, regulates a major epidermal antimicrobial peptide’s [cathelicidin antimicrobial peptide (CAMP)] expression via an NF-κB→C/EBPα-dependent pathway, independent of vitamin D receptor (VDR) in epithelial cells. Activation of estrogen receptors (ER) by either estrogens or phytoestrogens also is known to stimulate S1P production, but it is unknown whether ER activation increases CAMP production. We investigated whether a phytoestrogen, genistein, simulates CAMP expression in keratinocytes, a model of epithelial cells, by either a S1P-dependent mechanism(s) or the alternate VDR-regulated pathway. Exogenous genistein, as well as a ER-β ligand, WAY-200070, increased CAMP mRNA and protein expression in cultured human keratinocytes, while ER-β antagonist, ICI182780, attenuated the expected genistein- and WAY-200070-induced increase in CAMP mRNA/protein expression. Genistein treatment increased acidic and alkaline ceramidase expression and cellular S1P levels in parallel with increased S1P lyase inhibition, accounting for increased CAMP production. In contrast, siRNA against VDR did not alter genistein-mediated upregulation of CAMP. Taken together, genistein induces CAMP production via an ER-β→S1P→NF-κB→C/EBPα-rather than a VDR-dependent mechanism, illuminating a new role for estrogens in the regulation of epithelial innate immunity and pointing to potential additional benefits of dietary genistein in enhancing cutaneous antimicrobial defense.
PMCID: PMC4441818  PMID: 24768661
Cathelicidin antimicrobial peptide; Estrogen receptor β; Genistein; Keratinocytes; Innate immunity
10.  Functional Gastrointestinal Disorders in Young Military Men 
Gut and Liver  2014;9(4):509-515.
To estimate the prevalence and evaluate the associated psychological factors of functional gastrointestinal disorders (FGIDs) in males in their twenties who are currently enrolled in military service.
A total of 1,073 men in the Korean army were asked to complete questionnaires based on the Rome III criteria and Symptom Checklist-90-revised (SCL-90R). The prevalence of FGIDs was estimated, and the associated psychological factors were evaluated.
A total of 967 men participated. The total prevalence of FGIDs was 18.5% (age-adjusted prevalence, 18.1%; 95% confidence interval [CI], 15.3% to 20.8%). The total SCL-90R scores were higher in men with FGIDs than men without FGIDs (24 [interquartile range, 13 to 44] vs 13 [5 to 28], p<0.001) and higher in men with overlapping syndromes than in those with single FGIDs (31 [18 to 57] vs 14 [5.75 to 29], p<0.001). Somatization (odds ratio [OR], 1.141; 95% CI, 1.09 to 1.20; p<0.001), obsessive-compulsive behaviors (OR, 1.084; 95% CI, 1.03 to 1.14; p=0.002) and depression (OR, 0.943; 95% CI, 0.90 to 0.99; p=0.020) were identified as independent predictive factors for FGIDs.
FGIDs are common among men in their twenties who are fulfilling their military duty. Somatization and obsessive-compulsive features from the tense atmosphere are associated with the development or progression of FGIDs. Patients who exhibit overlapping syndromes require greater attention given their more severe psychopathology.
PMCID: PMC4477995  PMID: 25473077
Gastrointestinal diseases; Military; Psychologic factors
11.  Modified Peritoneal Dialysis Catheter Insertion: Comparison with a Conventional Method 
Yonsei Medical Journal  2015;56(4):981-986.
The conventional trocar and cannula method in peritoneal dialysis (PD) catheter insertion has its limitation in clinical setting. The aim of this study was to compare a modified method for percutaneous PD catheter insertion with the conventional method, and demonstrate advantages of the modified method.
Materials and Methods
Patients at a single center who had percutaneous PD catheters inserted by nephrologists from January 2006 until September 2012, using either a modified method (group M) or the conventional trocar and cannula method (group C), were retrospectively analyzed, in terms of baseline characteristics, complications experienced up to 3 months after the procedure, and the suitability of the procedure for patients.
