179 results on '"Yueh Chien"'
Search Results
2. Molecular target therapeutics of EGF-TKI and downstream signaling pathways in non-small cell lung cancers
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Chao-Yu, Liu, Heng-Fu, Lin, Wei-Yi, Lai, Yi-Ying, Lin, Tzu-Wei, Lin, Yi-Ping, Yang, Fu-Ting, Tsai, Chia-Lin, Wang, Yung-Hung, Luo, Yuh-Min, Chen, Po-Kuei, Hsu, Jit Kai, Loh, Alan Han-Kiat, Ong, Yueh, Chien, Shih-Hwa, Chiou, and Chien-Ying, Wang
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Phosphatidylinositol 3-Kinases ,Lung Neoplasms ,Epidermal Growth Factor ,Drug Resistance, Neoplasm ,Carcinoma, Non-Small-Cell Lung ,Mutation ,Humans ,General Medicine ,Protein Kinase Inhibitors ,Signal Transduction - Abstract
Lung carcinoma (LC) is the third most common cancer diagnosis and accounted for the most cancer-related mortality worldwide in 2018. Based on the type of cells from which it originates, LC is commonly classified into non-small cell lung cancers (NSCLC) and small cell lung cancers (SCLC). NSCLC account for the majority of LC and can be further categories into adenocarcinoma, large cell carcinoma, and squamous cell carcinoma. Accurate classification of LC is critical for its adequate treatment and therapeutic outcome. Since NSCLC express more epidermal growth factor receptor (EGFR) with activation mutations, targeted therapy EGFR-tyrosine kinase inhibitors (TKIs) have been considered as primary option of NSCLC patients with activation EGFR mutation. In this review, we present the genetic alterations, reported mutations in EGFR, and TKIs treatment in NSCLC patients with an emphasis on the downstream signaling pathways in NSCLC progression. Among the signaling pathways identified, mitogen activation protein kinase (MAPK), known also as extracellular signal-regulated protein kinase (Erk) pathway, is the most investigated among the related pathways. EGFR activation leads to the autophosphorylation of its kinase domain and subsequent activation of Ras, phosphorylation of Raf and MEK1/2, and the activation of ERK1/2. Phosphatidylinositol 3-kinase (PI3K)/Akt is another signal pathway that regulates cell cycle and has been linked to NSCLC progression. Currently, three generations of EGFR TKIs have been developed as a first-line treatment of NSCLC patients with EGFR activation and mutation in which these treatment options will be further discussed in this review. The Supplementary Appendix for this article is available at http://links.lww.com/JCMA/A138.
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- 2022
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3. Oncogenic circRNA C190 Promotes Non–Small Cell Lung Cancer via Modulation of the EGFR/ERK Pathway
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Yuh Min Chen, Jerry Chieh-Yu Chen, Chian Shiu Chien, Yueh Chien, Teh Ia Huo, Afeez Adekunle Ishola, Shih Hwa Chiou, Po-Kuei Hsu, Aliaksandr A. Yarmishyn, Mong Lien Wang, Ping-Hsing Tsai, Ming-Teh Chen, Yuan-Tzu Lan, Yung-Hung Luo, Yi-Ping Yang, Hsin-I Ma, and Kung-Hao Liang
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Male ,MAPK/ERK pathway ,Cancer Research ,Lung Neoplasms ,Cell ,Mice, Nude ,Mice ,Cyclin-dependent kinase ,Carcinoma, Non-Small-Cell Lung ,medicine ,Animals ,Humans ,Gene knockdown ,Cyclin-dependent kinase 1 ,biology ,Chemistry ,Kinase ,Oncogenes ,RNA, Circular ,Cell cycle ,ErbB Receptors ,Disease Models, Animal ,medicine.anatomical_structure ,Oncology ,Cancer research ,biology.protein ,Cyclin-dependent kinase 6 - Abstract
Lung cancers are the leading cause of cancer-related mortality worldwide, and the majority of lung cancers are non–small cell lung carcinoma (NSCLC). Overexpressed or activated EGFR has been associated with a poor prognosis in NSCLC. We previously identified a circular noncoding RNA, hsa_circ_0000190 (C190), as a negative prognostic biomarker of lung cancer. Here, we attempted to dissect the mechanistic function of C190 and test the potential of C190 as a therapeutic target in NSCLC. C190 was upregulated in both NSCLC clinical samples and cell lines. Activation of the EGFR pathway increased C190 expression through a MAPK/ERK-dependent mechanism. Transient and stable overexpression of C190 induced ERK1/2 phosphorylation, proliferation, and migration in vitro and xenograft tumor growth in vivo. RNA sequencing and Expression2Kinases (X2K) analysis indicated that kinases associated with cell-cycle and global translation are involved in C190-activated networks, including CDKs and p70S6K, which were further validated by immunoblotting. CRISPR/Cas13a-mediated knockdown of C190 decreased proliferation and migration of NSCLC cells in vitro and suppressed tumor growth in vivo. TargetScan and CircInteractome databases predicted that C190 targets CDKs by sponging miR-142-5p. Analysis of clinical lung cancer samples showed that C190, CDK1, and CDK6 expressions were significantly higher in advanced-stage lung cancer than in early-stage lung cancer. In summary, C190 is directly involved in EGFR–MAPK–ERK signaling and may serve as a potential therapeutic target for the treatment of NSCLC. Significance: The circRNA C190 is identified as a mediator of multiple pro-oncogenic signaling pathways in lung cancer and can be targeted to suppress tumor progression.
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- 2022
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4. Data from Oncogenic circRNA C190 Promotes Non–Small Cell Lung Cancer via Modulation of the EGFR/ERK Pathway
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Shih-Hwa Chiou, Mong-Lien Wang, Ming-Teh Chen, Hsin-I. Ma, Teh-Ia Huo, Yuan-Tzu Lan, Kung-Hou Liang, Yuh-Min Chen, Yung-Hung Luo, Po-Kuei Hsu, Jerry Chieh-Yu Chen, Ping-Hsing Tsai, Aliaksandr A. Yarmishyn, Yueh Chien, Yi-Ping Yang, Chian-Shiu Chien, and Afeez Adekunle Ishola
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Lung cancers are the leading cause of cancer-related mortality worldwide, and the majority of lung cancers are non–small cell lung carcinoma (NSCLC). Overexpressed or activated EGFR has been associated with a poor prognosis in NSCLC. We previously identified a circular noncoding RNA, hsa_circ_0000190 (C190), as a negative prognostic biomarker of lung cancer. Here, we attempted to dissect the mechanistic function of C190 and test the potential of C190 as a therapeutic target in NSCLC. C190 was upregulated in both NSCLC clinical samples and cell lines. Activation of the EGFR pathway increased C190 expression through a MAPK/ERK-dependent mechanism. Transient and stable overexpression of C190 induced ERK1/2 phosphorylation, proliferation, and migration in vitro and xenograft tumor growth in vivo. RNA sequencing and Expression2Kinases (X2K) analysis indicated that kinases associated with cell-cycle and global translation are involved in C190-activated networks, including CDKs and p70S6K, which were further validated by immunoblotting. CRISPR/Cas13a-mediated knockdown of C190 decreased proliferation and migration of NSCLC cells in vitro and suppressed tumor growth in vivo. TargetScan and CircInteractome databases predicted that C190 targets CDKs by sponging miR-142-5p. Analysis of clinical lung cancer samples showed that C190, CDK1, and CDK6 expressions were significantly higher in advanced-stage lung cancer than in early-stage lung cancer. In summary, C190 is directly involved in EGFR–MAPK–ERK signaling and may serve as a potential therapeutic target for the treatment of NSCLC.Significance:The circRNA C190 is identified as a mediator of multiple pro-oncogenic signaling pathways in lung cancer and can be targeted to suppress tumor progression.
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- 2023
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5. Supplementary Data from Oncogenic circRNA C190 Promotes Non–Small Cell Lung Cancer via Modulation of the EGFR/ERK Pathway
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Shih-Hwa Chiou, Mong-Lien Wang, Ming-Teh Chen, Hsin-I. Ma, Teh-Ia Huo, Yuan-Tzu Lan, Kung-Hou Liang, Yuh-Min Chen, Yung-Hung Luo, Po-Kuei Hsu, Jerry Chieh-Yu Chen, Ping-Hsing Tsai, Aliaksandr A. Yarmishyn, Yueh Chien, Yi-Ping Yang, Chian-Shiu Chien, and Afeez Adekunle Ishola
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List of differentially expressed genes from RNA-seq
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- 2023
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6. Supplementary Information from Oncogenic circRNA C190 Promotes Non–Small Cell Lung Cancer via Modulation of the EGFR/ERK Pathway
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Shih-Hwa Chiou, Mong-Lien Wang, Ming-Teh Chen, Hsin-I. Ma, Teh-Ia Huo, Yuan-Tzu Lan, Kung-Hou Liang, Yuh-Min Chen, Yung-Hung Luo, Po-Kuei Hsu, Jerry Chieh-Yu Chen, Ping-Hsing Tsai, Aliaksandr A. Yarmishyn, Yueh Chien, Yi-Ping Yang, Chian-Shiu Chien, and Afeez Adekunle Ishola
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Supplementary materials and methods, supplementary tables, and supplementary figures to support the main manuscript
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- 2023
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7. Characterization of Androgen Receptor Complex Associated Protein (ARCAP) in hepatocellular carcinoma and liver
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Cheng-Yuan Hsia, Anna F.Y. Li, Liang-Tsai Hsiao, Wing-Yiu Lui, Tai-Jay Chang, Kuang-Tzu Huang, Gar-Yang Chau, Chia-Lin Wang, Pin-Hsing Tsaia, Yueh Chien, Kung-Liang King, and Ta-Hsien Lin
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Male ,Hepatitis B virus ,Cell signaling ,Carcinoma, Hepatocellular ,business.industry ,Liver Neoplasms ,General Medicine ,Transfection ,In situ hybridization ,medicine.disease ,Androgen receptor ,Mice ,Transactivation ,Liver ,Receptors, Androgen ,Hepatocellular carcinoma ,Cancer research ,medicine ,Animals ,Receptor ,business ,Gene - Abstract
Background Hepatocellular carcinoma (HCC) ranks many tasks in clinical oncology due to possibly develop general tumor in men and, usually lead to malignant to death within years. Researches had reported about major factors for being HCC was male sex and HCC associated with cirrhosis in childhood was found more common in males than females. In certain mouse strains as studied, breeding with testosterone significantly increases the development of HCC. Furthermore, castration of male mice diminished the frequency of the development of liver tumors. Meanwhile Male hepatitis B virus transgenic mice have greater occurrence of HCC than females. Methods We apply degenerate priming PCR to observe the expression of various steroid receptors in livers. Yeast-two hybrid screening to search a novel RNA fragment helps to find a new full-length gene by RACE experiment. RT-PCR is applied to detect various of expression in tissues and cell lines. In situ hybridization detects DNA in Chromosome mapping. GFP-constructs transfection proves the gene localization in cells. Immunoprecipitation pulldown assay verifies protein interaction. Gene transfection followed with luciferase assay demonstrates interaction of genes within cellular signaling. Genomic alignment analysis for observing sequences data perform from NCBI database website (http://www.ncbi.nim.nih.gov/genebank/). Results The androgen receptor (AR) expression level is found at the highest level among the steroid receptors families detected in liver tumors. By yeast-two hybrid screening, we cloned an ARCAP (Androgen Receptor Complex Associated Protein), of 95 Kd in molecular weight and its cDNA. ARCAP locates at Chromosome 1. Our findings indicate ARCAP highly expresses in hepatoma cell lines and liver tumors and their adjacent tumors as observed. Yeast two-hybrid assay and in vitro immunoprecipitation assays demonstrated an interaction between AR and ARCAP. Conclusion Our aim is to search for different types and levels of steroid receptors expressed within human hepatocellular carcinomas and in the adjacent liver tissues. To verify possible molecular mechanisms by which AR might affect hepatoma cells, we had characterized a novel protein ARCAP which functions as a coregulator to interact with AR within liver. The ligand-dependent AR with its cofactor, ARCAP, can induce a signal cascade by transactivation.
