42 results on '"Chen, Chia-Ying"'
Search Results
2. Correction: A longer time to relapse is associated with a larger increase in differences between paired primary and recurrent IDH wild-type glioblastomas at both the transcriptomic and genomic levels.
- Author
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Ho WM, Chen CY, Chiang TW, and Chuang TJ
- Published
- 2024
- Full Text
- View/download PDF
3. A longer time to relapse is associated with a larger increase in differences between paired primary and recurrent IDH wild-type glioblastomas at both the transcriptomic and genomic levels.
- Author
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Ho WM, Chen CY, Chiang TW, and Chuang TJ
- Subjects
- Humans, Male, Female, Genomics methods, Mutation, Middle Aged, Time Factors, Glioblastoma genetics, Glioblastoma pathology, Isocitrate Dehydrogenase genetics, Brain Neoplasms genetics, Brain Neoplasms pathology, Transcriptome, Neoplasm Recurrence, Local genetics
- Abstract
Glioblastoma (GBM) is the most common malignant brain tumor in adults, which remains incurable and often recurs rapidly after initial therapy. While large efforts have been dedicated to uncover genomic/transcriptomic alternations associated with the recurrence of GBMs, the evolutionary trajectories of matched pairs of primary and recurrent (P-R) GBMs remain largely elusive. It remains challenging to identify genes associated with time to relapse (TTR) and construct a stable and effective prognostic model for predicting TTR of primary GBM patients. By integrating RNA-sequencing and genomic data from multiple datasets of patient-matched longitudinal GBMs of isocitrate dehydrogenase wild-type (IDH-wt), here we examined the associations of TTR with heterogeneities between paired P-R GBMs in gene expression profiles, tumor mutation burden (TMB), and microenvironment. Our results revealed a positive correlation between TTR and transcriptomic/genomic differences between paired P-R GBMs, higher percentages of non-mesenchymal-to-mesenchymal transition and mesenchymal subtype for patients with a short TTR than for those with a long TTR, a high correlation between paired P-R GBMs in gene expression profiles and TMB, and a negative correlation between the fitting level of such a paired P-R GBM correlation and TTR. According to these observations, we identified 55 TTR-associated genes and thereby constructed a seven-gene (ZSCAN10, SIGLEC14, GHRHR, TBX15, TAS2R1, CDKL1, and CD101) prognostic model for predicting TTR of primary IDH-wt GBM patients using univariate/multivariate Cox regression analyses. The risk scores estimated by the model were significantly negatively correlated with TTR in the training set and two independent testing sets. The model also segregated IDH-wt GBM patients into two groups with significantly divergent progression-free survival outcomes and showed promising performance for predicting 1-, 2-, and 3-year progression-free survival rates in all training and testing sets. Our findings provide new insights into the molecular understanding of GBM progression at recurrence and potential targets for therapeutic treatments., (© 2024. The Author(s).)
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- 2024
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4. FL-circAS: an integrative resource and analysis for full-length sequences and alternative splicing of circular RNAs with nanopore sequencing.
- Author
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Chiang TW, Jhong SE, Chen YC, Chen CY, Wu WS, and Chuang TJ
- Subjects
- Animals, Humans, Mice, Alternative Splicing genetics, MicroRNAs genetics, MicroRNAs metabolism, Nanopore Sequencing, RNA Isoforms genetics, RNA, Circular genetics, Databases, Nucleic Acid
- Abstract
Circular RNAs (circRNAs) are RNA molecules with a continuous loop structure characterized by back-splice junctions (BSJs). While analyses of short-read RNA sequencing have identified millions of BSJ events, it is inherently challenging to determine exact full-length sequences and alternatively spliced (AS) isoforms of circRNAs. Recent advances in nanopore long-read sequencing with circRNA enrichment bring an unprecedented opportunity for investigating the issues. Here, we developed FL-circAS (https://cosbi.ee.ncku.edu.tw/FL-circAS/), which collected such long-read sequencing data of 20 cell lines/tissues and thereby identified 884 636 BSJs with 1 853 692 full-length circRNA isoforms in human and 115 173 BSJs with 135 617 full-length circRNA isoforms in mouse. FL-circAS also provides multiple circRNA features. For circRNA expression, FL-circAS calculates expression levels for each circRNA isoform, cell line/tissue specificity at both the BSJ and isoform levels, and AS entropy for each BSJ across samples. For circRNA biogenesis, FL-circAS identifies reverse complementary sequences and RNA binding protein (RBP) binding sites residing in flanking sequences of BSJs. For functional patterns, FL-circAS identifies potential microRNA/RBP binding sites and several types of evidence for circRNA translation on each full-length circRNA isoform. FL-circAS provides user-friendly interfaces for browsing, searching, analyzing, and downloading data, serving as the first resource for discovering full-length circRNAs at the isoform level., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2024
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5. Detecting intragenic trans-splicing events from non-co-linearly spliced junctions by hybrid sequencing.
- Author
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Chen YC, Chen CY, Chiang TW, Chan MH, Hsiao M, Ke HM, Tsai IJ, and Chuang TJ
- Subjects
- Genome, RNA Splicing, RNA, Circular, Trans-Splicing, Sequence Analysis, RNA methods
- Abstract
Trans-spliced RNAs (ts-RNAs) are a type of non-co-linear (NCL) transcripts that consist of exons in an order topologically inconsistent with the corresponding DNA template. Detecting ts-RNAs is often interfered by experimental artifacts, circular RNAs (circRNAs) and genetic rearrangements. Particularly, intragenic ts-RNAs, which are derived from separate precursor mRNA molecules of the same gene, are often mistaken for circRNAs through analyses of RNA-seq data. Here we developed a bioinformatics pipeline (NCLscan-hybrid), which integrated short and long RNA-seq reads to minimize false positives and proposed out-of-circle and rolling-circle long reads to distinguish between intragenic ts-RNAs and circRNAs. Combining NCLscan-hybrid screening and multiple experimental validation steps successfully confirmed that four NCL events, which were previously regarded as circRNAs in databases, originated from trans-splicing. CRISPR-based endogenous genome modification experiments further showed that flanking intronic complementary sequences can significantly contribute to ts-RNA formation, providing an efficient/specific method to deplete ts-RNAs. We also experimentally validated that one ts-RNA (ts-ARFGEF1) played an important role for p53-mediated apoptosis through affecting the PERK/eIF2a/ATF4/CHOP signaling pathway in breast cancer cells. This study thus described both bioinformatics procedures and experimental validation steps for rigorous characterization of ts-RNAs, expanding future studies for identification, biogenesis, and function of these important but understudied transcripts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2023
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6. Large-scale benchmarking of circRNA detection tools reveals large differences in sensitivity but not in precision.
- Author
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Vromman M, Anckaert J, Bortoluzzi S, Buratin A, Chen CY, Chu Q, Chuang TJ, Dehghannasiri R, Dieterich C, Dong X, Flicek P, Gaffo E, Gu W, He C, Hoffmann S, Izuogu O, Jackson MS, Jakobi T, Lai EC, Nuytens J, Salzman J, Santibanez-Koref M, Stadler P, Thas O, Vanden Eynde E, Verniers K, Wen G, Westholm J, Yang L, Ye CY, Yigit N, Yuan GH, Zhang J, Zhao F, Vandesompele J, and Volders PJ
- Subjects
- Humans, RNA genetics, RNA metabolism, Sequence Analysis, RNA methods, RNA, Circular genetics, Benchmarking
- Abstract
The detection of circular RNA molecules (circRNAs) is typically based on short-read RNA sequencing data processed using computational tools. Numerous such tools have been developed, but a systematic comparison with orthogonal validation is missing. Here, we set up a circRNA detection tool benchmarking study, in which 16 tools detected more than 315,000 unique circRNAs in three deeply sequenced human cell types. Next, 1,516 predicted circRNAs were validated using three orthogonal methods. Generally, tool-specific precision is high and similar (median of 98.8%, 96.3% and 95.5% for qPCR, RNase R and amplicon sequencing, respectively) whereas the sensitivity and number of predicted circRNAs (ranging from 1,372 to 58,032) are the most significant differentiators. Of note, precision values are lower when evaluating low-abundance circRNAs. We also show that the tools can be used complementarily to increase detection sensitivity. Finally, we offer recommendations for future circRNA detection and validation., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2023
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7. Assessing the impacts of various factors on circular RNA reliability.
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Chuang TJ, Chiang TW, and Chen CY
- Subjects
- Reproducibility of Results, Alternative Splicing genetics, Exons genetics, RNA, Circular genetics, RNA genetics
- Abstract
Circular RNAs (circRNAs) are non-polyadenylated RNAs with a continuous loop structure characterized by a non-colinear back-splice junction (BSJ). Although millions of circRNA candidates have been identified, it remains a major challenge for determining circRNA reliability because of various types of false positives. Here, we systematically assess the impacts of numerous factors related to circRNA identification, conservation, biogenesis, and function on circRNA reliability by comparisons of circRNA expression from mock and the corresponding colinear/polyadenylated RNA-depleted datasets based on three different RNA treatment approaches. Eight important indicators of circRNA reliability are determined. The relative contribution to variability explained analyses reveal that the relative importance of these factors in affecting circRNA reliability in descending order is the conservation level of circRNA, full-length circular sequences, supporting BSJ read count, both BSJ donor and acceptor splice sites at the same colinear transcript isoforms, both BSJ donor and acceptor splice sites at the annotated exon boundaries, BSJs detected by multiple tools, supporting functional features, and both BSJ donor and acceptor splice sites undergoing alternative splicing. This study thus provides a useful guideline and an important resource for selecting high-confidence circRNAs for further investigations., (© 2023 Chuang et al.)
