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(1) Background: Sepsis is a life-threatening condition, and most patients with sepsis first present to the emergency department (ED) where early identification of sepsis is challenging due to the unavailability of an effective diagnostic model. (2) Methods: In this retrospective study, patients aged ≥20 years who presented to the ED of an academic hospital with systemic inflammatory response syndrome (SIRS) were included. The SIRS, sequential organ failure assessment (SOFA), and quick SOFA (qSOFA) scores were obtained for all patients. Routine complete blood cell testing in conjugation with the examination of new inflammatory biomarkers, namely monocyte distribution width (MDW), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), was performed at the ED. Propensity score matching was performed between patients with and without sepsis. Logistic regression was used for constructing models for early sepsis prediction. (3) Results: We included 296 patients with sepsis and 1184 without sepsis. A SIRS score of >2, a SOFA score of >2, and a qSOFA score of >1 showed low sensitivity, moderate specificity, and limited diagnostic accuracy for predicting early sepsis infection (c-statistics of 0.660, 0.576, and 0.536, respectively). MDW > 20, PLR > 9, and PLR > 210 showed higher sensitivity and moderate specificity. When we combined these biomarkers and scoring systems, we observed a significant improvement in diagnostic performance (c-statistics of 0.796 for a SIRS score of >2, 0.761 for a SOFA score of >2, and 0.757 for a qSOFA score of >1); (4) Conclusions: The new biomarkers MDW, NLR, and PLR can be used for the early detection of sepsis in the current sepsis scoring systems.
Sen-Kuang Hou; Hui-An Lin; Shao-Chun Chen; Chiou-Feng Lin; Sheng-Feng Lin. Monocyte Distribution Width, Neutrophil-to-Lymphocyte Ratio, and Platelet-to-Lymphocyte Ratio Improves Early Prediction for Sepsis at the Emergency. Journal of Personalized Medicine 2021, 11, 732 .
AMA StyleSen-Kuang Hou, Hui-An Lin, Shao-Chun Chen, Chiou-Feng Lin, Sheng-Feng Lin. Monocyte Distribution Width, Neutrophil-to-Lymphocyte Ratio, and Platelet-to-Lymphocyte Ratio Improves Early Prediction for Sepsis at the Emergency. Journal of Personalized Medicine. 2021; 11 (8):732.
Chicago/Turabian StyleSen-Kuang Hou; Hui-An Lin; Shao-Chun Chen; Chiou-Feng Lin; Sheng-Feng Lin. 2021. "Monocyte Distribution Width, Neutrophil-to-Lymphocyte Ratio, and Platelet-to-Lymphocyte Ratio Improves Early Prediction for Sepsis at the Emergency." Journal of Personalized Medicine 11, no. 8: 732.
The adverse effect of cisplatin administration causes acute kidney injury (AKI) following renal inflammation and nephrotoxicity, characterized by proximal tubular cell apoptosis and necrosis. Pro-apoptotic and pro-inflammatory roles of glycogen synthase kinase (GSK)-3β have been reported. This study investigated the therapeutic blockade of GSK-3β in cisplatin-induced AKI. A renal cisplatin nephrotoxicity model showed activation of GSK-3β in vivo, particularly in proximal tubular epithelial cells. Pharmacologically inhibiting GSK-3β abolished cisplatin nephrotoxicity, including proximal tubular injury, cell cytotoxicity, and biochemical dysfunction. Additionally, GSK-3β inhibitor treatment ameliorated renal inflammation by reducing immune cell infiltration, cell adhesion molecule expression, and pro-inflammatory cytokine/chemokine production. Cisplatin treatment caused GSK-3β activation in vitro in the human renal proximal tubular epithelial cell line HK-2, whereas either pharmacological administration of GSK-3β inhibitors or genetic transduction of GSK-3β short-hairpin RNA impeded cisplatin-induced cytotoxicity. These results indicate that cisplatin activates GSK-3β followed by GSK-3β-mediated renal inflammation and nephrotoxicity, contributing to AKI.
Chung-Hsi Hsing; Cheng-Chieh Tsai; Chia-Ling Chen; Yu-Hui Lin; Po-Chun Tseng; Rahmat Satria; Chiou-Feng Lin. Pharmacologically Inhibiting Glycogen Synthase Kinase-3β Ameliorates Renal Inflammation and Nephrotoxicity in an Animal Model of Cisplatin-Induced Acute Kidney Injury. Biomedicines 2021, 9, 887 .
AMA StyleChung-Hsi Hsing, Cheng-Chieh Tsai, Chia-Ling Chen, Yu-Hui Lin, Po-Chun Tseng, Rahmat Satria, Chiou-Feng Lin. Pharmacologically Inhibiting Glycogen Synthase Kinase-3β Ameliorates Renal Inflammation and Nephrotoxicity in an Animal Model of Cisplatin-Induced Acute Kidney Injury. Biomedicines. 2021; 9 (8):887.
Chicago/Turabian StyleChung-Hsi Hsing; Cheng-Chieh Tsai; Chia-Ling Chen; Yu-Hui Lin; Po-Chun Tseng; Rahmat Satria; Chiou-Feng Lin. 2021. "Pharmacologically Inhibiting Glycogen Synthase Kinase-3β Ameliorates Renal Inflammation and Nephrotoxicity in an Animal Model of Cisplatin-Induced Acute Kidney Injury." Biomedicines 9, no. 8: 887.
Patients receiving hemodialysis (HD) are at risk of TB development. IGRA-positive patients showed significant decrease in quantitative IGRA result with alterations in CD3+CD4+CD45RO+, NK cell, and monocyte subsets immediately upon HD procedure. Our result suggested that the timing of IGRA testing is crucial in end-stage renal disease population.