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- 2021
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8. Nanoparticles-mediated CRISPR-Cas9 gene therapy in inherited retinal diseases: applications, challenges, and emerging opportunities
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Yueh, Chien, Yu-Jer, Hsiao, Shih-Jie, Chou, Ting-Yi, Lin, Aliaksandr A, Yarmishyn, Wei-Yi, Lai, Meng-Shiue, Lee, Yi-Ying, Lin, Tzu-Wei, Lin, De-Kuang, Hwang, Tai-Chi, Lin, Shih-Hwa, Chiou, Shih-Jen, Chen, and Yi-Ping, Yang
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Retinal Diseases ,Biomedical Engineering ,Humans ,Nanoparticles ,Pharmaceutical Science ,Molecular Medicine ,Medicine (miscellaneous) ,Bioengineering ,Prospective Studies ,Genetic Therapy ,CRISPR-Cas Systems ,Applied Microbiology and Biotechnology ,Retina - Abstract
Inherited Retinal Diseases (IRDs) are considered one of the leading causes of blindness worldwide. However, the majority of them still lack a safe and effective treatment due to their complexity and genetic heterogeneity. Recently, gene therapy is gaining importance as an efficient strategy to address IRDs which were previously considered incurable. The development of the clustered regularly-interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system has strongly empowered the field of gene therapy. However, successful gene modifications rely on the efficient delivery of CRISPR-Cas9 components into the complex three-dimensional (3D) architecture of the human retinal tissue. Intriguing findings in the field of nanoparticles (NPs) meet all the criteria required for CRISPR-Cas9 delivery and have made a great contribution toward its therapeutic applications. In addition, exploiting induced pluripotent stem cell (iPSC) technology and in vitro 3D retinal organoids paved the way for prospective clinical trials of the CRISPR-Cas9 system in treating IRDs. This review highlights important advances in NP-based gene therapy, the CRISPR-Cas9 system, and iPSC-derived retinal organoids with a focus on IRDs. Collectively, these studies establish a multidisciplinary approach by integrating nanomedicine and stem cell technologies and demonstrate the utility of retina organoids in developing effective therapies for IRDs.
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- 2022
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9. Pluripotent Stem Cells in Clinical Cell Transplantation: Focusing on Induced Pluripotent Stem Cell-Derived RPE Cell Therapy in Age-Related Macular Degeneration
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Yi-Ping Yang, Yu-Jer Hsiao, Kao-Jung Chang, Shania Foustine, Yu-Ling Ko, Yi-Ching Tsai, Hsiao-Yun Tai, Yu-Chieh Ko, Shih-Hwa Chiou, Tai-Chi Lin, Shih-Jen Chen, Yueh Chien, and De-Kuang Hwang
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Cell Transplantation ,Organic Chemistry ,Induced Pluripotent Stem Cells ,Cell- and Tissue-Based Therapy ,General Medicine ,Retinal Pigment Epithelium ,Catalysis ,Computer Science Applications ,Inorganic Chemistry ,Macular Degeneration ,Retinal Diseases ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy - Abstract
Human pluripotent stem cells (PSCs), including both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), represent valuable cell sources to replace diseased or injured tissues in regenerative medicine. iPSCs exhibit the potential for indefinite self-renewal and differentiation into various cell types and can be reprogrammed from somatic tissue that can be easily obtained, paving the way for cell therapy, regenerative medicine, and personalized medicine. Cell therapies using various iPSC-derived cell types are now evolving rapidly for the treatment of clinical diseases, including Parkinson’s disease, hematological diseases, cardiomyopathy, osteoarthritis, and retinal diseases. Since the first interventional clinical trial with autologous iPSC-derived retinal pigment epithelial cells (RPEs) for the treatment of age-related macular degeneration (AMD) was accomplished in Japan, several preclinical trials using iPSC suspensions or monolayers have been launched, or are ongoing or completed. The evolution and generation of human leukocyte antigen (HLA)-universal iPSCs may facilitate the clinical application of iPSC-based therapies. Thus, iPSCs hold great promise in the treatment of multiple retinal diseases. The efficacy and adverse effects of iPSC-based retinal therapies should be carefully assessed in ongoing and further clinical trials.
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- 2022
10. Treatment of hyperprolactinemia: A single-institute experience
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Chiung-Chyi Shen, Yin-Ping Yang, Chung-Hsin Lee, Wen-Yu Cheng, Tse-Yu Chen, Chih-Ming Lai, Yu-Fen Huang, Meng-Yin Yang, and Yueh Chien
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Adult ,Male ,Transsphenoidal surgery ,medicine.medical_specialty ,Cabergoline ,Adenoma ,business.industry ,medicine.medical_treatment ,Urology ,General Medicine ,Middle Aged ,medicine.disease ,Bromocriptine ,Hyperprolactinemia ,Serum prolactin ,Tolerability ,Dopamine Agonists ,medicine ,Humans ,Effective treatment ,Female ,business ,Prolactinoma ,medicine.drug - Abstract
Background Dopamine agonists such as bromocriptine and cabergoline have been found to be an effective treatment for hyperprolactinemia, not only inducing adenoma shrinkage but also lowering serum prolactin levels. Among known dopamine agonists, cabergoline is the drug of choice due to its enhanced tolerability compared with bromocriptine. This study aimed to evaluate cabergoline's effectiveness, along with transsphenoidal surgery, in the treatment of hyperprolactinemia. Methods We retrieved all patients with a diagnosis of prolactinoma who were treated in our hospital during 2000-2018. A total of 208 patients were enrolled in the analysis after applying exclusion criteria. Patients were divided into four groups according to the treatments received. The demographic data, dosage and duration of cabergoline, and serum prolactin levels at different time points were collected for analysis. Results Normalization was achieved in 59 patients (83.10%) within a short median duration of 2.80 months among those treated with cabergoline only. Although cabergoline alone was effective and well-tolerated, our data showed that long-term remission rates were more favorable when surgery was involved. The long-term remission rate of all patients enrolled was 53.8% (112 patients among 208 patients). The long-term remission rates for the different treatment groups were 17.8% (8 of 45 patients) in Group 1 (Operation→Drug), 83.3% (5 of 6 patients) in Group 2 (Drug→Operation), 79.0% (68 of 86 patients) in Group 3 (Operation only), and 43.7% (31 of 71 patients) in Group 4 (Drug only). Conclusion Cabergoline has been demonstrated to be effective and should be considered as a first-line treatment for hyperprolactinemia. In our study, transsphenoidal surgery was also demonstrated to achieve good results compared with medical treatment. Surgical intervention may resurface as an alternative first-line treatment. When used in combination with cabergoline, surgery offers a higher disease remission rate than either drug or operation alone.
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- 2021
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11. Overview of the molecular mechanisms of migration and invasion in glioblastoma multiforme
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Ming Teh Chen, Liang Ting Lin, Yi Ping Yang, Yueh Chien, Ju Yu Chen, and Xian Liu
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Brain Neoplasms ,business.industry ,General Medicine ,030204 cardiovascular system & hematology ,Phenotype ,Extracellular matrix ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Transforming Growth Factor beta ,RNA interference ,030220 oncology & carcinogenesis ,microRNA ,Cancer research ,Humans ,Medicine ,Neoplasm Invasiveness ,Epithelial–mesenchymal transition ,Signal transduction ,Stem cell ,Glioblastoma ,business ,Protein kinase B ,Signal Transduction - Abstract
Glioblastoma (GBM) is one of the most devastating cancers, with an approximate median survival of only 16 months. Although some new insights into the fantastic heterogeneity of this kind of brain tumor have been revealed in recent studies, all subclasses of GBM still demonstrate highly aggressive invasion properties to the surrounding parenchyma. This behavior has become the main obstruction to current curative therapies as invasive GBM cells migrate away from these foci after surgical therapies. Therefore, this review aimed to provide a relatively comprehensive study of GBM invasion mechanisms, which contains an intricate network of interactions and signaling pathways with the extracellular matrix (ECM). Among these related molecules, TGF-β, the ECM, Akt, and microRNAs are most significant in terms of cellular procedures related to GBM motility and invasion. Moreover, we also review data indicating that Musashi-1 (MSI1), a neural RNA-binding protein (RBP), regulates GBM motility and invasion, maintains stem cell populations in GBM, and promotes drug-resistant GBM phenotypes by stimulating necessary oncogenic signaling pathways through binding and regulating mRNA stability. Importantly, these necessary oncogenic signaling pathways have a close connection with TGF-β, ECM, and Akt. Thus, it appears promising to find MSI-specific inhibitors or RNA interference-based treatments to prevent the actions of these molecules despite using RBPs, which are known as hard therapeutic targets. In summary, this review aims to provide a better understanding of these signaling pathways to help in developing novel therapeutic approaches with better outcomes in preclinical studies.
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- 2021
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12. A BERT-based Language Modeling Framework
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Chin-Yueh Chien and Kuan-Yu Chen
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- 2022
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13. Pandemic analysis of infection and death correlated with genomic open reading frame 10 mutation in severe acute respiratory syndrome coronavirus 2 victims
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Pin-Hsing Tsai, De Ming Yang, Yueh Chien, Mong Lien Wang, Fan-Chi Lin, Tai-Jay Chang, and Yi-Ping Yang
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Mutation rate ,biology ,SARS-CoV-2 ,business.industry ,Mortality rate ,COVID-19 ,RNA virus ,General Medicine ,030204 cardiovascular system & hematology ,biology.organism_classification ,Genome ,Virology ,Open Reading Frames ,03 medical and health sciences ,Open reading frame ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Mutation ,Pandemic ,Mutation (genetic algorithm) ,Mutation testing ,Humans ,Medicine ,business - Abstract
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues the pandemic spread of the coronavirus disease 2019 (COVID-19), over 60 million people confirmed infected and at least 1.8 million dead. One of the most known features of this RNA virus is its easiness to be mutated. In late 2020, almost no region of this SARS-CoV-2 genome can be found completely conserved within the original Wuhan coronavirus. Any information of the SARS-CoV-2 variants emerged through as time being will be evaluated for diagnosis, treatment, and prevention of COVID-19. METHODS: We extracted more than two million data of SARS-CoV-2 infected patients from the open COVID-19 dashboard. The sequences of the 38-amino acid putative open reading frame 10 (Orf10) protein within infected patients were gathered output through from National Center for Biotechnology Information and the mutation rates in each position were analyzed and presented in each month of 2020. The mutation rates of A8 and V30 within Orf10 are displayed in selected counties: United States, India, German, and Japan. RESULTS: The numbers of COVID-19 patients are correlated to the death numbers, but not with the death rates (stable and
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- 2021
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14. 0484 The association between obstructive sleep apnea, energy balance and body composition: a clinical cohort
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Pei-Lin Lee, Shang-Ru Lai, Joshua Gooley, Hsin-Chun Feng, Shih-Kuo Chen, Meng-Yueh Chien, Ming-Tzer Lin, Yung-Hsuan Chen, Hung-Chih Chiu, Po-Kang Liu, Bo-Wen Ku, Chin-Hao Chang, Wei-Shiung Yang, and Chong-Jen Yu
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Physiology (medical) ,Neurology (clinical) - Abstract
Introduction A couple of studies investigated the energy balance in patients with obstructive sleep apnea (OSA) but the results were inconclusive. Moreover, OSA have been associated with visceral adiposity but the mechanism has not been fully elucidated. We hypothesized that OSA was associated with lower basal metabolic rate (BMR) and increased nutrition intake which further attributed to body adiposity. The aim of the present study is to determine the association between OSA, and BMR, nutrition intake, and body composition (BC). Methods Patients were recruited from referrals to sleep lab for suspect OSA. Measurement of the BMR with indirect calorimetry and BC with bioelectrical impedance analysis, and blood sampling were conducted in the morning next to the overnight polysomnography. Afterward, participants were evaluated with short -form IPAQ, 3-day intake dietary, 7-day sleep log, and wore Actiwatch for 7 days. The outcomes are resting energy expenditure (REE) and respiratory quotien (RQ), total fat mass (TFM), fat free mass (FFM), nutrition intake, daily total activity count, nightly sleep hour, and hormone. The association between OSA □apnea hypopnea index (AHI) >=15/h□ and REE, RQ, TFM, and FFM was analyzed with multivariable linear regression. Results 85 patients were enrolled with median age 41.7 y/o, 78.6% male, body mass index (BMI) 25.4 kg/m2, and AHI 28.8/h. Compared to no OSA, patients with OSA had higher BMI, RQ, TFM, activity count, and similar age, gender, REE, FFM, nutrition intake, sleep hour, cortisol, leptin, and Ghrelin. OSA was independently associated with RQ (coefficient 0.031; 95% CI 0.004-0.057, p=0.022) with adjustment of age, gender, BMI, and activity count but not associated with REE, TFM, and FFM. Conclusion Though OSA may be associated with metabolic dysregulation, it was not associated with energy balance and BC. Further validation of the findings in a large scale and multi-ethnicity cohort to validate the findings of the present study is warranted. Support (if any) National Science and Technology Council, Taiwan (NST 111-2314-B-002-293; MOST 109-2314-B-002-252); Ministry of Education (NTU-107L900502, 108L900502, 109L900502)”, National Taiwan University Hospital (NTHU 108-S4331, 109-42, 111-S0298, 111-X0033); MediaTek Inc. (201802034 RIPD), and LARGAN Health AI-Tec CO., Ltd (202003021 RIPB)
