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Han Daewon,Kim Haeil,Kim Soojin,Le Qui Anh,Han Seung Yun,Bae Jeongyun,Shin Hye Won,Kang Hyun-Goo,한경호,Shin Jongdae,Park Hwan-Woo 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
Chronic exposure to bile acid in the liver due to impaired bile flow induces cholestatic liver disease, resulting in hepatotoxicity and liver fibrosis. Sestrin2, a highly conserved, stress-inducible protein, has been implicated in cellular responses to multiple stress conditions and the maintenance of cellular homeostasis. However, its role in cholestatic liver injury is not fully understood. In this study, we investigated the role of hepatic Sestrin2 in cholestatic liver injury and its underlying mechanisms using in vivo and in vitro approaches. Hepatic Sestrin2 expression was upregulated by activating transcription factor 4 (ATF4) and CCAAT/enhancer-binding protein-β (C/EBP-β) after treatment with bile acids and correlated with endoplasmic reticulum (ER) stress responses. Bile-duct ligation (BDL)-induced hepatocellular apoptosis and liver fibrosis were exacerbated in Sestrin2-knockout (Sesn2−/−) mice. Moreover, Sestrin2 deficiency enhanced cholestasis-induced hepatic ER stress, whereas Sestrin2 overexpression ameliorated bile acid-induced ER stress. Notably, the mammalian target of rapamycin (mTOR) inhibitor rapamycin and the AMP-activated protein kinase (AMPK) activator AICAR reversed bile acid-induced ER stress in Sestrin2-deficient cells. Furthermore, Sestrin2 deficiency promoted cholestasis-induced hepatic pyroptosis by activating NLRP3 inflammasomes. Thus, our study provides evidence for the biological significance of Sestrin2 and its relationship with cholestatic liver injury, suggesting the potential role of Sestrin2 in regulating ER stress and inflammasome activation during cholestatic liver injury.
한종대(Jongdae Han),박근덕(Geunduk Park),우치수(Chisu Wu) 한국정보과학회 2005 한국정보과학회 학술발표논문집 Vol.32 No.1
XML을 이용하면 다이어그램에서 변경 내용을 검출하는 문제는 트리 구조에서 변경 내용을 검출하는 문제로 전환할 수 있다. 트리 구조의 여러 버전(version) 간에 형제(sibling) 노드의 순서가 유지되지 않는 조건하에서, 트리 구조의 변경 내용을 검출하는 문제는 NP-complete임이 증명되어 있다. 그러므로 본 논문에서는, 트리 연산에 몇 가지 제한을 부가하여, 빠른 시간 내에 최적에 가까운 변경 내용을 검출하는 방법을 제안한다.
한종대(Jongdae Han),심재근(Jaekun Shim),이병정(Byungjeong Lee),오재원(Jaewon Oh),우치수(Chisu Wu) 한국정보과학회 2010 정보과학회 컴퓨팅의 실제 논문지 Vol.16 No.12
SaaS는 소프트웨어 개발 및 배포에 있어 전체적인 비용을 크게 줄일 수 있는 새로운 패러다임으로 분산 컴퓨팅, 그린 컴퓨팅, 클라우드 컴퓨팅 등의 최신 컴퓨팅 플랫폼에 있어 중요한 기반기술로 여겨지고 있다. 이러한 SaaS는 기존의 소프트웨어와 달리 높은 수준의 설정 가능성(Configurability)을 요구받고 있으며, 이에 따라 설정 요구사항(Configuration Requirements)의 추출에 있어 모든 설정 가능성을 빠짐 없이 고려하는 것이 매우 중요하다. 본 연구에서는 SaaS의 특성에 따라 각 요구사항에 대한 설정 가능성이 누락되지 않도록 결정할 수 있는 분류 기법을 제안한다. SaaS is an emerging paradigm for software development and deployment, expected to able to reduce cost. SaaS is also considered as a crucial technology for implementation of cutting-edge technology, such as distributed computing, green computing, and cloud computing. SaaS is requested to be configurable software to satisfy various customers, therefore it is very important to consider every configurability requirement during requirement elicitation. Our research suggests a classification technique to secure completeness of configuration requirement.