Denise Utami Putri; Chia-Ling Chen; Cheng-Hui Wang; Yuh-Mou Sue; Po-Chun Tseng; Chiou-Feng Lin; Ching-Wen Tsai; Yi-Jun Liu; Chih-Hsin Lee. Hemodialysis Acutely Altered Interferon-Gamma Release Assay Test Result and Immune Cell Profile. Journal of Microbiology, Immunology and Infection 2021, 1 .
AMA StyleDenise Utami Putri, Chia-Ling Chen, Cheng-Hui Wang, Yuh-Mou Sue, Po-Chun Tseng, Chiou-Feng Lin, Ching-Wen Tsai, Yi-Jun Liu, Chih-Hsin Lee. Hemodialysis Acutely Altered Interferon-Gamma Release Assay Test Result and Immune Cell Profile. Journal of Microbiology, Immunology and Infection. 2021; ():1.
Chicago/Turabian StyleDenise Utami Putri; Chia-Ling Chen; Cheng-Hui Wang; Yuh-Mou Sue; Po-Chun Tseng; Chiou-Feng Lin; Ching-Wen Tsai; Yi-Jun Liu; Chih-Hsin Lee. 2021. "Hemodialysis Acutely Altered Interferon-Gamma Release Assay Test Result and Immune Cell Profile." Journal of Microbiology, Immunology and Infection , no. : 1.
During the acute febrile phase of dengue virus (DENV) infection, viremia can cause severe systemic immune responses accompanied by hematologic disorders. This study investigated the potential induction and mechanism of the cytopathic effects of DENV on peripheral blood cells ex vivo. At one day postinfection, there was viral nonstructural protein NS1 but no further virus replication measured in the whole blood culture. Notably, DENV exposure caused significant vacuolization in monocytic phagocytes. With a minor change in the complete blood cell count, except for a minor increase in neutrophils and a significant decrease in monocytes, the immune profiling assay identified several changes, particularly a significant reduction in CD14-positive monocytes as well as CD11c-positive dendritic cells. Abnormal production of TNF-α was highly associated with the induction of vacuolization. Manipulating TNF-α expression resulted in cytopathogenic effects. These results demonstrate the potential hematological damage caused by ex vivo DENV-induced TNF-α.
Rahmat Dani Satria; Tzu-Wen Huang; Ming-Kai Jhan; Ting-Jing Shen; Po-Chun Tseng; Yun-Ting Wang; Zhen-Yu Yang; Chung-Hsi Hsing; Chiou-Feng Lin. Increased TNF-α Initiates Cytoplasmic Vacuolization in Whole Blood Coculture with Dengue Virus. Journal of Immunology Research 2021, 2021, 1 -10.
AMA StyleRahmat Dani Satria, Tzu-Wen Huang, Ming-Kai Jhan, Ting-Jing Shen, Po-Chun Tseng, Yun-Ting Wang, Zhen-Yu Yang, Chung-Hsi Hsing, Chiou-Feng Lin. Increased TNF-α Initiates Cytoplasmic Vacuolization in Whole Blood Coculture with Dengue Virus. Journal of Immunology Research. 2021; 2021 ():1-10.
Chicago/Turabian StyleRahmat Dani Satria; Tzu-Wen Huang; Ming-Kai Jhan; Ting-Jing Shen; Po-Chun Tseng; Yun-Ting Wang; Zhen-Yu Yang; Chung-Hsi Hsing; Chiou-Feng Lin. 2021. "Increased TNF-α Initiates Cytoplasmic Vacuolization in Whole Blood Coculture with Dengue Virus." Journal of Immunology Research 2021, no. : 1-10.
Propofol, 2,6-diisopropylphenol, is a short-acting intravenous sedative agent used in adults and children. Current studies show its various antimicrobial as well as anti-inflammatory effects. Dengue virus (DENV) is an emerging infectious pathogen transmitted by mosquitoes that causes mild dengue fever and progressive severe dengue diseases. In the absence of safe vaccines and antiviral agents, adjuvant treatments and supportive care are generally administered. This study investigated the antiviral effects of propofol against DENV infection and cellular inflammation by using an in vitro cell model. Treatment with propofol significantly inhibited DENV release 24 h postinfection in BHK-21 cells. Furthermore, it also blocked viral protein expression independent of the translational blockade. Propofol neither caused inhibitory effects on endosomal acidification nor prevented dsRNA replication. Either the proinflammatory TNF-α or the antiviral STAT1 signaling was reduced by propofol treatment. These results provide evidence to show the potential antiviral effects of the sedative propofol against DENV infection and cellular inflammation.
Ting-Jing Shen; Chia-Ling Chen; Ming-Kai Jhan; Po-Chun Tseng; Rahmat Dani Satria; Chung-Hsi Hsing; Chiou-Feng Lin. Antiviral Efficacy of the Anesthetic Propofol against Dengue Virus Infection and Cellular Inflammation. Journal of Immunology Research 2021, 2021, 1 -8.
AMA StyleTing-Jing Shen, Chia-Ling Chen, Ming-Kai Jhan, Po-Chun Tseng, Rahmat Dani Satria, Chung-Hsi Hsing, Chiou-Feng Lin. Antiviral Efficacy of the Anesthetic Propofol against Dengue Virus Infection and Cellular Inflammation. Journal of Immunology Research. 2021; 2021 ():1-8.
Chicago/Turabian StyleTing-Jing Shen; Chia-Ling Chen; Ming-Kai Jhan; Po-Chun Tseng; Rahmat Dani Satria; Chung-Hsi Hsing; Chiou-Feng Lin. 2021. "Antiviral Efficacy of the Anesthetic Propofol against Dengue Virus Infection and Cellular Inflammation." Journal of Immunology Research 2021, no. : 1-8.