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- 2023
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15. LBODP033 The Compliant Patient - When Adherence Hurts
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Zhen Fung Cheah and Yueh Chien Kuan
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Endocrinology, Diabetes and Metabolism - Abstract
Metformin is a biguanide oral antidiabetic agent which lowers blood glucose by decreasing hepatic gluconeogenesis. In the absence of contraindications, it is the initial treatment in most patients with type 2 diabetes along with lifestyle modifications. This drug however is commonly associated with gastrointestinal side effects especially diarrhoea which could be potentially life-threatening if prolonged. We report a case of chronic severe painless diarrhoea with weight loss over 8 months in a 40-year-old man after starting metformin for his newly diagnosed type 2 diabetes. Although the diarrhoea resolved when the patient temporarily stopped taking metformin, he decided to resume the medication to ensure his blood glucose is optimally controlled. He suspected metformin to be the cause of his diarrhoea but did not report this to his doctor during follow-up. The patient was later admitted for hypovolemic shock and severe metabolic acidosis with acute kidney injury when his diarrhoea worsened with acute gastroenteritis. He required mechanical ventilation, inotropic support and Continuous Renal Replacement Therapy in the ICU. This was further complicated by left eye ischemic optic neuropathy attributed to the acute volume loss as radiological investigations were unremarkable. Multiple laboratory and radiological investigations were done to look for the cause of the diarrhoea with no underlying pathology found. Metformin was discontinued upon admission and his diarrhoea subsequently resolved 8 days later. Upon follow-up a month later, the patient continued to be diarrhoea free without metformin. This case highlights the importance of patient education on the side effects of a medication like metformin upon commencement of the drug and to encourage the patient to notify their healthcare provider timely if they experience those side effects. This not only empowers patients to participate in their own healthcare but would avoid severe drug-related adverse events that can result in unwanted long-term sequelae. Presentation: No date and time listed
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- 2022
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16. Autophagy reprogramming stem cell pluripotency and multiple-lineage differentiation
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Yi-Ping Yang, Wei-Yi Lai, Tzu-Wei Lin, Yi-Ying Lin, Yueh Chien, Yi-Ching Tsai, Hsiao-Yun Tai, Chia-Lin Wang, Yung-Yang Liu, Pin-I Huang, Yi-Wei Chen, Wen-Liang Lo, and Chien-Ying Wang
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Osteogenesis ,Stem Cells ,Autophagy ,Cell Differentiation ,Mesenchymal Stem Cells ,General Medicine - Abstract
The cellular process responsible for the degradation of cytosolic proteins and subcellular organelles in lysosomes was termed "autophagy." This process occurs at a basal level in most tissues as part of tissue homeostasis that redounds to the regular turnover of components inside cytoplasm. The breakthrough in the autophagy field is the identification of key players in the autophagy pathway, compounded under the name "autophagy-related genes" (ATG) encoding for autophagy effector proteins. Generally, the function of autophagy can be classified into two divisions: intracellular clearance of defective macromolecules and organelles and generation of degradation products. Therapeutic strategies using stem cell-based approach come as a promising therapy and develop rapidly recently as stem cells have high self-renewability and differentiation capability as known as mesenchymal stem cells (MSCs). They are defined as adherent fibroblast-like population with the abilities to self-renew and multi-lineage differentiate into osteogenic, adipogenic, and chondrogenic lineage cells. To date, they are the most extensively applied adult stem cells in clinical trials. The properties of MSCs, such as immunomodulation, neuroprotection, and tissue repair pertaining to cell differentiation, processes to replace lost, or damaged cells, for aiding cell repair and revival. Autophagy has been viewed as a remarkable mechanism for maintaining homeostasis, ensuring the adequate function and survival of long-lived stem cells. In addition, authophagy also plays a remarkable role in protecting stem cells against cellular stress when the stem cell regenerative capacity is harmed in aging and cellular degeneration. Understanding the under-explored mechanisms of MSC actions and expanding the spectrum of their clinical applications may improve the utility of the MSC-based therapeutic approach in the future.
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- 2022
17. Nanodiamond-based microRNA delivery system promotes pluripotent stem cells toward myocardiogenic reprogramming
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Meng Yin Yang, Wei Yi Lai, Yong Yang Liu, Wen Liang Lo, Yuan Tzu Lan, Yueh Chien, Teh Ia Huo, Yi Ying Lin, Pin I. Huang, Ming Cheng Lee, Chao Yu Liu, Heng Fu Lin, and Yi Wei Chen
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Pluripotent Stem Cells ,Heart Diseases ,business.industry ,Genetic enhancement ,Genetic Therapy ,General Medicine ,030204 cardiovascular system & hematology ,Gene delivery ,Real-Time Polymerase Chain Reaction ,MyoD ,Regenerative medicine ,Nanodiamonds ,Cell biology ,MicroRNAs ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,microRNA ,Humans ,Medicine ,Myocytes, Cardiac ,Stem cell ,Induced pluripotent stem cell ,business ,Reprogramming - Abstract
Background Gene therapy is the advanced therapeutics for supplying or replacing the genetic material in patients with inherited disorders. Recent clinical studies have made some progress in a wide range of applications, including monogenic disorders, neurodegenerative diseases, malignant tumors, and congenital diseases. Heart diseases, especially myocardial ischemia, remain one of the leading causes of mortality worldwide and usually result in irreparable cardiomyocyte damage and severe heart failure. Methods Most advances in induced pluripotent stem cell (iPSC) technologies for promoting regenerative medicine and stem cell research. However, the driver molecules of myocardial-lineage differentiation and the functional reconstruction capacity of iPSC-derived cardiomyocytes are still an open question. Nanomedicine-based gene delivery provided a crucial platform to carry on the biogenomic materials for equipping functionalities and engineering the living organ environment. Nanodiamond (ND), a carbon-based nanomaterial, has been discovered and shown the high biocompatible and less toxicity for transporting protein, drug, and genomic plasmids. Results Here, we applied ND as a gene delivery vehicle to carry microRNA (miR-181a), and then transfected into iPS to promote cardiomyocyte-lineage differentiation. Notably, miR-181a plays a key role in iPS-derived cardiomyocyte differentiation which directly targets Hox-A11, leading to elevated MyoD expression and enhanced cardiomyocyte differentiation. Conclusion Our study demonstrated that miR-181a promotes iPSC differentiation into functional cardiomyocytes. Delivery of NANO-DIAMOND-miR-181a may host clinical potential to enhance the differentiation and recovery of the cardiogenic function in injured cardiomyocytes.
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- 2020
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18. Effects of exercise training on sleep quality and heart rate variability in middle-aged and older adults with poor sleep quality: a randomized controlled trial
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Meng-Yueh Chien, Tseng-Hau Tseng, Li-Ying Wang, and Hsi-Chung Chen
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Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,media_common.quotation_subject ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Heart Rate ,law ,Sleep Initiation and Maintenance Disorders ,Humans ,Medicine ,Heart rate variability ,Quality (business) ,Exercise ,Aged ,media_common ,Sleep quality ,business.industry ,Middle Aged ,Scientific Investigations ,Exercise Therapy ,Poor sleep ,030228 respiratory system ,Neurology ,Physical therapy ,Female ,Neurology (clinical) ,Sleep ,business ,030217 neurology & neurosurgery - Abstract
STUDY OBJECTIVES: We aimed (1) to investigate the effect of a 12-week exercise training on sleep quality and heart rate variability in middle-aged and older adults with poor sleep quality and (2) to examine the factors associated with the improvements in sleep quality and heart rate variability parameters. METHODS: Forty adults aged ≥ 40 years with poor sleep quality (mean age = 62 years; 82.5% female) participated in this study. They were randomized into the exercise group or control group. Each exercise training program consisted of 40 minutes of supervised aerobic exercise training and 10 minutes of stretching class, 3 times a week for 12 weeks. Outcome measures included both subjective (Pittsburgh Sleep Quality Index) and objective (actigraphy recordings) sleep quality assessments, a cardiopulmonary exercise test, and heart rate variability assessment. RESULTS: The exercise group showed significant improvements in the global score (P = .003), on all subscales of Pittsburgh Sleep Quality Index (P < .05), and in some heart rate variability parameters compared to the control group. Multiple regression analysis indicated that exercise participation was associated with either the sleep quality (β = −0.617, R(2) = .407; F = 6.226, P < .001) or heart rate monitor high frequency normalized units (β = 0.503, R(2) = .225; F = 3.200, P = .003) after adjustment for basic characteristics. However, the statistical significance between exercise participation and heart rate monitor high frequency normalized units diminished after controlling for the Pittsburgh Sleep Quality Index. CONCLUSIONS: Our results indicated that moderate-intensity exercise training had a beneficial effect on sleep quality and cardiac autonomic function. Middle-aged and older adults with poor sleep quality should be encouraged to engage in a moderate-intensity aerobic exercise training to improve their sleep quality and cardiac autonomic function. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: The Effects of Exercise Training in Community-dwelling Elderly With Sleep Disturbances With Follow-up; URL: https://clinicaltrials.gov/ct2/show/NCT03005990; Identifier: NCT03005990. CITATION: Tseng T-H, Chen H-C, Wang L-Y, Chien M-Y. Effects of exercise training on sleep quality and heart rate variability in middle-aged and older adults with poor sleep quality: a randomized controlled trial. J Clin Sleep Med. 2020;16(9):1483–1492.
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- 2020
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19. Development of polydimethylsiloxane-based biomimetic scaffolds with cylinder micropillars for retinal pigment epithelial cell cultivation
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Shih-Jen Chen, Yueh Chien, Wei Yi Lai, Tai Chi Lin, Chian Shiu Chien, Ying Hsiu Lai, Yi Ping Yang, Yu Li Lo, Yi Ying Lin, De Kuang Hwang, Shih Hwa Chiou, and Teh Ia Huo
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Scaffold ,Cell- and Tissue-Based Therapy ,Retinal Pigment Epithelium ,030204 cardiovascular system & hematology ,Regenerative medicine ,Cell therapy ,Macular Degeneration ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pluripotent stem cells ,Biomimetics ,Humans ,Medicine ,Dimethylpolysiloxanes ,Induced pluripotent stem cell ,Cells, Cultured ,chemistry.chemical_classification ,Retinal pigment epithelium ,Tissue Scaffolds ,Polydimethylsiloxane ,business.industry ,Biomolecule ,technology, industry, and agriculture ,Original Articles ,General Medicine ,Transplantation ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,business ,Biomedical engineering - Abstract
Background Age-related macular degeneration (AMD) is one of the leading causes of vision loss. Once the retinal pigment epithelium (RPE) layers are destroyed, the poor visual acuity and recognition are generally irreversible. Cell therapy that possesses enormous potential in regenerative medicine may provide an alternative treatment for several incurable diseases such as AMD. In this study, we developed an innovative polydimethylsiloxane (PDMS)-based biomimetic scaffolds with cylinder micropillars for the cultivation of induced pluripotent stem cell-derived RPEs (iPSC-RPEs). RPEs were cultured on the PDMS-based biomimetic scaffolds and validated the cells gene expression. Methods The biomimetic PDMS scaffold was fabricated through spin coating and lithography method. It was further modified on surface with biomolecules to improve cell affinity and stability. The iPSC-RPEs were seeded on the scaffold and analyzed with characteristic gene expression. Results PDMS biomimetic scaffold was analyzed with Fourier transform infrared spectroscopy and proved its chemical composition. iPSC-RPEs demonstrated confluent cell monolayer on the scaffold and maintained RPE-specific gene expression, which proved the PDMS-based biomimetic scaffold to be supportive for iPSC-RPEs growth. Conclusion The PDMS interface allowed regular growth of iPSC-RPEs and the design of cylinder micropillars further provided the bioscaffold high motion resistance may improve the engraftment stability of iPSC-RPEs after transplantation. Taken together, this innovative PDMS-based biomimetic scaffold may serve as an ideal interface for in vitro iPSC-RPE cultivation and subsequent transplantation in vivo. This novel device exhibits better bioavailability than conventional injection of donor cells and may be an alternative option for the treatment of AMD.