Group M included 82 subjects, while group C included 66 cases. The overall early complication rate in group M (1.2%) was significantly lower than that in group C (19.7%) (p<0.001). The catheter revision rate during timeframe for early complications was significantly lower in group M (0%) than in group C (6.1%) (p=0.024). When comparing Procedure time (1 h 3 min±16 min vs. 1 h 36 min±19 min, p<0.01), immediate post-procedural pain (2.43±1.80 vs. 3.14±2.07, p<0.05), and post-procedure days until ambulation (3.95±1.13 days vs. 6.17±1.34 days, p<0.01), group M was significantly lower than group C. There was no significant difference in total hospitalization period (14.71±7.05 days vs. 13.86±3.7 days).
Our modified PD catheter insertion method shows its advantages in early complication rate, early complications revision rate, and the patients' conveniences.
PMCID: PMC4479866  PMID: 26069120
Continuous ambulatory peritoneal dialysis; peritoneal catheter insertion; nephrologists; modified method; trocar and cannula method; complication rate
12.  Agmatine Attenuates Brain Edema and Apoptotic Cell Death after Traumatic Brain Injury 
Journal of Korean Medical Science  2015;30(7):943-952.
Traumatic brain injury (TBI) is associated with poor neurological outcome, including necrosis and brain edema. In this study, we investigated whether agmatine treatment reduces edema and apoptotic cell death after TBI. TBI was produced by cold injury to the cerebral primary motor cortex of rats. Agmatine was administered 30 min after injury and once daily until the end of the experiment. Animals were sacrificed for analysis at 1, 2, or 7 days after the injury. Various neurological analyses were performed to investigate disruption of the blood-brain barrier (BBB) and neurological dysfunction after TBI. To examine the extent of brain edema after TBI, the expression of aquaporins (AQPs), phosphorylation of mitogen-activated protein kinases (MAPKs), and nuclear translocation of nuclear factor-κB (NF-κB) were investigated. Our findings demonstrated that agmatine treatment significantly reduces brain edema after TBI by suppressing the expression of AQP1, 4, and 9. In addition, agmatine treatment significantly reduced apoptotic cell death by suppressing the phosphorylation of MAPKs and by increasing the nuclear translocation of NF-κB after TBI. These results suggest that agmatine treatment may have therapeutic potential for brain edema and neural cell death in various central nervous system diseases.
Graphical Abstract
PMCID: PMC4479950  PMID: 26130959
Agmatine; Traumatic Brain Injury; Brain Edema; Blood-Brain Barrier; Aquaporins; Mitogen-Activated Protein Kinases
13.  Semicircular Horizontal Approach in Breast Reduction: Clinical Experience in 38 Cases 
Archives of Plastic Surgery  2015;42(4):446-452.
Various techniques are used for performing breast reduction. Wise-pattern and vertical scar techniques are the most commonly employed approaches. However, a vertical scar in the mid-lower breast is prominent and aesthetically less pleasant. In contrast, a semicircular horizontal approach does not leave a vertical scar in the mid breast and transverse scars can be hidden in the inframammary fold. In this paper, we describe the experiences and results of semicircular horizontal breast reductions performed by a single surgeon.
Between September 1996 and October 2013, our senior author used this technique in 38 cases in the US and at our institution. We used a superiorly based semicircular incision, where the upper skin paddle was pulled down to the inframammary fold with the nipple-areola complex pulled through the keyhole.
The average total reduction per breast was 584 g, ranging from 286 to 794 g. The inferior longitudinal pedicle was used in all the cases. The average reduction of the distance from the sternal notch to the nipple was 13 cm (range, 11-15 cm). The mean decrease in the bra cup size was 1.7 cup sizes (range, a decrease of 1 to 3). We obtained very satisfactory results with a less noticeable scar, no complication such as necrosis of the nipple or the skin flap, wound infection, aseptic necrosis of the breast tissue, or wound dehiscence. One patient had a small hematoma that resolved spontaneously.
This technique is straightforward and easy to learn, and offers a safe, effective, and predictable way for treating mammary hypertrophy.