- Published
- 2023
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8. Trans-genetic effects of circular RNA expression quantitative trait loci and potential causal mechanisms in autism.
- Author
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Mai TL, Chen CY, Chen YC, Chiang TW, and Chuang TJ
- Subjects
- Humans, RNA, Circular genetics, Quantitative Trait Loci genetics, RNA, Messenger genetics, Sequence Analysis, RNA, Gene Expression Profiling, Gene Regulatory Networks, RNA genetics, Autism Spectrum Disorder genetics, MicroRNAs genetics
- Abstract
Genetic risk variants and transcriptional expression changes in autism spectrum disorder (ASD) were widely investigated, but their causal relationship remains largely unknown. Circular RNAs (circRNAs) are abundant in brain and often serve as upstream regulators of mRNAs. By integrating RNA-sequencing with genotype data from autistic brains, we assessed expression quantitative trait loci of circRNAs (circQTLs) that cis-regulated expression of nearby circRNAs and trans-regulated expression of distant genes (trans-eGenes) simultaneously. We thus identified 3619 circQTLs that were also trans-eQTLs and constructed 19,804 circQTL-circRNA-trans-eGene regulatory axes. We conducted two different types of approaches, mediation and partial correlation tests (MPT), to determine the axes with mediation effects of circQTLs on trans-eGene expression through circRNA expression. We showed that the mediation effects of the circQTLs (trans-eQTLs) on circRNA expression were positively correlated with the magnitude of circRNA-trans-eGene correlation of expression profile. The positive correlation became more significant after adjustment for the circQTLs. Of the 19,804 axes, 8103 passed MPT. Meanwhile, we performed causal inference test (CIT) and identified 2070 circQTL-trans-eGene-ASD diagnosis propagation paths. We showed that the CIT-passing genes were significantly enriched for ASD risk genes, genes encoding postsynaptic density proteins, and other ASD-relevant genes, supporting the relevance of the CIT-passing genes to ASD pathophysiology. Integration of MPT- and CIT-passing axes further constructed 352 circQTL-circRNA-trans-eGene-ASD diagnosis propagation paths, wherein the circRNA-trans-eGene axes may act as causal mediators for the circQTL-ASD diagnosis associations. These analyses were also successfully applied to an independent dataset from schizophrenia brains. Collectively, this study provided the first framework for systematically investigating trans-genetic effects of circQTLs and inferring the corresponding causal relations in diseases. The identified circQTL-circRNA-trans-eGene regulatory interactions, particularly the internal modules that were previously implicated in the examined disorders, also provided a helpful dataset for further investigating causative biology and cryptic regulatory mechanisms underlying the neuropsychiatric diseases., (© 2022. The Author(s).)
- Published
- 2022
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9. Comparative Analyses of Single-Cell Transcriptomic Profiles between In Vitro Totipotent Blastomere-like Cells and In Vivo Early Mouse Embryonic Cells.
- Author
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Lin PY, Yang D, Chuang CH, Lin H, Chen WJ, Chen CY, Chuang TJ, Lai CY, Li LY, Schuyler SC, Lu FL, Liu YC, and Lu J
- Subjects
- Animals, Cluster Analysis, Gene Expression Regulation, Gene Ontology, Mice, Pluripotent Stem Cells cytology, Pluripotent Stem Cells metabolism, Signal Transduction, Zygote metabolism, Blastomeres cytology, Embryo, Mammalian cytology, Mouse Embryonic Stem Cells cytology, Single-Cell Analysis, Totipotent Stem Cells cytology, Transcriptome genetics
- Abstract
The developmental potential within pluripotent cells in the canonical model is restricted to embryonic tissues, whereas totipotent cells can differentiate into both embryonic and extraembryonic tissues. Currently, the ability to culture in vitro totipotent cells possessing molecular and functional features like those of an early embryo in vivo has been a challenge. Recently, it was reported that treatment with a single spliceosome inhibitor, pladienolide B (plaB), can successfully reprogram mouse pluripotent stem cells into totipotent blastomere-like cells (TBLCs) in vitro. The TBLCs exhibited totipotency transcriptionally and acquired expanded developmental potential with the ability to yield various embryonic and extraembryonic tissues that may be employed as novel mouse developmental cell models. However, it is disputed whether TBLCs are 'true' totipotent stem cells equivalent to in vivo two-cell stage embryos. To address this question, single-cell RNA sequencing was applied to TBLCs and cells from early mouse embryonic developmental stages and the data were integrated using canonical correlation analyses. Differential expression analyses were performed between TBLCs and multi-embryonic cell stages to identify differentially expressed genes. Remarkably, a subpopulation within the TBLCs population expressed a high level of the totipotent-related genes Zscan4s and displayed transcriptomic features similar to mouse two-cell stage embryonic cells. This study underscores the subtle differences between in vitro derived TBLCs and in vivo mouse early developmental cell stages at the single-cell transcriptomic level. Our study has identified a new experimental model for stem cell biology, namely 'cluster 3', as a subpopulation of TBLCs that can be molecularly defined as near totipotent cells.
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- 2021
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10. Pathways of emotional autonomy, problem-solving ability, self-efficacy, and self-management on the glycemic control of adolescents with type 1 diabetes: A prospective study.
- Author
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Chen CY, Lo FS, Shu SH, and Wang RH
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- Adolescent, Diabetes Mellitus, Type 1 psychology, Female, Glycated Hemoglobin analysis, Humans, Male, Prospective Studies, Self Report, Surveys and Questionnaires, Taiwan, Glycemic Control, Personal Autonomy, Problem Solving, Self Efficacy, Self-Management
- Abstract
This prospective study tested a model to depict associations between a number of individual characteristics and 6-month glycated hemoglobin (HbA1c) levels in adolescents with type 1 diabetes (T1D). Adolescents (N = 232) aged 10-19 years with T1D were recruited from a medical center in Taiwan. Demographic characteristics, emotional autonomy, problem-solving ability, self-efficacy at baseline, and self-management information three months after baseline were collected using a self-reported questionnaire. HbA1c levels 6 months after study commencement were obtained from medical records. Structural equation modeling was used to test the model. Higher baseline self-efficacy and self-management at 3 months were directly associated with lower 6-month HbA1c levels. Higher baseline problem-solving ability and self-efficacy were directly associated with higher 3-month self-management, and higher baseline problem-solving ability was directly associated with higher baseline self-efficacy. Higher baseline emotional autonomy was directly associated with lower 6-month HbA1c levels but indirectly associated with higher 6-month HbA1c levels through the mediation of lower problem-solving ability, self-efficacy, and 3-month self-management. Findings indicate that improving self-management is essential to improving subsequent glycemic control, which might be achieved by enhancing problem-solving ability and self-efficacy. Strengthening problem-solving ability could diminish the negative impact of emotional autonomy on subsequent glycemic control in adolescents with T1D., (© 2021 Wiley Periodicals LLC.)
- Published
- 2021
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11. Roles of Emotional Autonomy, Problem-Solving Ability and Parent-Adolescent Relationships on Self-Management of Adolescents with Type 1 Diabetes in Taiwan.
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Chen CY, Lo FS, and Wang RH
- Subjects
- Adolescent, Cross-Sectional Studies, Humans, Parents, Self Care, Taiwan, Diabetes Mellitus, Type 1 diagnosis, Diabetes Mellitus, Type 1 therapy, Self-Management
- Abstract
Background: High emotional autonomy has a negative association, whereas good problem-solving ability and parent-adolescent relationships have positive association with self-management in adolescents with type 1 diabetes (T1D). Exploring roles of these variables is crucial to design specific interventions to improve self-management in such afflicted adolescents., Purpose: To explore the roles of emotional autonomy, problem-solving ability and parent-adolescent relationships on self-management in adolescents with T1D., Design and Methods: Cross-sectional design was used in this study. A total of 242 adolescents with T1D were recruited from an outpatient clinic of a medical center by convenience sampling in Taiwan. Self-reported questionnaires were used to collect personal characteristics, self-management, emotional autonomy, problem-solving ability, and parent-adolescent relationships., Results: Hierarchical multiple regressions indicated that body mass index, problem-solving ability, father-adolescent relationship, and emotional autonomy were significant factors associated with self-management. The interactions of emotional autonomy with problem-solving ability and with parent-adolescents relationship were not significantly associated with self-management. The overall model explained 47.5% variance of self-management., Conclusions: High emotional autonomy was significantly associated with poor self-management. Problem-solving ability and father-adolescent relationships could not moderate, but were independently and significantly associated with self-management in adolescents with T1D., Practice Implication: Healthcare providers should evaluate emotional autonomy earlier and provide more timely help to reduce any negative impact on self-management in adolescents with T1D. Improving problem-solving ability and encouraging fathers to develop optimal father-adolescents relationship might be promising strategies to enhance self-management in adolescents with T1D., Competing Interests: Declaration of Competing Interest The authors have no financial or other conflicts of interest in publishing this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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12. Genome-wide, integrative analysis of circular RNA dysregulation and the corresponding circular RNA-microRNA-mRNA regulatory axes in autism.
