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Article ; Online: Cysteinyl Leukotriene Pathway and Cancer

Ming-Ju Tsai / Wei-An Chang / Cheng-Hao Chuang / Kuan-Li Wu / Chih-Hung Cheng / Chau-Chyun Sheu / Ya-Ling Hsu / Jen-Yu Hung

International Journal of Molecular Sciences, Vol 23, Iss 120, p

2022 Volume 120

Abstract: Cancer remains a leading cause of death worldwide, despite many advances being made in recent decades. Changes in the tumor microenvironment, including dysregulated immunity, may contribute to carcinogenesis and cancer progression. The cysteinyl ... ...

Abstract	Cancer remains a leading cause of death worldwide, despite many advances being made in recent decades. Changes in the tumor microenvironment, including dysregulated immunity, may contribute to carcinogenesis and cancer progression. The cysteinyl leukotriene (CysLT) pathway is involved in several signal pathways, having various functions in different tissues. We summarized major findings of studies about the roles of the CysLT pathway in cancer. Many in vitro studies suggested the roles of CysLTs in cell survival/proliferation via CysLT 1 receptor (CysLT 1 R). CysLT 1 R antagonism decreased cell vitality and induced cell death in several types of cancer cells, such as colorectal, urological, breast, lung and neurological malignancies. CysLTs were also associated with multidrug resistance of cancer, and CysLT 1 R antagonism might reverse chemoresistance. Some animal studies demonstrated the beneficial effects of CysLT 1 R antagonist in inhibiting tumorigenesis and progression of some cancer types, particularly colorectal cancer and lung cancer. The expression of CysLT 1 R was shown in various cancer tissues, particularly colorectal cancer and urological malignancies, and higher expression was associated with a poorer prognosis. The chemo-preventive effects of CysLT 1 R antagonists were demonstrated in two large retrospective cohort studies. In summary, the roles of the CysLT pathway in cancer have been delineated, whereas further studies are still warranted.
Keywords	leukotriene ; montelukast ; zafirlukast ; chemoprevention ; cell death ; apoptosis ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610 ; 616
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The prevalence and clinical features of chronic obstructive pulmonary disease patients with traits of asthma in Taiwan

Wei-Chang Huang / Chau-Chyun Sheu / Jeng-Yuan Hsu / Diahn-Warng Perng / Hao-Chien Wang / Shih-Lung Cheng / Ben Cheng-Pin Chen

Journal of the Formosan Medical Association, Vol 121, Iss 1, Pp 25-

2022 Volume 35

Abstract: Background/Purpose: The application of the checkbox for identifying patients with traits of both chronic obstructive pulmonary disease (COPD) and asthma proposed by the 2015 Global Initiative for Asthma (GINA)/Global Initiative for Chronic Obstructive ... ...

Abstract	Background/Purpose: The application of the checkbox for identifying patients with traits of both chronic obstructive pulmonary disease (COPD) and asthma proposed by the 2015 Global Initiative for Asthma (GINA)/Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations has not been well studied although such identification is important in clinical practice. Thus, we aimed to investigate the prevalence and features of COPD coexistent with asthma traits diagnosed based on the 2015 GINA/GOLD strategies, and explore the gap between guidelines and routine practice in the diagnosis and pharmacological management of such condition in a COPD cohort. Methods: COPD subjects were enrolled retrospectively throughout Taiwan. A patient record form was completed for each participant and the data were analyzed. Results: Of 340 participants, the prevalence of COPD coexistent with traits of asthma was 39.4% and 30.3% based on guidelines and physician's judgment, respectively. Coexistent patients were characterized by blood eosinophilia, higher total immunoglobulin E (IgE) levels, preserved lung function, and the presence of gastro-esophageal reflux disease and atopic disease while total IgE level > 100 kU/L and the presence of atopic disease were predictors for coexistent patients. Gaps existed in the diagnosis (a weak agreement with kappa = 0.53) and treatment (non-adherence to the preferred therapy in 18.4% of physician-judged coexistent patients) in COPD patients with asthma traits. The exacerbation history was similar between coexistent and non-coexistent patients. Conclusion: We found that measuring circulatory eosinophil and total IgE levels may raise clinicians’ awareness of the presence of traits of asthma in the management of COPD.
Keywords	Clinical practice ; COPD ; GINA/GOLD guidelines ; Traits of asthma ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Novel mechanical ventilator weaning predictive model