PMCID: PMC4513053  PMID: 26217565
Breast; Nipples; Mammaplasty
14.  Pelvic Castleman's disease presenting as an adnexal tumor in a young woman 
Obstetrics & Gynecology Science  2015;58(4):323-326.
Castleman's disease (CD) is a rare benign disorder of unknown etiology characterized by proliferation of lymphoid tissues. Seventy percent of this tumor occurs in the mediastinum and it is seldom found in neck, pancreas or pelvis. We report a case of asymptomatic pelvic CD initially presenting as an adnexal tumor in a 27-year-old woman. Initial transvaginal sonography revealed 7-cm-sized hyperechoic mass adjacent to the right ovary and the following abdominal computed tomography scanning showed the same sized mass located on the right extraperitoneal pelvic cavity. Laparoscopic mass excision was performed without any complication and pathological diagnosis was made as CD. CD should be included in the differential diagnosis of female pelvic masses which are noted in the pelvic cavity. In this report, we review the clinicopathological findings in a presentation of CD.
PMCID: PMC4515484  PMID: 26217605
Adenxal tumor; Giant lymph node hyperplasia; Pelvis
15.  MED30 Regulates the Proliferation and Motility of Gastric Cancer Cells 
PLoS ONE  2015;10(6):e0130826.
MED30 is an essential member of the mediator complex that forms a hub between transcriptional activators and RNA polymerase II. However, the expressions and roles of MED30 have been poorly characterized in cancer. In this study, we examined the functional roles of MED30 during gastric cancer progression. It was found that MED30 was overexpressed in gastric cancer tissues and cell lines. Moreover, MED30 overexpression increased the proliferation, migration, and invasion of gastric cancer cells, whereas MED30 knockdown inhibited these effects. Furthermore the knockdown significantly inhibited tumorigenicity in SCID mice. MED30 also promoted the expressions of genes related to epithelial-mesenchymal transition and induced a fibroblast-like morphology. This study shows MED30 has pathophysiological roles in the proliferation, migration, and invasion of gastric cancer cells and suggests that MED30 should be viewed as a potent therapeutic target for malignant gastric carcinoma
PMCID: PMC4482445  PMID: 26110885
16.  The transcription factor NFATc3 modulates the function of macrophages in sepsis 
Journal of innate immunity  2014;6(6):754-764.
The role of the transcription factor, Nuclear Factor of Activated T-cells (NFAT), was initially identified in T and B cell gene expression, but their role in regulating gene expression in macrophage during sepsis is not known. Our data show that NFATc3 regulates expression of inducible Nitric Oxide Synthase (iNOS) in macrophages stimulated with lipopolysaccharide (LPS). Selective inhibition of NFAT by cyclosporine A and a competitive peptide inhibitor 11R-VIVIT inhibited endotoxin induced expression of iNOS-NO release. Macrophages from NFATc3 knock-out mice show reduced iNOS expression-NO release and attenuated bactericidal activity. Gel shift and chromatin immuno-precipitation (ChIP) assays show that endotoxin challenge increases the NFATc3 binding to iNOS promoter resulting in transcriptional activation of iNOS. The binding of NFATc3 to the iNOS promoter is abolished by NFAT inhibitors. NFATc3 KO mice subjected to sepsis show that NFATc3 is necessary for bacterial clearance in mouse lungs during sepsis. Our study demonstrates for the first time that NFATc3 is necessary for macrophage iNOS expression during sepsis which is essential for containment of bacterial infections.