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Chen YJ, Chen CY, Mai TL, Chuang CF, Chen YC, Gupta SK, Yen L, Wang YD, and Chuang TJ
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- Astrocytes metabolism, Autism Spectrum Disorder metabolism, Brain metabolism, Cell Line, Genome, Human, Humans, Neural Stem Cells metabolism, Neurons metabolism, Autism Spectrum Disorder genetics, Gene Expression Regulation, MicroRNAs metabolism, RNA, Circular metabolism, RNA, Messenger metabolism
- Abstract
Circular RNAs (circRNAs), a class of long noncoding RNAs, are known to be enriched in mammalian neural tissues. Although a wide range of dysregulation of gene expression in autism spectrum disorder (ASD) have been reported, the role of circRNAs in ASD remains largely unknown. Here, we performed genome-wide circRNA expression profiling in postmortem brains from individuals with ASD and controls and identified 60 circRNAs and three coregulated modules that were perturbed in ASD. By integrating circRNA, microRNA, and mRNA dysregulation data derived from the same cortex samples, we identified 8170 ASD-associated circRNA-microRNA-mRNA interactions. Putative targets of the axes were enriched for ASD risk genes and genes encoding inhibitory postsynaptic density (PSD) proteins, but not for genes implicated in monogenetic forms of other brain disorders or genes encoding excitatory PSD proteins. This reflects the previous observation that ASD-derived organoids show overproduction of inhibitory neurons. We further confirmed that some ASD risk genes ( NLGN1 , STAG1 , HSD11B1 , VIP , and UBA6 ) were regulated by an up-regulated circRNA (circARID1A) via sponging a down-regulated microRNA (miR-204-3p) in human neuronal cells. Particularly, alteration of NLGN1 expression is known to affect the dynamic processes of memory consolidation and strengthening. To the best of our knowledge, this is the first systems-level view of circRNA regulatory networks in ASD cortex samples. We provided a rich set of ASD-associated circRNA candidates and the corresponding circRNA-microRNA-mRNA axes, particularly those involving ASD risk genes. Our findings thus support a role for circRNA dysregulation and the corresponding circRNA-microRNA-mRNA axes in ASD pathophysiology., (© 2020 Chen et al.; Published by Cold Spring Harbor Laboratory Press.)
- Published
- 2020
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13. Comment on "A comprehensive overview and evaluation of circular RNA detection tools".
- Author
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Chen CY and Chuang TJ
- Subjects
- RNA
- Abstract
Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2019
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14. Transcriptomopathies of pre- and post-symptomatic frontotemporal dementia-like mice with TDP-43 depletion in forebrain neurons.
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Wu LS, Cheng WC, Chen CY, Wu MC, Wang YC, Tseng YH, Chuang TJ, and Shen CJ
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- Age Factors, Animals, DNA-Binding Proteins genetics, Frontotemporal Dementia genetics, Frontotemporal Dementia pathology, Gene Expression Profiling methods, Mice, Mice, Knockout, Mice, Transgenic, Neurons pathology, Prosencephalon pathology, DNA-Binding Proteins deficiency, Frontotemporal Dementia metabolism, Neurons metabolism, Prosencephalon metabolism, Transcriptome physiology
- Abstract
TAR DNA-binding protein (TDP-43) is a ubiquitously expressed nuclear protein, which participates in a number of cellular processes and has been identified as the major pathological factor in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Here we constructed a conditional TDP-43 mouse with depletion of TDP-43 in the mouse forebrain and find that the mice exhibit a whole spectrum of age-dependent frontotemporal dementia-like behaviour abnormalities including perturbation of social behaviour, development of dementia-like behaviour, changes of activities of daily living, and memory loss at a later stage of life. These variations are accompanied with inflammation, neurodegeneration, and abnormal synaptic plasticity of the mouse CA1 neurons. Importantly, analysis of the cortical RNA transcripts of the conditional knockout mice at the pre-/post-symptomatic stages and the corresponding wild type mice reveals age-dependent alterations in the expression levels and RNA processing patterns of a set of genes closely associated with inflammation, social behaviour, synaptic plasticity, and neuron survival. This study not only supports the scenario that loss-of-function of TDP-43 in mice may recapitulate key behaviour features of the FTLD diseases, but also provides a list of TDP-43 target genes/transcript isoforms useful for future therapeutic research.
- Published
- 2019
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15. NCLcomparator: systematically post-screening non-co-linear transcripts (circular, trans-spliced, or fusion RNAs) identified from various detectors.
- Author
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Chen CY and Chuang TJ
- Subjects
- Gene Fusion genetics, Genome genetics, RNA genetics, RNA Splicing genetics, Sequence Analysis, RNA methods
- Abstract
Background: Non-co-linear (NCL) transcripts consist of exonic sequences that are topologically inconsistent with the reference genome in an intragenic fashion (circular or intragenic trans-spliced RNAs) or in an intergenic fashion (fusion or intergenic trans-spliced RNAs). On the basis of RNA-seq data, numerous NCL event detectors have been developed and detected thousands of NCL events in diverse species. However, there are great discrepancies in the identification results among detectors, indicating a considerable proportion of false positives in the detected NCL events. Although several helpful guidelines for evaluating the performance of NCL event detectors have been provided, a systematic guideline for measurement of NCL events identified by existing tools has not been available., Results: We develop a software, NCLcomparator, for systematically post-screening the intragenic or intergenic NCL events identified by various NCL detectors. NCLcomparator first examine whether the input NCL events are potentially false positives derived from ambiguous alignments (i.e., the NCL events have an alternative co-linear explanation or multiple matches against the reference genome). To evaluate the reliability of the identified NCL events, we define the NCL score (NCL
score ) based on the variation in the number of supporting NCL junction reads identified by the tools examined. Of the input NCL events, we show that the ambiguous alignment-derived events have relatively lower NCLscore values than the other events, indicating that an NCL event with a higher NCLscore has a higher level of reliability. To help selecting highly expressed NCL events, NCLcomparator also provides a series of useful measurements such as the expression levels of the detected NCL events and their corresponding host genes and the junction usage of the co-linear splice junctions at both NCL donor and acceptor sites., Conclusion: NCLcomparator provides useful guidelines, with the input of identified NCL events from various detectors and the corresponding paired-end RNA-seq data only, to help users selecting potentially high-confidence NCL events for further functional investigation. The software thus helps to facilitate future studies into NCL events, shedding light on the fundamental biology of this important but understudied class of transcripts. NCLcomparator is freely accessible at https://github.com/TreesLab/NCLcomparator .- Published
- 2019
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16. Transcriptome Changes of Escherichia coli, Enterococcus faecalis , and Escherichia coli O157:H7 Laboratory Strains in Response to Photo-Degraded DOM.
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Oladeinde A, Lipp E, Chen CY, Muirhead R, Glenn T, Cook K, and Molina M
- Abstract
In this study, we investigated gene expression changes in three bacterial strains ( Escherichia coli C3000, Escherichia coli O157:H7 B6914, and Enterococcus faecalis ATCC 29212), commonly used as indicators of water quality and as control strains in clinical, food, and water microbiology laboratories. Bacterial transcriptome responses from pure cultures were monitored in microcosms containing water amended with manure-derived dissolved organic matter (DOM), previously exposed to simulated sunlight for 12 h. We used RNA sequencing (RNA-seq) and quantitative real-time reverse transcriptase (qRT-PCR) to compare differentially expressed temporal transcripts between bacteria incubated in microcosms containing sunlight irradiated and non-irradiated DOM, for up to 24 h. In addition, we used whole genome sequencing simultaneously with RNA-seq to identify single nucleotide variants (SNV) acquired in bacterial populations during incubation. These results indicate that E. coli and E. faecalis have different mechanisms for removal of reactive oxygen species (ROS) produced from irradiated DOM. They are also able to produce micromolar concentrations of H
2 O2 from non-irradiated DOM, that should be detrimental to other bacteria present in the environment. Notably, this study provides an assessment of the role of two conjugative plasmids carried by the E. faecalis and highlights the differences in the overall survival dynamics of environmentally-relevant bacteria in the presence of naturally-produced ROS.- Published
- 2018
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17. Integrative transcriptome sequencing reveals extensive alternative trans-splicing and cis-backsplicing in human cells.