The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted.
Denise Putri; Cheng-Hui Wang; Po-Chun Tseng; Wen-Sen Lee; Fu-Lun Chen; Han-Pin Kuo; Chih-Hsin Lee; Chiou-Feng Lin. Profiles of Peripheral Immune Cells of Uncomplicated COVID-19 Cases with Distinct Viral RNA Shedding Periods. Viruses 2021, 13, 514 .
AMA StyleDenise Putri, Cheng-Hui Wang, Po-Chun Tseng, Wen-Sen Lee, Fu-Lun Chen, Han-Pin Kuo, Chih-Hsin Lee, Chiou-Feng Lin. Profiles of Peripheral Immune Cells of Uncomplicated COVID-19 Cases with Distinct Viral RNA Shedding Periods. Viruses. 2021; 13 (3):514.
Chicago/Turabian StyleDenise Putri; Cheng-Hui Wang; Po-Chun Tseng; Wen-Sen Lee; Fu-Lun Chen; Han-Pin Kuo; Chih-Hsin Lee; Chiou-Feng Lin. 2021. "Profiles of Peripheral Immune Cells of Uncomplicated COVID-19 Cases with Distinct Viral RNA Shedding Periods." Viruses 13, no. 3: 514.
Global pandemic resulted from the coronavirus disease-19 (COVID-19) demands mental health concerns on the affected population. We examine the time-course shift of psychological burden among suspected and confirmed COVID-19 patients. Participants with suspected or confirmed COVID-19 were included in the cohort. Consecutive surveys were conducted upon hospital admission, discharge, and during outpatient follow-up by adapting the 5-item brief symptom rating scale (BSRS-5) assessing psychological symptoms including anxiety, depression, hostility, interpersonal sensitivity, and insomnia. The sixth measure to observe suicidal ideation was also included. A total of 109 eligible patients participated in the study, in which 83.49% reported no distress upon hospital admission, while 2.75%, 3.66%, and 10.1% patients were assessed as being with severe, moderate and mild psychological distress, respectively. Overall, age, sex, and history of contact did not significantly differ between patients with and without psychological distress. Multivariate logistic regression revealed that patients admitted during April–May (OR: 7.66, 95% CI: 1.46–40.28) and presented with symptoms including sore throat (OR: 4.24, 95% CI: 1.17–15.29) and malaise (OR: 5.24, 95% CI: 1.21–22.77) showed significantly higher risk of psychological distress. Cough symptom interestingly showed lower risk of emotional distress (OR: 0.25, 95% CI: 0.08–0.81). Subsequent surveys upon hospital discharge and during outpatient follow-up revealed steadily declining distress among all cohort. At least 16.5% of our cohort reported psychological distress upon hospital admission, with distinct time-dependent decline. Access to mental health support, alongside with promoting positive activities for good mental health are pivotal for those directly affected.
Denise Utami Putri; Yi-San Tsai; Jin-Hua Chen; Ching-Wen Tsai; Chung-Yi Ou; Chiao-Ru Chang; Hui-Chun Chen; Mong-Liang Lu; Ming-Chih Yu; Chih-Hsin Lee. Psychological distress assessment among patients with suspected and confirmed COVID-19: A cohort study. Journal of the Formosan Medical Association 2021, 1 .
AMA StyleDenise Utami Putri, Yi-San Tsai, Jin-Hua Chen, Ching-Wen Tsai, Chung-Yi Ou, Chiao-Ru Chang, Hui-Chun Chen, Mong-Liang Lu, Ming-Chih Yu, Chih-Hsin Lee. Psychological distress assessment among patients with suspected and confirmed COVID-19: A cohort study. Journal of the Formosan Medical Association. 2021; ():1.
Chicago/Turabian StyleDenise Utami Putri; Yi-San Tsai; Jin-Hua Chen; Ching-Wen Tsai; Chung-Yi Ou; Chiao-Ru Chang; Hui-Chun Chen; Mong-Liang Lu; Ming-Chih Yu; Chih-Hsin Lee. 2021. "Psychological distress assessment among patients with suspected and confirmed COVID-19: A cohort study." Journal of the Formosan Medical Association , no. : 1.
Dengue virus (DENV) is transmitted by Aedes mosquitoes to humans and is a threat worldwide. No effective new drugs have been used for anti-dengue treatment, and repurposing drugs is an alternative approach to treat this condition. Dopamine 2 receptor (D2R) is a host receptor positively associated with DENV infection. Metoclopramide (MCP), a D2R antagonist clinically used to control vomiting and nausea in patients with DENV infection, was putatively examined for inhibition of DENV infection by targeting D2R. In the mouse neural cell line Neuro-2a with D2R expression, a plaque assay demonstrated the antiviral efficacy of MCP treatment. However, in the cell line BHK-21, which did not express D2R, MCP treatment caused no further inhibition of DENV infection. Either MCP treatment or exogenous administration of a neutralizing D2R antibody blocked DENV binding. Treatment with MCP also reduced DENV dsRNA replication and DENV-induced neuronal cell cytotoxicity in vitro. An in vivo study demonstrated the antiviral effect of MCP against DENV-induced CNS neuropathy and mortality. These results showed that repurposing the D2R-targeting antiemetic MCP is a potential therapeutic strategy against DENV infection.
Ting-Jing Shen; Vu Thi Hanh; Thai Quoc Nguyen; Ming-Kai Jhan; Min-Ru Ho; Chiou-Feng Lin. Repurposing the Antiemetic Metoclopramide as an Antiviral Against Dengue Virus Infection in Neuronal Cells. Frontiers in Cellular and Infection Microbiology 2021, 10, 1 .
