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2. Defective formyl peptide receptor 2/3 and annexin A1 expressions associated with M2a polarization of blood immune cells in patients with chronic obstructive pulmonary disease

Author

Chen, Yung-Che, Lin, Meng-Chih, Lee, Chih-Hung, Liu, Shih-Feng, Wang, Chin-Chou, Fang, Wen-Feng, Chao, Tung-Ying, Wu, Chao-Chien, Wei, Yu-Feng, Chang, Huang-Chih, Tsen, Chia-Cheng, Chen, Hung-Chen, and Taiwan Clinical Trial Consortium of Respiratory Disease (TCORE) group

Published
2018
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4. Body Mass Index, Weight Loss, and Mortality Risk in Advanced-Stage Non-Small Cell Lung Cancer Patients: A Focus on EGFR Mutation

Author

Chen, Yu-Mu, primary, Lai, Chien-Hao, additional, Lin, Chiung-Yu, additional, Tsai, Yi-Hsuan, additional, Chang, Ya-Chun, additional, Chen, Hung-Chen, additional, Tseng, Chia-Cheng, additional, Chang, Huang-Chih, additional, Huang, Kuo-Tung, additional, Chen, Yung-Che, additional, Fang, Wen-Feng, additional, Wang, Chin-Chou, additional, Chao, Tung-Ying, additional, and Lin, Meng-Chih, additional

Published
2021
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5. MicroRNA-23a-3p Down-Regulation in Active Pulmonary Tuberculosis Patients with High Bacterial Burden Inhibits Mononuclear Cell Function and Phagocytosis through TLR4/TNF-α/TGF-β1/IL-10 Signaling via Targeting IRF1/SP1

Author

Chen, Yung-Che, primary, Lee, Chiu Ping, additional, Hsiao, Chang-Chun, additional, Hsu, Po-Yuan, additional, Wang, Ting-Ya, additional, Wu, Chao-Chien, additional, Chao, Tung-Ying, additional, Leung, Sum-Yee, additional, Chang, Yu-Ping, additional, and Lin, Meng-Chih, additional

Published
2020
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6. Whole Genome DNA Methylation Analysis of Active Pulmonary Tuberculosis Disease Identifies Novel Epigenotypes: PARP9/miR-505/RASGRP4/GNG12 Gene Methylation and Clinical Phenotypes

Author

Chen, Yung-Che, primary, Hsiao, Chang-Chun, additional, Chen, Ting-Wen, additional, Wu, Chao-Chien, additional, Chao, Tung-Ying, additional, Leung, Sum-Yee, additional, Eng, Hock-Liew, additional, Lee, Chiu-Ping, additional, Wang, Ting-Ya, additional, and Lin, Meng-Chih, additional

Published
2020
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7. Toll-like receptor 2 gene polymorphisms, pulmonary tuberculosis, and natural killer cell counts

Author

Tsen Chia-Cheng, Chao Tung-Ying, Eng Hock-Liew, Wu Chao-Chien, Liu Shih-Feng, Chin Chien-Hung, Chen Chung-Jen, Hsiao Chang-Chun, Chen Yung-Che, Wang Yi-Hsi, and Lin Meng-Chih

Subjects
Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background To investigate whether the toll-like receptor 2 polymorphisms could influence susceptibility to pulmonary TB, its phenotypes, and blood lymphocyte subsets. Methods A total of 368 subjects, including 184 patients with pulmonary TB and 184 healthy controls, were examined for TLR2 polymorphisms over locus -100 (microsatellite guanine-thymine repeats), -16934 (T>A), -15607 (A>G), -196 to -174 (insertion>deletion), and 1350 (T>C). Eighty-six TB patients were examined to determine the peripheral blood lymphocyte subpopulations. Results We newly identified an association between the haplotype [A-G-(insertion)-T] and susceptibility to pulmonary TB (p = 0.006, false discovery rate q = 0.072). TB patients with systemic symptoms had a lower -196 to -174 deletion/deletion genotype frequency than those without systemic symptoms (5.7% vs. 17.7%; p = 0.01). TB patients with the deletion/deletion genotype had higher blood NK cell counts than those carrying the insertion allele (526 vs. 243.5 cells/μl, p = 0.009). TB patients with pleuritis had a higher 1350 CC genotype frequency than those without pleuritis (12.5% vs. 2.1%; p = 0.004). TB patients with the 1350 CC genotype had higher blood NK cell counts than those carrying the T allele (641 vs. 250 cells/μl, p = 0.004). TB patients carrying homozygous short alleles for GT repeats had higher blood NK cell counts than those carrying one or no short allele (641 vs. 250 cells/μl, p = 0.004). Conclusions TLR2 genetic polymorphisms influence susceptibility to pulmonary TB. TLR2 variants play a role in the development of TB phenotypes, probably by controlling the expansion of NK cells.