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Chuang TJ, Chen YJ, Chen CY, Mai TL, Wang YD, Yeh CS, Yang MY, Hsiao YT, Chang TH, Kuo TC, Cho HH, Shen CN, Kuo HC, Lu MY, Chen YH, Hsieh SC, and Chiang TW
- Subjects
- Exons genetics, Gene Expression Profiling, Humans, RNA Splicing genetics, RNA, Circular, Alternative Splicing genetics, RNA genetics, Trans-Splicing genetics, Transcriptome genetics
- Abstract
Transcriptionally non-co-linear (NCL) transcripts can originate from trans-splicing (trans-spliced RNA; 'tsRNA') or cis-backsplicing (circular RNA; 'circRNA'). While numerous circRNAs have been detected in various species, tsRNAs remain largely uninvestigated. Here, we utilize integrative transcriptome sequencing of poly(A)- and non-poly(A)-selected RNA-seq data from diverse human cell lines to distinguish between tsRNAs and circRNAs. We identified 24,498 NCL events and found that a considerable proportion (20-35%) of them arise from both tsRNAs and circRNAs, representing extensive alternative trans-splicing and cis-backsplicing in human cells. We show that sequence generalities of exon circularization are also observed in tsRNAs. Recapitulation of NCL RNAs further shows that inverted Alu repeats can simultaneously promote the formation of tsRNAs and circRNAs. However, tsRNAs and circRNAs exhibit quite different, or even opposite, expression patterns, in terms of correlation with the expression of their co-linear counterparts, expression breadth/abundance, transcript stability, and subcellular localization preference. These results indicate that tsRNAs and circRNAs may play different regulatory roles and analysis of NCL events should take the joint effects of different NCL-splicing types and joint effects of multiple NCL events into consideration. This study describes the first transcriptome-wide analysis of trans-splicing and cis-backsplicing, expanding our understanding of the complexity of the human transcriptome.
- Published
- 2018
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18. An Evolutionary Landscape of A-to-I RNA Editome across Metazoan Species.
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Hung LY, Chen YJ, Mai TL, Chen CY, Yang MY, Chiang TW, Wang YD, and Chuang TJ
- Subjects
- Animals, Cluster Analysis, Evolution, Molecular, Humans, Sequence Analysis, RNA, Adenosine genetics, Inosine genetics, RNA genetics, RNA Editing
- Abstract
Adenosine-to-inosine (A-to-I) editing is widespread across the kingdom Metazoa. However, for the lack of comprehensive analysis in nonmodel animals, the evolutionary history of A-to-I editing remains largely unexplored. Here, we detect high-confidence editing sites using clustering and conservation strategies based on RNA sequencing data alone, without using single-nucleotide polymorphism information or genome sequencing data from the same sample. We thereby unveil the first evolutionary landscape of A-to-I editing maps across 20 metazoan species (from worm to human), providing unprecedented evidence on how the editing mechanism gradually expands its territory and increases its influence along the history of evolution. Our result revealed that highly clustered and conserved editing sites tended to have a higher editing level and a higher magnitude of the ADAR motif. The ratio of the frequencies of nonsynonymous editing to that of synonymous editing remarkably increased with increasing the conservation level of A-to-I editing. These results thus suggest potentially functional benefit of highly clustered and conserved editing sites. In addition, spatiotemporal dynamics analyses reveal a conserved enrichment of editing and ADAR expression in the central nervous system throughout more than 300 Myr of divergent evolution in complex animals and the comparability of editing patterns between invertebrates and between vertebrates during development. This study provides evolutionary and dynamic aspects of A-to-I editome across metazoan species, expanding this important but understudied class of nongenomically encoded events for comprehensive characterization., (© The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)
- Published
- 2018
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19. Assessment of imprinting- and genetic variation-dependent monoallelic expression using reciprocal allele descendants between human family trios.
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Chuang TJ, Tseng YH, Chen CY, and Wang YD
- Subjects
- Humans, Alleles, Family Health, Gene Expression Profiling methods, Genetic Variation, Genomic Imprinting, Genotype, Genotyping Techniques methods
- Abstract
Genomic imprinting is an important epigenetic process that silences one of the parentally-inherited alleles of a gene and thereby exhibits allelic-specific expression (ASE). Detection of human imprinting events is hampered by the infeasibility of the reciprocal mating system in humans and the removal of ASE events arising from non-imprinting factors. Here, we describe a pipeline with the pattern of reciprocal allele descendants (RADs) through genotyping and transcriptome sequencing data across independent parent-offspring trios to discriminate between varied types of ASE (e.g., imprinting, genetic variation-dependent ASE, and random monoallelic expression (RME)). We show that the vast majority of ASE events are due to sequence-dependent genetic variant, which are evolutionarily conserved and may themselves play a cis-regulatory role. Particularly, 74% of non-RAD ASE events, even though they exhibit ASE biases toward the same parentally-inherited allele across different individuals, are derived from genetic variation but not imprinting. We further show that the RME effect may affect the effectiveness of the population-based method for detecting imprinting events and our pipeline can help to distinguish between these two ASE types. Taken together, this study provides a good indicator for categorization of different types of ASE, opening up this widespread and complex mechanism for comprehensive characterization.
- Published
- 2017
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20. NanoRelease: Pilot interlaboratory comparison of a weathering protocol applied to resilient and labile polymers with and without embedded carbon nanotubes.
- Author
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Wohlleben W, Kingston C, Carter J, Sahle-Demessie E, Vázquez-Campos S, Acrey B, Chen CY, Walton E, Egenolf H, Müller P, and Zepp R
- Abstract
A major use of multi-walled carbon nanotubes (MWCNTs) is as functional fillers embedded in a solid matrix, such as plastics or coatings. Weathering and abrasion of the solid matrix during use can lead to environmental releases of the MWCNTs. Here we focus on a protocol to identify and quantify the primary release induced by weathering, and assess reproducibility, transferability, and sensitivity towards different materials and uses. We prepared 132 specimens of two polymer-MWCNT composites containing the same grade of MWCNTs used in earlier OECD hazard assessments but without UV stabilizer. We report on a pilot inter-laboratory comparison (ILC) with four labs (two US and two EU) aging by UV and rain, then shipping for analysis. Two labs (one US and one EU) conducted the release sampling and analysis by Transmission Electron Microscopy (TEM), Inductively Coupled Plasma- Mass Spectrometry (ICP-MS), UltravioleteVisible Spectroscopy (UVeVis), Analytical Ultracentrifugation (AUC), and Asymmetric Flow Field Flow Fractionation (AF4). We compare results between aging labs, between analysis labs and between materials. Surprisingly, we found quantitative agreement between analysis labs for TEM, ICP-MS, UVeVis; low variation between aging labs by all methods; and consistent rankings of release between TEM, ICP-MS, UVeVis, AUC. Significant disagreement was related primarily to differences in aging, but even these cases remained within a factor of two.
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- 2017
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21. Pathways of emotional autonomy, self-care behaviors, and depressive symptoms on health adaptation in adolescents with type 1 diabetes.
- Author
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Chen CY, Lo FS, Chen BH, Lu MH, Hsin YM, and Wang RH
- Subjects
- Adolescent, Cross-Sectional Studies, Female, Humans, Male, Personal Autonomy, Surveys and Questionnaires, Taiwan, Adaptation, Physiological, Adaptation, Psychological, Adolescent Behavior psychology, Attitude to Health, Diabetes Mellitus, Type 1 psychology, Quality of Life psychology, Self Care psychology
- Abstract
Background: Adolescents with type 1 diabetes mellitus (T1DM) need to adapt physically and psychologically to the impact of diabetes., Purpose: The purpose of this study was to examine the pathways of emotional autonomy, depressive symptoms, and self-care behaviors to glycosylated hemoglobin (HbA1c) levels and quality of life (QoL) in adolescents with T1DM., Methods: Cross-sectional design was used in this study. Self-reported questionnaires and medical records were used to collect data from 265 adolescents with T1DM by convenience sampling in Taiwan., Discussion: Structural equation modeling indicated that self-care behaviors directly positively influenced life satisfaction QoL but negatively influenced HbA1c levels. Depressive symptoms directly negatively influenced self-care behaviors and life satisfaction QoL. Emotional autonomy directly negatively influenced self-care behaviors and life-satisfaction QoL but directly positively influenced depressive symptoms., Conclusion: Emotional autonomy seems to be a risk factor contributing to poor health adaptation. Health care providers need to help adolescents with T1DM to balance the pursuit of emotional autonomy and health adaptation., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2017
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22. Purifying selection shapes the coincident SNP distribution of primate coding sequences.
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Chen CY, Hung LY, Wu CS, and Chuang TJ
- Subjects
- Animals, Databases, Genetic, Evolution, Molecular, Humans, Mutation Rate, Selection, Genetic, Pan troglodytes genetics, Polymorphism, Single Nucleotide, Sequence Analysis, DNA methods
- Abstract
Genome-wide analysis has observed an excess of coincident single nucleotide polymorphisms (coSNPs) at human-chimpanzee orthologous positions, and suggested that this is due to cryptic variation in the mutation rate. While this phenomenon primarily corresponds with non-coding coSNPs, the situation in coding sequences remains unclear. Here we calculate the observed-to-expected ratio of coSNPs (coSNPO/E) to estimate the prevalence of human-chimpanzee coSNPs, and show that the excess of coSNPs is also present in coding regions. Intriguingly, coSNPO/E is much higher at zero-fold than at nonzero-fold degenerate sites; such a difference is due to an elevation of coSNPO/E at zero-fold degenerate sites, rather than a reduction at nonzero-fold degenerate ones. These trends are independent of chimpanzee subpopulation, population size, or sequencing techniques; and hold in broad generality across primates. We find that this discrepancy cannot fully explained by sequence contexts, shared ancestral polymorphisms, SNP density, and recombination rate, and that coSNPO/E in coding sequences is significantly influenced by purifying selection. We also show that selection and mutation rate affect coSNPO/E independently, and coSNPs tend to be less damaging and more correlated with human diseases than non-coSNPs. These suggest that coSNPs may represent a "signature" during primate protein evolution.