PMCID: PMC4201910  PMID: 24970700
iNOS; Macrophage; NFAT; Sepsis; VIVIT
17.  Cloning, expression analysis, and RNA interference study of a HORMA domain containing autophagy-related gene 13 (ATG13) from the coleopteran beetle, Tenebrio molitor 
Autophagy is a process that is necessary during starvation, as it replenishes metabolic precursors by eliminating damaged organelles. Autophagy is mediated by more than 35 autophagy-related (Atg) proteins that participate in the nucleation, elongation, and curving of the autophagosome membrane. In a pursuit to address the role of autophagy during development and immune resistance of the mealworm beetle, Tenebrio molitor, we screened ATG gene sequences from the whole-larva transcriptome database. We identified a homolog of ATG13 gene in T. molitor (designated as TmATG13) that comprises a cDNA of 1176 bp open reading frame (ORF) encoding a protein of 391 amino acids. Analyses of the structure-specific features of TmAtg13 showed an intrinsically disordered middle and C-terminal region that was rich in regulatory phosphorylation sites. The N-terminal Atg13 domain had a HORMA (Hop1, Rev7, and Mad2) fold containing amino acid residues conserved across the Atg13 insect orthologs. A quantitative reverse-transcription-polymerase chain reaction analysis revealed that TmATG13 was expressed ubiquitously during all developmental stages of the insect. TmATG13 mRNA expression was high in the fat body and gut of the larval and adult stages of the insect. The TmATG13 transcripts were expressed at a high level until 6 days of ovarian development, followed by a significant decline. Silencing of ATG13 transcripts in T. molitor larvae showed a reduced survivability of 39 and 38% in response to Escherichia coli and Staphylococcus aureus infection. Furthermore, the role of TmAtg13 in initiating autophagy as a part of the host cell autophagic complex of the host cells against the intracellular pathogen Listeria monocytogenes is currently under study and will be critical to unfold the structure-function relationships.
PMCID: PMC4470068  PMID: 26136688
Tenebrio molitor; autophagy; ATG13; HORMA domain; expression analysis; RNA interference
18.  The Influence of a Vitrectomy on the Diurnal Intraocular Pressure 
Journal of Ophthalmology  2015;2015:427808.
Purpose. To evaluate the diurnal intraocular pressure (IOP) in eyes after vitrectomy compared to that of healthy eyes. Methods. Twenty-one patients who had undergone vitrectomy and 21 age- and gender-matched normal controls were enrolled during the same period. We measured the diurnal IOP every two hours between 9 a.m. and 11 p.m. in all patients who were admitted for cataract surgery. Patients with a history of eye surgery (not including vitrectomy) or use of a medication that is associated with IOP were excluded. The IOP and ocular parameters of patients were compared with the same patients' fellow healthy eyes and with normal eyes of age- and gender-matched controls. Results. There were no significant differences between vitrectomized eyes and normal fellow eyes with regard to all IOP parameters including the maximum, minimum, and IOP fluctuation values. Diurnal fluctuation of IOP (or the difference between the maximum and minimum IOP) was larger in vitrectomized eyes than it was in age- and gender-matched control eyes. Conclusions. Vitrectomy did not markedly affect the IOP. Although there were no severe complications after vitrectomy, the IOP fluctuation was wider in vitrectomized eyes than it was in normal eyes.
PMCID: PMC4486259  PMID: 26161266
19.  Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment 
Genome Biology  2015;16(1):118.
Interindividual epigenetic variation that occurs systemically must be established prior to gastrulation in the very early embryo and, because it is systemic, can be assessed in easily biopsiable tissues. We employ two independent genome-wide approaches to search for such variants.
First, we screen for metastable epialleles by performing genomewide bisulfite sequencing in peripheral blood lymphocyte (PBL) and hair follicle DNA from two Caucasian adults. Second, we conduct a genomewide screen for genomic regions at which PBL DNA methylation is affected by season of conception in rural Gambia. Remarkably, both approaches identify the genomically imprinted VTRNA2-1 as a top environmentally responsive epiallele. We demonstrate systemic and stochastic interindividual variation in DNA methylation at the VTRNA2-1 differentially methylated region in healthy Caucasian and Asian adults and show, in rural Gambians, that periconceptional environment affects offspring VTRNA2-1 epigenotype, which is stable over at least 10 years. This unbiased screen also identifies over 100 additional candidate metastable epialleles, and shows that these are associated with cis genomic features including transposable elements.
The non-coding VTRNA2-1 transcript (also called nc886) is a putative tumor suppressor and modulator of innate immunity. Thus, these data indicating environmentally induced loss of imprinting at VTRNA2-1 constitute a plausible causal pathway linking early embryonic environment, epigenetic alteration, and human disease. More broadly, the list of candidate metastable epialleles provides a resource for future studies of epigenetic variation and human disease.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-015-0660-y) contains supplementary material, which is available to authorized users.