Published
2010
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8. Epigenome-wide association study on asthma and chronic obstructive pulmonary disease overlap reveals aberrant DNA methylations related to clinical phenotypes.

Author

Chen, Yung-Che, Tsai, Ying-Huang, Wang, Chin-Chou, Liu, Shih-Feng, Chen, Ting-Wen, Fang, Wen-Feng, Lee, Chiu-Ping, Hsu, Po-Yuan, Chao, Tung-Ying, Wu, Chao-Chien, Wei, Yu-Feng, Chang, Huang-Chih, Tsen, Chia-Cheng, Chang, Yu-Ping, Lin, Meng-Chih, Taiwan Clinical Trial Consortium of Respiratory Disease (TCORE) group, Yu, Chong-Jen, Wang, Hao-Chien, Chiang, Chi-Huei, and Perng, Diahn-Warng

Subjects
LUNG diseases, DNA methylation, DNA microarrays, DISEASE exacerbation, CIGARETTE smoke
Abstract

We hypothesized that epigenetics is a link between smoking/allergen exposures and the development of Asthma and chronic obstructive pulmonary disease (ACO). A total of 75 of 228 COPD patients were identified as ACO, which was independently associated with increased exacerbations. Microarray analysis identified 404 differentially methylated loci (DML) in ACO patients, and 6575 DML in those with rapid lung function decline in a discovery cohort. In the validation cohort, ACO patients had hypermethylated PDE9A (+ 30,088)/ZNF323 (− 296), and hypomethylated SEPT8 (− 47) genes as compared with either pure COPD patients or healthy non-smokers. Hypermethylated TIGIT (− 173) gene and hypomethylated CYSLTR1 (+ 348)/CCDC88C (+ 125,722)/ADORA2B (+ 1339) were associated with severe airflow limitation, while hypomethylated IFRD1 (− 515) gene with frequent exacerbation in all the COPD patients. Hypermethylated ZNF323 (− 296) / MPV17L (+ 194) and hypomethylated PTPRN2 (+ 10,000) genes were associated with rapid lung function decline. In vitro cigarette smoke extract and ovalbumin concurrent exposure resulted in specific DNA methylation changes of the MPV17L / ZNF323 genes, while 5-aza-2′-deoxycytidine treatment reversed promoter hypermethylation-mediated MPV17L under-expression accompanied with reduced apoptosis and decreased generation of reactive oxygen species. Aberrant DNA methylations may constitute a determinant for ACO, and provide a biomarker of airflow limitation, exacerbation, and lung function decline. [ABSTRACT FROM AUTHOR]

Published
2021
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9. Histone H3K14 hypoacetylation and H3K27 hypermethylation along with HDAC1 up-regulation and KDM6B down-regulation are associated with active pulmonary tuberculosis disease

Author

Chen, Yung-Che, Chao, Tung-Ying, Leung, Sum-Yee, Chen, Chung-Jen, Wu, Chao-Chien, Fang, Wen-Feng, Wang, Yi-Hsi, Chang, Huang-Chih, Wang, Ting-Ya, Lin, Yong-Yong, Zheng, Yi-Xin, Lin, Meng-Chih, and Hsiao, Chang-Chun

Subjects
Original Article
Abstract

The aim of this study is to determine the roles of global histone acetylation (Ac)/methylation (me), their modifying enzymes, and gene-specific histone enrichment in active pulmonary tuberculosis (TB) disease. Global histone H3K27me3, H3K27me2, H3K9me3, H3K9Ac, and H3K14Ac expressions, and their modifying enzyme expressions, including KDM1A, KDM6B, EZH2, HDAC1, and HDAC2, were assessed in blood leukocytes from 81 patients with active pulmonary TB disease and 44 matched healthy subjects (HS). TLR2, TNF-α, IFN-γ, and IL12B-specific histone enrichment of peripheral blood mononuclear cells was measured by chromatin immunoprecipitation method. We found that Global H3K14Ac was decreased and H3K27me2 was increased in TB patients as compared with that in HS. TB patients with low H3K14Ac had lower one-year survival. Global H3K27me3 was increased in TB patients with high bacterial burden, or systemic symptoms as compared with that in those without the attribute or HS. HDAC1 gene/protein expressions were increased in TB patients as compared with that in HS, whereas KDM6B gene/protein expressions were decreased. Global H3K27me2, HDAC1 and KDM6B protein expressions were all reversed to normal after 6-month anti-TB treatment. TNF-α/IL12B promoter-specific H3K14Ac and TNF-α/IL12B/IFN-γ promoter-specific H3K27me2 enrichment were all decreased in 10 TB patients as compared with that in 10 HS. Among them, IL12B-specific H3K27me2 enrichment was reversed to normal after treatment, while the other 4 remained depressed. In conclusions, H3K14 hypoacetylation and H3K27 hypermethylation play a role in the development of active pulmonary TB disease or its clinical phenotypes, probably through up-regulation of HDAC1 and down-regulation of KDM6B, respectively.