- Published
- 2016
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23. NCLscan: accurate identification of non-co-linear transcripts (fusion, trans-splicing and circular RNA) with a good balance between sensitivity and precision.
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Chuang TJ, Wu CS, Chen CY, Hung LY, Chiang TW, and Yang MY
- Subjects
- Limit of Detection, RNA, Circular, Reproducibility of Results, RNA genetics, RNA Splicing, RNA, Messenger genetics
- Abstract
Analysis of RNA-seq data often detects numerous 'non-co-linear' (NCL) transcripts, which comprised sequence segments that are topologically inconsistent with their corresponding DNA sequences in the reference genome. However, detection of NCL transcripts involves two major challenges: removal of false positives arising from alignment artifacts and discrimination between different types of NCL transcripts (trans-spliced, circular or fusion transcripts). Here, we developed a new NCL-transcript-detecting method ('NCLscan'), which utilized a stepwise alignment strategy to almost completely eliminate false calls (>98% precision) without sacrificing true positives, enabling NCLscan outperform 18 other publicly-available tools (including fusion- and circular-RNA-detecting tools) in terms of sensitivity and precision, regardless of the generation strategy of simulated dataset, type of intragenic or intergenic NCL event, read depth of coverage, read length or expression level of NCL transcript. With the high accuracy, NCLscan was applied to distinguishing between trans-spliced, circular and fusion transcripts on the basis of poly(A)- and nonpoly(A)-selected RNA-seq data. We showed that circular RNAs were expressed more ubiquitously, more abundantly and less cell type-specifically than trans-spliced and fusion transcripts. Our study thus describes a robust pipeline for the discovery of NCL transcripts, and sheds light on the fundamental biology of these non-canonical RNA events in human transcriptome., (© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2016
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24. Probing Photosensitization by Functionalized Carbon Nanotubes.
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Chen CY and Zepp RG
- Subjects
- Dynamic Light Scattering, Furans chemistry, Oxidation-Reduction, Reactive Oxygen Species chemistry, Singlet Oxygen chemistry, Sorbic Acid chemistry, Sunlight, Water, Nanotubes, Carbon chemistry, Photochemical Processes, Water Pollutants, Chemical chemistry
- Abstract
Carbon nanotubes (CNTs) photosensitize the production of reactive oxygen species that may damage organisms by biomembrane oxidation or mediate environmental transformations of CNTs. Photosensitization by derivatized carbon nanotubes from various synthetic methods, and thus with different intrinsic characteristics (e.g., diameter and electronic properties), has been investigated under environmentally relevant aquatic conditions. We used the CNT-sensitized photoisomerization of sorbic acid ((2E,4E)-hexa-2,4-dienoic acid) and singlet oxygen formation to quantify the triplet states ((3)CNT*) formed upon irradiation of selected single-walled carbon nanotubes (SWCNTs) and multiwalled carbon nanotubes (MWCNTs). The CNTs used in our studies were derivatized by carboxyl groups to facilitate their dispersion in water. Results indicate that high-defect-density (thus well-stabilized), small-diameter, and semiconducting-rich CNTs have higher-measured excited triplet state formation and therefore singlet oxygen ((1)O2) yield. Derivatized SWCNTs were significantly more photoreactive than derivatized MWCNTs. Moreover, addition of sodium chloride resulted in increased aggregation and small increases in (1)O2 production of CNTs. The most photoreactive CNTs exhibited comparable photoreactivity (in terms of (3)CNT* formation and (1)O2 yield) to reference natural organic matter (NOM) under sunlight irradiation with the same mass-based concentration. Selected reference NOM could therefore be useful in evaluating environmental photoreactivity or intended antibacterial applications of CNTs.
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- 2015
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25. The Efficacy of a Family-Based Intervention Program on Childhood Obesity: A Quasi-Experimental Design.
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Chen CY, Kao CC, Hsu HY, Wang RH, and Hsu SH
- Subjects
- Adolescent, Body Mass Index, Body Weight, Child, Child, Preschool, Energy Intake, Female, Health Promotion statistics & numerical data, Humans, Male, Pediatric Obesity psychology, Research Design, Taiwan, Health Education methods, Parent-Child Relations, Pediatric Obesity therapy
- Abstract
The purpose of this quasi-experimental study was to assess the efficacy of a family-based (FB) weight-loss and behavior-modification intervention among overweight/obese children (age 9-11 years) and their parents in Taiwan. The intervention group (52 child-parent dyads) participated in an FB program for 7 weeks. The control group (55 child-parent dyads) received an educational pamphlet about obesity prevention. The children's body mass index (BMI) z-scores were the primary outcome variable. The parents' BMI, high-calorie (HC) food-intake behaviors, screen-related behaviors, and restrictions on children's consumption of HC foods and screen-related behaviors and the availability of HC foods at home were the secondary outcome variables. Outcome variables were measured at baseline (T0), at the end of the intervention (T1), and 4 weeks after the end of the intervention (T2). A linear mixed model was used to assess the efficacy of the FB program. Results indicated that the children's BMI z-scores decreased significantly more from T0 to T2 in the experimental group than in the control group. The decreases in parents' HC food-intake behaviors and availability of HC foods at home and the increase in parental restrictions on children's consumption of HC foods were significantly greater in the experimental than in the control group from T0 to T1 and T0 to T2. The FB program was effective in modifying parental behaviors and the weight of overweight/obese children in a Taiwanese population., (© The Author(s) 2015.)
- Published
- 2015
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26. Biogenesis, identification, and function of exonic circular RNAs.
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Chen I, Chen CY, and Chuang TJ
- Subjects
- Animals, Humans, Exons, Nucleic Acid Conformation, RNA genetics, RNA metabolism, RNA Processing, Post-Transcriptional physiology
- Abstract
Circular RNAs (circRNAs) arise during post-transcriptional processes, in which a single-stranded RNA molecule forms a circle through covalent binding. Previously, circRNA products were often regarded to be splicing intermediates, by-products, or products of aberrant splicing. But recently, rapid advances in high-throughput RNA sequencing (RNA-seq) for global investigation of nonco-linear (NCL) RNAs, which comprised sequence segments that are topologically inconsistent with the reference genome, leads to renewed interest in this type of NCL RNA (i.e., circRNA), especially exonic circRNAs (ecircRNAs). Although the biogenesis and function of ecircRNAs are mostly unknown, some ecircRNAs are abundant, highly expressed, or evolutionarily conserved. Some ecircRNAs have been shown to affect microRNA regulation, and probably play roles in regulating parental gene transcription, cell proliferation, and RNA-binding proteins, indicating their functional potential for development as diagnostic tools. To date, thousands of ecircRNAs have been identified in multiple tissues/cell types from diverse species, through analyses of RNA-seq data. However, the detection of ecircRNA candidates involves several major challenges, including discrimination between ecircRNAs and other types of NCL RNAs (e.g., trans-spliced RNAs and genetic rearrangements); removal of sequencing errors, alignment errors, and in vitro artifacts; and the reconciliation of heterogeneous results arising from the use of different bioinformatics methods or sequencing data generated under different treatments. Such challenges may severely hamper the understanding of ecircRNAs. Herein, we review the biogenesis, identification, properties, and function of ecircRNAs, and discuss some unanswered questions regarding ecircRNAs. We also evaluate the accuracy (in terms of sensitivity and precision) of some well-known circRNA-detecting methods., (© 2015 The Authors. WIREs RNA published by Wiley Periodicals, Inc.)
- Published
- 2015
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27. Proteomic analysis of hypothalamic injury in heatstroke rats.
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Chao CM, Cheng BC, Chen CY, Lin MT, Chang CP, and Yang ST
- Subjects
- Animals, Cytokines metabolism, Electrophoresis, Gel, Two-Dimensional, Enzyme-Linked Immunosorbent Assay, Heat Stroke mortality, Heat Stroke physiopathology, Hydroxybenzoates metabolism, Hypothermia, Induced, Neurons metabolism, Neurons pathology, Nitric Oxide metabolism, Oxidative Stress, Rats, Sprague-Dawley, Tandem Mass Spectrometry, Heat Stroke metabolism, Hypothalamus metabolism, Hypothalamus physiopathology, Proteome analysis
- Abstract
Ischemic and oxidative damage to the hypothalamus may be associated with decreased heat tolerance as well as heatstroke formation. The present study explores the hypothalamic proteome mechanisms associated with heatstroke-mediated hypothalamic ischemia, and oxidative damage. Heatstroke rats had hypotension, hypothalamic ischemia, and lethality. In addition, they had hyperthermia and hypothalamic blood-brain-barrier disruption, oxidative stress, activated inflammation, and neuronal apoptosis and degeneration. 2DE combined LC-MS/MS revealed that heatstroke-induced ischemic injury and apoptosis were associated with upregulation of L-lactate dehydrogenase but downregulation of both dihydropyriminase-related protein and 14-3-3 Zeta isoform protein. Heat-induced blood-brain-barrier disruption might be related to upregulation of glial fibrillary acidic protein. Oxidative stress caused by heatstroke might be related to upregulation of cytosolic dehydrogenase-1. Also, heat-induced overproduction of proinflammatory cytokines might be associated with downregulation of stathmin 1. Heat-induced hypothalamic ischemia, apoptosis, injury (or upregulation of L-lactate dehydrogenase), blood-brain-barrier disruption (or upregulation of glial fibrillary acidic protein), oxidative stress (or upregulation of cytosolic dehydrogenase-1), and activated inflammation (or downregulation of stathmin 1) were all significantly reversed by whole body cooling. Our data indicate that cooling therapy improves outcomes of heatstroke by modulating hypothalamic proteome mechanisms., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2015
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28. Development of a microarray for two rice subspecies: characterization and validation of gene expression in rice tissues.