AMA StyleTing-Jing Shen, Vu Thi Hanh, Thai Quoc Nguyen, Ming-Kai Jhan, Min-Ru Ho, Chiou-Feng Lin. Repurposing the Antiemetic Metoclopramide as an Antiviral Against Dengue Virus Infection in Neuronal Cells. Frontiers in Cellular and Infection Microbiology. 2021; 10 ():1.
Chicago/Turabian StyleTing-Jing Shen; Vu Thi Hanh; Thai Quoc Nguyen; Ming-Kai Jhan; Min-Ru Ho; Chiou-Feng Lin. 2021. "Repurposing the Antiemetic Metoclopramide as an Antiviral Against Dengue Virus Infection in Neuronal Cells." Frontiers in Cellular and Infection Microbiology 10, no. : 1.
Therapeutic drug monitoring is important for achieving desirable outcomes in tuberculosis treatment. In this study, microwave-assisted extraction was used to extract levofloxacin, ciprofloxacin, and moxifloxacin from dried plasma spots for subsequent detection and quantification with ultra-high performance liquid chromatography-tandem mass spectrometry. Dried plasma spotting was performed by dropping 15 µL of plasma on a protein saver card. Analyte extraction was performed with microwave-assisted extraction at 400 W for 40 seconds in 90% methanol. Samples were analyzed with a core-shell C18 column (100 mm × 2.1 mm, 2.6 μm, 100 Å). Multiple reaction monitoring was used and the ion source was operated in positive electrospray ionization mode. The correlation coefficients of the calibration curves were > 0.999 for all three drugs over a range of 0.2-20 µg/mL. The intraday precision (n = 5) of the peak area ratios of the analyte to the internal standard was between 1.3 and 4.0% relative standard deviation (RSD). The intraday accuracy ranged from 93.6 to 106.9%. The interday (n = 3) precision of the peak area ratios ranged from 1.9 to 8.8% RSD, and the accuracy ranged from 94.9 to 107.1%. Regarding clinical application, the quantification results for moxifloxacin from dried plasma spots (DPSs) were strongly similar to the results from the plasma samples, which showed that Pearson’s rho > 0.949. The validation and application results showed that the developed method can be used as an efficient analytical technique for therapeutic drug monitoring of fluoroquinolones for patients with tuberculosis.
Ageng Brahmadhi; Michael X. Chen; San-Yuan Wang; Yun-Yu Cho; Ming-Chih Yu; Chih-Hsin Lee; I-Lin Tsai. Determination of fluoroquinolones in dried plasma spots by using microwave-assisted extraction coupled to ultra-high performance liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring. Journal of Pharmaceutical and Biomedical Analysis 2020, 195, 113821 .
AMA StyleAgeng Brahmadhi, Michael X. Chen, San-Yuan Wang, Yun-Yu Cho, Ming-Chih Yu, Chih-Hsin Lee, I-Lin Tsai. Determination of fluoroquinolones in dried plasma spots by using microwave-assisted extraction coupled to ultra-high performance liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring. Journal of Pharmaceutical and Biomedical Analysis. 2020; 195 ():113821.
Chicago/Turabian StyleAgeng Brahmadhi; Michael X. Chen; San-Yuan Wang; Yun-Yu Cho; Ming-Chih Yu; Chih-Hsin Lee; I-Lin Tsai. 2020. "Determination of fluoroquinolones in dried plasma spots by using microwave-assisted extraction coupled to ultra-high performance liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring." Journal of Pharmaceutical and Biomedical Analysis 195, no. : 113821.
Dengue virus (DENV) infection in the brain causes severe dengue disease with neuropathic complications. In addition to viral effects, immunogenic or pathogenic central nervous system (CNS) inflammation can be induced during DENV infection. By using an immunocompetent outbred ICR (Institute of Cancer Research) mouse model for investigating CNS immunity upon DENV infection, we conducted single-panel immune cell profiling and a multiplex cytokine assay. The ICR mice infected with DENV presented with progressive hunchback posture, limbic seizures, limbic weakness, paralysis, and lethality. When the virions were released, the viral non-structural protein 1 was expressed in the brain in a time-dependent manner. Isolated brain CD45-positive cells revealed a significant population of resident CD14-positive cells, which was considerably decreased 8 days post-infection. We found an unexpected time-kinetic decrease in CD19-positive cells and CD11c/MHC II-positive cells and an increase in NK1.1-positive cells. Further assays showed the time-dependent induction of proinflammatory and NK1.1-associated cytokines in the DENV-infected brains. These results indicate a CNS immune profile of DENV infection and hypothetical CNS immunity in response to DENV infection.
Ting-Jing Shen; Chia-Ling Chen; Ming-Kai Jhan; Po-Chun Tseng; Chiou-Feng Lin. CNS Immune Profiling in a Dengue Virus-Infected Immunocompetent Outbred ICR Mice Strain. Frontiers in Cellular and Infection Microbiology 2020, 10, 1 .
AMA StyleTing-Jing Shen, Chia-Ling Chen, Ming-Kai Jhan, Po-Chun Tseng, Chiou-Feng Lin. CNS Immune Profiling in a Dengue Virus-Infected Immunocompetent Outbred ICR Mice Strain. Frontiers in Cellular and Infection Microbiology. 2020; 10 ():1.
Chicago/Turabian StyleTing-Jing Shen; Chia-Ling Chen; Ming-Kai Jhan; Po-Chun Tseng; Chiou-Feng Lin. 2020. "CNS Immune Profiling in a Dengue Virus-Infected Immunocompetent Outbred ICR Mice Strain." Frontiers in Cellular and Infection Microbiology 10, no. : 1.