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- 2020
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20. Enhancing induced pluripotent stem cell toward differentiation into functional cardiomyocytes
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Hsiao-Yun Tai, Meng-Yin Yang, Yi-Ping Yang, Chia-Lin Wang, Yu-Ling Ko, Hsin-Bang Leu, Wen-Chung Yu, Shih Jie Chou, Chien-Ying Wang, Chian Shiu Chien, Yueh Chien, and Fu-Ting Tsai
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Myocardial ischemia ,Induced Pluripotent Stem Cells ,030204 cardiovascular system & hematology ,Regenerative medicine ,Small hairpin RNA ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ,Animals ,Medicine ,Myocytes, Cardiac ,Induced pluripotent stem cell ,Cells, Cultured ,business.industry ,Cell Differentiation ,General Medicine ,medicine.disease ,Cell biology ,Mice, Inbred C57BL ,Functional reconstruction ,MicroRNAs ,030220 oncology & carcinogenesis ,Heart failure ,Heart repair ,Stem cell ,business - Abstract
BACKGROUND Heart diseases, especially myocardial ischemia, remain one of the leading causes of mortality worldwide and usually result in irreparable cardiomyocyte damage and severe heart failure. Recent advances in induced pluripotent stem cell (iPSC) technologies for applied regenerative medicine and stem cell research, especially for iPSC-derived cardiomyocytes have increased the hope for heart repair. However, the driver molecules of myocardial differentiation and the functional reconstruction capacity of iPSC-derived cardiomyocytes are still questionable. METHODS Herein, we established a rapid differentiated platform that is involved in cardiomyogenic differentiation and maturation from iPSCs in vitro. Functional analysis is performed in miR-181a-transfected iPSC-derived cardiomyocyte (iPSC-cardio/miR-181a) under a time-lapse microscope. In addition, we calculated the beating area and frequency of iPSC-cardio/miR-181a cells in the presence of HCN4 shRNA or miR-181a SPONGE. RESULTS miR-181a enhanced the beating area and maintained the beating frequency of iPSC-derived cardiomyocytes by enhancing HCN4 expression. CONCLUSION miR-181a would play a key role on maintaining proper beating function in iPSC-derived cardiomyocytes.
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- 2020
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21. Intramyocellular Lipids, Insulin Resistance, and Functional Performance in Patients with Severe Obstructive Sleep Apnea
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Chih-Wei Yu, Tiffany Ting-Fang Shih, Meng-Yueh Chien, Pei-Lin Lee, and Shwu Yuan Wei
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medicine.medical_specialty ,business.industry ,Insulin ,medicine.medical_treatment ,Skeletal muscle ,medicine.disease ,Obesity ,Obstructive sleep apnea ,03 medical and health sciences ,Behavioral Neuroscience ,0302 clinical medicine ,Insulin resistance ,Endocrinology ,medicine.anatomical_structure ,030228 respiratory system ,Internal medicine ,medicine ,Intramyocellular lipids ,business ,Body mass index ,030217 neurology & neurosurgery ,Applied Psychology ,Dyslipidemia - Abstract
Purpose An increasing number of studies have linked the severity of obstructive sleep apnea (OSA) with metabolic dysfunction. However, little is known about the lipid compartments (intramyocellular [IMCL] and extramyocellular [EMCL] lipids) inside the musculature in these patients. The present study was designed to investigate the IMCL and EMCL, biochemical data, and functional performance in patients with severe OSA, and to examine the correlations between intramuscular lipid contents and test variables. Participants and Methods Twenty patients with severe OSA (apnea-hypopnea index [AHI]: ≥30/h; body mass index [BMI]: 26.05±2.92) and 20 age- and BMI-matched controls (AHI
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- 2020
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22. Clinical manifestation and current therapeutics in X-juvenile retinoschisis
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Yi-Ping Yang, Ying-Chun Jheng, Yueh Chien, Ping-Hsing Tsai, De-Kuang Hwang, Chang-Chi Weng, Yi-Ming Huang, Chih-Chien Hsu, Yu-Bai Chou, Shih-Jen Chen, and Tai-Chi Lin
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Male ,Retinoschisis ,Electroretinography ,Humans ,General Medicine ,Genetic Therapy ,Eye Proteins ,Retina - Abstract
X-linked juvenile retinoschisis (XLRS) is one of the common early-onset hereditary retinal degenerative diseases in men. The common symptoms of XLRS range from mild to severe central vision loss and radial stripes created by the fovea, the division of the inner layer of the retina in the peripheral retina and the significant decrease in b-wave amplitude (ERG). Retinoschisin, the 224-amino-acid protein product of the retinoschisis 1 (RS1) gene, contains a discoid domain as the primary structural unit, an N-terminal cleavable signal sequence, and an oligomerization-area component. Retinoschisin is a homo-octamer complex with disulfide links that are released by retinal cells. It helps preserve the retina's integrity by binding to the surface of photoreceptors and bipolar cells. As a recessive genetic disease, XLRS was usually treated by prescribing low vision aids in most clinical cases. A gene replacement therapy based on adeno-associated virus vectors was initiated and showed a breakthrough in treating XLRS in 2014. Understanding the revolution of gene therapy for treating XLRS may accelerate its development and make this gene therapy the template for developing therapeutics against other inherited retinal diseases.
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- 2022
23. Retinal Circular RNA hsa_circ_0087207 Expression Promotes Apoptotic Cell Death in Induced Pluripotent Stem Cell-Derived Leber's Hereditary Optic Neuropathy-like Models
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Yi-Ping Yang, Yuh-Lih Chang, Yun-Hsien Lai, Ping-Hsing Tsai, Yu-Jer Hsiao, Long Hoang Nguyen, Xue-Zhen Lim, Chang-Chi Weng, Yu-Ling Ko, Chang-Hao Yang, De-Kuang Hwang, Shih-Jen Chen, Shih-Hwa Chiou, Guang-Yuh Chiou, An-Guor Wang, and Yueh Chien
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Leber’s hereditary optic neuropathy ,unaffected carrier ,hsa_circ_0087207 ,retinal ganglion cells ,induced pluripotent stem cells ,genetic structures ,Medicine (miscellaneous) ,sense organs ,General Biochemistry, Genetics and Molecular Biology ,eye diseases - Abstract
Backgrounds: Leber’s hereditary optic neuropathy (LHON) is known as an inherited retinal disorder characterized by the bilateral central vision loss and degeneration of retinal ganglion cells (RGCs). Unaffected LHON carriers are generally asymptomatic, suggesting that certain factors may contribute to the disease manifestations between carriers and patients who carry the same mutated genotypes. Methods: We first aimed to establish the iPSC-differentiated RGCs from the normal healthy subject, the carrier, and the LHON patient and then compared the differential expression profile of circular RNAs (CircRNAs) among RGCs from these donors in vitro. We further overexpressed or knocked down the most upregulated circRNA to examine whether this circRNA contributes to the distinct phenotypic manifestations between the carrier- and patient-derived RGCs. Results: iPSCs were generated from the peripheral blood cells from the healthy subject, the carrier, and the LHON patient and successfully differentiated into RGCs. These RGCs carried equivalent intracellular reactive oxygen species, but only LHON-patient iPSC-derived RGCs exhibited remarkable apoptosis. Next-generation sequencing and quantitative real-time PCR revealed the circRNA hsa_circ_0087207 as the most upregulated circRNA in LHON-patient iPSC-derived RGCs. Overexpression of hsa_circ_0087207 increased the apoptosis in carrier iPSC-derived RGCs, while knockdown of hsa_circ_0087207 attenuated the apoptosis in LHON-patient iPSC-derived RGCs. Predicted by bioinformatics approaches, hsa_circ_0087207 acts as the sponge of miR-665 to induce the expression of a variety of apoptosis-related genes in LHON patient iPSC-derived RGCs. Conclusions: Our data indicated that hsa_circ_0087207 upregulation distinguishes the disease phenotype manifestations between iPSC-derived RGCs generated from the LHON patient and carrier. Targeting the hsa_circ_0087207/miR-665 axis might hold therapeutic promises for the treatment of LHON.
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- 2022
24. Calreticulin Regulates β1-Integrin mRNA Stability in PC-3 Prostate Cancer Cells
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Yueh-Chien Lin, Yuan-Li Huang, Ming-Hua Wang, Chih-Yu Chen, Wei-Min Chen, Yi-Cheng Weng, and Pei-Yi Wu
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Medicine (miscellaneous) ,General Biochemistry, Genetics and Molecular Biology ,calreticulin ,integrin ,mRNA stability ,AU-rich element - Abstract
Prostate cancer (PCa) is the major cause of cancer-related death among aging men worldwide. Recent studies have suggested that calreticulin (CRT), a multifunctional chaperon protein, may play an important role in the regulation of PCa tumorigenesis and progression. However, the underlying mechanisms are still unclear. Integrin is an important regulator of cancer metastasis. Our previous study demonstrated that in J82 bladder cancer cells, CRT affects integrin activity through FUBP-1-FUT-1-dependent fucosylation, rather than directly affecting the expression of β1-integrin itself. However, whether this regulatory mechanism is conserved among different cell types remains to be determined. Herein, we attempted to determine the effects of CRT on β1-integrin in human prostate cancer PC-3 cells. CRT expression was suppressed in PC-3 cells through siRNA treatment, and then the expression levels of FUT-1 and β1-integrin were monitored through RT-PCR. We found that knockdown of CRT expression in PC-3 cells significantly affected the expression of β1-integrin itself. In addition, the lower expression level of β1-integrin was due to affecting the mRNA stability. In contrast, FUT-1 expression level was not affected by knockdown of CRT. These results strongly suggested that CRT regulates cellular behavior differently in different cell types. We further confirmed that CRT directly binds to the 3′UTR of β1-integrin mRNA by EMSA and therefore affects its stability. The suppression of CRT expression also affects PC-3 cell adhesion to type I collagen substrate. In addition, the levels of total and activated β1-integrin expressed on cell surface were both significantly suppressed by CRT knockdown. Furthermore, the intracellular distribution of β1-integrin was also affected by lowering the expression of CRT. This change in distribution is not lysosomal nor proteosomal pathway-dependent. The treatment of fucosydase significantly affected the activation of surface β1-integrin, which is conserved among different cell types. These results suggested that CRT affects the expression of β1-integrin through distinct regulatory mechanisms.
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- 2022
25. Identification of plasma hsa_circ_0000190 and 0001649 as biomarkers for predicting the recurrence and treatment response of patients with oral squamous cell carcinoma
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Kai-Feng Hung, Bing-Hong Chen, Tsui-Ying Wang, Yi-Ping Yang, Yueh Chien, Jeng-Fan Lo, Lin Yang, Bou-Yue Peng, Shou-Yen Kao, and Cheng-Hsien Wu
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Head and Neck Neoplasms ,Squamous Cell Carcinoma of Head and Neck ,Biomarkers, Tumor ,Carcinoma, Squamous Cell ,Humans ,RNA ,Mouth Neoplasms ,General Medicine ,Neoplasm Recurrence, Local ,Biomarkers - Abstract
Oral squamous cell carcinoma (OSCC) is a type of malignancy characterized by high relapse and recurrence rates in the late stage despite optimal surgical intervention and postoperative chemoradiotherapy. Because the management of relapse following definitive treatment is challenging, accurate risk stratification is of clinical significance to improve treatment outcomes. Circular RNAs (circRNAs) are noncoding RNAs featured with cell-type specificity and high stability, owing to their circular structure, making these molecules excellent biomarkers for a variety of diseases.The levels of hsa_circ_0000190 and 0001649 in plasma samples from 30 healthy controls and 66 OSCC patients were determined by droplet digital polymerase chain reaction. The same primer sets were used with PCR to examine the expression of these two circRNAs in cancerous and adjacent normal tissues. A receiver operating characteristics curve was generated to evaluate the diagnostic value. The Kaplan-Meier method with a log-rank test was used for survival analysis.We identified two circRNAs as potential biomarkers for OSCC, showing that the plasma level of hsa_circ_0000190 was significantly decreased in the late stage and marginally correlated with the development of second primary OSCC. We also found that the decreased plasma hsa_circ_0001649 was correlated with the recurrence and poor prognosis of patients. Additionally, we found that high plasma hsa_circ_0000190, but not hsa_circ_0001649, possibly predicted a better response of patients to induction chemotherapy.Our study demonstrated the potential of biomarkers in plasma to inform not just the tumor but the entire oral cavity, thereby offering a prediction for early recurrence and second primary OSCC. The plasma circRNAs remain valuable for OSCC, albeit the easy accessibility to the oral cavity.