- Author
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Chen JS, Lin SC, Chen CY, Hsieh YT, Pai PH, Chen LK, and Lee S
- Subjects
- Base Sequence, Molecular Sequence Data, Organ Specificity, Oryza classification, Oryza metabolism, Oxidative Stress genetics, Plant Proteins biosynthesis, Plant Proteins genetics, Plant Roots chemistry, Plant Shoots chemistry, Quality Control, RNA, Plant analysis, Reproducibility of Results, Species Specificity, Gene Expression Profiling, Gene Expression Regulation, Plant, Genes, Plant, Oligonucleotide Array Sequence Analysis, Oryza genetics, RNA, Plant genetics
- Abstract
Background: Rice is one of the major crop species in the world helping to sustain approximately half of the global population's diet especially in Asia. However, due to the impact of extreme climate change and global warming, rice crop production and yields may be adversely affected resulting in a world food crisis. Researchers have been keen to understand the effects of drought, temperature and other environmental stress factors on rice plant growth and development. Gene expression microarray technology represents a key strategy for the identification of genes and their associated expression patterns in response to stress. Here, we report on the development of the rice OneArray® microarray platform which is suitable for two major rice subspecies, japonica and indica., Results: The rice OneArray® 60-mer, oligonucleotide microarray consists of a total of 21,179 probes covering 20,806 genes of japonica and 13,683 genes of indica. Through a validation study, total RNA isolated from rice shoots and roots were used for comparison of gene expression profiles via microarray examination. The results were submitted to NCBI's Gene Expression Omnibus (GEO). Data can be found under the GEO accession number GSE50844 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE50844). A list of significantly differentially expressed genes was generated; 438 shoot-specific genes were identified among 3,138 up-regulated genes, and 463 root-specific genes were found among 3,845 down-regulated genes. GO enrichment analysis demonstrates these results are in agreement with the known physiological processes of the different organs/tissues. Furthermore, qRT-PCR validation was performed on 66 genes, and found to significantly correlate with the microarray results (R = 0.95, p < 0.001***)., Conclusion: The rice OneArray® 22 K microarray, the first rice microarray, covering both japonica and indica subspecies was designed and validated in a comprehensive study of gene expression in rice tissues. The rice OneArray® microarray platform revealed high specificity and sensitivity. Additional information for the rice OneArray® microarray can be found at http://www.phalanx.com.tw/index.php.
- Published
- 2014
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29. Biochemical and functional characterization of charge-defined subfractions of high-density lipoprotein from normal adults.
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Hsieh JY, Chang CT, Huang MT, Chang CM, Chen CY, Shen MY, Liao HY, Wang GJ, Chen CH, Chen CJ, and Yang CY
- Subjects
- Adult, Anion Exchange Resins chemistry, Female, Humans, Male, Middle Aged, Chemical Fractionation methods, Lipoproteins, HDL analysis, Lipoproteins, HDL chemistry
- Abstract
High-density lipoprotein (HDL) is regarded as atheroprotective because it provides antioxidant and anti-inflammatory benefits and plays an important role in reverse cholesterol transport. In this paper, we outline a novel methodology for studying the heterogeneity of HDL. Using anion-exchange chromatography, we separated HDL from 6 healthy individuals into five subfractions (H1 through H5) with increasing charge and evaluated the composition and biologic activities of each subfraction. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis showed that apolipoprotein (apo) AI and apoAII were present in all 5 subfractions; apoCI was present only in H1, and apoCIII and apoE were most abundantly present in H4 and H5. HDL-associated antioxidant enzymes such as lecithin-cholesterol acyltransferase, lipoprotein-associated phospholipase A2, and paraoxonase 1 were most abundant in H4 and H5. Lipoprotein isoforms were analyzed in each subfraction by using matrix-assisted laser desorption-time-of-flight mass spectrometry. To quantify other proteins in the HDL subfractions, we used the isobaric tags for the relative and absolute quantitation approach followed by nanoflow liquid chromatography-tandem mass spectrometry analysis. Most antioxidant proteins detected were found in H4 and H5. The ability of each subfraction to induce cholesterol efflux from macrophages increased with increasing HDL electronegativity, with the exception of H5, which promoted the least efflux activity. In conclusion, anion-exchange chromatography is an attractive method for separating HDL into subfractions with distinct lipoprotein compositions and biologic activities. By comparing the properties of these subfractions, it may be possible to uncover HDL-specific proteins that play a role in disease.
- Published
- 2013
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30. Hypothermia may attenuate ischemia/reperfusion-induced cardiomyocyte death by reducing autophagy.
- Author
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Cheng BC, Huang HS, Chao CM, Hsu CC, Chen CY, and Chang CP
- Subjects
- Blotting, Western, Cell Survival, Cells, Cultured, Humans, Myocardial Reperfusion Injury therapy, Apoptosis physiology, Autophagy, Hypothermia, Induced, Myocardial Reperfusion Injury pathology, Myocytes, Cardiac pathology
- Abstract
Objective: We sought to assess the effect of therapeutic hypothermia on the autophagy that occurred in ischemia-reperfused (IR) H9c2 cardiomyocytes., Methods: In control studies, the H9c2 cells at a density of 1 × 10(5) per culture dish in six-well plate were exposed to normoxic culture medium at 37 °C for 12h. All assays contained appropriate controls and were performed in triplicate and repeated on three separately initiated cultures. In hypothermia-treated group, the ischemic and hypoxic cells were maintained in a 32 °C incubation. The trypan blue exclusion method was used to assess the cell viability. Autophagy was evaluated by determining both the microtubule-associated protein 1 light chain 3 [LC3] levels and punctuate distribution of the autophagic vesicle associated form [LC3-II]., Results: The results were mean ± standard error of mean of triplicates. The viable cell percentage for control group, IR group, and IR group treated with hypothermia at the start of ischemia, or reperfusion were 100% ± 9%, 20% ± 1%, 32% ± 3%, and 41% ± 3%, respectively. The cell death in I/R H9c2 cells was positively associated with increased LC3 levels and punctuate distribution of (LC3-II). Mild hypothermia adopted at the start of ischemia or reperfusion significantly reduced both the cell death and the autophagy in H9c2 cells., Conclusion: Our data indicate that in H9c2, IR stimulates cell autophagy and causes cell death, which can be attenuated by mild hypothermia. Our results, if further confirmed in vivo, may have important clinical implications during IR injury., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2013
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31. Divergent selection and local adaptation in disjunct populations of an endangered conifer, Keteleeria davidiana var. formosana (Pinaceae).
- Author
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Fang JY, Chung JD, Chiang YC, Chang CT, Chen CY, and Hwang SY
- Subjects
- Amplified Fragment Length Polymorphism Analysis, Genomics, Linkage Disequilibrium, Logistic Models, Adaptation, Physiological, Endangered Species, Evolution, Molecular, Genetic Variation, Pinaceae genetics, Pinaceae physiology, Selection, Genetic
- Abstract
The present study investigated the genetic diversity, population structure, F ST outliers, and extent and pattern of linkage disequilibrium in five populations of Keteleeria davidiana var. formosana, which is listed as a critically endangered species by the Council of Agriculture, Taiwan. Twelve amplified fragment length polymorphism primer pairs generated a total of 465 markers, of which 83.74% on average were polymorphic across populations, with a mean Nei's genetic diversity of 0.233 and a low level of genetic differentiation (approximately 6%) based on the total dataset. Linkage disequilibrium and HICKORY analyses suggested recent population bottlenecks and inbreeding in K. davidiana var. formosana. Both STRUCTURE and BAPS observed extensive admixture of individual genotypes among populations based on the total dataset in various clustering scenarios, which probably resulted from incomplete lineage sorting of ancestral variation rather than a high rate of recent gene flow. Our results based on outlier analysis revealed generally high levels of genetic differentiation and suggest that divergent selection arising from environmental variation has been driven by differences in temperature, precipitation, and humidity. Identification of ecologically associated outliers among environmentally disparate populations further support divergent selection and potential local adaptation.
- Published
- 2013
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32. Oxidized ApoC1 on MALDI-TOF and glycated-ApoA1 band on gradient gel as potential diagnostic tools for atherosclerotic vascular disease.
