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      • KCI등재

        Comparative global immune-related gene profiling of somatic cells, human pluripotent stem cells and their derivatives: implication for human lymphocyte proliferation

        Chia-Eng Wu,Chen-Wei Yu,Kai-Wei Chang,Wen-Hsi Chou,Chen-Yu Lu,Elisa Ghelfi,Fang-Chun Wu,Pey-Shynan Jan,Mei-Chi Huang,Patrick Allard,Shau-Ping Lin,Hong-Nerng Ho,Hsin-Fu Chen 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

        Human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced PSCs (iPSCs), represent potentially unlimited cell sources for clinical applications. Previous studies have suggested that hPSCs may benefit from immune privilege and limited immunogenicity, as reflected by the reduced expression of major histocompatibility complex class-related molecules. Here we investigated the global immune-related gene expression profiles of human ESCs, hiPSCs and somatic cells and identified candidate immune-related genes that may alter their immunogenicity. The expression levels of global immune-related genes were determined by comparing undifferentiated and differentiated stem cells and three types of human somatic cells: dermal papilla cells, ovarian granulosa cells and foreskin fibroblast cells. We identified the differentially expressed genes CD24, GATA3, PROM1, THBS2, LY96, IFIT3, CXCR4, IL1R1, FGFR3, IDO1 and KDR, which overlapped with selected immune-related gene lists. In further analyses, mammalian target of rapamycin complex (mTOR) signaling was investigated in the differentiated stem cells following treatment with rapamycin and lentiviral transduction with specific short-hairpin RNAs. We found that the inhibition of mTOR signal pathways significantly downregulated the immunogenicity of differentiated stem cells. We also tested the immune responses induced in differentiated stem cells by mixed lymphocyte reactions. We found that CD24- and GATA3-deficient differentiated stem cells including neural lineage cells had limited abilities to activate human lymphocytes. By analyzing the transcriptome signature of immune-related genes, we observed a tendency of the hPSCs to differentiate toward an immune cell phenotype. Taken together, these data identify candidate immune-related genes that might constitute valuable targets for clinical applications.

      • KCI등재

        Combined Assessment of Serum Alpha-Synuclein and Rab35 is a Better Biomarker for Parkinson’s Disease

        Hung-Li Wang,Chin-Song Lu,Tu-Hsueh Yeh,Yu-Ming Shen,Yi-Hsin Weng,Ying-Zu Huang,Rou-Shayn Chen,Yu-Chuan Liu,Yi-Chuan Cheng,Hsiu-Chen Chang,Ying-Ling Chen,Yu-Jie Chen,Yan-Wei Lin,Chia Chen Hsu,Huang-Li 대한신경과학회 2019 Journal of Clinical Neurology Vol.15 No.4

        Background and Purpose It is essential to develop a reliable predictive serum biomarker for Parkinson’s disease (PD). Te accumulation of alpha-synuclein (αSyn) and up-regulated expression of Rab35 participate in the etiology of PD. Te purpose of this investigation was to determine whether the combined assessment of serum αSyn and Rab35 is a useful predictive biomarker for PD. Methods Serum levels of αSyn or Rab35 were determined in serum samples from 59 sporadic PD patients, 19 progressive supranuclear palsy (PSP) patients, 20 multiple system atrophy (MSA) patients, and 60 normal controls (NC). Receiver operating characteristics (ROC) curves were calculated to determine the diagnostic accuracy of αSyn or/and Rab35 in discriminating PD patients from NC or atypical parkinsonian patients. Results The levels of αSyn and Rab35 were increased in PD patients. The serum level of Rab35 was positively correlated with that of αSyn in PD patients. Compared to analyzing αSyn or Rab35 alone, the combined analysis of αSyn and Rab35 produced a larger area under the ROC curve and performed better in discriminating PD patients from NC, MSA patients, or PSP patients. When age was dichotomized at 55, 60, 65, or 70 years, the combined assessment of αSyn and Rab35 for classifying PD was better in the group below the cutof age than in the group above the cutof age. Conclusions Combined assessment of serum αSyn and Rab35 is a better biomarker for discriminating PD patients from NC or atypical parkinsonian patients, and is a useful predictive biomarker for younger sporadic PD patients.