Aging and chronic condition increase the incidence of dengue virus (DENV) infection, generally through a mechanism involving immunosenescence; however, the alternative effects of cellular senescence, which alters cell susceptibility to viral infection, remain unknown. Human monocytic THP-1 cells (ATCC TIB-202) treated with D-galactose to induce cellular senescence were susceptible to DENV infection. These senescent cells showed increased viral entry/binding, gene/protein expression, and dsRNA replication. The use of a replicon system showed that pharmacologically induced senescence did not enhance the effects on viral protein translation. By examining viral receptor expression, we found increased expression of CD209 (DC-SIGN) in the senescent cells. Interleukin (IL)-10 was aberrantly produced at high levels by the senescent cells, and the expression of the DENV receptor DC-SIGN was increased in these senescent cells, partially via IL-10-mediated regulation of the JAK2-STAT3 signaling pathway. The results demonstrate that a senescent phenotype facilitates DENV infection, probably by increasing DC-SIGN expression.
Tzu-Han Hsieh; Tsung-Ting Tsai; Chia-Ling Chen; Ting-Jing Shen; Ming-Kai Jhan; Po-Chun Tseng; Chiou-Feng Lin. Senescence in Monocytes Facilitates Dengue Virus Infection by Increasing Infectivity. Frontiers in Cellular and Infection Microbiology 2020, 10, 375 .
AMA StyleTzu-Han Hsieh, Tsung-Ting Tsai, Chia-Ling Chen, Ting-Jing Shen, Ming-Kai Jhan, Po-Chun Tseng, Chiou-Feng Lin. Senescence in Monocytes Facilitates Dengue Virus Infection by Increasing Infectivity. Frontiers in Cellular and Infection Microbiology. 2020; 10 ():375.
Chicago/Turabian StyleTzu-Han Hsieh; Tsung-Ting Tsai; Chia-Ling Chen; Ting-Jing Shen; Ming-Kai Jhan; Po-Chun Tseng; Chiou-Feng Lin. 2020. "Senescence in Monocytes Facilitates Dengue Virus Infection by Increasing Infectivity." Frontiers in Cellular and Infection Microbiology 10, no. : 375.
Cytokines are the major immune regulators secreted from activated CD4+ T lymphocytes that activate adaptive immunity to eradicate nonself cells, including pathogens, tumors, and allografts. The regulation of glycogen synthase kinase (GSK)-3β, a serine/threonine kinase, controls cytokine production by regulating transcription factors. The artificial in vitro activation of CD4+ T lymphocytes by a combination of 12-O-tetradecanoylphorbol-13-acetate and ionomycin, the so-called T/I model, led to an inducible production of cytokines, such as interferon-γ, tumor necrosis factor-α, and interleukin-2. As demonstrated by the approaches of pharmacological targeting and genetic knockdown of GSK-3β, T/I treatment effectively caused GSK-3β activation followed by GSK-3β-regulated cytokine production. In contrast, pharmacological inhibition of the proline-rich tyrosine kinase 2 and calcineurin signaling pathways blocked cytokine production, probably by deactivating GSK-3β. The blockade of GSK-3β led to the inhibition of the nuclear translocation of T-bet, a vital transcription factor of T lymphocyte cytokines. In a mouse model, treatment with the GSK-3β inhibitor 6-bromoindirubin-3’-oxime significantly inhibited T/I-induced mortality and serum cytokine levels. In summary, targeting GSK-3β effectively inhibits CD4+ T lymphocyte activation and cytokine production.
Cheng-Chieh Tsai; Chin-Kun Tsai; Po-Chun Tseng; Chiou-Feng Lin; Chia-Ling Chen. Glycogen Synthase Kinase-3β Facilitates Cytokine Production in 12-O-Tetradecanoylphorbol-13-Acetate/Ionomycin-Activated Human CD4+ T Lymphocytes. Cells 2020, 9, 1424 .
AMA StyleCheng-Chieh Tsai, Chin-Kun Tsai, Po-Chun Tseng, Chiou-Feng Lin, Chia-Ling Chen. Glycogen Synthase Kinase-3β Facilitates Cytokine Production in 12-O-Tetradecanoylphorbol-13-Acetate/Ionomycin-Activated Human CD4+ T Lymphocytes. Cells. 2020; 9 (6):1424.
Chicago/Turabian StyleCheng-Chieh Tsai; Chin-Kun Tsai; Po-Chun Tseng; Chiou-Feng Lin; Chia-Ling Chen. 2020. "Glycogen Synthase Kinase-3β Facilitates Cytokine Production in 12-O-Tetradecanoylphorbol-13-Acetate/Ionomycin-Activated Human CD4+ T Lymphocytes." Cells 9, no. 6: 1424.
Treatment of latent tuberculosis infection (LTBI) is an important strategy for active disease prevention. Conventional in-person DOT (CDOT) programs are challenged by patient dissatisfaction over problems of convenience and privacy. The present study assessed satisfaction to DOT program and treatment adherence of synchronous video observed treatment (SVOT) programs from patients’ perspectives. A two-part questionnaire was presented to 240 subjects with LTBI who received a 9-month isoniazid treatment regimen along with mandatory DOT monitoring during January 2014 to December 2017. Satisfactions with location arrangement (p < 0.001), ensuring treatment adherence (p = 0.027), and privacy issues (p = 0.005) were superior in the SVOT group. The overall rate of LTBI treatment completion was 91.25%. One (1.25%) and 20 (12.50%) of the participants in the SVOT and CDOT groups, respectively, quit LTBI treatment (p = 0.008). Development of adverse events [adjusted hazard ratio, aHR 8.01 (3.42–18.79)], and the concern of privacy infringement [aHR 5.86 (2.69–12.76)] by the DOT program independently increase the risk of withdrawal. SVOT program [aHR 0.21 (0.06–0.68)] and a belief in the importance of adherence on treatment efficacy [aHR 0.29 (0.08–0.98)] were independent predictors preventing patients from withdrawing from treatment. A comprehensive patient-centered DOT program enables high treatment adherence for the 9-month isoniazid LTBI treatment. Furthermore, SVOT was associated with superior patients’ satisfactions which translate into higher treatment completion rates. As treatment adherence is the key to the efficacy of LTBI treatment, SVOT should be a reasonable supplement for LTBI treatment.