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- 2022
26. Corrigendum to ‘Characterizing deep brain biosignals: The advances and applications of implantable MEMS-based devices’ [Materials Today Advances 16 (2022) 100322]
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Hsin-Yu Wu, Kao-Jung Chang, Ximiao Wen, Aliaksandr A. Yarmishyn, He-Jhen Dai, Kai-Hsiang Chan, Yu-Jer Hsiao, Ming-Teh Chen, Yueh Chien, Hsin-I Ma, Wensyang Hsu, Meng-Shiue Lee, and Shih-Hwa Chiou
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Mechanical Engineering ,General Materials Science - Published
- 2023
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27. Nature-Inspired Surface Structures Design for Antimicrobial Applications
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Meng-Shiue Lee, Hussein Reda Hussein, Sheng-Wen Chang, Chia-Yu Chang, Yi-Ying Lin, Yueh Chien, Yi-Ping Yang, Lik-Voon Kiew, Ching-Yun Chen, Shih-Hwa Chiou, and Chia-Ching Chang
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Inorganic Chemistry ,Organic Chemistry ,General Medicine ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy ,Catalysis ,Computer Science Applications - Abstract
Surface contamination by microorganisms such as viruses and bacteria may simultaneously aggravate the biofouling of surfaces and infection of wounds and promote cross-species transmission and the rapid evolution of microbes in emerging diseases. In addition, natural surface structures with unique anti-biofouling properties may be used as guide templates for the development of functional antimicrobial surfaces. Further, these structure-related antimicrobial surfaces can be categorized into microbicidal and anti-biofouling surfaces. This review introduces the recent advances in the development of microbicidal and anti-biofouling surfaces inspired by natural structures and discusses the related antimicrobial mechanisms, surface topography design, material application, manufacturing techniques, and antimicrobial efficiencies.
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- 2023
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28. Recognizing the Differentiation Degree of Human Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Cells Using Machine Learning and Deep Learning-Based Approaches
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Chung-Yueh Lien, Tseng-Tse Chen, En-Tung Tsai, Yu-Jer Hsiao, Ni Lee, Chong-En Gao, Yi-Ping Yang, Shih-Jen Chen, Aliaksandr A. Yarmishyn, De-Kuang Hwang, Shih-Jie Chou, Woei-Chyn Chu, Shih-Hwa Chiou, and Yueh Chien
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induced pluripotent stem cells ,retinal pigment epithelial cells ,artificial intelligence ,deep learning ,convolutional neural network ,traditional machine learning ,General Medicine - Abstract
Induced pluripotent stem cells (iPSCs) can be differentiated into mesenchymal stem cells (iPSC-MSCs), retinal ganglion cells (iPSC-RGCs), and retinal pigmental epithelium cells (iPSC-RPEs) to meet the demand of regeneration medicine. Since the production of iPSCs and iPSC-derived cell lineages generally requires massive and time-consuming laboratory work, artificial intelligence (AI)-assisted approach that can facilitate the cell classification and recognize the cell differentiation degree is of critical demand. In this study, we propose the multi-slice tensor model, a modified convolutional neural network (CNN) designed to classify iPSC-derived cells and evaluate the differentiation efficiency of iPSC-RPEs. We removed the fully connected layers and projected the features using principle component analysis (PCA), and subsequently classified iPSC-RPEs according to various differentiation degree. With the assistance of the support vector machine (SVM), this model further showed capabilities to classify iPSCs, iPSC-MSCs, iPSC-RPEs, and iPSC-RGCs with an accuracy of 97.8%. In addition, the proposed model accurately recognized the differentiation of iPSC-RPEs and showed the potential to identify the candidate cells with ideal features and simultaneously exclude cells with immature/abnormal phenotypes. This rapid screening/classification system may facilitate the translation of iPSC-based technologies into clinical uses, such as cell transplantation therapy.
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- 2023
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29. Characterizing deep brain biosignals: The advances and applications of implantable MEMS-based devices
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Hsin-Yu Wu, Kao-Jung Chang, Ximiao Wen, Aliaksandr A. Yarmishyn, He-Jhen Dai, Kai-Hsiang Chan, Hsiao Yu-Jer, Ming-Teh Chen, Yueh Chien, Hsin-I Ma, Wensyang Hsu, Meng-Shiue Lee, and Shih-Hwa Chiou
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Mechanical Engineering ,General Materials Science - Published
- 2022
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30. Efficacy and cost-effectiveness analysis of post-acute care for elderly patients with hip fractures
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Min-Chang Lee, Chia-Wei Chang, Shih-Liang Shih, Sheng-Jean Huang, Jau-Yih Tsauo, Kai-Lun Hsiao, and Meng-Yueh Chien
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Hip Fractures ,Cost-Benefit Analysis ,Quality of Life ,Humans ,General Medicine ,Prospective Studies ,Subacute Care ,Aged - Abstract
Hip fractures are associated with physical dysfunction, and poor quality of life in the elderly. Post-acute care (PAC) would facilitate functional recovery in patients with hip fractures after surgeries. Taiwan has proposed a nationwide PAC program for hip fractures since 2017, but little has been known about its effectiveness. Therefore, this study aimed to evaluate the efficacy and cost-effectiveness of the PAC program for hip fracture patients in Taiwan.This was a prospective study. Patients aged ≥ 65 years with hip fractures after surgeries were recruited and divided into home-based, hospital-based, and control groups. Outcome measures included pain, physical function (sit-to-stand test, Barthel Index [BI], and Harris hip score [HHS]), and quality of life (EuroQol instrument [EQ-5D]). Direct medical and non-medical costs were recorded. Cost-effectiveness ratio (CER) was calculated as the amount of New Taiwanese Dollars (NTDs) paid per BI and EQ-5D unit improvement.Forty-one patients participated in this study, with 17, 12, and 12 in the home-based, hospital-based, and control groups, respectively. The home-based group showed significant improvements in BI and HHS compared to the controls (p = 0.018 and p = 0.029, respectively). The hospital-based group demonstrated significant improvement in EQ-5D compared to the controls (p = 0.015). The home-based PAC program demonstrated the best CER for BI (NTD 554) and EQ-5D (NTD 41948).Both PAC programs would significantly improve the physical function and quality of life in patients with hip fractures. However, the home-based PAC provided the best CER for BI and EQ-5D.
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- 2021
31. Dual DNA Transfection Using 1,6-Hexanedithiol-Conjugated Maleimide-Functionalized PU-PEI600 For Gene Correction in a Patient iPSC-Derived Fabry Cardiomyopathy Model
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Chian-Shiu Chien, Yueh Chien, Yi-Ying Lin, Ping-Hsing Tsai, Shih-Jie Chou, Aliaksandr A. Yarmishyn, Elham Rastegari, Ting-Xian Wang, Hsin-Bang Leu, Yi-Ping Yang, Mong-Lien Wang, Ying-Chun Jheng, Henkie Isahwan Ahmad Mulyadi Lai, Lo-Jei Ching, Teh-Ia Huo, Jong-Yuh Cherng, and Chien-Ying Wang
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0301 basic medicine ,induced pluripotent stem cells ,QH301-705.5 ,Gene delivery ,medicine.disease_cause ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Plasmid ,medicine ,Biology (General) ,Induced pluripotent stem cell ,CRISPR/Cas9 ,Gene ,Fabry disease ,Reporter gene ,Mutation ,Cell Biology ,Transfection ,Cell biology ,030104 developmental biology ,chemistry ,polyurethane ,030220 oncology & carcinogenesis ,polyethyleneimine ,cardiomyopathy ,DNA ,Developmental Biology - Abstract
Non-viral gene delivery holds promises for treating inherited diseases. However, the limited cloning capacity of plasmids may hinder the co-delivery of distinct genes to the transfected cells. Previously, the conjugation of maleimide-functionalized polyurethane grafted with small molecular weight polyethylenimine (PU-PEI600-Mal) using 1,6-hexanedithiol (HDT) could promote the co-delivery and extensive co-expression of two different plasmids in target cells. Herein, we designed HDT-conjugated PU-PEI600-Mal for the simultaneous delivery of CRISPR/Cas9 components to achieve efficient gene correction in the induced pluripotent stem cell (iPSC)-derived model of Fabry cardiomyopathy (FC) harboring GLA IVS4 + 919 G > A mutation. This FC in vitro model recapitulated several clinical FC features, including cardiomyocyte hypertrophy and lysosomal globotriaosylceramide (Gb3) deposition. As evidenced by the expression of two reporter genes, GFP and mCherry, the addition of HDT conjugated two distinct PU-PEI600-Mal/DNA complexes and promoted the co-delivery of sgRNA/Cas9 and homology-directed repair DNA template into target cells to achieve an effective gene correction of IVS4 + 919 G > A mutation. PU-PEI600-Mal/DNA with or without HDT-mediated conjugation consistently showed neither the cytotoxicity nor an adverse effect on cardiac induction of transfected FC-iPSCs. After the gene correction and cardiac induction, disease features, including cardiomyocyte hypertrophy, the mis-regulated gene expressions, and Gb3 deposition, were remarkably rescued in the FC-iPSC-differentiated cardiomyocytes. Collectively, HDT-conjugated PU-PEI600-Mal-mediated dual DNA transfection system can be an ideal approach to improve the concurrent transfection of non-viral-based gene editing system in inherited diseases with specific mutations.
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- 2021
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32. Activation of Aryl Hydrocarbon Receptor by Kynurenine Impairs Progression and Metastasis of Neuroblastoma
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Kuan-Hung Lin, Yu-Tzu Chang, Wei Min Chen, Shiu-Feng Huang, Mati Kargren, Yueh-Chien Lin, Chi-Hao Chang, Hsinyu Lee, I-Shing Yu, Ya-Yun Chan, Tzu-Hsuan Tseng, Yen Lin Liu, Tang-Long Shen, Yung-Feng Liao, Chien-Chin Chen, Yu-Ling Tai, Wen-Ming Hsu, Bo-Jeng Wang, Pei-Yi Wu, and Hsueh Fen Juan
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Male ,0301 basic medicine ,Cancer Research ,Cellular differentiation ,Metastasis ,Mice ,Neuroblastoma ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Movement ,Basic Helix-Loop-Helix Transcription Factors ,Medicine ,Genes, Tumor Suppressor ,Child ,Kynurenine ,Kisspeptins ,Mice, Inbred BALB C ,N-Myc Proto-Oncogene Protein ,biology ,Cell Differentiation ,respiratory system ,Gene Expression Regulation, Neoplastic ,Oncology ,Child, Preschool ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,Childhood Neuroblastoma ,Mice, Nude ,03 medical and health sciences ,Cell Line, Tumor ,Animals ,Humans ,Metastasis suppressor ,neoplasms ,Cell Proliferation ,business.industry ,Cell growth ,Gene Amplification ,Infant, Newborn ,Infant ,Aryl hydrocarbon receptor ,medicine.disease ,respiratory tract diseases ,030104 developmental biology ,Receptors, Aryl Hydrocarbon ,chemistry ,biology.protein ,Cancer research ,business - Abstract
Neuroblastoma is the most common malignant disease of infancy, and amplification of the MYCN oncogene is closely associated with poor prognosis. Recently, expression of MYCN was shown to be inversely correlated with aryl hydrocarbon receptor (AHR) expression in neuroblastoma, and overexpression of AHR downregulated MYCN expression, promoting cell differentiation. Therefore, we further investigated the potential of AHR to serve as a prognostic indicator or a therapeutic target in neuroblastoma. First, the clinical significance of AHR in neuroblastoma was examined. Positive AHR immunostaining strongly correlated with differentiated histology of neuroblastoma and predicted better survival for patients. The mouse xenograft model showed that overexpression of AHR significantly suppressed neuroblastoma tumor growth. In addition, activation of AHR by the endogenous ligand kynurenine inhibited cell proliferation and promoted cell differentiation in vitro and in vivo. kynurenine treatment also upregulated the expression of KISS1, a tumor metastasis suppressor, and attenuated metastasis in the xenograft model. Finally, analysis of KISS1 levels in neuroblastoma patient tumors using the R2: Genomics Analysis and Visualization Platform revealed that KISS1 expression positively correlated with AHR, and high KISS1 expression predicted better survival for patients. In conclusion, our results indicate that AHR is a novel prognostic biomarker for neuroblastoma, and that overexpression or activation of AHR offers a new therapeutic possibility for patients with neuroblastoma. Significance: These findings show that AHR may function as a tumor suppressor in childhood neuroblastoma, potentially influencing the aetiologic and therapeutic targeting of the disease.