      • 다수제적 혼합선거제도 하에서의 투표행태에 대한 다차원 분석

        ( Chia Hung Tsai ),( Lu Huei Chen ),( Chao Chi Lin ),( Su Feng Cheng ) 한국선거학회 2011 선거연구 Vol.1 No.2

        혼합선거제도는 영국의 전통적 소선거구제와 비례제 양자 모두의 좋은 점을 제공한다고 언급된다. 학자들은 후보자와 정당들이 이러한 선거 규칙에 어떻게 반응하는지 고찰해 왔으며, 이 제도 하에서는 상이한 유인 요인이 존재한다고 주장해 왔다. 두 개의 서로 다른 층 간의 상호작용 또한 연구의 대상이 되어 왔다. 본 논문은 소선거구제에서의 투표 행태가 정당의 명성에 의해 영향 받는 정도를 평가해 보고자 하는데, 이는 소선거구 선거 결과와 비례대표 선거 결과 간의 차이에 의해서 측정된다. 대부분의 유권자가 비례대표 표를 던질 때 자신들의 선호를 따르며, 소선거구 표를 던질 때는 현직자를 고려할 것이라고 우리는 가정한다. 한국, 대만, 그리고 일본에서의 투표 행태를 비교함으로써, 사회적 배경, 정치적 태도, 쟁점에 대한 의견 등이 투표 행태에 미치는 상대적 영향력을 이들 세 국가에 걸쳐서 평가할 수 있다. 분석에 사용되는 자료는 선거제도 비교연구(CSES) 2차조사 (2001-2006), 21세기 전국적 장기 설문조사 자료 (JES 3차), 대만의 선거 및 민주화 연구 자료 (TEDS 2008L)이며, 이를 통해 각기 한국의 2004년 총선, 대만의 2008년 의회선거, 그리고 일본의 총선을 고찰한다. It is said that mixed-member systems offer the best of both the traditional British single-member district system (SMD) and proportional representation systems (PR). Scholars have examined how candidates and parties respond to the electoral rule, arguing that there are different incentives for them. The interaction between the two tiers is also investigated. This paper attempts to assess the extent to which voting behavior in the SMD districts would be influenced by party reputation measured by the difference between the SMD and PR voting results. We assume that most voters follow their preferences when they cast their PR votes, but that they consider the incumbents when they cast their SMD ballots. Comparing voting behavior in Korea, Taiwan, and Japan, we are able to assess the relative effect of social backgrounds, political predispositions, and issue opinions on voting behavior across three countries. We use CSES Module 2 (2001-2006) data, the Nation-wide Longitudinal Survey Study on Voting Behavior in the 21st Century (JES III) data, and Taiwan`s Election and Democratization Study (TEDS 2008L) data to examine voting behavior in the 2004 National Assembly election of Korea, the 2008 legislative election of Taiwan, and the 2005 general election of Japan respectively.

      • KCI등재

        Monacolin K affects lipid metabolism through SIRT1/AMPK pathway in HepG2 cells

        Chia-Hsin Huang,Shin-Mau Shiu,Min-Tze Wu,Wei-Lu Chen,Shyang-Guang Wang,Horng-Mo Lee 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.12

