Synthesis, Characterization and Identification of In Vitro and In Vivo DNA adducts of 1 - and 2-Bromopropane

Lee EungSeok,Moon YoonSoo,Basnet Arjun,Zhao LongXuan,Kim Eunkyung,Lim HyunTae,Chae Whigun,Jeong TaeCheon 大韓藥學會 2003 大韓藥學會 總會 및 學術大會 Vol.2003 No.1

Detection, Identification and Characterization of In vitro GSH Metabolites Formed by 1- and 2-Bromopropane

Lee EungSeok,Moon YoonSoo,Kim EunKyung,Basnet Arjun,Zhao LongXuan,Kim DaeOk,Kim NamHee,Chae Whigun,Jeong TaeCheon 大韓藥學會 2003 大韓藥學會 總會 및 學術大會 Vol.2003 No.2

Dysport and Botox at a Ratio of 2.5:1 Units in Cervical Dystonia: A Double-Blind, Randomized Study

Yun, Ji Young,Kim, Jae Woo,Kim, Hee-Tae,Chung, Sun Ju,Kim, Jong-Min,Cho, Jin Whan,Lee, Jee-Young,Lee, Ha Neul,You, Sooyeoun,Oh, Eungseok,Jeong, Heejeong,Kim, Young Eun,Kim, Han-Joon,Lee, Won Yong,Jeon BlackWell Publishing Ltd 2015 Movement disorders Vol.30 No.2

<P>We aimed to compare Dysport (abobotulinumtoxinA, Ipsen Biopharm, Slough, UK) and Botox (onabotulinumtoxinA, Allergan, Irvine, CA, USA) at a 2.5:1 ratio in the treatment of cervical dystonia (CD). A Dysport/Botox ratio of lower than 3:1 was suggested as a more appropriate conversion ratio, considering its higher efficacy and more frequent incidence of adverse effects not only in the treatment of CD but also in other focal movement disorders. A randomized, double-blind, multicenter, non-inferiority, two-period crossover study was done in CD, with a duration of at least 18 months. Patients were randomly assigned to treatment for the first period with Dysport or Botox, and they were followed up for 16 weeks after the injection. After a 4-week washout period, they were switched to the other formulation and then followed up for 16 weeks. The primary outcome was the changes in the Tsui scale between the baseline value and that at 1 month after each injection. A total of 103 patients were enrolled, and 94 completed the study. Mean changes in the Tsui scale between baseline and 4 weeks after each injection tended to favor Botox; however, this was not statistically significant (4.0 ± 3.9 points for the Dysport treatment vs. 4.8 ± 4.1 points for Botox; 95% confidence interval, −0.1-1.7; <I>P</I> = 0.091). The mean change of the Toronto western spasmodic torticollis rating scale score, the proportion of improvement in clinical global impression and patient global impression, and the incidences of adverse events were not significantly different between the two treatments. With regard to safety and efficacy, Dysport was not inferior to Botox in patients with CD at a conversion factor of 2.5:1. [http//clinicaltrial.gov: NCT00950664] © The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.</P>

Characterization of novel Phase 2 conjugates of loxoprofen in vivo

Sanjita Paudel(산지타 파우델),Riya Shrestha(리아쉬레샤),Piljoung Cho(조필정),Tae Cheon Jeong(정태천),EungSeok Lee(이응석),Taeho Lee(이태호),Sangkyu Lee(이상규) 환경독성보건학회 2019 한국독성학회 심포지움 및 학술발표회 Vol.2019 No.4