Published
2017

10. Whole genome gene expression changes and hematological effects of rikkunshito in patients with advanced non-small cell lung cancer receiving first line chemotherapy

Author

Chen, Yung-Che, primary, Lin, An-Shen, additional, Hung, Yu-Chiang, additional, Chen, Kuang-Den, additional, Wu, Ching-Yuan, additional, Lie, Chien-Hao, additional, Hsiao, Chang-Chun, additional, Chen, Chung-Jen, additional, Liu, Shih-Feng, additional, Fang, Wen-Feng, additional, Chang, Jen-Chieh, additional, Wang, Ting-Ya, additional, Wang, Yi-Hsi, additional, Chung, Yu-Hsiu, additional, Chao, Tung-Ying, additional, Leung, Sum-Yee, additional, Su, Mao-Chang, additional, and Lin, Meng-Chih, additional

Published
2017
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11. PUB001 Advanced NSCLC Patients at the Extremes of Age in the Era of EGFR-TKIs

Author

Chen, Yu-Mu, primary, Lai, Chien-Hao, additional, Chang, Huang-Chih, additional, Chao, Tung-Ying, additional, Tseng, Chia-Cheng, additional, Fang, Wen-Feng, additional, Chung, Yu-Hsiu, additional, Wang, Yi-Hsi, additional, Su, Mao-Chang, additional, Huang, Kuo-Tung, additional, Wang, Chin-Chou, additional, and Lin, Meng-Chih, additional

Published
2017
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12. A Survival Scoring System for Non-Small Cell Lung Cancer Patients with De Novo Bone Metastases

Author

Chen, Yu-Mu, primary, Fang, Ying-Tang, additional, Lai, Chien-Hao, additional, Rau, Kun-Ming, additional, Huang, Cheng-Hua, additional, Chang, Huang-Chih, additional, Chao, Tung-Ying, additional, Tseng, Chia-Cheng, additional, Fang, Wen-Feng, additional, Wang, Chin-Chou, additional, Chen, Yung-Che, additional, Chung, Yu-Hsiu, additional, Wang, Yi-Hsi, additional, Su, Mao-Chang, additional, Liu, Shih-Feng, additional, Huang, Kuo-Tung, additional, Chen, Hung-Chen, additional, Chang, Ya-Chun, additional, Chang, Yu-Ping, additional, and Lin, Meng-Chih, additional

Published
2016
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13. Impact of clinical parameters and systemic inflammatory status on epidermal growth factor receptor-mutant non-small cell lung cancer patients readministration with epidermal growth factor receptor tyrosine kinase inhibitors

Author

Chen, Yu-Mu, primary, Lai, Chien-Hao, additional, Rau, Kun-Ming, additional, Huang, Cheng-Hua, additional, Chang, Huang-Chih, additional, Chao, Tung-Ying, additional, Tseng, Chia-Cheng, additional, Fang, Wen-Feng, additional, Chung, Yu-Hsiu, additional, Wang, Yi-Hsi, additional, Su, Mao-Chang, additional, Huang, Kuo-Tung, additional, Liu, Shih-Feng, additional, Chen, Hung-Chen, additional, Chang, Ya-Chun, additional, Chang, Yu-Ping, additional, Wang, Chin-Chou, additional, and Lin, Meng-Chih, additional

Published
2016
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15. Antacid Use and De Novo Brain Metastases in Patients with Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer Who Were Treated Using First-Line First-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Author

Chen, Yu-Mu, primary, Lai, Chien-Hao, additional, Chang, Huang-Chih, additional, Chao, Tung-Ying, additional, Tseng, Chia-Cheng, additional, Fang, Wen-Feng, additional, Wang, Chin-Chou, additional, Chung, Yu-Hsiu, additional, Wang, Yi-Hsi, additional, Su, Mao-Chang, additional, Liu, Shih-Feng, additional, Huang, Kuo-Tung, additional, Chen, Hung-Chen, additional, Chang, Ya-Chun, additional, and Lin, Meng-Chih, additional