        Monacolin K is the secondary metabolite isolatedfrom Monascus spp. It is the natural form of lovastatin,which is clinically used to reduce the synthesis of cholesterolby inhibiting 3-hydroxy-3-methylglutaryl coenzyme Areductase. In the present study, monacolin K increased proteinexpression of SIRT1 and phosphorylation level of AMPactivatedprotein kinase (AMPK) in HepG2 cells. Throughactivation of SIRT1/AMPK pathway, monacolin Kincreased phosphorylation of acetyl CoA carboxylase andcaused nuclear translocation of forkhead box O1. The westernblotting results showed that monacolin K increasedexpression of adipose triglyceride lipase but decreasedabundances of fatty acid synthase (FAS) and sterol regulatory element-binding protein 1 (SREBP1). MonacolinK also decreased the intracellular accumulation of lipids asdemonstrated by Oil Red O staining. In addition, theimmunostaining showed that monacolin K prevented thenuclear translocation of SREBP1, indicating the associationwith down-regulation of FAS. All the demonstrated effectsof monacolin K were counteracted by nicotinamide orcompound C, the inhibitors of SIRT1 orAMPK. In summary,monacolin K reduces the lipid content through SIRT1/AMPK pathway in HepG2 cells, which promotes catabolismand inhibits anabolism of lipid.

      • SCOPUSKCI등재SCIE

        Overall and cause-specific mortality in patients with dementia: a population-based cohort study in Taiwan

        Chia-Lun Kuo,Pei-Chen Lee,Li-Jung Elizabeth Ku,Yu Sun,Tsung-Hsueh Lu,Muhammad Atoillah Isfandiari,Chung-Yi Li 한국역학회 2023 Epidemiology and Health Vol.45 No.-

        OBJECTIVES: Information regarding the underlying causes of death (UCODs) and standardized mortality ratio (SMR) of dementia is instrumental in formulating medical strategies to prolong life in persons with dementia (PWD). We examined the leading UCODs among PWD and estimated the overall and cause-specific SMRs in relation to dementia in Taiwan. METHODS: Data were retrieved from 2 national datasets: the Taiwan Death Registry and the medical claim datasets of the National Health Insurance program. The observed person-years for each study participant were counted from the date of cohort enrollment to either the date of death or the final day of 2016. Sex-specific and age-specific SMRs were then calculated. RESULTS: The leading UCOD was circulatory disease, accounting for 26.0% of total deaths (n=3,505), followed by respiratory disease at 21.3% (n=2,875). PWD were at significantly increased risk of all-cause mortality (SMR, 2.01), with SMR decreasing with advancing age. A cause-specific analysis revealed that the highest SMRs were associated with nervous system diseases (SMR, 7.58) and mental, behavioral, and neurodevelopmental disorders (SMR, 4.80). Age appeared to modify SMR, suggesting that younger age at cohort enrollment was linked to higher SMRs for nearly all causes of mortality. CONCLUSIONS: Circulatory and respiratory diseases were the leading UCODs among PWD. The particularly elevated mortality due to nervous system diseases and mental disorders suggests that allocating more resources to neurological and psychiatric services is warranted. The elevated SMRs of various UCODs among younger PWD underscore the need for clinicians to pay particular attention to the medical care provided to these patients.

      • Does the Impact of Agricultural zoning Policy on Paddy Planting Areas in Taivan Really Take Effect?

        ( Chia Yi Cheng ),( Chen Fu Lu ) 한국정책학회 2016 한국정책학회 추계학술발표논문집 Vol.2016 No.-

        Agricultural zoning is a major mean of farmland conservation and it has been a key component in policy for the prevention of urban sprawl and nonagricultural development of farmland in Thaiwan. However, despite political commitments to the policy, there is currently little empirical evidence regarding the actual economic impact and effectiveness of this policy. This study adds to current knowledge by asssessing the effect of agricultural zoning policy based on the Regional Planning Act which was amended in 2000 in Taiwan and using big data in combination with datasets from a management information system(MIS) and geographic information system (GIS). With GIS, we extrated anaalytic data from map profiles along with data from a social economic dataset. Using the repeated cross-sectional zoning data at a village level and information about paddy planting areas for the first crop season in 2010 and in 2014, we applied a random effects panel regression to examine the influences of the planned zoing on cropland. Our results demonstrate that the zoning impact on paddy fields located in common agricultural zones is a significant decrease in area of about 4hectares. However, wihin special agricultural districts and urban plannng areas, the zoing effects seem to be positive but insignificant. THis suggests the agricultural zoning policy in Taiwan is likely to disourage farmers from faming, which may prompt them to engage in alternative land use.

