Assessment of Hepatic Steatosis Improvement Using Controlled Attenuation Parameter in Patients with Non-Alcoholic Fatty Liver Disease under Regular Follow Up

( Kyu Sik Jung ),( Jun Yong Park ),( Mi Na Kim ),( Hana Park ),( Yun Bin Lee ),( Joo Ho Lee ),( Yeonjung Ha ),( Beom Kyung Kim ),( Seung Up Kim ),( Sang Hoon Ahn ),( Do Young Kim ),( Hana Park ),( Kyu 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: The change of hepatic steatosis in non-alcoholic fatty liver disease (NAFLD) patients under regular follow up has not been widely investigated. We investigated the serial changes of hepatic steatosis assessed by controlled attenuation parameter (CAP) and the predictors for improvement of hepatic steatosis in NAFLD patients. Methods: Among 513 NAFLD patients diagnosed upon ultrasound and CAP > 250 dB/m at baseline, 304 patients underwent repeated CAP measurement at baseline and at follow up. The improvement of hepatic steatosis was defined as a >10% decline of CAP value from the baseline. Results: Mean age of 304 patients was 58.8 ± 11.4 years and 80.1% were male. The mean CAP value significantly decreased from baseline to follow up (292.3 dB/m to 277.1 dB/m, P<0.001). During the median follow up of 15.3 (9.5-20.3) months, 34.5% patients showed improvement of hepatic steatosis. In a univariate analysis, low body mass index (BMI), low weight, low liver stiffness value, low triglyceride level, and low ALT at follow up were predictors for improvement of hepatic steatosis. In multivariate analyses, low weight (P=0.004; hazard ratio [HR],0.965; confidence interval [CI], 0.941-0.988) and low ALT (P=0.004; HR,0.971;CI, 0.951-0.990) at follow up, or low BMI (P=0.006; HR,0.881; CI, 0.805-0.964) and low ALT (P=0.004; HR,0.971; CI, 0.951-0.990) at follow up were the independent predictors. In patients with weight reduction more than 10% (n=22), CAP value significantly decreased (from 288.0 dB/m to 228.9dB/m, P<0.001). Conclusions: Weight reduction, and ALT decrease were independent predictors for improvement of hepatic steatosis. Long term effect of weight reduction on improvement of hepatic steatosis and fibrosis should be investigated further.

Dkk-1 Promotes Angiogenesis through Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma

( Sang Hyun Seo ),( Hye Jung Park ),( Kyungjoo Cho ),( Hye Won Lee ),( Beom Kyung Kim ),( Jun Yong Park ),( Do Young Kim ),( Sang Hoon Ahn ),( Seung Up Kim ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Dickkopf-1(DKK1), a negative regulator of the Wnt/ ß-catenin pathway, has been recently found to be up-regulated in hepatocellular carcinoma (HCC). However, the biological function of DKK1 in HCC has not yet been well documented. Our previous in vitro data suggest that DKK1 can enhance angiogenesis by endothelial cell, independent of the Wnt signaling pathway. This study aimed to investigate the tumorigenic potential and angiogenic role of DKK1 in mouse model. Methods: We assessed tumorigenic functions of DKK1 in Hep3B cells expressing endogenous DKK-1 and in DKK1-deficient Hep3B cells created using CRISPR/Cas9 technology. These edited cells were injected subcutaneously in immunosuppressed mice and tumor growth was followed for 6 weeks. With the evidence of tumorigenic potential in DKK1, transgenic mouse models expressing DKK-1 or luciferase were developed using hydrodynamic transfection. Transposons encoding an activated form of human H-RAS were mixed with transposons encoding either DKK1 or luciferase. All mice were monitored at least twice per week and sacrificed when moribund. Subcutaneous tumors and tumor-bearing livers were formalin fixed for hematoxylin- eosin and immunofluoroscence staining. Results: DKK1-deficient Hep3B xenografts exhibited significantly less growth compared to control Hep3B cells expressing DKK1. In addition, the forced expression of DKK1 with H-RAS through the hydrodynamic transfection formed many tumors in the liver, compared to luciferase liver. We investigated the expression of angiogenesis markers, including CD31, VEGFR2 and mesenchymal markers, including vimentin, fibronectin in the subcutaneous tumors and tumor-bearing livers. Quantity of angiogenic and mesenchymal cells were found to be reduced in the established DKK1 homozygous knockout mice (all P<0.05). Taken together, it was confirmed that the expression of CD31 (P<0.0001), VEGFR2 (P<0.0001), vimentin, and fibronectin (P<0.0001) were up-regulated with DKK1 in the mouse liver. Conclusions: Our findings indicate that DKK1 appears to facilitate angiogenesis, and the progression of HCC through inducing the EMT.