- Author
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Chang CT, Liao HY, Chang CM, Chen CY, Chen CH, Yang CY, Tsai FJ, and Chen CJ
- Subjects
- Adult, Electrophoresis, Polyacrylamide Gel, Female, Glycosylation, Humans, Male, Middle Aged, Oxidation-Reduction, Apolipoprotein C-I blood, Atherosclerosis diagnosis, Biomarkers blood, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Vascular Diseases diagnosis
- Abstract
Background: Atherosclerotic vascular disease (ASVD), including coronary artery disease, ischemic stroke, and peripheral vascular disease, is the most common cause of death both in the general population and in high-risk patients; patients with diabetes mellitus (DM), uremia (UM), primary hyperlipidemia (HP) have increased risks for developing ASVD., Methods: To identify new biomarkers for early prediction of ASVD, HDL samples from patients with disease (ASVD) and patients with increased risks but no documented ASVD (non-ASVD) were collected for Bis-Tris gradient gel and MALDI-TOF (matrix-assisted laser desorption ionization-time of flight) analyses., Results: Oxidation of ApoC1 was detected specifically in ASVD samples by MALDI-TOF. On the Bis-Tris gradient gel, non-ASVD ApoA1 was displayed into 2 distinct bands A and B. An additional C band of ApoA1 appeared exclusively in ASVD patients. The extraordinary C band of ApoA1 was characterized by high levels of glycation and oxidation. MALDI-TOF analyses of ApoA1 peptides after trypsin digestion confirmed higher levels of glycation and oxidation levels in the ASVD than non-ASVD samples., Conclusions: Gel identification of the highly-glycated and oxidized C band of ApoA1 and MALDI-TOF detection of oxidized ApoC1 in HDL may provide a new approach for early ASVD diagnosis., (Copyright © 2012. Published by Elsevier B.V.)
- Published
- 2013
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33. Agreement of cardiac output measurement between pulse contour analysis and thermodilution in various body positions: a porcine study.
- Author
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Shih PC, Hung YC, Chen YL, Tsai HJ, Chen CY, and Huang CJ
- Subjects
- Animals, Catheterization, Peripheral, Female, Linear Models, Pulmonary Artery, Pulse, Reproducibility of Results, Swine, Thermodilution, Cardiac Output, Patient Positioning methods
- Abstract
Background: We elucidated the effects of various body positions on the agreement of cardiac output (CO) measurement between pulse contour analysis with the PiCCO monitor and thermodilution with pulmonary artery catheterization., Methods: Fifteen anesthetized and mechanically ventilated pigs (40 ± 2 kg) were sequentially placed in various positions to facilitate simultaneous CO measurement. Between-methods agreement was assessed using the Bland-Altman method. Trending ability was assessed using Pearson product-moment correlation coefficient analysis., Results: In supine, reverse Trendelenburg, Trendelenburg, and left lateral decubitus (lateral) positions, CO measured by these two methods was comparable (4.9 ± 1.5 versus 4.6 ± 1.6 L/min, 4.6 ± 2.2 versus 4.8 ± 1.8 L/min, 5.1 ± 2.1 versus 4.9 ± 2.1 L/min, and 5.4 ± 1.8 versus 5.0 ± 1.6 L/min; all P > 0.05). Mean bias between methods and limits of agreement (percentage error) were 0.3 ± 2.9 L/min (61%), -0.3 ± 3.3 L/min (71%), 0.1 ± 4.1 L/min (77%), and 0.5 ± 3.7 L/min (71%). Directional changes of paired CO revealed 66% (reverse Trendelenburg), 57% (Trendelenburg), and 66% (lateral) concordance. The correlation coefficient (r(2)) was 0.199, 0.127, and 0.108. For paired CO ≤6 L/min, mean bias between methods and limits of agreement (percentage error) were 0.2 ± 1.0 L/min (25%), -0.1 ± 1.0 L/min (28%), 0.2 ± 1.1 L/min (29%), and 0.5 ± 0.9 L/min (23%). Directional changes of paired CO revealed 84% (reverse Trendelenburg), 76% (Trendelenburg), and 65% (lateral) concordance. The correlation coefficient (r2) was 0.583, 0.626, and 0.213., Conclusions: The mean CO measured by pulse contour analysis and thermodilution did not agree well in various body positions. Moreover, the measurements tended to trend differently in response to positional changes. For paired CO ≤6 L/min, however, the between-methods agreement and the trending ability improved significantly., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
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34. Quantum dot-sensitized solar cells incorporating nanomaterials.
- Author
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Yang Z, Chen CY, Roy P, and Chang HT
- Abstract
Quantum dot-sensitized solar cells (QDSSCs) are interesting energy devices because of their (i) impressive ability to harvest sunlight and generate multiple electron/hole pairs, (ii) ease of fabrication, and (iii) low cost. The power conversion efficiencies (η) of most QDSSCs (typically <4%) are, however, less than those (up to 12%) of dye-sensitized solar cells, mainly because of narrow absorption ranges and charge recombination occurring at the QD-electrolyte and TiO(2)-electrolyte interfaces. To further increase the values of η of QDSSCs, it will be necessary to develop new types of working electrodes, sensitizers, counter electrodes and electrolytes. This Feature Article describes the nanomaterials that have been used recently as electronic conductors, sensitizers and counter electrodes in QDSSCs. The nature, size, morphology and quantity of these nanomaterials all play important roles affecting the efficiencies of electron injection and light harvesting. We discuss the behavior of several important types of semiconductor nanomaterials (sensitizers, including CdS, Ag(2)S, CdSe, CdTe, CdHgTe, InAs and PbS) and nanomaterials (notably TiO(2), ZnO and carbon-based species) that have been developed to improve the electron transport efficiency of QDSSCs. We point out the preparation of new generations of nanomaterials for QDSSCs and the types of electrolytes, particularly iodide/triiodide electrolytes (I(-)/I(3)(-)), polysulfide electrolytes (S(2-)/S(x)(2-)), and cobalt redox couples ([Co(o-phen)(3)(2+)/(3+)]), that improve their lifetimes. With advances in nanotechnology, we foresee significant improvements in the efficiency (η > 6%) and durability (>3000 h) of QDSSCs., (This journal is © The Royal Society of Chemistry 2011)
- Published
- 2011
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35. Photoreactivity of carboxylated single-walled carbon nanotubes in sunlight: reactive oxygen species production in water.
- Author
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Chen CY and Jafvert CT
- Subjects
- Chlorobenzoates chemistry, Furans chemistry, Hydrogen-Ion Concentration, Singlet Oxygen chemistry, Tetrazolium Salts chemistry, Thioinosine analogs & derivatives, Thioinosine chemistry, Carboxylic Acids chemistry, Nanotubes, Carbon chemistry, Reactive Oxygen Species chemistry, Sunlight, Water chemistry
- Abstract
Very limited information exists on transformation processes of carbon nanotubes in the natural aquatic environment. Because the conjugated pi-bond structure of these materials is efficient in absorbing sunlight, photochemical transformations are a potential fate process with reactivity predicted to vary with their diameter, chirality, number and type of defects, functionalization, residual metal catalyst and amorphous carbon content, and with the composition of the water, including the type and composition of materials that act to disperse them into the aqueous environment. In this study, the photochemical reactions involving colloidal dispersions of carboxylated single-walled carbon nanotubes (SWNT-COOH) in sunlight were examined. Production of reactive oxygen species (ROS) during irradiation occurs and is evidence for potential further phototransformation and may be significant in assessing their overall environmental impacts. In aerated samples exposed to sunlight or to lamps that emit light only within the solar spectrum, the probe compounds, furfuryl alcohol (FFA), tetrazolium salts (NBT2+ and XTT), and p-chlorobenzoic acid (pCBA), were used to indicate production of 1O2, O2.-, and .OH, respectively. All three ROS were produced in the presence of SWNT-COOH and molecular oxygen (3O2). 1O2 production was confirmed by observing enhanced FFA decay in deuterium oxide, attenuated decay of FFA in the presence of azide ion, and the lack of decay of FFA in deoxygenated solutions. Photogeneration of O2.- and .OH was confirmed by applying superoxide dismutase (SOD) and tert-butanol assays, respectively. In air-equilibrated suspensions, the loss of 0.2 mM FFA in 10 mg/L SWNT-COOH was approximately 85% after 74 h. Production of 1O2 was not dependent on pH from 7 to 11; however photoinduced aggregation was observed at pH 3.
- Published
- 2010
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36. Electrocatalytic sulfur electrodes for CdS/CdSe quantum dot-sensitized solar cells.
- Author
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Yang Z, Chen CY, Liu CW, and Chang HT
- Abstract
We have fabricated highly efficient CdS/CdSe quantum dot-sensitized solar cells (QDSSCs) featuring low-cost cobalt sulfide (CoS) counter electrodes. Under 100 mW cm(-2) irradiation, the CdS/CdSe QDSSC featuring a CoS electrode provided an energy conversion efficiency as high as 3.4%.
- Published
- 2010
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37. Sorption of Buckminsterfullerene (C60) to saturated soils.
- Author
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Chen CY and Jafvert CT
- Subjects
- Adsorption, Environmental Monitoring, Fullerenes chemistry, Soil analysis, Soil Pollutants chemistry, Water chemistry
- Abstract
With the increasing use of C60 in many industrial and commercial sectors, it is likely that it will eventually appear in the environment however, its environmental fate and transport is still largely unknown. The extent to which C60 partitions to soil will contribute to its environmental fate and bioavailability. Because C60 is extremely hydrophobic, in this study the distribution between soil and mixtures of ethanol (EOH) and water were measured at ethanol mole fractions ranging from X(EOH) = 1.0-0.4 for two soils. By measuring K(p) at X(EOH) = 1.0 for a series of soils that ranged in organic carbon and clay mineral content, possible mineral contribution to the overall partition process was found for some of the soils. After correcting for any mineral contribution to sorption, the organic carbon normalized partition coefficient, K(oc), at each value of X(EDH) was calculated from the measured K(p) values. Through a classical thermodynamic relationship, the K(oc) values determined at X(EOH) = 1.0-0.4 were extrapolated to estimate the pure water (i.e., X(EOH) = 0) K(oc) value of 10(7.1) (L/kg). Accounting for any dissolved organic matter (DOM) in any pure water-soil mixtures may lower this estimate by over a factor of 2, placing this estimate in good agreement with C60's octanol-water partition coefficient, K(ow) (= 10(6.7)).