      • SCISCIESCOPUS
      • KCI등재

        Impact of Interleukin-10 Gene Polymorphisms on Survival in Patients with Colorectal Cancer

        Wen-Chien Ting,Lu-Min Chen,Li-Chia Huang,Mann-Jen Hour,Yu-Hsuan Lan,Hong-Zin Lee,Bang-Jau You,Ta-Yuan Chang,Bo-Ying Bao 대한의학회 2013 Journal of Korean medical science Vol.28 No.9

        Chronic inflammation is thought to be the leading cause of colorectal cancer, and interleukin-10 (IL10) has been identified as a potent immunomodulatory cytokine that regulates inflammatory responses in the gastrointestinal tract. Although several single nucleotide polymorphisms (SNPs) in IL10 have been associated with the risk of colorectal cancer, their prognostic significance has not been determined. Two hundred and eightytwo colorectal cancer patients were genotyped for two candidate cancer-associated SNPs in IL10. The associations of these SNPs with distant metastasis-free survival and overall survival were evaluated by Kaplan-Meier analysis and Cox regression model. The minor homozygote GG genotype of IL10 rs3021094 was significantly associated with a 3.30-fold higher risk of death compared with the TT+TG genotypes (P = 0.011). The patients with IL10rs3021094 GG genotype also had a poorer overall survival in Kaplan-Meier analysis (log-rank P = 0.007) and in multivariate Cox regression model (P = 0.044) adjusting for age, gender,carcinoembryonic antigen levels, tumor differentiation, stage, lymphovascular invasion,and perineural invasion. In conclusion, our results suggest that IL10 rs3021094 might be a valuable prognostic biomarker for colorectal cancer patients.

      • KCI등재

        Differentiation of the Infarct Core from Ischemic Penumbra within the First 4.5 Hours, Using Diffusion Tensor Imaging-Derived Metrics: A Rat Model

        Duen-Pang Kuo,Chia-Feng Lu,Michelle Liou,Yung-Chieh Chen,Hsiao-Wen Chung,Cheng-Yu Chen 대한영상의학회 2017 Korean Journal of Radiology Vol.18 No.2

        Objective: To investigate whether the diffusion tensor imaging-derived metrics are capable of differentiating the ischemic penumbra (IP) from the infarct core (IC), and determining stroke onset within the first 4.5 hours. Materials and Methods: All procedures were approved by the local animal care committee. Eight of the eleven rats having permanent middle cerebral artery occlusion were included for analyses. Using a 7 tesla magnetic resonance system, the relative cerebral blood flow and apparent diffusion coefficient maps were generated to define IP and IC, half hour after surgery and then every hour, up to 6.5 hours. Relative fractional anisotropy, pure anisotropy (rq) and diffusion magnitude (rL) maps were obtained. One-way analysis of variance, receiver operating characteristic curve and nonlinear regression analyses were performed. Results: The evolutions of tensor metrics were different in ischemic regions (IC and IP) and topographic subtypes (cortical, subcortical gray matter, and white matter). The rL had a significant drop of 40% at 0.5 hour, and remained stagnant up to 6.5 hours. Significant differences (p < 0.05) in rL values were found between IP, IC, and normal tissue for all topographic subtypes. Optimal rL threshold in discriminating IP from IC was about -29%. The evolution of rq showed an exponential decrease in cortical IC, from -26.9% to -47.6%; an rq reduction smaller than 44.6% can be used to predict an acute stroke onset in less than 4.5 hours. Conclusion: Diffusion tensor metrics may potentially help discriminate IP from IC and determine the acute stroke age within the therapeutic time window.

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