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- 2019
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33. Ash2l interacts with Oct4-stemness circuitry to promote super-enhancer-driven pluripotency network
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Jui-Hung Hung, Chian Shiu Chien, Mong Lien Wang, Teh Ia Huo, Chung-Hsuan Chen, Chih-Hung Hsu, Shih Jie Chou, Benoit Laurent, Shih Hwa Chiou, Yueh Chien, Hsin Chen Lee, Hsin Yang Li, Ping Hsing Tsai, and Wei Chao Chang
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Pluripotent Stem Cells ,Homeobox protein NANOG ,Biology ,Transfection ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Super-enhancer ,SOX2 ,Genetics ,Animals ,Humans ,Cell Lineage ,Cell Self Renewal ,Induced pluripotent stem cell ,Enhancer ,030304 developmental biology ,Regulation of gene expression ,0303 health sciences ,Gene knockdown ,SOXB1 Transcription Factors ,Gene regulation, Chromatin and Epigenetics ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Mouse Embryonic Stem Cells ,Nanog Homeobox Protein ,Cellular Reprogramming ,Cell biology ,DNA-Binding Proteins ,Enhancer Elements, Genetic ,Mutation ,embryonic structures ,sense organs ,CRISPR-Cas Systems ,Octamer Transcription Factor-3 ,030217 neurology & neurosurgery ,Transcription Factors - Abstract
Pluripotency and cell fates can be modulated through the regulation of super-enhancers; however, the underlying mechanisms are unclear. Here, we showed a novel mechanism in which Ash2l directly binds to super-enhancers of several stemness genes to regulate pluripotency and self-renewal in pluripotent stem cells. Ash2l recruits Oct4/Sox2/Nanog (OSN) to form Ash2l/OSN complex at the super-enhancers of Jarid2, Nanog, Sox2 and Oct4, and further drives enhancer activation, upregulation of stemness genes, and maintains the pluripotent circuitry. Ash2l knockdown abrogates the OSN recruitment to all super-enhancers and further hinders the enhancer activation. In addition, CRISPRi/dCas9-mediated blocking of Ash2l-binding motifs at these super-enhancers also prevents OSN recruitment and enhancer activation, validating that Ash2l directly binds to super-enhancers and initiates the pluripotency network. Transfection of Ash2l with W118A mutation to disrupt Ash2l–Oct4 interaction fails to rescue Ash2l-driven enhancer activation and pluripotent gene upregulation in Ash2l-depleted pluripotent stem cells. Together, our data demonstrated Ash2l formed an enhancer-bound Ash2l/OSN complex that can drive enhancer activation, govern pluripotency network and stemness circuitry.
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- 2019
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34. Trajectories of functional exercise capacity in patients undergoing pulmonary rehabilitation
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Li-Ying Wang, Pei-Yu Yang, Hsiao-Chen Lin, Meng-Yueh Chien, Huey-Dong Wu, Ping-Lun Hsieh, Jung-Yien Chien, Chien-Tzu Lee, and Jia-Shin Lin
- Subjects
COPD ,medicine.medical_specialty ,Group based ,business.industry ,Functional exercise ,medicine.medical_treatment ,Respiratory disease ,General Medicine ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,Internal medicine ,Cohort ,Medicine ,Pulmonary rehabilitation ,In patient ,030212 general & internal medicine ,business ,Generalized estimating equation - Abstract
Background: Pulmonary rehabilitation (PR) is now considered fundamental when managing patients with chronic respiratory disease. The individual variation in functional exercise capacity (FEC) response to PR within the cohort is unknown. The purpose of this study was to identify FEC patterns in response to PR in patients with chronic respiratory disease using the trajectory modeling method. Methods: The data of 67 patients with the chronic respiratory disease were retrospectively reviewed and analyzed in this study. All patients received once-weekly supervised training for 8 weeks. Six-minute walk distance (6MWD) was used to measure FEC. Muscle strength and 6MWD were assessed at baseline, Week 4, Week 8 and monthly for two months after PR completion. Group-based trajectory modeling (GBTM) was used to identify patterns in 6MWD in response to PR. The generalized estimating equation method was then used to detect the differences within and between the trajectories of identified groups across time. Results: Patients were grouped into low- (n=13), moderate- (n=34) and high- (n=20) FEC group based on GBTM analysis. All groups demonstrated significant improvements in 6MWD and leg muscle strength after 8-week PR. Compared to the high-FEC group, a greater proportion of the patients in the low-FEC group required oxygen supplementation during training and had worse baseline leg muscle strength. Conclusions: Patients showed distinct patterns of 6MWD changes in response to 8-week PR. Distinct characteristics for the low-FEC group included poor lower extremity strength and a greater proportion of required oxygen use at home and during training.
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- 2019
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35. Tunable Luminescence of Sm3+/Tb3+ Co-Doped CaMoO4 Phosphors Synthesized by Microwave-Assisted Heating
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Wen-Te Wu, Kwong-Kau Tiong, Yu-Wei Lee, Sheng-Yao Hu, Yueh-Chien Lee, and Wei Huang
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Fluid Flow and Transfer Processes ,Process Chemistry and Technology ,General Engineering ,General Materials Science ,Instrumentation ,Computer Science Applications - Abstract
We present a series of Sm3+/Tb3+ co-doped CaMoO4 phosphors synthesized by an efficient method of microwave-assisted heating. The prepared CaMoO4 samples were characterized by X-ray diffraction, photoluminescence, and Commission Internationale de l’Elcairage (CIE) chromaticity diagram. The X-ray diffraction results confirmed that all synthesized CaMoO4 samples are crystallized in a pure tetragonal phase. The photoluminescence spectra significantly show both red- and green emissions in the synthesized Sm3+/Tb3+ co-doped CaMoO4 phosphors. It is obvious that the variations in the intensity ratio of red/green emissions depend on the molar ratio of Sm3+/Tb3+ co-doping and dominate the CIE color coordinates on the chromaticity diagram. The investigations showed the functionality of the material system as advanced color-tunable phosphors for white-LEDs as evidenced by the controllability of the light-emitting region of Sm3+/Tb3+ co-doped CaMoO4 phosphors through the adjustment of the molar ratio of Sm3+/Tb3+ ions.
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- 2022
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36. Frontier review of the roles of exosomes in osteoarthritis
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Shih En Huang, Aliaksandr A. Yarmishyn, Ying Chun Jheng, Chung Lan Kao, Po Yin Chen, Ding Hao Liu, Chian Shiu Chien, Yi Ping Yang, Yueh Chien, and Pin Hsing Tsai
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Male ,business.industry ,Liquid Biopsy ,General Medicine ,Osteoarthritis ,Bioinformatics ,Chondrogenesis ,medicine.disease ,Exosomes ,Microvesicles ,Degenerative disease ,Platelet-rich plasma ,microRNA ,Synovial Fluid ,Synovial fluid ,Medicine ,Humans ,Female ,Liquid biopsy ,business ,Biomarkers - Abstract
Osteoarthritis (OA) is a common degenerative disease; however, its exact pathophysiology and early diagnosis are still a challenge. Growing attention to the exosomes may inspire innovations that would make the current management of OA more effective. The exosomes in synovial fluid are relatively stable, and they can be easily isolated by the relatively noninvasive procedure of liquid biopsy to provide diagnostic and monitoring value. Some miRNAs (miR-504, miR-146a, miR-26a, miR-200c, and miR-210) have been known to be secreted in exosomes of OA patients. On the other hand, intraarticular injection of platelet-rich plasma (PRP) is becoming a popular therapy for OA patients. PRP is also a source of exosomes and their numerous contents. It is evident from the literature that PRP-derived exosomes can induce chondrogenic gene expression in OA chondrocytes. Here, we review the latest findings on the roles of exosomes in OA with the emphasis on PRP-derived exosomes and their potential applications for treating OA.
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- 2021
37. Single-cell RNA sequencing in human lung cancer: Applications, challenges, and pathway towards personalized therapy
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Mong Lien Wang, Zhi-Xiong Chong, Swee Keong Yeap, Nalini Devi Verusingam, Yueh Chien, Wan Yong Ho, and Han-Kiat Ong
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Lung Neoplasms ,genetic processes ,Cell ,Cancer therapy ,Computational biology ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Molecular level ,Exome Sequencing ,Medicine ,Humans ,natural sciences ,Personalized therapy ,Precision Medicine ,Lung cancer ,business.industry ,Human lung cancer ,Sequence Analysis, RNA ,RNA ,General Medicine ,medicine.disease ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,business - Abstract
Lung cancer is one of the most prevalent human cancers, and single-cell RNA sequencing (scRNA-seq) has been widely used to study human lung cancer at the cellular, genetic, and molecular level. Even though there are published reviews, which summarized the applications of scRNA-seq in human cancers like breast cancer, there is lack of a comprehensive review, which could effectively highlight the broad use of scRNA-seq in studying lung cancer. This review, therefore, was aimed to summarize the various applications of scRNA-seq in human lung cancer research based on the findings from different published in vitro, in vivo, and clinical studies. The review would first briefly outline the concept and principle of scRNA-seq, followed by the discussion on the applications of scRNA-seq in studying human lung cancer. Finally, the challenges faced when using scRNA-seq to study human lung cancer would be discussed, and the potential applications and challenges of scRNA-seq to facilitate the development of personalized cancer therapy in the future would be explored.
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- 2021
38. The Elastic Stable Intramedullary Nails as an Alternative Treatment for Adult Humeral Shaft Fractures
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Cheng Fong Chen, Meng-Yin Yang, Yueh Chien, Kai-Cheng Lin, and Yih-Wen Tarng
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Adult ,Male ,Humeral Fractures ,medicine.medical_specialty ,Elbow ,Osteoporosis ,Bone Nails ,030204 cardiovascular system & hematology ,law.invention ,Intramedullary rod ,Young Adult ,03 medical and health sciences ,Fixation (surgical) ,0302 clinical medicine ,law ,medicine ,Humans ,Outpatient clinic ,Humerus ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Spiral fracture ,Implant failure ,General Medicine ,Middle Aged ,medicine.disease ,Fracture Fixation, Intramedullary ,Surgery ,Treatment Outcome ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,business - Abstract
BACKGROUND Plate and locked intramedullary nailing for humeral fractures are golden standard procedure, but the humerus is a nonweight-bearing bone and can tolerate a larger range of acceptable alignment. We believe the elastic stable intramedullary nails (ESINs) can provide enough relative stability for humeral shaft fractures in certain adult patients. METHODS There are four new indications for using ESINs: (1) patient could not tolerate a sugar-tong splint but was a high risk for general anesthesia, (2) intramedullary canal narrowing (
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- 2021
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39. METTL3-dependent N
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Chian-Shiu, Chien, Julie Yi-Shuan, Li, Yueh, Chien, Mong-Lien, Wang, Aliaksandr A, Yarmishyn, Ping-Hsing, Tsai, Chi-Chang, Juan, Phu, Nguyen, Hao-Min, Cheng, Teh-Ia, Huo, Shih-Hwa, Chiou, and Shu, Chien
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Adenosine ,THP-1 Cells ,Kruppel-Like Transcription Factors ,NF-kappa B ,RNA-Binding Proteins ,NLR Proteins ,Methyltransferases ,Biological Sciences ,Atherosclerosis ,Epigenesis, Genetic ,Mice, Inbred C57BL ,Kruppel-Like Factor 4 ,Mice ,Human Umbilical Vein Endothelial Cells ,Animals ,Humans ,Endothelium, Vascular ,RNA, Messenger ,RNA Processing, Post-Transcriptional ,Transcriptome - Abstract
Atherosclerosis is characterized by the plaque formation that restricts intraarterial blood flow. The disturbed blood flow with the associated oscillatory stress (OS) at the arterial curvatures and branch points can trigger endothelial activation and is one of the risk factors of atherosclerosis. Many studies reported the mechanotransduction related to OS and atherogenesis; however, the transcriptional and posttranscriptional regulatory mechanisms of atherosclerosis remain unclear. Herein, we investigated the role of N(6)-methyladenosine (m(6)A) RNA methylation in mechanotransduction in endothelial cells (ECs) because of its important role in epitranscriptome regulation. We have identified m(6)A methyltransferase METTL3 as a responsive hub to hemodynamic forces and atherogenic stimuli in ECs. OS led to an up-regulation of METTL3 expression, accompanied by m(6)A RNA hypermethylation, increased NF-κB p65 Ser(536) phosphorylation, and enhanced monocyte adhesion. Knockdown of METTL3 abrogated this OS-induced m(6)A RNA hypermethylation and other manifestations, while METTL3 overexpression led to changes resembling the OS effects. RNA-sequencing and m(6)A-enhanced cross-linking and immunoprecipitation (eCLIP) experiments revealed NLRP1 and KLF4 as two hemodynamics-related downstream targets of METTL3-mediated hypermethylation. The METTL3-mediated RNA hypermethylation up-regulated NLRP1 transcript and down-regulated KLF4 transcript through YTHDF1 and YTHDF2 m(6)A reader proteins, respectively. In the in vivo atherosclerosis model, partial ligation of the carotid artery led to plaque formation and up-regulation of METTL3 and NLRP1, with down-regulation of KLF4; knockdown of METTL3 via repetitive shRNA administration prevented the atherogenic process, NLRP3 up-regulation, and KLF4 down-regulation. Collectively, we have demonstrated that METTL3 serves a central role in the atherogenesis induced by OS and disturbed blood flow.
