Inhibitory Effects of α-Lipoic Acid on Oxidative Stress-Induced Adipogenesis in Orbital Fibroblasts From Patients With Graves Ophthalmopathy

Hwang, Sena,Byun, Jung Woo,Yoon, Jin Sook,Lee, Eun Jig Wolters Kluwer Health 2016 Medicine Vol.95 No.2

<▼1><P>Supplemental Digital Content is available in the text</P></▼1><▼2><P><B>Abstract</B></P><P>A choice of the optimal treatment for Graves ophthalmopathy (GO) is a challenge due to the complexity of the pathogenesis. Alpha-lipoic acid (ALA) is well known as a multifunctional antioxidant, helping to protect cells against oxidative stress and inflammatory damage.</P><P>The aim of this study was to investigate the effects of ALA on intracellular production of reactive oxygen species (ROS), inflammation, and adipogenesis using primary cultured orbital fibroblasts from patients with GO.</P><P>Intracellular ROS levels and mRNA expressions of proinflammatory cytokines and chemokines including intercellular adhesion molecule-1 (ICAM-1), interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, and regulated upon activation normal T cell expressed and presumably secreted (RANTES) were measured. After adipogenesis, the expressions of peroxisome proliferator-activated receptor (PPAR)γ, CCAAT-enhancer-binding proteins (C/EBP)α and β, and heme oxygenase-1 (HO-1) were investigated.</P><P>H<SUB>2</SUB>O<SUB>2</SUB> dose-dependently stimulated ROS production and HO-1 expression. Addition of ALA strongly attenuated ROS production and further increased HO-1 expression. However, by pretreatment of zinc protoporphyrin (ZnPP), HO-1 inhibitor, ALA inhibition of ROS generation by H<SUB>2</SUB>O<SUB>2</SUB> was abolished. Tumor necrosis factor (TNF)α-induced mRNA expressions of ICAM-1, IL-6, MCP-1, and RANTES were inhibited by ALA treatment. In this context, TNFα-induced phosphorylation of P65 was also inhibited. In addition, ALA dose-dependently inhibited H<SUB>2</SUB>O<SUB>2</SUB>-induced intracellular accumulation of lipid droplets. The expression of adipogenic transcription factors, including PPARγ, C/EBPα, and β, was also inhibited.</P><P>ALA is a potential therapeutic agent for GO because of the inhibitory effects on ROS production and gene expression of proinflammatory cytokines and chemokines, resulting in prevention of adipose-tissue expansion.</P></▼2>

Slide Session : OS-END-29 ; Endocrinology : High Diagnostic Performance of Tshrab Assays in Graves` Disease with Different Cut-Off Values in Early GD

( Sena Hwang ),( Dong Yeob Shin ),( Eun Jig Lee ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Graves` disease (GD) is caused by autoantibodies stimulated to thyroid- stimulating hormone receptor (TSHR). Two frequent assays were compared in relations to the diagnostic accuracy for GD. One is an inhibition assay using the monoclonal antibody (M22) closely mimicking the binding to TSH (M22-TRAb), and one is a bioreporter assay using the chimera transfected cell (Mc4-TSAb) and measuring stimulation of cAMP production. Methods: This cross-sectional study examined 216 sera from thyrotoxicosis patients (including 67 subclinical thyrotoxicosis); 94 sera from GD diagnosed within one month and 120 sera from transient thyrotoxicosis (TT). We compared the diagnostic performance of two TSHRAb assays. Results: The M22-TRAb assay and Mc4-TSAb assay were positive in 96.1 and 92.2% of the GD patients, whereas they were negative in 92.5% and 91.7% of the TT patients. We found the cut-off values of the two tests for GD diagnosis were 2.00 IU/ L and 158.0 %. However, 7 of 94 GD (7.4%) showed discordant results and 2 of them were treated with antithyroid drug that could have effects on the TSHRAb titer. In GD patients with subclinical thyrotoxicosis, the specificities for GD diagnosis of both assays were decreased to 82.1% and the proper cut-off levels of M22-TRAb and of Mc4- TSAb were 2.56 IU/L and 217%. M22-TRAb showed stronger correlations with T3 level (P=0.026) and thyroid I-131 uptake (P=0.025) than that of Mc4-TSAb in untreated GD. Conclusion: Similar and high diagnostic accuracy was shown for Mc4-TSAb and M22-TRAb in GD patients. However, considering a 7.4% discordance rate between two tests, we suggest a combination of both assays can reduce the presence of TSHRAb- seronegative GD, especially for those under the therapy. Higher cut-off values of both assays should be considered for diagnosis of early GD.