PMCID: PMC4464629  PMID: 26062908
20.  dbHiMo: a web-based epigenomics platform for histone-modifying enzymes 
Over the past two decades, epigenetics has evolved into a key concept for understanding regulation of gene expression. Among many epigenetic mechanisms, covalent modifications such as acetylation and methylation of lysine residues on core histones emerged as a major mechanism in epigenetic regulation. Here, we present the database for histone-modifying enzymes (dbHiMo; aimed at facilitating functional and comparative analysis of histone-modifying enzymes (HMEs). HMEs were identified by applying a search pipeline built upon profile hidden Markov model (HMM) to proteomes. The database incorporates 11 576 HMEs identified from 603 proteomes including 483 fungal, 32 plants and 51 metazoan species. The dbHiMo provides users with web-based personalized data browsing and analysis tools, supporting comparative and evolutionary genomics. With comprehensive data entries and associated web-based tools, our database will be a valuable resource for future epigenetics/epigenomics studies.
Database URL:
PMCID: PMC4460409  PMID: 26055100
21.  An Endoplasmic Reticulum Stress-Initiated Sphingolipid Metabolite, Ceramide-1-Phosphate, Regulates Epithelial Innate Immunity by Stimulating β-Defensin Production 
Molecular and Cellular Biology  2014;34(24):4368-4378.
Antimicrobial peptides (AMP) are ubiquitous innate immune elements in epithelial tissues. We recently discovered that a signaling lipid, the ceramide metabolite sphingosine-1-phosphate (S1P), regulates production of a major AMP, cathelicidin antimicrobial peptide (CAMP), in response to a subtoxic level of endoplasmic reticulum (ER) stress that can be induced by external perturbants in keratinocytes. We hypothesized that an ER stress-initiated signal could also regulate production of another major class of AMPs: i.e., the human beta-defensins 2 (hBD2) and 3 (hBD3). Keratinocytes stimulated with a pharmacological ER stressor, thapsigargin (Tg), increased hBD2/hBD3 as well as CAMP mRNA expression. While inhibition of sphingosine-1-phosphate production did not alter hBD expression following ER stress, blockade of ceramide-1-phosphate (C1P) suppressed Tg-induced hBD2/hBD3 but not CAMP expression. Exogenous C1P also increased hBD2/hBD3 production, indicating that C1P stimulates hBD expression. We showed further that C1P-induced hBD2/hBD3 expression is regulated by a novel pathway in which C1P stimulates downstream hBD via a cPLA2a→15d-PGJ2→PPARα/PPARβ/δ→Src kinase→STAT1/STAT3 transcriptional mechanism. Finally, conditioned medium from C1P-stimulated keratinocytes showed antimicrobial activity against Staphylococcus aureus. In summary, our present and recent studies discovered two new regulatory mechanisms of key epidermal AMP, hBD2/hBD3 and CAMP. The C1P and S1P pathways both signal to enhance innate immunity in response to ER stress.
PMCID: PMC4248733  PMID: 25312644
22.  Epigenetic Alterations of IL-6/STAT3 Signaling by Placental Stem Cells Promote Hepatic Regeneration in a Rat Model with CCl4-induced Liver Injury 
Human chorionic plate-derived mesenchymal stem cells (CP-MSCs) isolated from the placenta have been reported to demonstrate therapeutic effects in animal models of liver injury; however, the underlying epigenetic mechanism of this effect has not been elucidated. Thus, we investigated whether CP-MSCs influence epigenetic processes during regeneration of the injured liver.
CP-MSCs were engrafted into a carbon tetrachloride (CCl4)-injured rat model through direct transplantation into the liver (DTX), intrasplenic transplantation (STX), and intravenous transplantation via the tail vein (TTX). Non-transplanted (NTX) rats were maintained as sham controls. Liver tissues were analyzed after transplantation using immunohistochemistry, western blot analysis, and quantitative methylation-specific polymerase chain reaction. Proliferation and human interleukin-6 (hIL-6) enzyme-linked immunosorbent assays were performed using CCl4-treated hepatic cells that were co-cultured with CP-MSCs.