Wei‐Chan Chung / Chau‐Chyun Sheu / Jen‐Yu Hung / Tuan‐Jung Hsu / Ssu‐Han Yang / Jong‐Rung Tsai

Kaohsiung Journal of Medical Sciences, Vol 36, Iss 10, Pp 841-

2020 Volume 849

Abstract: Abstract Mechanical ventilation (MV) is a common life support system in intensive care units. Accurate identification of patients who are capable of being extubated can shorten the MV duration and potentially reduce MV‐related complications. Therefore, ... ...

Abstract	Abstract Mechanical ventilation (MV) is a common life support system in intensive care units. Accurate identification of patients who are capable of being extubated can shorten the MV duration and potentially reduce MV‐related complications. Therefore, prediction of patients who can successfully be weaned from the mechanical ventilator is an important issue. The electronic medical record system (EMRs) has been applied and developed in respiratory therapy in recent years. It can increase the quality of critical care. However, there is no perfect index available that can be used to determine successful MV weaning. Our purpose was to establish a novel model that can predict successful weaning from MV. Patients' information was collected from the Kaohsiung Medical University Hospital respiratory therapy EMRs. In this retrospective study, we collected basic information, classic weaning index, and respiratory parameters during spontaneous breathing trials of patients eligible for extubation. According to the results of extubation, patients were divided into successful extubation and extubation failure groups. This retrospective cohort study included 169 patients. Statistical analysis revealed successful extubation predictors, including sex; height; oxygen saturation; Glasgow Coma Scale; Acute Physiology and Chronic Health Evaluation II score; pulmonary disease history; and the first, 30th, 60th, and 90th minute respiratory parameters. We built a predictive model based on these predictors. The area under the curve of this model was 0.889. We established a model for predicting the successful extubation. This model was novel to combine with serial weaning parameters and thus can help intensivists to make extubation decisions easily.
Keywords	critical care ; mechanical ventilation ; weaning ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Corrigendum to “Novel mechanical ventilator weaning predictive model”[Kaohsiung J Med Sci. 2020;36(10):841‐849]

Wei‐Chan Chung / Chau‐Chyun Sheu / Jen‐Yu Hung / Tuan‐Jung Hsu / Ssu‐Han Yang / Jong‐Rung Tsai

Kaohsiung Journal of Medical Sciences, Vol 36, Iss 11, Pp n/a-n/a (2020)

2020

Keywords	Medicine (General) ; R5-920
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Clinical outcome of nosocomial pneumonia caused by Carbapenem-resistant gram-negative bacteria in critically ill patients

Chih-Yu Chen / Kuang-Yao Yang / Chung-Kan Peng / Chau-Chyun Sheu / Ming-Cheng Chan / Jia-Yih Feng / Sheng-Huei Wang / Chia-Min Chen / Zhe-Rong Zheng / Shinn-Jye Liang / Yu-Chao Lin / T-CARE (Taiwan Critical Care and Infection) Group

Scientific Reports, Vol 12, Iss 1, Pp 1-

a multicenter retrospective observational study

2022 Volume 10

Abstract: Abstract Nosocomial pneumonia caused by carbapenem-resistant gram-negative bacteria (CRGNB) is a growing threat due to the limited therapeutic choices and high mortality rate. The aim of this study was to evaluate the prognostic factors for mortality in ... ...