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- 2021
40. METTL3-dependent N 6 -methyladenosine RNA modification mediates the atherogenic inflammatory cascades in vascular endothelium
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Mong Lien Wang, Shu Chien, Phu Nguyen, Chian Shiu Chien, Aliaksandr A. Yarmishyn, Hao Min Cheng, Teh Ia Huo, Chi Chang Juan, Julie Yi Shuan Li, Ping Hsing Tsai, Yueh Chien, and Shih Hwa Chiou
- Subjects
Endothelial activation ,Small hairpin RNA ,chemistry.chemical_compound ,Gene knockdown ,Multidisciplinary ,Chemistry ,RNA methylation ,DNA methylation ,RNA ,N6-Methyladenosine ,Mechanotransduction ,Cell biology - Abstract
Atherosclerosis is characterized by the plaque formation that restricts intraarterial blood flow. The disturbed blood flow with the associated oscillatory stress (OS) at the arterial curvatures and branch points can trigger endothelial activation and is one of the risk factors of atherosclerosis. Many studies reported the mechanotransduction related to OS and atherogenesis; however, the transcriptional and posttranscriptional regulatory mechanisms of atherosclerosis remain unclear. Herein, we investigated the role of N6-methyladenosine (m6A) RNA methylation in mechanotransduction in endothelial cells (ECs) because of its important role in epitranscriptome regulation. We have identified m6A methyltransferase METTL3 as a responsive hub to hemodynamic forces and atherogenic stimuli in ECs. OS led to an up-regulation of METTL3 expression, accompanied by m6A RNA hypermethylation, increased NF-κB p65 Ser536 phosphorylation, and enhanced monocyte adhesion. Knockdown of METTL3 abrogated this OS-induced m6A RNA hypermethylation and other manifestations, while METTL3 overexpression led to changes resembling the OS effects. RNA-sequencing and m6A-enhanced cross-linking and immunoprecipitation (eCLIP) experiments revealed NLRP1 and KLF4 as two hemodynamics-related downstream targets of METTL3-mediated hypermethylation. The METTL3-mediated RNA hypermethylation up-regulated NLRP1 transcript and down-regulated KLF4 transcript through YTHDF1 and YTHDF2 m6A reader proteins, respectively. In the in vivo atherosclerosis model, partial ligation of the carotid artery led to plaque formation and up-regulation of METTL3 and NLRP1, with down-regulation of KLF4; knockdown of METTL3 via repetitive shRNA administration prevented the atherogenic process, NLRP3 up-regulation, and KLF4 down-regulation. Collectively, we have demonstrated that METTL3 serves a central role in the atherogenesis induced by OS and disturbed blood flow.
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- 2021
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41. Exercise Capacity and Quality of Life in Pulmonary Arterial Hypertension
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Ling-Wei, Chen, Ssu-Yuan, Chen, Hsao-Hsun, Hsu, Yen-Wen, Wu, Yu-Mei, Lai, and Meng-Yueh, Chien
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Original Article - Abstract
BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease with a high mortality rate that can be divided into different groups according to etiology and prognosis. Few studies have investigated differences in the exercise capacity and quality of life (QOL) among the different groups of PAH patients. Therefore, we aimed to (1) compare the hemodynamic exercise responses between patients with idiopathic pulmonary arterial hypertension (IPAH) and PAH associated with other diseases (APAH), and (2) determine the factors associated with exercise capacity in patients with PAH. METHODS: Six patients diagnosed with IPAH and eight with APAH [congenital heart disease (CHD)-dominant PAH] were included in this study. The main outcome measures included body composition, exercise capacity, hemodynamic measurements, physical activity levels, fatigue severity, and QOL. RESULTS: The CHD-dominant PAH group had a significantly lower predicted peak oxygen consumption (VO(2pred) %), pressure of end-tidal carbon dioxide at the peak and at anaerobic threshold (PETCO(2peak) and PETCO(2@AT)), and significantly elevated ventilatory equivalent (VE/VCO(2slope) and VE/VCO(2@AT)) compared with the IPAH group. Multiple regression analysis indicated that PETCO(2@AT) was significantly associated with either VO(2peak) (β = 0.805, adjusted R(2) = 0.619, p = 0.001) or 6-minute walk distance (β = 0.816, adjusted R(2) = 0.638, p < 0.001). CONCLUSIONS: Patients with CHD-dominant PAH had poor exercise capacity and exercise responses compared to those with IPAH. Evaluating exercise capacity and the patient response to exercise using cardiopulmonary exercise testing is increasingly important in view of the etiology of PAH.
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- 2021
42. Expression of Endogenous Angiotensin-Converting Enzyme 2 in Human Induced Pluripotent Stem Cell-Derived Retinal Organoids
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Chih Chien Hsu, Shih Jie Chou, Shih Hwa Chiou, Tai Chi Lin, Yi Ping Yang, Yueh Chien, Chian Shiu Chien, De Kuang Hwang, Ying Chun Jheng, Henkie Isahwan Ahmad Mulyadi Lai, Ping Hsing Tsai, Yu Bai Chou, Shih-Jen Chen, and Mong Lien Wang
- Subjects
0301 basic medicine ,induced pluripotent stem cells ,Cell Culture Techniques ,Gene Expression ,ACE2 ,Biology ,spike protein ,TMPRSS2 ,Catalysis ,Retina ,Article ,Green fluorescent protein ,Cell Line ,Inorganic Chemistry ,lcsh:Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Organoid ,medicine ,Humans ,Physical and Theoretical Chemistry ,Receptor ,Induced pluripotent stem cell ,Molecular Biology ,lcsh:QH301-705.5 ,Spectroscopy ,SARS-CoV-2 ,Organic Chemistry ,fungi ,Serine Endopeptidases ,COVID-19 ,SARS-CoV-2 pseudovirus ,Retinal ,General Medicine ,Virus Internalization ,Computer Science Applications ,Cell biology ,Organoids ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,lcsh:Biology (General) ,lcsh:QD1-999 ,Cell culture ,Angiotensin-Converting Enzyme 2 ,030217 neurology & neurosurgery - Abstract
Angiotensin-converting enzyme 2 (ACE2) was identified as the main host cell receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its subsequent infection. In some coronavirus disease 2019 (COVID-19) patients, it has been reported that the nervous tissues and the eyes were also affected. However, evidence supporting that the retina is a target tissue for SARS-CoV-2 infection is still lacking. This present study aimed to investigate whether ACE2 expression plays a role in human retinal neurons during SARS-CoV-2 infection. Human induced pluripotent stem cell (hiPSC)-derived retinal organoids and monolayer cultures derived from dissociated retinal organoids were generated. To validate the potential entry of SARS-CoV-2 infection in the retina, we showed that hiPSC-derived retinal organoids and monolayer cultures endogenously express ACE2 and transmembrane serine protease 2 (TMPRSS2) on the mRNA level. Immunofluorescence staining confirmed the protein expression of ACE2 and TMPRSS2 in retinal organoids and monolayer cultures. Furthermore, using the SARS-CoV-2 pseudovirus spike protein with GFP expression system, we found that retinal organoids and monolayer cultures can potentially be infected by the SARS-CoV-2 pseudovirus. Collectively, our findings highlighted the potential of iPSC-derived retinal organoids as the models for ACE2 receptor-based SARS-CoV-2 infection.
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- 2020
43. Dual DNA Transfection Using 1,6-Hexanedithiol-Conjugated Maleimide-Functionalized PU-PEI
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Chian-Shiu, Chien, Yueh, Chien, Yi-Ying, Lin, Ping-Hsing, Tsai, Shih-Jie, Chou, Aliaksandr A, Yarmishyn, Elham, Rastegari, Ting-Xian, Wang, Hsin-Bang, Leu, Yi-Ping, Yang, Mong-Lien, Wang, Ying-Chun, Jheng, Henkie Isahwan Ahmad Mulyadi, Lai, Lo-Jei, Ching, Teh-Ia, Huo, Jong-Yuh, Cherng, and Chien-Ying, Wang
- Subjects
Cell and Developmental Biology ,Fabry disease ,induced pluripotent stem cells ,polyurethane ,GLA ,polyethyleneimine ,cardiomyopathy ,CRISPR/Cas9 ,Original Research - Abstract
Non-viral gene delivery holds promises for treating inherited diseases. However, the limited cloning capacity of plasmids may hinder the co-delivery of distinct genes to the transfected cells. Previously, the conjugation of maleimide-functionalized polyurethane grafted with small molecular weight polyethylenimine (PU-PEI600-Mal) using 1,6-hexanedithiol (HDT) could promote the co-delivery and extensive co-expression of two different plasmids in target cells. Herein, we designed HDT-conjugated PU-PEI600-Mal for the simultaneous delivery of CRISPR/Cas9 components to achieve efficient gene correction in the induced pluripotent stem cell (iPSC)-derived model of Fabry cardiomyopathy (FC) harboring GLA IVS4 + 919 G > A mutation. This FC in vitro model recapitulated several clinical FC features, including cardiomyocyte hypertrophy and lysosomal globotriaosylceramide (Gb3) deposition. As evidenced by the expression of two reporter genes, GFP and mCherry, the addition of HDT conjugated two distinct PU-PEI600-Mal/DNA complexes and promoted the co-delivery of sgRNA/Cas9 and homology-directed repair DNA template into target cells to achieve an effective gene correction of IVS4 + 919 G > A mutation. PU-PEI600-Mal/DNA with or without HDT-mediated conjugation consistently showed neither the cytotoxicity nor an adverse effect on cardiac induction of transfected FC-iPSCs. After the gene correction and cardiac induction, disease features, including cardiomyocyte hypertrophy, the mis-regulated gene expressions, and Gb3 deposition, were remarkably rescued in the FC-iPSC-differentiated cardiomyocytes. Collectively, HDT-conjugated PU-PEI600-Mal-mediated dual DNA transfection system can be an ideal approach to improve the concurrent transfection of non-viral-based gene editing system in inherited diseases with specific mutations.
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- 2020
44. Highlight of severe acute respiratory syndrome coronavirus-2 vaccine development against COVID-19 pandemic
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Cheng-Hsuan, Liu, Hsuan-Yang, Huang, Yung-Fang, Tu, Wei-Yi, Lai, Chia-Lin, Wang, Jun-Ren, Sun, Yueh, Chien, Tzu-Wei, Lin, Yi-Ying, Lin, Chian-Shiu, Chien, Chih-Heng, Huang, Yuh-Min, Chen, Pin-I, Huang, Fu-Der, Wang, and Yi-Ping, Yang
- Subjects
Vaccines, Synthetic ,COVID-19 Vaccines ,SARS-CoV-2 ,Vaccines, Subunit ,Vaccines, DNA ,COVID-19 ,Humans - Abstract
The pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has brought an unprecedented impact upon the global economy and public health. Although the SARS-CoV-2 virology has been gradually investigated, measures to combat this new threat in public health are still absent. To date, no certificated drug or vaccine has been developed for the treatment or prevention of coronavirus disease Extensive researches and international coordination has been conducted to rapidly develop novel vaccines against SARS-CoV-2 pandemic. Several major breakthroughs have been made through the identification of the genetic sequence and structural/non-structural proteins of SARS-CoV-2, which enabled the development of RNA-, DNA-based vaccines, subunit vaccines, and attenuated viral vaccines. In this review article, we present an overview of the recent advances of SARS-CoV-2 vaccines and the challenges that may be encountered in the development process, highlighting the advantages and disadvantages of these approaches that may help in effectively countering COVID-19.
