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Preclinical Long-term Magnetic Resonance Imaging Study of Silymarin Liver-protective Effects

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Journal of Clinical and Translational Hepatology 2022年第6期10卷 1167-1175页

作者： yeon Ji Chae Hwon Heo Chul-Woong Woo Sang-Tae Kim Jae-Im Kwon Monica Young choi Yu Sub Sung Kyung Won Kim Jeong Kon Kim Yoonseok choi Dong-Cheol Woo Department of Convergence Medicine Asan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea Convergence Medicine Research Center Asan Institute for Life SciencesAsan Medical CenterSeoulRepublic of Korea Clinical Research Center Asan Medical CenterSeoulRepublic of Korea Department of Radiology Asan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea Medical Research Institute Gangneung Asan HospitalGangneung-siGangwon-doRepublic of Korea

Background and Aims:Efficacy evaluations with preclini-cal magnetic resonance imaging(MRI)are uncommon,but MRI in the preclinical phase of drug development provides information that is useful for longitudinal *** study aim was to monitor the protective effectiveness of silymarin with multiparameter MRI and biomarkers in a thioacetamide(TAA)-induced model of liver injury in *** analysis was conducted to assess compare the monitoring of liver function by MRI and ***-ods:TAA was injected three times a week for 8 weeks to generate a disease model(TAA group).In the TAA and sily-marin-treated(TAA-SY)groups,silymarin was administered three times weekly from week *** images were acquired at 0,2,4,6,and 8 weeks in the control,TAA,and TAA-SY ***:The area under the curve to maximum time(AUCtmax)and T_(2)*values of the TAA group decreased over the study period,but the serological markers of liver abnormality increased significantly more than those in the control *** the TAA-SY group,MRI and serological biomarkers indicated attenuation of liver function as in the TAA ***,pattern changes were observed from week 6 to comparable levels in the control group with si-lymarin *** correlations between either AUCtmax or T_(2)*values and the serological biomarkers were ***:Silymarin had hepatoprotective effects on TAA-induced liver injury and demonstrated the usefulness of multiparametric MRI to evaluate efficacy in preclinical studies of liver drug development.

关键词： Liver fibrosis Magnetic resonance imaging Silymarin T1-weight-ed dynamic contrast-enhanced T_(2)*

Profitability Prediction Model for NPD Projects Under RisK

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Management Studies 2017年第2期5卷 108-119页

作者： Tae yeon hwang Hoo-Gon choi VMS Solutions Daejeon Republic of Korea Sungkyunkwan University Suwon Republic of Korea

Only a few successful new product development （NPD） projects are continuously supported by the firm when they are expected to assure profitability in the market. The profitability of a project is measured as profit ratio （PR）, the profit is divided by the cost. The profit figure is changed depending on either internal risks or uncertainties occurring externally. More risks require higher response costs to them and uncontrollable uncertainties affect NPD projects either positively or negatively. In this study, a PR model is developed to predict the profitability of a project at a given time. The model minimizes the response cost computed under two extreme response strategies, such as ＂Avoid＂ and ＂Acceptance＂ for the internal threats. Also, the model reflects the sales volume changes due to external uncertainties. The linear programming （LP） method determines the optimal probability of the response strategy under three scenarios of defining the relationship between risk avoidance and risk acceptance. It can be utilized to make a GO/NOGO decision on the project based on the prediction results at any gate of the NPD process. The solving procedure is provided to apply the developed model for real cases.

关键词： NPD risk assessment response costs profit ratio model profitability prediction GO/NOGO decisionmaking

Soluble components of Hericium erinaceum induce NK cell activation via production of interleukin-12 in mice splenocytes

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Acta Pharmacologica Sinica 2007年第6期28卷 901-907页

作者： Myung-hyun YIM Jang-woo SHIN Jin-young SON Se-mi OH Seung-hyun HAN Jung-hyo CHO Chong-kwan CHO hwa-seung YOO yeon-weol LEE Chang-gue SON East-West Cancer Center Dunsan Oriental Hospital of Daejeon UniversityDaejeon 302-122Korea