Abstract	Abstract Nosocomial pneumonia caused by carbapenem-resistant gram-negative bacteria (CRGNB) is a growing threat due to the limited therapeutic choices and high mortality rate. The aim of this study was to evaluate the prognostic factors for mortality in patients with nosocomial pneumonia caused by CRGNB and the impact of colistin-based therapy on the outcomes of intensive care unit (ICU) patients. We conducted a retrospective study of the ICUs in five tertiary teaching hospitals in Taiwan. Patients with nosocomial pneumonia caused by CRGNB from January 2016 to December 2016 were included. Prognostic factors for mortality were analyzed using multivariate logistic regression. The influence of colistin-based therapy on mortality and clinical and microbiological outcomes were evaluated in subgroups using different severity stratification criteria. A total of 690 patients were enrolled in the study, with an in-hospital mortality of 46.1%. The most common CRGNB pathogens were Acinetobacter baumannii (78.7%) and Pseudomonas aeruginosa (13.0%). Significant predictors (odds ratio and 95% confidence interval) of mortality from multivariate analysis were a length of hospital stay (LOS) prior to pneumonia of longer than 9 days (2.18, 1.53–3.10), a sequential organ failure assessment (SOFA) score of more than 7 (2.36, 1.65–3.37), supportive care with vasopressor therapy (3.21, 2.26–4.56), and escalation of antimicrobial therapy (0.71, 0.50–0.99). There were no significant differences between the colistin-based therapy in the deceased and survival groups (42.1% vs. 42.7%, p = 0.873). In the subgroup analysis, patients with multiple organ involvement (> 2 organs) or higher SOFA score (> 7) receiving colistin-based therapy had better survival outcomes. Prolonged LOS prior to pneumonia onset, high SOFA score, vasopressor requirement, and timely escalation of antimicrobial therapy were predictors for mortality in critically ill patients with nosocomial CRGNB pneumonia. Colistin-based therapy was associated with better ...
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Establishing Aspergillus-Specific IgG Cut-Off Level for Chronic Pulmonary Aspergillosis Diagnosis

Meng-Rui Lee / Hung-Ling Huang / Li-Ta Keng / Hsu-Liang Chang / Chau-Chyun Sheu / Pin-Kuei Fu / Jann-Yuan Wang / Inn-Wen Chong / Jin-Yuan Shih / Chong-Jen Yu

Journal of Fungi, Vol 7, Iss 480, p

Multicenter Prospective Cohort Study

2021 Volume 480

Abstract: Objectives: Aspergillus -specific IgG ( Asp -IgG) cut-off level in diagnosing chronic pulmonary aspergillosis (CPA) remains unknown. Methods: We prospectively recruited participants with clinical suspicion of CPA in three centers in Taiwan during 2019 ... ...

Abstract	Objectives: Aspergillus -specific IgG ( Asp -IgG) cut-off level in diagnosing chronic pulmonary aspergillosis (CPA) remains unknown. Methods: We prospectively recruited participants with clinical suspicion of CPA in three centers in Taiwan during 2019 June to 2020 August. Serum Aspergillus fumigatus -specific IgG ( Asp -IgG) (Phadia, Uppsala, UPPS, Sweden) was examined. Optimal cut-off level was determined by Youden’s index and validated. Results: A total of 373 participants were recruited. In the derivation cohort ( n = 262), Asp -IgG had an area under the receiver-operating-characteristic curve (AUC) of 0.832. The optimal cut-off level was 40.5 mgA/L. While applying this cut-off level to the validation cohort ( n = 111), the sensitivity and specificity were 86.7% and 80.2%. Lowering the cut-off level from 40.5 to 27 mgA/L, the sensitivity was steady (30/36, 83.3% to 31/36, 86.1%) while specificity dropped from 81.9% (276/337) to 63.5% (214/337). Restricting CPA diagnosis to only chronic cavitary pulmonary aspergillosis (CCPA) and chronic fibrosing pulmonary aspergillosis (CFPA) yielded a cut-off level of 42.3 mgA/L in the derivation cohort with a sensitivity of 100% and specificity of 84.4% in the validation cohort. Conclusions: Serum Asp -IgG performs well for CPA diagnosis and provides a low false-positive rate when using a higher cut-off level (preferably around 40 mgA/L).
Keywords	Aspergillus fumigatus ; Aspergillus IgG ; chronic pulmonary aspergillus ; cut-off value ; Taiwan ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comparing Patient Characteristics, Clinical Outcomes, and Biomarkers of Severe Asthma Patients in Taiwan

Shih-Lung Cheng / Kuo-Chin Chiu / Hsin-Kuo Ko / Diahn-Warng Perng / Hao-Chien Wang / Chong-Jen Yu / Chau-Chyun Sheu / Sheng-Hao Lin / Ching-Hsiung Lin

Biomedicines, Vol 9, Iss 764, p

2021 Volume 764

Abstract: Purpose: To understand the association between biomarkers and exacerbations of severe asthma in adult patients in Taiwan. Materials and Methods: Demographic, clinical characteristics and biomarkers were retrospectively collected from the medical charts ... ...