[PG-0011] A Sesame variety ‘Haniall’ with non-shattering capsule and early maturity

Sung-Up Kim(Sung-Up Kim ),Jeongeun Lee(Jeongeun Lee ),Eunyoung Oh(Eunyoung Oh ),Jung In Kim(Jung In Kim ),Sang Woo Kim(Sang Woo Kim ),Min Young Kim(Min Young Kim ),Eunsoo Lee(Eunsoo Lee ),Kwang-Soo Ch 한국육종학회 2022 한국육종학회 공동학술발표집 Vol.2022 No.-

PE-162: The Degree of Liver Fibrosis Assessed Using Transient Elastography Independently Correlates with the Risk of Stroke: A Case-control Study

( Young Dae Kim ),( Dongbeom Song ),( Ji Hoe Heo ),( Beom Kyung Kim ),( Jun Yong Park ),( Do Young Kim ),( Sang Hoon Ahn ),( Kwang-hyub Han ),( Kwang Joon Kim ),( Seung Up Kim ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: Transient elastography (TE) assess the degree of liver fibrosis and steatosis. The degree of liver fibrosis was associated with the presence and burden of cerebral microbleeds in healthy, asymptomatic participants. We investigated the correlation between the degree of liver fibrosis, as assessed using TE, and the risk of stroke. Methods: Patients who were admitted due to the management of stroke and received TE examination from April 2013 to August 2014 and subjects who underwent a medical health check-up including TE during the same period were recruited. Significant fibrosis was defined as a liver stiffness (LS) value of ≥8 kPa and hepatic steatosis was defined as a controlled attenuation parameter (CAP) of ≥250 dB/m. Subjects with inappropriate TE results and alcoholic/ chronic viral liver diseases were excluded. Further, we conducted propensity score matching to reduce the potential effects of selection bias and confounding factors. Results: A total of 295 patients with stroke and 2,936 subjects with health check-up were analyzed. The mean age and the proportion of hypertension, diabetes, hypercholesterolemia, chronic kidney disease, and metabolic syndrome were significantly higher in patients with stroke than those of subjects with health check-up (all P<0.05). The mean LS value (5.6 kPa, vs. 4.2 kPa) and the proportion of significant fibrosis (9.2% vs. 2.7%) were significantly higher in patients with stroke than those of subjects with health check-up (all P<0.05), whereas the mean CAP value and the proportion of hepatic steatosis were statistically similar between two groups (all P>0.05). When fibrotic burden was assessed using TE, it was significantly higher in patients with stroke than that of subjects with health check-up, regardless of body mass index (BMI) (mean 5.3 kPa vs. 3.9 kPa in BMI<25 kg/m2 and 6.3 kPa vs. 4.7 kPa in BMI ≥25 kg/m2), CAP value (mean 5.3 kPa vs. 3.9 kPa in CAP<250 dB/m and 6.3 kPa vs. 4.7 kPa in CAP≥250 dB/m), and metabolic syndrome (mean 5.3 kPa vs. 4.1 kPa in the absence of metabolic syndrome and 5.9 kPa vs. 5.0 kPa in the presence of metabolic syndrome) (all P<0.05). As a continuous variable, unadjusted odd ratio (OR) of LS value for stroke was 1.161 and adjusted ORs were calculated as between 1.132 to 1.213 according to varying multivariate models. As a categorical variable, unadjusted OR of significant fibrosis was 4.388 and adjusted ORs were calculated as between 3.474 to 6.397 according to varying multivariate models. In a propensity matched analysis using 1:1 ratio (n=197 for each group), LS value was independently associated with the risk of stroke (OR of 1.080 as a continuous variable and 8.488 as a categorical variable) (all P<0.001). Conclusions: In our case-control study, we found that the degree of liver fibrosis, as assessed using TE, was significantly associated with the risk of stroke. Further studies investigating the dynamic link between these two disease entities are required.