Aim:To investigate the immunoregulatory functions of water extracts of Hericiumerinaceum （WEHE） focusing on natural killer （NK） cell-based anticancer ***:Mouse splenocytes or purely isolated NK ceils were stimulated with1-100 mg/L WEHE for 24 h followed by co-culture with51Cr-labled Yac-1 cells for4 h,then NK cell-derived cytolytic activity was measured using a *** antibodies against mouse interleukin-12 （IL-12） were addedinto the WEHE-stimulated splenocytes,thereafter,cytotoxicity was measured toexamine the involvement of ***-PCR and ELISA analyses were performed toconfirm the induction of transcription and the translation of IL-12 and interferon-gamma （IFN-gamma） in the WEHE-treated ***:WEHE enhancedthe cytolytic activity of total splenocytes towards Yac-1 ceils in a ***,this activation was not observed when the NK cells isolatedfrom the splenocytes were treated with ***,the treatment withantibodies against IL-12 abolished the effect of WEHE on splenocyte-derivedcytolytic ***-PCR and ELISA analyses showed the induction of IL-12 andIFN-gamma in the WEHE-treated ***:WEHE indirectlyactivates the cytolytic ability of NK cells via the induction of IL-12 in totalsplenocytes,and possibly via other immuno-mediators or cellular components.

关键词： Hericium erinaceum NK cells interleukin-12

Spontaneous resolution of multiple lymphangiomas of the colon:A case report

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World Journal of Gastroenterology 2011年第11期17卷 1515-1518页

作者： Ji Min Lee Woo Chul Chung Kang-Moon Lee Chang Nyol Paik yeon-Ji Kim Bo-In Lee Young Seok Cho Hyun Joo choi Department of Internal Medicine College of Medicine the Catholic University of KoreaSt.Vincent's Hospital 93-6Ji dongPaldal-guSuwonGyeonggi-do442-723South Korea

Lymphangioma of the colon is a relatively rare nonepithelial tumor and usually presents as a submucosal polypoid *** cases incidentally discovered are usually ***,they may present as abdominal pain or bleeding,and their resection is normally *** itself is generally recognized as a benign tumor and no cases of malignant transformation have yet been reported,although its natural history is currently *** the best of our knowledge,this study is the first to describe a case of spontaneous resolution in multiple colonic lymphangiomas without any specific treatment.

关键词： Lymphangioma Colon Natural history

Induction of clusterin Expression by Neuronal Cell Death in Zebrafish

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Journal of Genetics and Genomics 2014年第11期41卷 583-589页

作者： Yun-Mi Jeong Tae-Eun Jin Jung-hwa choi Mi-Sun Lee Hyun-Taek Kim Kyu-Seok hwang Doo-Sang Park Hyun-Woo Oh Joong-Kook choi Vladimir Korzh Melitta Schachner Kwan-Hee You Cheol-Hee Kim Department of Biology Chungnam National University Korea Research Institute of Bioscience and Biotechnology Department of Biochemistry College of MedicineChungbuk National University Institute of Molecular and Cell Biology Agency for ScienceTechnology and Research Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience Rutgers University Center for Neuroscience Shantou University Medical College

Clusterin, a protein associated with multiple functions, is expressed in a wide variety of mammalian tissues. Although clusterin is known to be involved in neurodegenerative diseases, ageing, and tumorigenesis, a detailed analysis of the consequences of gain- or loss-of- function approaches has yet to be performed to understand the underlying mechanisms of clusterin functions. Since clusterin levels change in neurological diseases, it is likely that clusterin contributes to cell death and degeneration in general. Zebrafish was investigated as a model system to study human diseases. During development, zebrafish clusterin was expressed in the notochord and nervous system. Embryonic overexpression of clusterin by mRNA microinjection did not affect axis formation, whereas its knock-down by anti-sense morpholino treatment resulted in neuronal cell death. To analyze the function of clusterin in neurodegeneration, a transgenic zebrafish was investigated, in which nitroreductase expression is regulated under the control of a neuron-specifc huC promoter which is active between the stages of early neuronal precursors and mature neurons. Nitroreductase turns metronidazole into a cytotoxic agent that induces cell death within 12 h. After metronidazole treatment, transgenic zebrafish showed neuron-specific cell death. Interestingly, we also observed a dramatic induction of clusterin expression in the brain and spinal cord in these fish, suggesting a direct or indirect role of clusterin in neuronal cell death and thus, more generally, in neurodegeneration.

关键词： Clusterin Neuronal cell death Neurodegeneration Zebrafish

Biocompatible custom ceria nanoparticles against reactive oxygen species resolve acute inflammatory reaction after intracerebral hemorrhage

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Nano Research 2017年第8期10卷 2743-2760页

作者： Dong-Wan Kang Chi Kyung Kim Han-Gil Jeong Min Soh Taeho Kim In-Young choi SeuI-Ki Ki Do yeon Kim Wookjin Yang Taeghwan Hyeon Seung-Hoon Lee Laboratory of Innovative Nanobiotechnology Biomedical Research Institute Seoul National University Hospital Seoul 03080 Republic of Korea Department of Neurology Seoul National University Hospital Seou103080 Republic of Korea Department of Neurology Korea University Guro Hospital and Korea University College of Medicine Seou108308 Republic of Korea Center for Nanoparticle Research Institute for Basic Science (IBS) Seoul 151-742 Republic of Korea School of Chemical and Biological Engineering and Institute of Chemical Processes Seoul National University Seoul 151-742 Republic of Korea