Abstract	Purpose: To understand the association between biomarkers and exacerbations of severe asthma in adult patients in Taiwan. Materials and Methods: Demographic, clinical characteristics and biomarkers were retrospectively collected from the medical charts of severe asthma patients in six hospitals in Taiwan. Exacerbations were defined as those requiring asthma-specific emergency department visits/hospitalizations, or systemic steroids. Enrolled patients were divided into: (1) those with no exacerbations (non-exacerbators) and (2) those with one or more exacerbations (exacerbators). Receiver operating characteristic curves were used to determine the optimal cut-off value for biomarkers. Generalized linear models evaluated the association between exacerbation and biomarkers. Results: 132 patients were enrolled in the study with 80 non-exacerbators and 52 exacerbators. There was no significant difference in demographic and clinical characteristics between the two groups. Exacerbators had significantly higher eosinophils (EOS) counts (367.8 ± 357.18 vs. 210.05 ± 175.24, p = 0.0043) compared to non-exacerbators. The optimal cut-off values were 292 for EOS counts and 19 for the Fractional exhaled Nitric Oxide (FeNO) measure. Patients with an EOS count ≥ 300 (RR = 1.88; 95% CI, 1.26–2.81; p = 0.002) or FeNO measure ≥ 20 (RR = 2.10; 95% CI, 1.05–4.18; p = 0.0356) had a significantly higher risk of exacerbation. Moreover, patients with both an EOS count ≥ 300 and FeNO measure ≥ 20 had a significantly higher risk of exacerbation than those with lower EOS count or lower FeNO measure (RR = 2.16; 95% CI, 1.47–3.18; p = < 0.0001). Conclusions: Higher EOS counts and FeNO measures were associated with increased risk of exacerbation. These biomarkers may help physicians identify patients at risk of exacerbations and personalize treatment for asthma patients.
Keywords	asthma ; eosinophil ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Effects of Epigallocatechin Gallate (EGCG) on Pulmonary Fibroblasts of Idiopathic Pulmonary Fibrosis (IPF)—A Next-Generation Sequencing and Bioinformatic Approach

Ming-Ju Tsai / Wei-An Chang / Ssu-Hui Liao / Kuo-Feng Chang / Chau-Chyun Sheu / Po-Lin Kuo

International Journal of Molecular Sciences, Vol 20, Iss 8, p

2019 Volume 1958

Abstract: Idiopathic pulmonary fibrosis (IPF) is a disabling and lethal chronic progressive pulmonary disease. Epigallocatechin gallate (EGCG) is a polyphenol, which is the major biological component of green tea. The anti-oxidative, anti-inflammatory, and anti- ... ...

Abstract	Idiopathic pulmonary fibrosis (IPF) is a disabling and lethal chronic progressive pulmonary disease. Epigallocatechin gallate (EGCG) is a polyphenol, which is the major biological component of green tea. The anti-oxidative, anti-inflammatory, and anti-fibrotic effects of EGCG have been shown in some studies, whereas its effects in altering gene expression in pulmonary fibroblasts have not been systematically investigated. This study aimed to explore the effect of EGCG on gene expression profiles in fibroblasts of IPF. The pulmonary fibroblasts from an IPF patient were treated with either EGCG or water, and the expression profiles of mRNAs and microRNAs were determined by next-generation sequencing (NGS) and analyzed with the bioinformatics approach. A total of 61 differentially expressed genes and 56 differentially expressed microRNAs were found in EGCG-treated IPF fibroblasts. Gene ontology analyses revealed that the differentially expressed genes were mainly involved in the biosynthetic and metabolic processes of cholesterol. In addition, five potential altered microRNA–mRNA interactions were found, including hsa-miR-939-5p– PLXNA4 , hsa-miR-3918– CTIF , hsa-miR-4768-5p– PDE5A , hsa-miR-1273g-3p– VPS53 , and hsa-miR-1972– PCSK9. In summary, differentially expressed genes and microRNAs in response to EGCG treatment in IPF fibroblasts were identified in the current study. Our findings provide a scientific basis to evaluate the potential benefits of EGCG in IPF treatment, and warrant future studies to understand the role of molecular pathways underlying cholesterol homeostasis in the pathogenesis of IPF.
Keywords	bioinformatics ; fibroblast ; next-generation sequencing ; epigallocatechin gallate ; EGCG ; PCSK9 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	500
Language	English
Publishing date	2019-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Potential Effects of Curcumin on Pulmonary Fibroblasts of Idiopathic Pulmonary Fibrosis (IPF)—Approaching with Next-Generation Sequencing and Bioinformatics