Szu-Hsuan Chen; Irene Wang; Han-Lin Hsu; Chi-Ching Huang; Yi-Jun Liu; Denise Utami Putri; Chih-Hsin Lee. Advantage in privacy protection by using synchronous video observed treatment enhances treatment adherence among patients with latent tuberculosis infection. Journal of Infection and Public Health 2020, 13, 1354 -1359.
AMA StyleSzu-Hsuan Chen, Irene Wang, Han-Lin Hsu, Chi-Ching Huang, Yi-Jun Liu, Denise Utami Putri, Chih-Hsin Lee. Advantage in privacy protection by using synchronous video observed treatment enhances treatment adherence among patients with latent tuberculosis infection. Journal of Infection and Public Health. 2020; 13 (9):1354-1359.
Chicago/Turabian StyleSzu-Hsuan Chen; Irene Wang; Han-Lin Hsu; Chi-Ching Huang; Yi-Jun Liu; Denise Utami Putri; Chih-Hsin Lee. 2020. "Advantage in privacy protection by using synchronous video observed treatment enhances treatment adherence among patients with latent tuberculosis infection." Journal of Infection and Public Health 13, no. 9: 1354-1359.
Little remains known regarding whether newer FQ with less anti-mycobacterial activity (gemifloxacin) would reduce treatment delay. We identified one hospital-based cohort (HBC) and one population-based cohort (PBC) including patients receiving amoxicillin/clavulanate acid (Beta-lactam), gemifloxacin (Gemi), and fluoroquinolones other than gemifloxacin (Non-Gemi FQ) prior to TB treatment. A total of 201 patients in the HBC and 3544 patients in the PBC were recruited. After 1:1 propensity score matching, TB treatment delay was statistically insignificant between Beta-lactam, Gemi group, and Non-Gemi FQ group in HBC (Beta-lactam vs Gemi: 22.3 ± 21.4 d vs 28.6 ± 27.9 d, p = 0.292; Beta-lactam vs Non-Gemi FQ: 33.3 ± 26.5 d vs 50.3 ± 47.3 d, p = 0.135) and PBC (Beta-lactam vs Gemi: 26.4 ± 29.1 vs 25.0 ± 28.1, p = 0.638; Beta-lactam vs Non-Gemi FQ: 29.4 ± 36.0 d vs 32.7 ± 35.0 d, p = 0.124, Non-Gemi FQ vs Gemi: 28.4 ± 33.0 d vs 25.0 ± 28.1 d, p = 0.29). While limited by relatively low case number, our study showed that use of gemifloxacin neither results in nor reduces delay in TB treatment. The issue of FQ use on TB treatment delay was also not observed in our study. Early survey and maintaining high clinical alertness remains the key to reducing TB treatment delay.
Meng-Rui Lee; Chih-Hsin Lee; Jann-Yuan Wang; Shih-Wei Lee; Jen-Chung Ko; Li-Na Lee. Clinical impact of using fluoroquinolone with low antimycobacterial activity on treatment delay in tuberculosis: Hospital-based and population-based cohort study. Journal of the Formosan Medical Association 2019, 119, 367 -376.
AMA StyleMeng-Rui Lee, Chih-Hsin Lee, Jann-Yuan Wang, Shih-Wei Lee, Jen-Chung Ko, Li-Na Lee. Clinical impact of using fluoroquinolone with low antimycobacterial activity on treatment delay in tuberculosis: Hospital-based and population-based cohort study. Journal of the Formosan Medical Association. 2019; 119 (1):367-376.
Chicago/Turabian StyleMeng-Rui Lee; Chih-Hsin Lee; Jann-Yuan Wang; Shih-Wei Lee; Jen-Chung Ko; Li-Na Lee. 2019. "Clinical impact of using fluoroquinolone with low antimycobacterial activity on treatment delay in tuberculosis: Hospital-based and population-based cohort study." Journal of the Formosan Medical Association 119, no. 1: 367-376.
While evidence is accumulating that platelets contribute to tissue destruction in tuberculosis (TB) disease, it is still not known whether antiplatelet agents are beneficial to TB patients. We performed this retrospective cohort study and identified incident TB cases in the Taiwan National Tuberculosis Registry from 2008 to 2014. These cases were further classified into antiplatelet users and non-users according to the use of antiplatelet agents prior to the TB diagnosis, and the cohorts were matched using propensity scores (PSs). The primary outcome was survival after a TB diagnosis. In total, 74,753 incident TB cases were recruited; 9497 (12.7%) were antiplatelet users, and 7764 (10.4%) were aspirin (ASA) users. A 1:1 PS-matched cohort with 8864 antiplatelet agent users and 8864 non-users was created. After PS matching, antiplatelet use remained associated with a longer survival (adjusted hazard ratio (HR): 0.91, 95% confidence interval (CI): 0.88-0.95, p < 0.0001). The risk of major bleeding was not elevated in antiplatelet users compared to non-users (p = 0.604). This study shows that use of antiplatelet agents has been associated with improved survival in TB patients. The immunomodulatory and anti-inflammatory effects of antiplatelet agents in TB disease warrant further investigation. Antiplatelets are promising as an adjunct anti-TB therapy.