Intracerebral hemorrhage （ICH） is a devastating subtype of stroke with a high mortality rate, for which there currently is no effective treatment. A perihematomal edema caused by an intense inflammatory reaction is more deleterious than the hematoma itself and can result in neurological deterioration and death. Ceria nanoparticles （CeNPs） are potent free radical scavengers with potential for biomedical applications. As oxidative stress plays a major role in post-ICH inflammation, we hypothesized that CeNPs might protect against ICH. To test this hypothesis, core CeNPs were synthesized using a modified reverse micelle method and covered with phospholipid-polyethylene glycol （PEG） to achieve biocompatibility. We investigated whether our custom-made biocompatible CeNPs have protective effects against ICH. The CeNPs reduced oxidative stress, hemin-induced cytotoxicity, and inflammation in vitro. In a rodent ICH model, intravenously administered CeNPs were mainly distributed in the hemorrhagic hemisphere, suggesting that they could diffuse through the damaged blood-brain barrier. Moreover, CeNPs attenuated microglia/macrophage recruitment around the hemorrhagic lesion and inflammatory protein expression. Finally, CeNP treatment reduced the brain edema by 68.4% as compared to the control. These results reveal the great potential of CeNPs as a novel therapeutic agent for patients with ICH.

关键词： ceria nanoparticles intracerebral hemorrhage free radical injury anti-inflammation neuroprotective agents biomedical application

Hepatocellular carcinoma,decompensation,and mortality based on hepatitis C treatment:A prospective cohort study

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World Journal of Gastroenterology 2022年第30期28卷 4182-4200页

作者： Gwang Hyeon choi Eun Sun Jang Young Seok Kim Youn Jae Lee In Hee Kim Sung Bum Cho Han Chu Lee Jeong Won Jang Moran Ki hwa Young choi Dahye Baik Sook-Hyang Jeong Department of Internal Medicine Seoul National University Bundang HospitalSeoul National University College of MedicineSeongnam 13620South Korea Department of Internal Medicine Soonchunhyang University Bucheon HospitalBucheon 14584South Korea Department of Internal Medicine Inje University Busan Paik HospitalBusan 47392South Korea Department of Internal Medicine Chonbuk National University HospitalJeonju 54907JeonbukSouth Korea Department of Internal Medicine Chonnam National University Hwasun HospitalHwasun 58128South Korea Department of Gastroenterology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505South Korea Department of Internal Medicine The Catholic University of KoreaSeoul 06591South Korea Cancer Control and Population Health Graduate School of Cancer Science and PolicyNational Cancer CenterGoyang 10408South Korea

BACKGROUND Prospective studies of the long-term outcomes of patients with hepatitis C virus(HCV)infection after treatment with interferon-based therapy(IBT)or directacting antivirals(DAA)are limited in many Asian *** To elucidate the incidences of hepatocellular carcinoma(HCC)and death/transplantation based on treatment with IBT or DAA,to compare the outcomes of the sustained virologic response(SVR)to IBT and DAA,and to investigate outcome-determining factors after *** This cohort included 2054 viremic patients(mean age,57 years;46.5%male;27.4%with cirrhosis)prospectively enrolled at seven hospitals between 2007 and *** were classified as the untreated group(n=619),IBT group(n=578),and DAA group(n=857).Outcomes included the incidences of HCC and death/*** incidences of the outcomes for each group according to treatment were calculated using an exact method based on the Poisson distribution.A multivariate Cox regression analysis was performed to determine the factors associated with HCC or death/transplantation,followed by propensity score matching to confirm the *** During a median of 4.1 years of follow-up,HCC and death/transplantation occurred in 113 and 206 patients,respectively,in the entire *** with the untreated group,the incidences of HCC and death/transplantation were significantly lower in the IBT group[adjusted hazard ratio(aHR)0.47,95%CI:0.28-0.80 and aHR 0.28,95%CI:0.18-0.43,respectively]and the DAA group(aHR 0.58,95%CI:0.35-0.96,and aHR 0.19,95%CI:0.20-0.68,respectively).Among 1268 patients who attained SVR with IBT(n=451)or DAA(n=816),the multivariable-adjusted analysis showed no differences in the risks of HCC(HR 2.03;95%CI:0.76-5.43)and death/transplantation(HR 1.38;95%CI:0.55-3.49)between the two *** was confirmed by a propensity score-matching *** factors for HCC after SVR were age,genotype 1,and the presence of *** Treatment and achieving SVR