홍수취약성과 홍수피해잠재능을 이용한 도시지역 평가비교

김응석(Eungseok Kim),이승현(Seunghyun Lee ) 한국방재학회 2022 한국방재학회논문집 Vol.22 No.5

최근 기후변화와 급격한 도시화, 빈번히 발생되는 게릴라성 집중호우로 인해 도시 홍수피해가 급증하고 있다. 따라서 도시지역의홍수와 관련되어 효과적인 정책수립에 필요한 정량적인 홍수 피해분석 기법이 필요하다. 본 연구에서는 도시지역을 대상으로홍수피해 정도를 분석하는 대표적인 방법인 홍수취약성 방법과 홍수피해잠재능(PFD) 방법을 적용 하였다. 또한, 홍수방어시설용량-피해(PCD) 매트릭스 기법을 이용하여 각 분석 방법별 결과를 비교 분석하였다. PCD 매트릭스 기법은 기존의 홍수방어시설이 많이 건설되어 있어도 관리 미흡 또는 설계강우 이상의 호우가 발생시에는 홍수피해가 클 수 있다는 것을 직관적으로보여주는 기법이다. 기존의 홍수피해 기법 2개를 적용한 결과에서는 서초구는 재정자립도가 높고 홍수피해 방어시설물이많은 구축되어 있어서 홍수취약성이 낮은 것으로 산정되었다. 그러나 PCD 매트릭스를 적용한 결과에서 서초구는 홍수취약성이높게 분류되었다. 따라서 이러한 상반된 결과에서 보듯이 홍수방어 정책 수립시에는 보다 세밀한 검토 및 분석이 필요할것으로 판단되었다. Recently, urban flood damage has rapidly increased due to climate change, rapid urbanization, and frequent guerrilla heavy rains. Therefore, a quantitative flood damage analysis technique is required for effective policy regarding flooding in urban areas. In this study, the flood vulnerability and potential flood damage (PFD) methods, which are representative methods for analyzing the degree of flood damage in urban areas, were applied. In addition, the results of each analysis method were compared and analyzed using the flood prevention capacity-damage (PCD) matrix technique, which intuitively shows that even if many existing flood protection facilities are built, flood damage can be large when there is insufficient management or heavy rainfall exceeding the design rainfall occurs. The two existing flood damage techniques estimated Seocho-gu to have low flood vulnerability due to high financial independence and many flood damage protection facilities. However, application of the PCD matrix resulted in classifying Seocho-gu as highly vulnerable to flooding. These conflicting results thus demonstrate that a more detailed review and analysis are necessary when establishing a flood protection policy.

보의 설치에 따른 하천수질변화 분석

김응석(Eungseok Kim),이승현(Seunghyun Lee) 한국방재학회 2022 한국방재학회논문집 Vol.22 No.3

There has been an increase in the amount of pollutants such as biochemical water and factory wastewater discharged from urban areas as a result of urbanization and industrialization. Therefore, research on securing water resources and improving water quality in rivers around cities is being actively conducted. This study analyzed the pattern of change of water quality due to the installation of overflow type weirs among the hand structures in the existing river. The target watershed was performed at Gilancheon, located in Andong-si, Gyeongsangbuk-do. The flow coefficient was calculated by analyzing the flow velocity and water level according to weir installation using the HEC-RAS. Afterwards, the QUALKO model was built, and the water quality analysis according to weir installation was performed by applying the flow coefficient calculated using HEC-RAS. As a result of the analysis, the flow rate was found to have decreased, and a stagnation section occurred due to the influence of weir installation, resulting in an increase in Chl-a. Due to the increase of Chl-a, BOD increased by 29%-32%, and T-N and T-P, which are nutrients for Chl-a, decreased. Therefore, an increase in Chl-a concentration due to weir installation can cause eutrophication due to the growth of green algae in the river, and it is believed that it can greatly affect the deterioration of water quality. Furthermore, it is considered that it will be able to help predict changes in water quality for the installation and operation of weirs in the future. 도시화 및 산업화로 인해 도시지역에서 배출되는 생화하수, 공장 폐수 등의 오염물질의 발생량 증가로 도시주변 하천의 수자원 확보 및 수질개선에 대한 연구가 활발히 진행되어지고 있다. 따라서 본 연구에서는 기존 하천에 수공구조물 중 월류형보를 설치에 따른 수질변화 양상을 분석하였다. 대상유역은 경상북도 안동시에 위치한 길안천을 대상으로 수행하였다. HEC-RAS를 이용하여 보 설치에 따른 유속 및 수위 등을 분석하여 유량계수를 산정하였다. 이후 QUALKO 모형을 구축하였으며, 보 설치에 따른 수질분석은 HEC-RAS를 이용해 산정한 유량계수를 적용하여 분석을 수행하였다. 분석결과 보 설치의 영향으로 인해 유속 감소 및 정체구간이 발생되어 Chl-a가 증가하게 된다. Chl-a의 증가로 인해 BOD의 경우 29~32% 증가하며, Chl-a에 영양분이 되는 T-N, T-P의 경우 감소되는 양상을 나타내었다. 따라서 보 설치에 따른 Chl-a 농도증가는 하천에 녹조류 번식으로 인한 부영양화를 발생시킬 수 있으며, 수질악화에 큰 영향을 미칠 수 있을 것으로 판단된다. 추후 보 설치 및 운영에 대한 수질변화 예측에 도움을 줄 수 있을 것으로 판단된다.