Meng-Rui Lee; Ming-Chia Lee; Chia-Hao Chang; Chia-Jung Liu; Lih-Yu Chang; Jun-Fu Zhang; Jann-Yuan Wang; Chih-Hsin Lee. Use of Antiplatelet Agents and Survival of Tuberculosis Patients: A Population-Based Cohort Study. Journal of Clinical Medicine 2019, 8, 923 .
AMA StyleMeng-Rui Lee, Ming-Chia Lee, Chia-Hao Chang, Chia-Jung Liu, Lih-Yu Chang, Jun-Fu Zhang, Jann-Yuan Wang, Chih-Hsin Lee. Use of Antiplatelet Agents and Survival of Tuberculosis Patients: A Population-Based Cohort Study. Journal of Clinical Medicine. 2019; 8 (7):923.
Chicago/Turabian StyleMeng-Rui Lee; Ming-Chia Lee; Chia-Hao Chang; Chia-Jung Liu; Lih-Yu Chang; Jun-Fu Zhang; Jann-Yuan Wang; Chih-Hsin Lee. 2019. "Use of Antiplatelet Agents and Survival of Tuberculosis Patients: A Population-Based Cohort Study." Journal of Clinical Medicine 8, no. 7: 923.
The interferon- (IFN-) γ expression is elicited in response to microbial infections and activates immune surveillance by antimicrobial immune elements to induce microbial killing. Patients with adult-onset immunodeficiency who suffer from recurrent infections with microbes, particularly nontuberculous mycobacteria (NTM), commonly display genetic defects in IFN-γ signaling as well as the generation of anti-IFN-γ autoantibodies (autoAbs). Because IFN-γ is an activator of macrophage differentiation and a proinflammatory activator of innate immunity, the blockade effects of the autoAbs present in NTM patient serum on IFN-γ are hypothesized to regulate the antimicrobial function of macrophages. In the presence of patient serum, IFN-γ-induced type 1 macrophage (M1) differentiation was inhibited in PMA-stimulated human monocytic THP-1 cells. Treatment with patient serum significantly blocked the production of proinflammatory factors, including cytokines/chemokines and reactive oxygen/nitrogen species, by M1 macrophages. Importantly, IFN-γ-facilitated phagocytosis and degradation of heat-killed mycobacterium were decreased by cotreatment with patient serum. These results show the blockade activity of anti-IFN-γ autoAbs on IFN-γ-mediated antimicrobial immunity in macrophages.
Dyah Ika Krisnawati; Yung-Ching Liu; Yuarn-Jang Lee; Yun-Ting Wang; Chia-Ling Chen; Po-Chun Tseng; Ting-Jing Shen; Chiou-Feng Lin. Blockade Effects of Anti-Interferon- (IFN-) γ Autoantibodies on IFN-γ-Regulated Antimicrobial Immunity. Journal of Immunology Research 2019, 2019, 1629258 -7.
AMA StyleDyah Ika Krisnawati, Yung-Ching Liu, Yuarn-Jang Lee, Yun-Ting Wang, Chia-Ling Chen, Po-Chun Tseng, Ting-Jing Shen, Chiou-Feng Lin. Blockade Effects of Anti-Interferon- (IFN-) γ Autoantibodies on IFN-γ-Regulated Antimicrobial Immunity. Journal of Immunology Research. 2019; 2019 ():1629258-7.
Chicago/Turabian StyleDyah Ika Krisnawati; Yung-Ching Liu; Yuarn-Jang Lee; Yun-Ting Wang; Chia-Ling Chen; Po-Chun Tseng; Ting-Jing Shen; Chiou-Feng Lin. 2019. "Blockade Effects of Anti-Interferon- (IFN-) γ Autoantibodies on IFN-γ-Regulated Antimicrobial Immunity." Journal of Immunology Research 2019, no. : 1629258-7.
Dengue virus (DENV), an arthropod-borne virus transmitted by mosquitoes, may cause the severe disease known as dengue hemorrhagic fever, which is characterized by lethal complications due to plasma leakage, ascites, pleural effusion, respiratory distress, severe bleeding, and organ impairment. A few cases of DENV infection present neurological manifestations; however, studies have not explored DENV-induced neuropathogenesis further. In this study, we present a protocol to use an immunocompetent outbred ICR (Institute of Cancer Research) mouse for investigating the induction of central nervous system (CNS) infection with DENV, followed by the progression of acute viral encephalitis-like disease.
Ting-Jing Shen; Ming-Kai Jhan; Jo-Chi Kao; Min-Ru Ho; Tsung-Ting Tsai; Po-Chun Tseng; Yung-Ting Wang; Chiou-Feng Lin. A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease. Journal of Visualized Experiments 2019, e59132 .
AMA StyleTing-Jing Shen, Ming-Kai Jhan, Jo-Chi Kao, Min-Ru Ho, Tsung-Ting Tsai, Po-Chun Tseng, Yung-Ting Wang, Chiou-Feng Lin. A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease. Journal of Visualized Experiments. 2019; (146):e59132.
Chicago/Turabian StyleTing-Jing Shen; Ming-Kai Jhan; Jo-Chi Kao; Min-Ru Ho; Tsung-Ting Tsai; Po-Chun Tseng; Yung-Ting Wang; Chiou-Feng Lin. 2019. "A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease." Journal of Visualized Experiments , no. 146: e59132.