- Published
- 2009
- Full Text
- View/download PDF
38. [The intravenous medication calculation abilities in registered nurses at a teaching hospital in southern taiwan].
- Author
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Chen CY
- Subjects
- Adult, Hospitals, Teaching, Humans, Mathematics, Taiwan, Clinical Competence, Medication Errors prevention & control, Nurses
- Abstract
Medication errors, especially related to intravenous medications, can lead to the prolonged hospitalization and even patient death. Subtherapeutic dose and dose calculation errors represent the major cause of intravenous medication errors in hospitals. Many investigators have undertaken studies to evaluate the dose calculation ability of healthcare professionals. However, little is known about the dose calculation ability for intravenous medication among nurse staff and nursing students in Taiwan. Goals of this study were to evaluate the intravenous medication calculation ability of registered nurses and nursing students and determine the relationship between dose calculation ability and various nurse demographic characteristics. The study was approved by the institutional research ethics committee. A convenience sample of 185 nurse staff and 70 nursing students were recruited from a teaching hospital in southern Taiwan. A self-developed questionnaire containing demographic information and a sixteen item dose calculation examination (CVI = 80% approximately 100%, test-retest reliability alpha = .808) were used. Descriptive Statistics, Chi-Square test, Spearman correlation, Mann-Whitney U test, and Kruskal-Wallis test were analyzed using SPSS Windows 13.0. Findings showed an overall mean score of dose calculation ability for intravenous medication of 11.77 +/- 3.20 among nurses and 3.90 +/- 2.94 among nursing students. The dose calculation ability of nurses was higher than that of nursing students, and the dose calculation ability of the nurses was positively associated with working years and clinical ladders. Findings are discussed in terms of implications of continuous quality improvement as well as continue education for hospital managers and nursing educators.
- Published
- 2009
39. [Promoting the use of the nasopharyngeal airway to treat watery diarrhea].
- Author
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Chuang WL, Chiang HY, Chen CY, Wang SM, and Ma SC
- Subjects
- Humans, Nasopharynx, Diarrhea nursing, Drainage methods
- Abstract
Using the nasopharyngeal airway to promote stool drainage is currently limited in general clinical practice. This situation has led to periannal skin care administered by nursing staff not meeting patient expectations for treatment efficacy and speed of recovery. According to previous statistics, the incidence of perianal excoriation was 60.71% in critically ill patients with liquid stool. This project was designed to promote more widespread use of the nasopharyngeal airway to contain watery diarrhea and improve skin lesions. Reasons for not using the nasopharyngeal airway to promote stool drainage identified by the authors included: 1. unclear nursing standards with regard to such procedures; 2. physician resistance to the use of such and 3. lack of education programs related to such procedures. Improvement strategies included: 1. modifying nursing standards with detailed explanations and pictures; 2. earning physician acceptance of such procedures through case conference meetings in ICUs; 3. rescheduling education programs on the implementation of nasopharyngeal airway and skin care for patients with watery diarrhea and 4. establishing case management and nursing consultation systems. Results showed that use of the nasopharyngeal airway increased from an initial 60% to 100% at eight months following project implementation. The perianal excoriation rate fell from 60.71% to 0%. We found that drainage of liquid stool using the nasopharyngeal airway can reduce perianal skin complications. This project may be a valuable reference for other clinical practice to improve care quality.
- Published
- 2009
40. Magnesium sulfate diminishes the effects of amide local anesthetics in rat sciatic-nerve block.
- Author
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Hung YC, Chen CY, Lirk P, Wang CF, Cheng JK, Chen CC, Wang GK, and Gerner P
- Subjects
- Amides, Anesthetics, Local administration & dosage, Animals, Bupivacaine, Dose-Response Relationship, Drug, Lidocaine, Magnesium Sulfate administration & dosage, Motor Activity drug effects, Nerve Block methods, Pain Measurement drug effects, Proprioception drug effects, Rats, Rats, Sprague-Dawley, Ropivacaine, Sciatic Nerve drug effects, Anesthetics, Local pharmacology, Magnesium Sulfate pharmacology, Sciatic Nerve metabolism, Sodium Channels drug effects
- Abstract
Background and Objectives: Magnesium sulfate (MgSO(4)) is well known as an antagonist of N-methyl-d-aspartate receptors and was used for intrathecal analgesia a century ago. However, the effects of MgSO(4) combined with local anesthetics (LAs) on peripheral nerves are unclear. We tested the hypothesis that MgSO(4) could be used as an adjuvant to prolong and intensify conduction block by amide-type LAs in a rat sciatic-nerve block model. Further, the mechanism of possible synergy between LAs and MgSO(4) was investigated in whole-cell mode patch-clamp experiments., Methods: Sciatic nerves were exposed to 2%/73.9 mM lidocaine, 0.25%/7.7 mM bupivacaine, and 0.5%/15.4 mM ropivacaine, with or without addition of 1.25%, 2.5%, or 5% MgSO(4)/50.7 mM, and nerve block characteristics were assessed. To elucidate the LA-MgSO(4) interaction, voltage-dependent inactivation curves were determined in cultured rat GH(3) cells that expressed neuronal Na(+) channels., Results: Unexpectedly, the addition of MgSO(4) overall significantly shortened the duration of block by lidocaine, bupivacaine, and ropivacaine. The steady-state inactivation of Na(+) channels in the presence of 300 muM lidocaine was almost unchanged by the addition of 10 mM MgSO(4), indicating that MgSO(4) does not affect the potency of lidocaine toward the inactivated Na(+) channel., Conclusions: MgSO(4) coadministered with amide-type LAs shortened the duration of sciatic-nerve block in rats. Therefore, it does not seem to be useful as an adjuvant for peripheral-nerve block. The mechanism of this observed antagonism is unclear but appears to be independent of the action of LAs and MgSO(4) at the LA receptor within the Na(+) channel.
- Published
- 2007
- Full Text
- View/download PDF
41. Reliability and validity of a chinese version of the pediatric asthma symptoms scale.
- Author
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Chen CY and Lo LH
- Subjects
- Adolescent, Child, Child, Preschool, China ethnology, Female, Humans, Infant, Male, Taiwan, Asthma physiopathology
- Abstract
As a construct, asthmatic severity provides a framework to understand the different reaction in children to their condition. Assessing asthmatic severity is a challenging task for most researchers and clinicians due to a lack of valid instruments to measure the severity of asthma of children in home settings. The purpose of this study was to examine the psychometric properties of a Chinese version of the Pediatric Asthma Symptoms Scale (C-PASS) as applied to an ethnic Chinese population in Taiwan. Firstly, five pediatric nurses holding masters' degrees assessed consistency between Chinese and English versions of the Pediatric Asthma Symptoms Scale. Secondly, internal consistent reliability, split-half reliability, content validity, criterion-related validity, and construct validity were established. An 8-item C-PASS was completed by mothers of 70 children (65.7% boys) of ages 8.35 years. Both the internal consistency and Guttman split-half reliability were .87. The content validity index (CVI) was over .80. The correlation coefficient between C-PASS and concurrent measures of the rating of lost control of life by mothers was .273 (p = .022). The criterion-related validity was supported for C-PASS. Factor analysis indicated that a scale of two dimensions accounted for 67.92% of the variance. A high inter-correlation was further identified between these two dimensions. Results showed C-PASS to be a reliable and valid instrument when used on Taiwanese children with asthma. It can serve as a valuable assessment tool in clinical practice to identify asthmatic severity levels for which intervention is advised.
- Published
- 2007
- Full Text
- View/download PDF
42. Lipopolysaccharide increases resistin gene expression in vivo and in vitro.
- Author
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Lu SC, Shieh WY, Chen CY, Hsu SC, and Chen HL
- Subjects
- 3T3 Cells, Animals, Base Sequence, DNA Primers, Hypoglycemic Agents pharmacology, Male, Mice, Nerve Growth Factor, RNA, Messenger genetics, Rats, Rats, Wistar, Resistin, Rosiglitazone, Thiazoles pharmacology, Gene Expression Regulation drug effects, Hormones, Ectopic genetics, Intercellular Signaling Peptides and Proteins, Lipopolysaccharides pharmacology, Proteins, Thiazolidinediones
- Abstract
Although resistin has been thought to be an important link between obesity and diabetes, recent results do not support this hypothesis. We speculated that resistin may be involved in inflammatory processes and be induced by inflammatory stimuli. In this study, we tested whether lipopolysaccharide (LPS) induced resistin expression in rats. The results show that resistin mRNA levels in white adipose tissue and white blood cells were increased by LPS treatment. LPS also increased resistin mRNA levels in 3T3-L1 adipocytes and human peripheral blood monocytes. The results suggest that resistin is involved in insulin resistance and probably in other inflammatory responses.
- Published
- 2002
- Full Text
- View/download PDF
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