DNA methylation and not allelic variation regulates STAT6 expression in human T cells

Kim, Eu-Gene,Shin, Hyun-Jin,Lee, Chang Geun,Park, Hye-Young,Kim, Yoon-Keun,Park, Heung-Woo,Cho, Sang-Heon,Min, Kyung-Up,Cho, Mi-La,Park, Sung-Hwan,Lee, Chang-Woo Springer-Verlag 2010 Clinical and experimental medicine Vol.10 No.3

Evaluation of lignan contents in two sesame (Sesamum indicum L.) RIL populations

Sung Up Kim,Jeongeun Lee,Eunyoung Oh,Jung In Kim,Sang Woo Kim,Min Young Kim,Kwang Soo Cho,Myoung Hee Lee 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10

Sesame lignan is antioxidant that prevents the scattering of sesame oil and has anti-inflammatory and anti-cancer effects. This study was performed to investigate lignan contents in two sesame (Sesamum indicum L.) RIL populations. First population is 257 Goenbaek x YCS71 F6:7 recombinant inbred lines. Second population is 141 Arum x YCS71 F6:7 recombinant inbred lines. Average sesamin, sesamolin and lignan content of first population is 5.2±1.7, 2.2±0.6, 7.5±2.1 mg/g and it ranged from 1.0∼9.4, 0.7∼3.7, 1.7∼12.8 mg/g. Average sesamin, sesamolin and lignan content of second population is 3.5±2.2, 1.8±0.7, 5.4±2.8 mg/g and it ranged from 0.6∼9.4, 0.7∼4.2, 1.4∼12.4 mg/g. Sesamin, lignan contents showed regular distribution in Goenbaek x YCS71 RILs populations. But sesamin and lignan contents showed a skewed distributions in Arum x YCS71 RILs populations. It showed a positive correlation between sesamin, sesamolin and lignan content. 47 lines with lignan content of 10mg/g or more were selected for investigating the agricultural characteristics.

Risk Assessment of Liver-related Events Using Transient Elastography in Patients With Chronic Hepatitis B Receiving Entecavir

Kim, Mi Na,Kim, Seung Up,Park, Jun Yong,Kim, Do Young,Han, Kwang-Hyub,Chon, Chae Yoon,Ahn, Sang Hoon RAVEN PRESS PUBLISHERS 2014 JOURNAL OF CLINICAL GASTROENTEROLOGY Vol.48 No.3

GOALS:: We investigated whether liver stiffness (LS) values can predict liver-related events (LREs) development in patients with chronic hepatitis B (CHB). BACKGROUND:: LS values using transient elastography provides accurate assessment of liver fibrosis in patients with chronic liver disease. METHODS:: Between June 2007 and May 2010, a total of 162 patients with CHB who completed 2-year entecavir (ETV) treatment were evaluated. The primary endpoint was LRE development (hepatic decompensation, hepatocellular carcinoma, or liver-related death) during the 2-year ETV treatment. RESULTS:: The median age of the patients (99 men, 63 women) was 51 years, and the median LS value was 14.8 kPa. During the 2-year ETV treatment, 15 (9.3%) patients experienced LREs. On univariate analysis, age, the proportion of patients with liver cirrhosis, platelet counts, and baseline LS values were significantly associated with LRE development (all P<0.05). Together with age, multivariate analysis identified baseline LS values as an independent predictor of LRE development (P=0.046; hazard ratio, 1.040; 95% confidence interval, 1.101-1.084). The cutoff LS value maximizing the sum of sensitivity and specificity was 12.0 kPa (area under the receiver operating characteristics curve, 0.736; P=0.003; sensitivity, 93.3%; specificity, 42.2%). In addition, the changes in LS values between baseline and 1-year ETV treatment showed significant correlations with LRE development (P=0.030). CONCLUSIONS:: Our data suggest that LS values are predictive of LRE development during 2-year ETV treatment in patients with CHB. The potential role of LS value as a monitoring tool for predicting dynamic changes in the risk of LRE development during long-term ETV treatment should be investigated further.

Effects of topical application of EGCG on testosterone‐induced hair loss in a mouse model

Kim, Yoon Young,up No, Sun,Kim, Min Ho,Kim, Hei Sung,Kang, Hoon,Kim, Hyung Ok,Park, Young Min Blackwell Publishing Ltd 2011 Experimental dermatology Vol.20 No.12

<P><B>Abstract: </B> We investigated the effect of topical epigallocatechin‐3‐gallate (EGCG) on testosterone (T)‐induced hair loss in mice. Marked hair loss was observed at the T‐injected site, and topical EGCG significantly reduced the hair loss (<I>P </I><<I> </I>0.05). TUNEL staining showed apoptosis of follicular epithelial cells in the T‐injected groups where topical EGCG was found to significantly diminish T‐induced apoptosis (<I>P </I><<I> </I>0.05). Topical EGCG down‐regulated the T‐induced expression of androgen receptor but did not down‐regulate 17β‐hydroxysteroid dehydrogenase (HSD) and three β‐HSD expression. Analysis using liquid chromatography tandem mass spectrometry (LC‐MS/MS) on serum and tissue samples revealed no significant difference in T and dihydrotestosterone concentrations between the T‐injected and T + EGCG groups. Thus, we found that T injection in a mouse model induces hair loss by apoptosis of the hair follicles rather than through the androgen metabolic pathway and also saw that T‐induced apoptosis of hair follicles was reduced by topical EGCG.</P>