김종대 ( Jongdae Kim ),한상무 ( Sangmoo Han ),정병곤 ( Byunggon Jeong ) 한국물환경학회 2015 한국물환경학회지 Vol.31 No.5
Water permeable block was manufactured using waste sewage sludge, loess and clay for the purpose of recycling waste sludge due to the prohibition of waste sludge ocean dumping. Experiments for determining optimum mixing ratio was conducted by changing sludge content in water permeable block as 5~20%. In respect of compressive strength, 1,600 N/cm2 (163.3 kg/cm2) was obtained when the mixing ratio of sludge : loess : clay were maintained by 5% : 65% : 30%, 10% : 65% : 25% and 15% : 65% : 20%, respectively. These mean that relatively high compressive strength can be obtained when the sludge content is maintained 5, 10, 15% at the 65% of loess content. In terms of water permeability and absorption rate, the higher values can be obtained as the sludge content increases. The optimum mixing ratio of sludge : loess : clay came out to be 15% : 65% : 20% when water permeability, absorption and strength were considered altogether, which matches the result observed by an electron microscope. The heavy metal leaching test result of the prepared permeable block appeared to satisfy the environmental standard in the content of Cd, Cu, Pb and As.
Lee, Solji,Han, Daewon,Kang, Hyun-Goo,Jeong, Su Jin,Jo, Jae-Eun,Shin, Jongdae,Kim, Do Kyung,Park, Hwan-Woo Elsevier 2019 Biomaterials Vol.197 No.-
<P><B>Abstract</B></P> <P>Obesity and overweight, the most serious health problems, are associated with chronic metabolic complications such as type 2 diabetes, insulin resistance, and nonalcoholic fatty liver disease (NAFLD). However, current pharmacological therapies for obesity are challenged by potential side effects, low effectiveness, and low aqueous solubility, which limit their clinical application. Here, we develop nifedipine-loaded nanoparticles (NFD-NPs) that alleviate obesity-related metabolic dysfunction to be used as instruments for translational medicine. Nanoparticles (NPs) composed of poly (lactic-co-glycolic acid) (PLGA) not only enhance water solubility of hydrophobic nifedipine (NFD), a calcium channel blocker, without modifying the chemical structure of NFD for intravenous administration, but also allow prolonged release of NFD <I>in vivo</I>. NFD-NPs do not show cytotoxicity and reduce palmitate-induced protein inclusions and endoplasmic reticulum stress in human hepatoma HepG2 cells. Importantly, tail-vein injection of NFD-NPs into diet-induced obese mice results in sustained retention of NFD-NPs in the liver and suppression of metabolic derangements associated with NAFLD by enhancing autophagic clearance through Ca2+/calmodulin-dependent kinase II (CaMKII) phosphorylation, consequently decreasing diet-induced insulin resistance and improving glucose tolerance. Our findings offer new clinical tools for NP-mediated pharmaceutical strategies to treat NAFLD and its related metabolic dysfunction.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Kim, Soojin,Han, Seung Yun,Yu, Kwang Sik,Han, Daewon,Ahn, Hyo-Ju,Jo, Jae-Eun,Kim, Jin-Hoi,Shin, Jongdae,Park, Hwan-Woo Elsevier 2018 Biochemical and biophysical research communication Vol.495 No.1
<P><B>Abstract</B></P> <P>Chronic exposure to hydrophobic bile acids such as chenodeoxycholic acid (CDCA) and cholic acid (CA) in the liver during cholestasis causes hepatotoxicity and inflammatory response. However, the detailed mechanisms regarding the role of autophagy in cholestatic hepatotoxicity remain largely unknown. Here we determined autophagic clearance in livers of bile duct-ligated mice, in which bile acids accumulate, and in human hepatoma HepG2 cells treated with CDCA and CA. The accumulation of bile acids caused defective autophagic clearance, shown by the accumulation of insoluble p62 and ubiquitinated proteins and cell death accompanied by caspase-3 processing. Hepatocytes exposed to bile acids also showed the accumulation of autophagosomes via suppressed autophagy flux. Treatment of CDCA markedly suppressed Beclin-1 expression, which exhibits a higher cytotoxicity than CA. Moreover, pharmacological or genetic inhibition of autophagy enhanced bile acid-induced cell death. Finally, <I>in vivo</I>, bile duct ligation led to aberrant accumulation of p62 and ubiquitinated proteins in the liver. Our data demonstrate that inhibited autophagy is an essential component of liver injury during cholestasis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> CDCA, CA and bile duct ligation caused defective autophagic clearance. </LI> <LI> CDCA suppressed Beclin-1 expression, which exhibits a higher cytotoxicity than CA. </LI> <LI> Pharmacological or genetic inhibition of autophagy enhanced bile acid-induced cell death. </LI> <LI> Reduced Beclin-1 expression may lead to higher cytotoxicity of CDCA. </LI> </UL> </P>