Metformin Inhibits Nuclear Receptor TR4–Mediated Hepatic Stearoyl-CoA Desaturase 1 Gene Expression With Altered Insulin Sensitivity

Kim, Eungseok,Liu, Ning-Chun,Yu, I-Chen,Lin, Hung-Yun,Lee, Yi-Fen,Sparks, Janet D.,Chen, Lu-Min,Chang, Chawnshang American Diabetes Association 2011 Diabetes Vol.60 No.5

<P><B>OBJECTIVE</B></P><P>TR4 is a nuclear receptor without clear pathophysiological roles. We investigated the roles of hepatic TR4 in the regulation of lipogenesis and insulin sensitivity in vivo and in vitro.</P><P><B>RESEARCH DESIGN AND METHODS</B></P><P>TR4 activity and phosphorylation assays were carried out using hepatocytes and various TR4 wild-type and mutant constructs. Liver tissues from TR4 knockout, C57BL/6, and <I>db/db</I> mice were examined to investigate TR4 target gene stearoyl-CoA desaturase (<I>SCD</I>) 1 regulation.</P><P><B>RESULTS</B></P><P>TR4 transactivation is inhibited via phosphorylation by metformin-induced AMP-activated protein kinase (AMPK) at the amino acid serine 351, which results in the suppression of SCD1 gene expression. Additional mechanistic dissection finds TR4-transactivated <I>SCD1</I> promoter activity via direct binding to the TR4-responsive element located at −243 to −255 on the promoter region. The pathophysiological consequences of the metformin→AMPK→TR4→SCD1 pathway are examined via TR4 knockout mice and primary hepatocytes with either knockdown or overexpression of TR4. The results show that the suppression of <I>SCD1</I> via loss of TR4 resulted in reduced fat mass and increased insulin sensitivity with increased β-oxidation and decreased lipogenic gene expression.</P><P><B>CONCLUSIONS</B></P><P>The pathway from metformin→AMPK→TR4→SCD1→insulin sensitivity suggests that TR4 may function as an important modulator to control lipid metabolism, which sheds light on the use of small molecules to modulate TR4 activity as a new alternative approach to battle the metabolic syndrome.</P>

TR4 nuclear receptor functions as a fatty acid sensor to modulate CD36 expression and foam cell formation.

Xie, Shaozhen,Lee, Yi-Fen,Kim, Eungseok,Chen, Lu-Min,Ni, Jing,Fang, Lei-Ya,Liu, Su,Lin, Shin-Jen,Abe, Jun-Ichi,Berk, Bradford,Ho, Feng-Ming,Chang, Chawnshang National Academy of Sciences 2009 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.106 No.32