Surface analysis of N-doped TiO₂ nanorods and their enhanced photocatalytic oxidation activity

Hwang, Yun Jeong,Yang, Sena,Lee, Hangil Elsevier BV 2017 Applied Catalysis B Vol.204 No.-

<P><B>Abstract</B></P> <P>We investigated the presence of Ti<SUP>3+</SUP> defect sites on the surfaces of N-doped TiO<SUB>2</SUB> nanorods by using scanning transmission X-ray microscopy (STXM) and high-resolution photoemission spectroscopy (HRPES). The photo-oxidation activities of different types of N-doped TiO<SUB>2</SUB> nanorods were compared with each other and with their undoped nanorods. These nanorods were used to photocatalyze the oxidation of thiol molecules (i.e. 2-mercaptoethanol, benzenethiol, and 2-aminothiophenol) to disulfide and sulfonic (SO<SUB>3</SUB>H) species, and the conversion of CO to CO<SUB>2</SUB>, and their photocatalytic activities towards these reactions were assessed using HRPES and a residual gas analyzer, respectively. Conversion to further oxidized sulfonic species was only achieved on the N-doped TiO<SUB>2</SUB> surface compared to the non-doped TiO<SUB>2</SUB> nanorods. In addition, we found that longer N-doped TiO<SUB>2</SUB> nanorods (NTR-150) showed higher photo-oxidation activity than NTR-60, which resulted from their increased number of defect sites and narrowed band-gap.</P> <P><B>Highlights</B></P> <P> <UL> <LI> N-doped TiO<SUB>2</SUB> nanorod (NTR) has Ti<SUP>3+</SUP> and oxygen vacancy defect states on the surface. </LI> <LI> Longer NTR has higher photoactivity for thiol molecules oxidation and CO conversion. </LI> <LI> NTR can further oxidize −SH to sulfonic species unlike undoped TiO<SUB>2</SUB> nanorod. </LI> <LI> Greater number of defect states on NTR contribute to improved photocatalytic activity. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Case Report : A Case of Esophageal Intramural Pseudodiverticulosis

( Young Eun Chon ),( Sena Hwang ),( Kyu Sik Jung ),( Hyun Jung Lee ),( Sang Gil Lee ),( Sung Kwan Shin ),( Yong Chan Lee ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2011 Gut and Liver Vol.5 No.1

Esophageal intramural pseudodiverticulosis (EIP) is a rare benign disease that is characterized by multiple tiny flaskshaped outpouching lesions of the esophageal wall. The etiology is unknown, but the pathologic fi ndings include dilatation of excretory ducts of submucosal glands. The predominant symptom is dysphagia, and esophageal stricture occurs frequently. Diseases such as diabetes mellitus, esophageal candidiasis, gastroesophageal reflux disease, and chronic alcoholism are often combined. Since most EIP cases are benign, the mainstream treatment is symptom relief by endoscopic dilatation or medical treatment of accompanied diseases. This report describes the case of a 68-year-old male patient who suffered from chest tightness for 2 months and was diagnosed with EIP. This symptom disappeared after 2 months of medical treatment, and the patient is now being regularly followed up. (Gut Liver 2011;5:93-95)

Epithelial Barrier Theory: The Role of Exposome, Microbiome, and Barrier Function in Allergic Diseases

Losol Purevsuren,Sokolowska Milena,Hwang Yu-Kyoung,Ogulur Ismail,Mitamura Yasutaka,Yazici Duygu,Pat Yagiz,Radzikowska Urszula,Ardicli Sena,Yoon Jeong-Eun,Choi Jun-Pyo,Kim Sae-Hoon,van de Veen Willem,A 대한천식알레르기학회 2023 Allergy, Asthma & Immunology Research Vol.15 No.6