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- 2020
45. Concordance analysis of intrapartum cardiotocography between physicians and artificial intelligence-based technique using modified one-dimensional fully convolutional networks
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Yueh Chien, Cheng-Chang Chang, Chi-Kang Lin, Keng-Hao Chang, Yu-Ching Chou, Ya-Hui Tsai, Yi-Pin Yang, Li-Chun Liu, Ying-Chun Jheng, Ning-Yuan Lyu, Peng-Hui Wang, Yi-Liang Lee, Ta-Wei Chu, and Kao-Jung Chang
- Subjects
Adult ,Cardiotocography ,Common method ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Cohen's kappa ,Artificial Intelligence ,Pregnancy ,Medicine ,Humans ,Fetal Monitoring ,Retrospective Studies ,Concordance analysis ,Medical Audit ,medicine.diagnostic_test ,Receiver operating characteristic ,business.industry ,Deep learning ,General Medicine ,Heart Rate, Fetal ,Clinical Practice ,030220 oncology & carcinogenesis ,Female ,Artificial intelligence ,business ,Intrapartum Cardiotocography - Abstract
Background Cardiotocography is a common method of electronic fetal monitoring (EFM) for fetal well-being. Data-driven analyses have shown potential for automated EFM assessment. For this preliminary study, we used a novel artificial intelligence method based on fully convolutional networks (FCNs), with deep learning for EFM evaluation and correct recognition, and its possible role in evaluation of nonreassuring fetal status. Methods We retrospectively collected 3239 EFM labor records from 292 deliveries and neonatal Apgar scores between December 2018 and July 2019 at a single medical center. We analyzed these data using an FCN model and compared the results with clinical practice. Results The FCN model recognized EFM traces like physicians, with an average Cohen's kappa coefficient of agreement of 0.525 and average area under the receiver operating characteristic curve of 0.892 for six fetal heart rate (FHR) categories. The FCN model showed higher sensitivity for predicting fetal compromise (0.528 vs 0.132) but a higher false-positive rate (0.632 vs 0.012) compared with clinical practice. Conclusion FCN is a modern technique that may be useful for EFM trace recognition based on its multiconvolutional layered analysis. Our model showed a competitive ability to identify FHR patterns and the potential for evaluation of nonreassuring fetal status.
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- 2020
46. A systematic review of the methodology of sonographic assessment of upper limb activities-associated carpal tunnel syndrome
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Cheng Fong Chen, Liang Ting Lin, Yi Ying Lin, Tsun Ming Wong, Chun Lok Sin, Yueh Chien, Yih Wen Tarng, Sze Wah Fong, Bosco Wang Fung Liu, Ka Sin Choi, King Sang Lee, and Yi Ping Yang
- Subjects
Diagnostic Imaging ,Male ,medicine.medical_specialty ,Cumulative Trauma Disorders ,030204 cardiovascular system & hematology ,Wrist ,Upper Extremity ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Medicine ,Humans ,Carpal tunnel syndrome ,Ultrasonography ,business.industry ,Clinical study design ,Confounding ,General Medicine ,Anthropometry ,medicine.disease ,Carpal Tunnel Syndrome ,nervous system diseases ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Upper limb activities ,Upper limb ,Female ,business - Abstract
Background Various upper limb activities were speculated to be associated with the development of carpal tunnel syndrome (CTS). Nonetheless, there are currently no standardization on the uses of parameters in CTS assessments, nor are there any conclusive findings regarding the usefulness of various sonographic measurements in studies of different upper limb activities. In this review, we intend to evaluate the methodology of assessing Carpal Tunnel Syndrome (CTS) induced by upper limb activities with ultrasonographic technique and provide corresponding suggestions. Methods Clinical studies on the association between upper limb activities and prevalence of CTS using ultrasonography were recruited in a database research on the basis of a procedural selection criteria and reviewed. The following qualitative items were extracted: characteristics of studies, scanning methods, selection of sonographic parameters and related article findings. Results Eleven studies were qualified for this review. Three studies were computer keyboard typing-related, five studies were electronic device-related, and three studies were wheelchair-related. All sampled articles included cross-sectional area (CSA) at the pisiform level. The swelling ratio (SR) and flattening ratio (FR) at the hamate level are also used in most studies in addition to the CSA at the pisiform level. The effectiveness of such parameters are subjected to various confounding factors such as age, weight, BMI and wrist anthropometrics, suggesting CSA and SR with sufficient levels had significant values as sonographic parameters. Values of parameters were found affecting symptomatic signs and hand dominance. Conclusion Ultrasound scan is a suitable tool to assess the relationship between upper limb activity and CTS. CSA at the pisiform level, SR and the FR at the hamate levels are generally suitable in upper limb associated-CTS investigations. Specific study designs are required to eliminate different confounding factors accordingly.
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- 2020
47. Lysophosphatidic acid receptors 2 and 3 regulate erythropoiesis at different hematopoietic stages
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Benjamin P C Chen, Wei Min Chen, Hsinyu Lee, Kuan-Hung Lin, Shih-Kuo Chen, Yueh Chien Lin, Jen Her Lu, Chao-Ling Yao, Ya Hsuan Ho, Tang-Long Shen, Jui Chung Chiang, and Kai Hsia
- Subjects
0301 basic medicine ,Premature aging ,Male ,Anemia, Hemolytic ,Myeloid ,medicine.medical_treatment ,Phosphatidic Acids ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Erythroid Cells ,Erythroblast ,hemic and lymphatic diseases ,Lysophosphatidic acid ,Erythrocyte differentiation ,medicine ,Animals ,Humans ,Cell Lineage ,Erythropoiesis ,Myeloid Cells ,Receptors, Lysophosphatidic Acid ,Molecular Biology ,Mice, Inbred BALB C ,Chemistry ,Growth factor ,Stem Cells ,Organothiophosphates ,Cell Differentiation ,Cell Biology ,Isoquinolines ,Cell biology ,Phenylhydrazines ,Haematopoiesis ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,lipids (amino acids, peptides, and proteins) ,biological phenomena, cell phenomena, and immunity ,Lysophospholipids ,K562 Cells - Abstract
Hematopoiesis, the complex developmental process that forms blood components and replenishes the blood system, involves multiple intracellular and extracellular mechanisms. We previously demonstrated that lysophosphatidic acid (LPA), a lipid growth factor, has opposing regulatory effects on erythrocyte differentiation through activation of LPA receptors 2 and 3; yet the mechanisms underlying this process remain unclear. In this study, LPA(2) is observed that highly expressed in common myeloid progenitors (CMP) in murine myeloid cells, whereas the expression of LPA(3) displaces in megakaryocyte-erythroid progenitors (MEP) of later stage of myeloid differentiation. Therefore, we hypothesized that the switching expression of LPA(2) and LPA(3) determine the hematic homeostasis of mammalian megakaryocytic-erythroid lineage. In vitro colony-forming unit assays of murine progenitors reveal that LPA(2) agonist GRI reduces the erythroblast differentiation potential of CMP. In contrast, LPA(3) agonist OMPT increases the production of erythrocytes from megakaryocyte-erythrocyte progenitor cells (MEP). In addition, treatment with GRI reduces the erythroid, CMP, and MEP populations in mice, indicating that LPA(2) predominantly inhibits myeloid differentiation at an early stage. In contrast, activation of LPA(3) increases the production of terminally differentiated erythroid cells through activation of erythropoietic transcriptional factor. We also demonstrate that the LPA(3) signaling is essential for restoration of phenylhydrazine (PHZ)-induced acute hemolytic anemia in mice and correlates to erythropoiesis impairment of Hutchinson-Gilford progeria Symptom (HGPS) premature aging expressed K562 model. Our results reveal the distinct roles of LPA(2) and LPA(3) at different stages of hematopoiesis in vivo, providing potentiated therapeutic strategies of anemia treatment.
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- 2020
48. SAT-247 Use of Double Dopamine Agonists in Giant Prolactinomas: A Series of 6 Cases
- Author
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Yueh Chien Kuan
- Subjects
Neuroendocrinology and Pituitary ,Text mining ,Series (mathematics) ,business.industry ,Dopamine ,Endocrinology, Diabetes and Metabolism ,medicine ,Biology ,Bioinformatics ,business ,AcademicSubjects/MED00250 ,Case Reports in Secretory Pituitary Pathologies, Their Treatments and Outcomes ,medicine.drug - Abstract
Dopamine agonist monotherapy is first line therapy in giant prolactinomas even when visual field defect is present. The costlier cabergoline is often preferred over bromocriptine due to higher efficacy and tolerability profile. Described herein combined cabergoline and bromocriptine therapy in 6 cases of giant prolactinomas. Retrospective records review of 6 patients with giant prolactinoma (3 males: M1-M3, 3 females: F1-F3) in a single tertiary centre was performed. Mean age at diagnosis: 29 years (range 17-39). Mean duration of follow up: 7 years (range 3-11). Headache and visual field defect were the presenting symptoms in all cases. Basal prolactin concentration: 100000 to 468851 mIU/L (
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- 2020
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49. LPA1/3 signaling mediates tumor lymphangiogenesis through promoting CRT expression in prostate cancer
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Yueh-Chien Lin, Yasunori Kanaho, Yuan-Li Huang, Yeong-Chin Jou, Chien-Chin Chen, Wei Min Chen, Hsinyu Lee, Cheng-Huang Shen, Norihiko Ohbayashi, Tang-Long Shen, and Kuan-Ying Lu
- Subjects
0301 basic medicine ,Angiogenesis ,Growth factor ,medicine.medical_treatment ,Cell Biology ,Lymphangiogenesis ,Vascular endothelial growth factor ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,chemistry ,Vascular endothelial growth factor C ,030220 oncology & carcinogenesis ,Lysophosphatidic acid ,Cancer research ,medicine ,lipids (amino acids, peptides, and proteins) ,biological phenomena, cell phenomena, and immunity ,Autotaxin ,Signal transduction ,Molecular Biology - Abstract
Lysophosphatidic acid (LPA) is a bioactive lipid growth factor which is present in high levels in serum and platelets. LPA binds to its specific G-protein-coupled receptors, including LPA1 to LPA6, thereby regulating various physiological functions, including cancer growth, angiogenesis, and lymphangiogenesis. Our previous study showed that LPA promotes the expression of the lymphangiogenic factor vascular endothelial growth factor (VEGF)-C in prostate cancer (PCa) cells. Interestingly, LPA has been shown to regulate the expression of calreticulin (CRT), a multifunctional chaperone protein, but the roles of CRT in PCa progression remain unclear. Here we investigated the involvement of CRT in LPA-mediated VEGF-C expression and lymphangiogenesis in PCa. Knockdown of CRT significantly reduced LPA-induced VEGF-C expression in PC-3 cells. Moreover, LPA promoted CRT expression through LPA receptors LPA1 and LPA3, reactive oxygen species (ROS) production, and phosphorylation of eukaryotic translation initiation factor 2α (eIF2α). Tumor-xenografted mouse experiments further showed that CRT knockdown suppressed tumor growth and lymphangiogenesis. Notably, clinical evidence indicated that the LPA-producing enzyme autotaxin (ATX) is related to CRT and that CRT level is highly associated with lymphatic vessel density and VEGF-C expression. Interestingly, the pharmacological antagonist of LPA receptors significantly reduced the lymphatic vessel density in tumor and lymph node metastasis in tumor-bearing nude mice. Together, our results demonstrated that CRT is critical in PCa progression through the mediation of LPA-induced VEGF-C expression, implying that targeting the LPA signaling axis is a potential therapeutic strategy for PCa.
- Published
- 2018
- Full Text
- View/download PDF
50. Time-resolved photoluminescence studies on localization effects in orthorhombic phase of CH3NH3PbI3 perovskite thin film
- Author
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Kwong-Kau Tiong, F. J. Cheng, G. Z. Yin, S.Y. Hu, Yueh-Chien Lee, L. Y. Chen, and J. L. Shen
- Subjects
Materials science ,Photoluminescence ,Biophysics ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,Biochemistry ,Atomic and Molecular Physics, and Optics ,0104 chemical sciences ,Tetragonal crystal system ,Crystallography ,Phase (matter) ,Orthorhombic crystal system ,Thin film ,0210 nano-technology ,Luminescence ,Perovskite (structure) - Abstract
We present the localization effects in orthorhombic phase of CH3NH3PbI3 perovskite materials by temperature-dependent photoluminescence and time-resolved photoluminescence. Our investigations indicate that the tetragonal inclusions in the orthorhombic phase of MAPbI3 at low temperature are the main reason for the formation of localization states with a depth of about 22.3 meV. The coexistence of the tetragonal and orthorhombic phases also results in an abnormal behavior of luminescence intensity from 12 to 80 K. The detailed understanding of luminescence characteristics upon the orthorhombic phase in MAPbI3 at low temperature can expand ideally the application fields of perovskite materials.
- Published
- 2018
- Full Text
- View/download PDF
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