Published
2016
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16. Baseline, Trend, and Normalization of Carcinoembryonic Antigen as Prognostic Factors in Epidermal Growth Factor Receptor-Mutant Nonsmall Cell Lung Cancer Patients Treated With First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Author

Chen, Yu-Mu, primary, Lai, Chien-Hao, additional, Chang, Huang-Chih, additional, Chao, Tung-Ying, additional, Tseng, Chia-Cheng, additional, Fang, Wen-Feng, additional, Wang, Chin-Chou, additional, Chung, Yu-Hsiu, additional, Huang, Kuo-Tung, additional, Chen, Hung-Cheng, additional, Chang, Ya-Chun, additional, and Lin, Meng-Chih, additional

Published
2015
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17. Baseline and Trend of Lymphocyte-to-Monocyte Ratio as Prognostic Factors in Epidermal Growth Factor Receptor Mutant Non-Small Cell Lung Cancer Patients Treated with First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Author

Chen, Yu-Mu, primary, Lai, Chien-Hao, additional, Chang, Huang-Chih, additional, Chao, Tung-Ying, additional, Tseng, Chia-Cheng, additional, Fang, Wen-Feng, additional, Wang, Chin-Chou, additional, Chung, Yu-Hsiu, additional, Wang, Yi-Hsi, additional, Su, Mao-Chang, additional, Huang, Kuo-Tung, additional, Chen, Hung-Chen, additional, Chang, Ya-Chun, additional, and Lin, Meng-Chih, additional

Published
2015
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18. Influencing factors of successful eradication of multidrug-resistant Acinetobacter baumannii in the respiratory tract with aerosolized colistin

Author

Wang, Chin-Chou, primary, Chao, Tung-Ying, primary, Chen, Yu-Mu, additional, Fang, Wen-Feng, additional, Kao, HsuChing, additional, Chen, Hung-Chen, additional, Tsai, Yuh-Chyn, additional, Shen, Lien-Shi, additional, Li, Chin-Ling, additional, Chang, Huang-Chih, additional, Huang, Kuo-Tung, additional, and Lin, Meng-Chih, additional

Published
2014
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19. Peripheral Immune Cell Gene Expression Changes in Advanced Non-Small Cell Lung Cancer Patients Treated with First Line Combination Chemotherapy

Author

Chen, Yung-Che, primary, Hsiao, Chang-Chun, additional, Chen, Kuang-Den, additional, Hung, Yu-Chiang, additional, Wu, Ching-Yuan, additional, Lie, Chien-Hao, additional, Liu, Shih-Feng, additional, Sung, Ming-Tse, additional, Chen, Chung-Jen, additional, Wang, Ting-Ya, additional, Chang, Jen-Chieh, additional, Tang, Petrus, additional, Fang, Wen-Feng, additional, Wang, Yi-Hsi, additional, Chung, Yu-Hsiu, additional, Chao, Tung-Ying, additional, Leung, Sum-Yee, additional, Su, Mao-Chang, additional, Wang, Chin-Chou, additional, and Lin, Meng-Chih, additional

Published
2013
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20. Baseline, Trend, and Normalization of Carcinoembryonic Antigen as Prognostic Factors in Epidermal Growth Factor Receptor-Mutant Nonsmall Cell Lung Cancer Patients Treated With First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.

Author

Yu-Mu Chen, Chien-Hao Lai, Huang-Chih Chang, Tung-Ying Chao, Chia-Cheng Tseng, Wen-Feng Fang, Chin-Chou Wang, Yu-Hsiu Chung, Kuo-Tung Huang, Hung-Cheng Chen, Ya-Chun Chang, Meng-Chih Lin, Chen, Yu-Mu, Lai, Chien-Hao, Chang, Huang-Chih, Chao, Tung-Ying, Tseng, Chia-Cheng, Fang, Wen-Feng, Wang, Chin-Chou, and Chung, Yu-Hsiu

Published
2015
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26. Risk factors of multidrug-resistant Acinetobacter baumanniirecurrence after successful eradication in ventilated patients

Author

Lin, Chiung-Yu, Chen, Yu-Mu, Lin, Meng-Chih, Chang, Yu-Ping, Chao, Tung-Ying, Wang, Chin-Chou, Tsai, Yuh-Chyn, Shen, Lien Shi, Li, Chin-Ling, and Lin, An-Shen

Abstract

Clinically, multidrug-resistant Acinetobacter baumannii(MDR-AB) recurrence is found in some patients although identified as successfully eradicated. We aim to discover the characteristics of patients with MDR-AB recurrence in the respiratory tract.