Allergic diseases are a major public health problem with increasing prevalence. These immune-mediated diseases are characterized by defective epithelial barriers, which are explained by the epithelial barrier theory and continuously emerging evidence. Environmental exposures (exposome) including global warming, changes and loss of biodiversity, pollution, pathogens, allergens and mites, laundry and dishwasher detergents, surfactants, shampoos, body cleaners and household cleaners, microplastics, nanoparticles, toothpaste, enzymes and emulsifiers in processed foods, and dietary habits are responsible for the mucosal and skin barrier disruption. Exposure to barrier-damaging agents causes epithelial cell injury and barrier damage, colonization of opportunistic pathogens, loss of commensal bacteria, decreased microbiota diversity, bacterial translocation, allergic sensitization, and inflammation in the periepithelial area. Here, we review scientific evidence on the environmental components that impact epithelial barriers and microbiome composition and their influence on asthma and allergic diseases. We also discuss the historical overview of allergic diseases and the evolution of the hygiene hypothesis with theoretical evidence.

Thyroid Isthmus Length and Iodine Turnover as Predictors of Successful Radioactive Iodine Therapy in Patients with Graves' Disease

Park, Se Hee,Hwang, Sena,Han, Seunghee,Shin, Dong Yeob,Lee, Eun Jig Hindawi 2017 International Journal of endocrinology Vol.2017 No.-

<P>Radioactive iodine (RAI) therapy is an effective treatment option for Graves' disease. However, predicting treatment failures after RAI therapy remains controversial. The objective of this study was to investigate the factors associated with the success rate of RAI therapy for treatment of Graves' hyperthyroidism. Thyroid functional outcome, pre-RAI ultrasonographic features, and clinical parameters were evaluated retrospectively in 98 patients followed up for at least 12 months after RAI (mean RAI dose was 11.7 ± 1.8 mCi). Hypothyroidism was achieved in 59 patients (60.2%), and euthyroidism in 16 patients (16.3%), while 23 patients (23.5%) remained hyperthyroid. Age, sex, body mass index, pre-RAI thyroid function, or thyroid-stimulating immunoglobulin levels were not associated with treatment outcome. Length of thyroid isthmus (<I>p</I> = 0.028) and 2- to 24-hour iodine uptake ratios (<I>p</I> = 0.002) were significantly associated with treatment failure, which was defined as a persistent hyperthyroid status after RAI therapy. Patients with a longer isthmus had a higher risk of remaining hyperthyroid, with a threshold for isthmus length of 5.2 mm, with a sensitivity of 69.6% and specificity of 70.3% for treatment success. Measuring the length of the thyroid isthmus can be a simple and useful way to predict RAI treatment outcome.</P>

Biguanides Metformin and Phenformin Generate Therapeutic Effects via AMP-Activated Protein Kinase/Extracellular-Regulated Kinase Pathways in an <i>In Vitro</i> Model of Graves' Orbitopathy

Han, Ye Eon,Hwang, Sena,Kim, Jin Hee,Byun, Jung Woo,Yoon, Jin Sook,Lee, Eun Jig Mary Ann Liebert 2018 Thyroid Vol.2018 No.-

Distinct Features of Nonthyroidal Illness in Critically Ill Patients With Infectious Diseases

Lee, Woo Kyung,Hwang, Sena,Kim, Daham,Lee, Seul Gi,Jeong, Seonhyang,Seol, Mi-Youn,Kim, Hyunji,Ku, Cheol Ryong,Shin, Dong Yeop,Chung, Woong Youn,Lee, Eun Jig,Lee, Jandee,Jo, Young Suk Wolters Kluwer Health 2016 Medicine Vol.95 No.14