<P>Testicular orphan nuclear receptor 4 (TR4) is an orphan member of the nuclear receptor superfamily with diverse physiological functions. Using TR4 knockout (TR4(-/-)) mice to study its function in cardiovascular diseases, we found reduced cluster of differentiation (CD)36 expression with reduced foam cell formation in TR4(-/-) mice. Mechanistic dissection suggests that TR4 induces CD36 protein and mRNA expression via a transcriptional regulation. Interestingly, we found this TR4-mediated CD36 transactivation can be further enhanced by polyunsaturated fatty acids (PUFAs), such as omega-3 and -6 fatty acids, and their metabolites such as 15-hydroxyeico-satetraonic acid (15-HETE) and 13-hydroxy octa-deca dieonic acid (13-HODE) and thiazolidinedione (TZD)-rosiglitazone. Both electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) assays demonstrate that TR4 binds to the TR4 response element located on the CD36 5'-promoter region for the induction of CD36 expression. Stably transfected TR4-siRNA or functional TR4 cDNA in the RAW264.7 macrophage cells resulted in either decreased or increased CD36 expression with decreased or increased foam cell formation. Restoring functional CD36 cDNA in the TR4 knockdown macrophage cells reversed the decreased foam cell formation. Together, these results reveal an important signaling pathway controlling CD36-mediated foam cell formation/cardiovascular diseases, and findings that TR4 transactivation can be activated via its ligands/activators, such as PUFA metabolites and TZD, may provide a platform to screen new drug(s) to battle the metabolism syndrome, diabetes, and cardiovascular diseases.</P>

Reactive microglia and mitochondrial unfolded protein response following ventriculomegaly and behavior defects in kaolin-induced hydrocephalus

( Jiebo Zhu ),( Min Joung Lee ),( Hee Jin Chang ),( Xianshu Ju ),( Jianchen Cui ),( Yu Lim Lee ),( Dahyun Go ),( Woosuk Chung ),( Eungseok Oh ),( Jun Young Heo ) 생화학분자생물학회 2022 BMB Reports Vol.55 No.4

Ventriculomegaly induced by the abnormal accumulation of cerebrospinal fluid (CSF) leads to hydrocephalus, which is accompanied by neuroinflammation and mitochondrial oxidative stress. The mitochondrial stress activates mitochondrial unfolded protein response (UPRmt), which is essential for mitochondrial protein homeostasis. However, the association of inflammatory response and UPRmt in the pathogenesis of hydrocephalus is still unclear. To assess their relevance in the pathogenesis of hydrocephalus, we established a kaolin-induced hydrocephalus model in 8-week-old male C57BL/6J mice and evaluated it over time. We found that kaolin-injected mice showed prominent ventricular dilation, motor behavior defects at the 3-day, followed by the activation of microglia and UPRmt in the motor cortex at the 5-day. In addition, PARP-1/NF-κB signaling and apoptotic cell death appeared at the 5-day. Taken together, our findings demonstrate that activation of microglia and UPRmt occurs after hydrocephalic ventricular expansion and behavioral abnormalities which could be lead to apoptotic neuronal cell death, providing a new perspective on the pathogenic mechanism of hydrocephalus. [BMB Reports 2022; 55(4): 181-186]

진동해머의 기계적 진동특성에 대한 연구

이승현,윤기용,김응석,Lee. Seunghyun,Yoon. Kiyong,Kim. Eungseok 한국방재학회 2013 한국방재학회논문집 Vol.13 No.4

진동해머의 진동특성을 살펴보고 편심모멘트, 진동수, 진동질량, 스프링상수가 진동해머의 진폭, 가속도, 스프링작용력 그리고 이론적일률에 미치는 영향을 분석하였다. 진동해머에 의해 시공되는 말뚝의 해석을 위한 말뚝머리하중결정에 관하여 기존의 접근법에 있어서의 오류를 파악하고 합리적 접근법을 제시하였다. 또한 진동해머/말뚝의 진동시스템을 표현하는 기존의 지배방정식을 합리적으로 수정 제안하였다. Vibrational properties of vibro-hammer were studied and the influences of eccentric moment, frequency, vibratory mass and spring constant to the amplitude, acceleration, spring force and theoretical power were analyzed. Existing approach of determining input of pile head force which is necessary for analyzing a pile constructed by vibro-hammer were reviewed and rational one was suggested. In addition, existing governing equation shown in the literature, which simulates the vibrating system of vibrator/pile was modified through rational evaluation.