Published
2016
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27. Whole Genome DNA Methylation Analysis of Active Pulmonary Tuberculosis Disease Identifies Novel Epigenotypes: PARP9 / miR-505 / RASGRP4 / GNG12 Gene Methylation and Clinical Phenotypes.

Author

Chen YC, Hsiao CC, Chen TW, Wu CC, Chao TY, Leung SY, Eng HL, Lee CP, Wang TY, and Lin MC

Subjects
Cohort Studies, DNA Methylation genetics, Forkhead Box Protein O3 genetics, GTP-Binding Protein gamma Subunits genetics, Humans, Membrane Proteins genetics, Neoplasm Proteins genetics, Phosphate-Binding Proteins genetics, Poly(ADP-ribose) Polymerases genetics, Regulatory-Associated Protein of mTOR genetics, ras Guanine Nucleotide Exchange Factors genetics, DNA Methylation physiology, Promoter Regions, Genetic genetics, Tuberculosis, Pulmonary genetics
Abstract

We hypothesized that DNA methylation patterns may contribute to the development of active pulmonary tuberculosis (TB). Illumina's DNA methylation 450 K assay was used to identify differentially methylated loci (DML) in a discovery cohort of 12 active pulmonary TB patients and 6 healthy subjects (HS). DNA methylation levels were validated in an independent cohort of 64 TB patients and 24 HS. Microarray analysis identified 1028 DMLs in TB patients versus HS, and 3747 DMLs in TB patients after versus before anti-TB treatment, while autophagy was the most enriched signaling pathway. In the validation cohort, PARP9 and miR505 genes were hypomethylated in the TB patients versus HS, while RASGRP4 and GNG12 genes were hypermethylated, with the former two further hypomethylated in those with delayed sputum conversion, systemic symptoms, or far advanced lesions. MRPS18B and RPTOR genes were hypomethylated in TB patients with pleural involvement. RASGRP4 gene hypermethylation and RPTOR gene down-regulation were associated with high mycobacterial burden. TB patients with WIPI2 / GNG12 hypermethylation or MRPS18B / FOXO3 hypomethylation had lower one-year survival. In vitro ESAT6 and CFP10 stimuli of THP-1 cells resulted in DNA de-methylation changes of the PARP9 , RASGRP4 , WIPI2 , and FOXO3 genes. In conclusions, aberrant DNA methylation over the PARP9/miR505/RASGRP4/GNG12 genes may contribute to the development of active pulmonary TB disease and its clinical phenotypes, while aberrant DNA methylation over the WIPI2 / GNG12 / MARPS18B / FOXO3 genes may constitute a determinant of long-term outcomes.

Published
2020
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28. Influencing factors of successful eradication of multidrug-resistant Acinetobacter baumannii in the respiratory tract with aerosolized colistin.

Author

Chen YM, Fang WF, Kao HC, Chen HC, Tsai YC, Shen LS, Li CL, Chang HC, Huang KT, Lin MC, Wang CC, and Chao TY

Subjects
Administration, Inhalation, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Pneumonia, Respiratory System drug effects, Retrospective Studies, Treatment Outcome, Acinetobacter Infections drug therapy, Acinetobacter baumannii isolation & purification, Anti-Bacterial Agents therapeutic use, Colistin therapeutic use, Drug Resistance, Multiple, Bacterial drug effects
Abstract

Background: The increased prevalence of multidrug-resistant Acinetobacter baumannii (MDRAB) poses a worldwide treatment challenge. Although aerosolized colistin therapy for MDRAB pneumonia has attracted increasing interest, factors influencing successful eradication remain unclear., Methods: This retrospective study evaluated 135 consecutively admitted adult patients showing positive respiratory secretion cultures for MDRAB who underwent aerosolized colistin therapy between January 2007 and November 2011. Possible factors related to pneumonia and MDRAB eradication were collected for analysis., Results: Patients with successful MDRAB eradication on Day 14 had a shorter interval between the day the positive MDRAB sputum cultures were yielded and the day colistin inhalation treatment began (4.0 ± 2.5 vs. 7.3 ± 6.5; p = 0.002). Patients with a worsening chest X-ray on Day 7 of the colistin inhalation had a lower chance of 14-day MDRAB eradication [1/44 (2.3%) vs. 8/37 (21.6%); p = 0.006]. Patients with diabetes mellitus also had a lower chance of early MDRAB eradication [13/44 (29.5%) vs. 20/37 (54.1%); p = 0.025]., Conclusions: Early intervention using aerosolized colistin in patients with MDRAB pneumonia or colonization can achieve better eradication.

Published
2014
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