<▼1><P>Supplemental Digital Content is available in the text</P></▼1><▼2><P><B>Abstract</B></P><P>Nonthyroidal illness (NTI), often observed in critically ill patients, arises through diverse alterations in the hypothalamus-pituitary-thyroid (HPT) axis. However, the causal relationship between underlying disease and NTI diversity in critically ill patients is poorly understood.</P><P>The aim of this study was to examine NTI severity and adverse outcomes in critically ill patients with respect to their underlying disease(s).</P><P>The medical records of 616 patients admitted to the intensive care unit (ICU) between January 2009 and October 2014 were retrospectively reviewed. Patients with known diseases or taking medications that affect thyroid function were excluded. All-cause mortality (ACM) and length of stay (LOS) in the ICU were assessed as adverse outcomes.</P><P>The enrolled patients (n = 213) were divided into the following 4 groups according to the severity of NTI at the nadir of their thyroid function test (TFT): normal (n = 11, 5.2%), mild NTI (n = 113, 53.1%), moderate NTI (n = 78, 36.6%), and severe NTI (n = 11, 5.2%). There was no significant difference between the groups in terms of age and gender. NTI severity showed a significantly strong association with ACM (<I>P</I> < 0.0001) and a significant positive association with LOS in the ICU (<I>P</I> = 0.031). After adjusting for age, gender, and current medications affecting TFT, increasing NTI severity led to increased ACM (odds ratio = 3.101; 95% confidence interval = 1.711–5.618; <I>P</I> < 0.0001). Notably, the prevalence of moderate-to-severe NTI was markedly higher in patients with infectious disease than in those with noninfectious disease (<I>P</I> = 0.012). Consistent with this, serum C-reactive protein levels were higher in patients with moderate-to-severe NTI (<I>P</I> = 0.016).</P><P>NTI severity is associated with increased ACM, LOS, and underlying infectious disease. Future studies will focus on the biological and clinical implications of infectious disease on the HPT axis.</P></▼2>

A case of esophageal intramural pseudodiverticulosis.

Chon, Young Eun,Hwang, Sena,Jung, Kyu Sik,Lee, Hyun Jung,Lee, Sang Gil,Shin, Sung Kwan,Lee, Yong Chan Editorial Office of Gut and Liver 2011 Gut and Liver Vol.5 No.1

<P>Esophageal intramural pseudodiverticulosis (EIP) is a rare benign disease that is characterized by multiple tiny flask-shaped outpouching lesions of the esophageal wall. The etiology is unknown, but the pathologic findings include dilatation of excretory ducts of submucosal glands. The predominant symptom is dysphagia, and esophageal stricture occurs frequently. Diseases such as diabetes mellitus, esophageal candidiasis, gastroesophageal reflux disease, and chronic alcoholism are often combined. Since most EIP cases are benign, the mainstream treatment is symptom relief by endoscopic dilatation or medical treatment of accompanied diseases. This report describes the case of a 68-year-old male patient who suffered from chest tightness for 2 months and was diagnosed with EIP. This symptom disappeared after 2 months of medical treatment, and the patient is now being regularly followed up.</P>

S-325 : The size and lymph node metastatic risk of benign looking thyroid cancers

( Young Ki Lee ),( Dong Yeob Shin ),( Kwang Joon Kim ),( Kyeong Hye Park ),( Sena Hwang ),( Eun Jig Lee ) 대한내과학회 2013 대한내과학회 추계학술대회 Vol.2013 No.1

Objective: A decision to perform fine needle aspiration (FNA) on thyroid nodules mainly depends on sonographic features. We investigated if lymph node metastasis (LNM) risk differed by tumor size of thyroid cancers without suspicious sonographic features. Methods: 360 patients with thyroid cancers with benign looking sonographic features were grouped by nodule size on ultrasonography (US) (≤ or >1 cm). The clinicopathologic parameters were compared between the groups. A multivariate analysis was performed to discover the independent factors predicting the presence of LNM. Results: The nodules greater than 10 mm on US (n=157) demonstrated larger tumor size on histology (17.9±14.5 mm vs. 5.6±2.4 mm, p<0.001), lower frequency of classical papillary thyroid carcinoma (PTC) (58.6% vs. 87.2%, p<0.001), and higher frequency of follicular variant PTC and follicular thyroid carcinoma (19.7% and 17.8% vs. 9.4% and 1.5% respectively, p<0.01). On subgroup-analyzing 269 patients with classical PTC, the larger nodule size on US was associated with higher prevalence of LNM (28.3% vs. 14.7%, p=0.007). A multivariate analysis revealed that classical PTC, extra-thyroidal extension, and the US nodule size >10 mm were independent predictive factors of LNM after adjustment for age, sex, TSH level, and multifocality. Conclusions: Thyroid nodules larger than 10 mm with benign US features are more likely to be non-classical PTC than those with smaller diameter. The larger nodules also have increased risk of LNM in classical PTC. These cases require a more aggressive approach to FNA.