关键词： Hepatitis C virus Direct-acting antiviral Sustained virologic response Hepatocellular carcinoma Mortality

Acute idiopathic pancreatitis in pregnancy:A case study

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World Journal of Gastroenterology 2014年第43期20卷 16364-16367页

作者： Ji yeon Kim Sung Hoon Jung Hyung Wook choi Dong Jin Song Cheol Yoon Jeong Dong Hyun Lee Il Soon Whang Department of Internal Medicine Cheil General Hospital and Women’s Healthcare CenterKwandong University College of MedicineSeoul KS013South Korea

Acute pancreatitis during pregnancy is a rare event,and can be associated with high maternal mortality and fetal *** disease is thought to be the most common causative factor of acute pancreatitis,but,in many cases,the cause remains *** report a case of a 36-year-old woman at 35 wk of gestation,who presented with severe pain confined to the upper abdomen and radiating to the *** patient was diagnosed with acute idiopathic pancreatitis,which was managed conservatively;she recovered within several days and then delivered a healthy *** it is important to consider acute pancreatitis when a pregnant woman presents with upper abdominal pain,nausea and vomiting in order to improve fetal and maternal outcomes for patients with acute pancreatitis.

关键词： Acute pancreatitis Pregnancy Pancreatitis in pregnancy Idiopathic Idiopathic acute pancreatitis

Calcium channel blocker monotherapy versus combination with reninangiotensin system inhibitors on the development of new-onset diabetes mellitus in hypertensive Korean patients

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Journal of Geriatric Cardiology 2019年第6期16卷 439-447页

作者： Yong Hoon Kim Ae-Young Her Seung-Woon Rha Byoung Geol choi Se yeon choi Jae Kyeong Byun Yoonjee Park Dong Oh Kang Won Young Jang Woohyeun Kim Woong Gil choi Tae Soo Kang Jihun Ahn Sang-Ho Park Ji Young Park Min-Ho Lee Cheol Ung choi Chang Gyu Park Hong Seog Seo Division of Cardiology Department of Internal Medicine Kangwon National University School of Medicine Chuncheon South Korea Cardiovascular Center Korea University Guro Hospital Seoul South Korea Department of Medicine Korea University Graduate School Seoul South Korea Cardiology Department Konkuk University Chungju Hospital Chungju South Korea Department of Internal Medicine Cardiovascular Division Dankook University Hospital Cheonan South Korea Department of Cardiology Soonchunhyang University Gumi Hospital Gumi South Korea Cardiology Department Soonchunhyang University Cheonan Hospital Cheonan South Korea Division of Cardiology Department of Internal Medicine Cardiovascular Center Nowon Eulji Medical Center Eulji University Seoul South Korea Department of Cardiology Soonchunhyang University College of Medicine Seoul South Korea

Background In real practice, two or more antihypertensive drugs are needed to achieve target blood pressure. We investigated the comparative beneficial actions of combination therapy of renin-angiotensin system inhibitors (RASI), with calcium channel blockers (CCB) over CCB monotherapy on the development of new-onset diabetes mellitus (NODM) in Korean patients during four-year follow-up periods. Methods A total of 3208 consecutive hypertensive patients without a history of diabetes mellitus who had been prescribed CCB were retrospectively enrolled from January 2004 to December 2012. These patients were divided into the two groups according to the additional use of RASI (the RASI group, n = 1221 and the no RASI group, n = 1987). Primary endpoint was NODM, defined as a fasting blood glucose ≥ 126 mg/dL or hemoglobin A1c ≥ 6.5%. Secondary endpoint was major adverse cardiac events (MACE) defined as total death, myocardial infarction (MI) and percutaneous coronary intervention (PCI). Results After propensity score-matched (PSM) analysis, two propensity- matched groups (939 pairs, n = 1878, C-statistic = 0.743) were generated. The incidences of NODM (HR = 1.009, 95% CI: 0.700–1.452, P = 0.962), MACE (HR = 0.877, 95% CI: 0.544–1.413, P = 0.589), total death, MI, PCI were similar between the two groups after PSM during four years. Conclusions The use of RASI in addition to CCB showed comparable incidences of NODM and MACE compared to CCB monotherapy in non-diabetic hypertensive Korean patients during four-year follow-up period. However, large-scaled randomized controlled clinical trials will be required for a more definitive conclusion.

关键词： Calcium channel blocker Diabetes mellitus Renin-angiotensin system inhibitors