Liver stiffness measurement using FibroScan^® is influenced by serum total bilirubin in acute hepatitis

Kim, Seung Up,Han, Kwang-Hyub,Park, Jun Yong,Ahn, Sang Hoon,Chung, Moon Jae,Chon, Chae Yoon,Choi, Eun Hee,Kim, Do Young Blackwell Publishing Ltd 2009 Liver international Vol.29 No.6

<P>Abstract</P><P>Background</P><P>Liver stiffness measurement (LSM) using FibroScan<SUP>®</SUP> is accepted as a highly reproducible and accurate technique for assessment of liver fibrosis. However, several studies have indicated that the LSM value can be significantly influenced by major changes in aminotransferases in patients with chronic viral hepatitis and LSM is unreliable for diagnosing underlying liver cirrhosis in patients with acute liver damage. We aimed to determine biochemical factors influencing the LSM value in patients with acute hepatitis.</P><P>Methods</P><P>From July to December 2007, a total of 60 patients with acute hepatitis of varying aetiologies were recruited prospectively. LSM and biochemical tests were performed at diagnosis and recovery from acute hepatitis.</P><P>Results</P><P>The mean age of the patients (38 men and 22 women) was 40.7±15.4 years. The aetiology of acute hepatitis included hepatitis A virus in 31 patients, drug induced in 19 and hepatitis B virus in 10. The mean LSM value was 19.6 kPa at diagnosis and 15.9 kPa at recovery. Correlation analysis showed that the LSM value at diagnosis was significantly associated with platelet count (<I>P</I>=0.023), alanine aminotransferase (<I>P</I>=0.045), albumin (<I>P</I><0.001), total bilirubin (<I>P</I>=0.004) and prothrombin time (<I>P</I>=0.005). However, additional correlation analysis between the changes in LSM value and biochemical factors from diagnosis to recovery showed that the change in total bilirubin was found to be the only factor associated with the change in the LSM value (<I>P</I><0.001).</P><P>Conclusions</P><P>Our data suggest that the LSM value might be influenced by serum total bilirubin in patients with acute hepatitis without pre-existing underlying chronic liver disease.</P>

Association between genetic variations of the transforming growth factor ${\beta}$ receptor type III and asthma in a Korean population

Kim, Hee-Kyoo,Jang, Tae-Won,Jung, Mann-Hong,Park, Heung-Woo,Lee, Jong-Eun,Shin, Eun-Soon,Cho, Sang-Heon,Min, Kyung-Up,Kim, You-Young Korean Society for Biochemistry and Molecular Bion 2010 Experimental and molecular medicine Vol.42 No.6

Transforming growth factor-beta (TGF-${\beta}$) and its receptors have been suggested to play key roles in the pathogenesis of asthma. The aim of this study was to evaluate the effects of genetic variations in the TGF-${\beta}$ receptor type III (TGFBR3) on asthma and on its related phenotypes in the general population. A cohort of 2,118 subjects aged from 10 to 18 years responded to a questionnaire concerning asthma symptoms and risk factors. Methacholine airway hyperresponsiveness (AHR), skin test responses to common aeroallergens, and serum total IgE levels were evaluated in the cohort. A total of 19 SNPs for TGFBR3 were found using direct re-sequencing in 24 healthy adults. Of these, informative SNPs [+44T>C (S15F) and +2753G>A at 3'UTR] were selected and scored using the high throughput single base extension method. Atopy was identified in subjects with 44T>C allele [P = 0.04, OR (95% CI) = 0.79 (0.62-0.99)] and in subjects with Ht1 (CG) more frequently than in subjects with other haplotypes [P = 0.04, OR (95% CI) = 1.27 (1.01-1.59)]. The A allele in 2753G>A was more common in subjects with non-atopic asthma [OR (95% CI) = 1.76 (1.01-3.05)]. A significant association was found between non-atopic asthma and 44T_2753A [OR (95% CI) = 2.16 (1.22-3.82)]. Genetic variations in TGFBR3 appear to be associated with a genetic predisposition to development of asthma and to phenotypes of asthma. Also, the minor allele 2753G and the haplotype TA in the TGFBR3 gene were associated with a pathogenesis of non-atopic asthma.