The Ki67 labeling index, cell cyclins, albumin, IL-6, and gp130 levels were elevated in the CP-MSC transplantation groups. The concentration of hIL-6 in supernatants and the proliferation of CCl4-treated rat hepatic cells were enhanced by co-culturing with CP-MSCs (p<0.05), while the methylation of IL-6/IL-6R and STAT3 by CP-MSC transplantation decreased.
These results suggest that administration of CP-MSCs promotes IL-6/STAT3 signaling by decreasing the methylation of the IL-6/SATA3 promoters and thus inducing the proliferation of hepatic cells in a CCl4-injured liver rat model. These data advance our understanding of the therapeutic mechanisms in injured livers, and can facilitate the development of cell-based therapies using placenta-derived stem cells.
PMCID: PMC4445712  PMID: 26019757
Placenta stem cells; Liver regeneration; Transplantation routes; IL-6 signaling; DNA methylation
23.  Transection of a Coopdech bronchial blocker tip during bronchial resection for right upper lobectomy: a case report 
Korean Journal of Anesthesiology  2015;68(3):287-291.
A bronchial blocker (BB) is preferred for lung separation in patients with difficult airways. However, BBs, unlike double-lumen tubes, must be placed in the bronchus of the lung being operated on, hence can be damaged by surgical manipulation. Intubation was unexpectedly difficult in this male patient, so a Coopdech BB was placed in the right mainstem bronchus through a single-lumen tracheoscopic ventilation tube for a thoracoscopic right upper lobectomy. During the bronchial resection, however, the distal tip of the BB was transected and pinched in the staple line, so the staple line was partially opened, and the BB was withdrawn into the trachea. The opened bronchial stump was sutured manually under apnea without conversion to an open thoracotomy, and there was no significant air leakage through the suture line. This case underlines the importance of frequently evaluating the position of a BB during lung surgery.
PMCID: PMC4452674  PMID: 26045933
Airway management; Bronchi; One-lung ventilation; Thoracoscopy
24.  GLTSCR2 is an upstream negative regulator of nucleophosmin in cervical cancer 
Nucleophosmin (NPM)/B23, a multifunctional nucleolar phosphoprotein, plays an important role in ribosome biogenesis, cell cycle regulation, apoptosis and cancer pathogenesis. The role of NPM in cells is determined by several factors, including total expression level, oligomerization or phosphorylation status, and subcellular localization. In the nucleolus, NPM participates in rRNA maturation to enhance ribosomal biogenesis. Consistent with this finding, NPM expression is increased in rapidly proliferating cells and many types of human cancers. In response to ribosomal stress, NPM is redistributed to the nucleoplasm, where it inactivates mouse double minute 2 homologue to stabilize p53 and inhibit cell cycle progression. These observations indicate that nucleolus-nucleoplasmic mobilization of NPM is one of the key molecular mechanisms that determine the role of NPM within the cell. However, the regulatory molecule(s) that control(s) NPM stability and subcellular localization, crucial to the pluripotency of intercellular NPM, remain(s) unidentified. In this study, we showed that nucleolar protein GLTSCR2/Pict-1 induced nucleoplasmic translocation and enhanced the degradation of NPM via the proteasomal polyubiquitination pathway. In addition, we showed that GLTSCR2 expression decreased the transforming activity of cells mediated by NPM and that the expression of NPM is reciprocally related to that of GLTSCR2 in cervical cancer tissue. In this study, we demonstrated that GLTSCR2 is an upstream negative regulator of NPM.
PMCID: PMC4459840  PMID: 25818168
GLTSCR2; nucleophosmin; cervical cancer; nucleoplasmic translocation
25.  Dipeptidyl Peptidase-4 Inhibitor Alarms: Is Heart Failure Caused by a Class Effect? 
Diabetes & Metabolism Journal  2015;39(3):204-206.
PMCID: PMC4483605  PMID: 26124990

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