Wei-An Chang / Chia-Min Chen / Chau-Chyun Sheu / Ssu-Hui Liao / Ya-Ling Hsu / Ming-Ju Tsai / Po-Lin Kuo

Molecules, Vol 25, Iss 5458, p

2020 Volume 5458

Abstract: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease. Currently, therapeutic options are limited for this fatal disease. Curcumin, with its pleiotropic effects, has been studied for its potential therapeutic ... ...

Abstract	Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease. Currently, therapeutic options are limited for this fatal disease. Curcumin, with its pleiotropic effects, has been studied for its potential therapeutic utilities in various diseases, including pulmonary fibrosis. However, the detailed mechanisms have not been studied comprehensively. We conducted a next-generation sequencing and bioinformatics study to investigate changes in the profiles of mRNA and microRNA after curcumin treatment in IPF fibroblasts. We identified 23 downregulated and 8 upregulated protein-coding genes in curcumin-treated IPF fibroblasts. Using STRING and IPA, we identified that suppression of cell cycle progression was the main cellular function associated with these differentially expressed genes. We also identified 13 downregulated and 57 upregulated microRNAs in curcumin-treated IPF fibroblasts. Further analysis identified a potential microRNA-mediated gene expression alteration in curcumin-treated IPF fibroblasts, namely, downregulated hsa-miR-6724-5p and upregulated KLF10 . Therefore, curcumin might decrease the level of hsa-miR-6724-5p, leading to increased KLF10 expression, resulting in cell cycle arrest in curcumin-treated IPF fibroblasts. In conclusion, our findings might support the potential role of curcumin in the treatment of IPF, but further in-depth study is warranted to confirm our findings.
Keywords	bioinformatics ; curcumin ; fibroblasts ; idiopathic pulmonary fibrosis ; microRNA ; next-generation sequencing ; Organic chemistry ; QD241-441
Subject code	616
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Blood tryptase and thymic stromal lymphopoietin levels predict the risk of exacerbation in severe asthma

Hsin-Kuo Ko / Shih-Lung Cheng / Ching-Hsiung Lin / Sheng-Hao Lin / Yi-Han Hsiao / Kang-Cheng Su / Chong-Jen Yu / Hao-Chien Wang / Chau-Chyun Sheu / Kuo-Chin Chiu / Diahn-Warng Perng

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 10

Abstract: Abstract Some patients with severe asthma experience exacerbations despite receiving multiple therapy. The risk of exacerbation and heterogeneous response to treatment may be associated with specific inflammatory molecules that are responsive or ... ...

Abstract	Abstract Some patients with severe asthma experience exacerbations despite receiving multiple therapy. The risk of exacerbation and heterogeneous response to treatment may be associated with specific inflammatory molecules that are responsive or resistant to corticosteroids. We aimed to identify the independent factors predictive for the future risk of exacerbation in patients with severe asthma. In this multi-center prospective observational study, 132 patients with severe asthma were enrolled and divided into exacerbation (n = 52) and non-exacerbation (n = 80) groups on the basis of exacerbation rate after a 1-year follow-up period. We found that previous history of severe-to-serious exacerbation, baseline blood eosinophil counts (≥ 291cells/μL), and serum tryptase (≤ 1448 pg/mL) and thrymic stromal lymphopoietin (TSLP) levels (≥ 25 pg/mL) independently predicted the future development of exacerbation with adjusted odds ratios (AOR) of 3.27, 6.04, 2.53 and 8.67, respectively. Notably, the patients with high blood eosinophil counts and low tryptase levels were likely to have more exacerbations than those with low blood eosinophil counts and high tryptase levels (AOR 16.9). TSLP potentially played the pathogenic role across different asthma phenotypes. TSLP and tryptase levels may be implicated in steroid resistance and responsiveness in the asthma inflammatory process. High blood eosinophil counts and low serum tryptase levels predict a high probability of future asthma exacerbation.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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