Interferon (IFN)-γ is crucial for normal immune surveillance and exhibits immunomodulatory, antimicrobial, and anticancer activity. Patients with nontuberculous mycobacteria (NTM) infection commonly express high levels of anti-IFN-γ autoantibodies (autoAbs) and suffer from recurrent infections due to adult-onset immunodeficiency with defects in IFN-γ immune surveillance. In this study, we developed the methods for determination of anti-IFN-γ autoAbs and then characterized their neutralizing activity in patients with NTM infection. A modified sandwich ELISA-based colorimetric assay followed by immunoblot analysis detected the presence of autoAbs in three out of five serum samples. Serum levels of IFN-γ were decreased. Synthetic peptide binding assay showed variable patterns of epitope recognition in patients positive for anti-IFN-γ autoAbs. Functional tests confirmed that patient serum blocked IFN-γ-activated STAT1 activation and IRF1 transactivation. Furthermore, IFN-γ-regulated inflammation, chemokine production and cytokine production were also blocked. These results provide potentially useful methods to assay anti-IFN-γ autoAbs and to characterize the effects of neutralizing autoAbs on IFN-γ signaling and bioactivity.
Dyah Ika Krisnawati; Yung-Ching Liu; Yuarn-Jang Lee; Yun-Ting Wang; Chia-Ling Chen; Po-Chun Tseng; Chiou-Feng Lin. Functional neutralization of anti-IFN-γ autoantibody in patients with nontuberculous mycobacteria infection. Scientific Reports 2019, 9, 5682 .
AMA StyleDyah Ika Krisnawati, Yung-Ching Liu, Yuarn-Jang Lee, Yun-Ting Wang, Chia-Ling Chen, Po-Chun Tseng, Chiou-Feng Lin. Functional neutralization of anti-IFN-γ autoantibody in patients with nontuberculous mycobacteria infection. Scientific Reports. 2019; 9 (1):5682.
Chicago/Turabian StyleDyah Ika Krisnawati; Yung-Ching Liu; Yuarn-Jang Lee; Yun-Ting Wang; Chia-Ling Chen; Po-Chun Tseng; Chiou-Feng Lin. 2019. "Functional neutralization of anti-IFN-γ autoantibody in patients with nontuberculous mycobacteria infection." Scientific Reports 9, no. 1: 5682.
Group A Streptococcus (GAS) infection is associated with a variety of human diseases. Previous studies indicate GAS infection leads to RAW264.7 cell death, but the mechanism is unclear. Here, analyzing the timing of reactive oxygen species (ROS) production and using mitochondrial ROS scavenger, we found the wild type GAS-induced RAW264.7 cell death was associated with mitochondrial ROS. The wild type GAS infection could activate glycogen synthase kinase-3β (GSK-3β). Inhibition of GSK-3β activity by lithium chloride or decreasing GSK-3β expression by lentivirus-mediated short hairpin RNA for GSK-3β could not only decrease the wild type GAS-induced mitochondrial ROS generation, mitochondria damage and cell death, but also reduced GAS intracellular replication. Streptolysin S (SLS), a GAS toxin, played the important role on GAS-induced macrophage death. Compared to the wild type GAS with its isogenic sagB mutant (SLS mutant)-infected macrophages, we found sagB mutant infection caused less mitochondrial ROS generation and cell death than those of the wild type GAS-infected ones. Furthermore, the sagB mutant, but not the wild type or the sagB-complementary mutant, could induce GSK-3β degradation via a proteasome-dependent pathway. These results suggest that a new mechanism of SLS-induced macrophage death was through inhibiting GSK-3β degradation and further enhancing mitochondrial damage.
Nina Tsao; Chih-Feng Kuo; Miao-Hui Cheng; Wei-Chen Lin; Chiou-Feng Lin; Yee-Shin Lin. Streptolysin S induces mitochondrial damage and macrophage death through inhibiting degradation of glycogen synthase kinase-3β in Streptococcus pyogenes infection. Scientific Reports 2019, 9, 5371 .
AMA StyleNina Tsao, Chih-Feng Kuo, Miao-Hui Cheng, Wei-Chen Lin, Chiou-Feng Lin, Yee-Shin Lin. Streptolysin S induces mitochondrial damage and macrophage death through inhibiting degradation of glycogen synthase kinase-3β in Streptococcus pyogenes infection. Scientific Reports. 2019; 9 (1):5371.
Chicago/Turabian StyleNina Tsao; Chih-Feng Kuo; Miao-Hui Cheng; Wei-Chen Lin; Chiou-Feng Lin; Yee-Shin Lin. 2019. "Streptolysin S induces mitochondrial damage and macrophage death through inhibiting degradation of glycogen synthase kinase-3β in Streptococcus pyogenes infection." Scientific Reports 9, no. 1: 5371.
Fractionated ionizing radiation (FIR) is a radiotherapy regimen that is regularly performed as part of lung cancer treatment. In contrast to the growth inhibition caused by DNA damage, immunomodulation in post‐irradiated cancer cells is not well documented. Interferon (IFN)‐γ confers anticancer activity by triggering both growth inhibition and cytotoxicity. This study investigated the priming effects of FIR with immunomodulation on the anticancer IFN‐γ. Cell morphology, cell growth, and cytotoxicity were observed in FIR‐treated A549 lung adenocarcinoma. Induction of p53 and epithelial–mesenchymal transition (EMT) were monitored. Following FIR, activation of IFN‐γ signaling pathways were detected. FIR caused changes in cell morphology, inhibited cell growth, and induced cytotoxicity. While p53 was induced by FIR, no epithelial–mesenchymal transition could be found. Following IFN‐γ stimulation, FIR‐induced p53‐associated cell cytotoxicity was significantly enhanced. Additionally, FIR increased the downstream response to IFN‐γ by facilitating IFN‐γ‐induced signal transducer and activator of transcription 1 (STAT1) signaling without affecting the receptor expression. FIR‐facilitated STAT1 activation through the mechanism involving mitogen‐activated protein kinase activation and Src‐homology 2 domain‐containing tyrosine phosphatase 2 inactivation. These results demonstrate the FIR‐facilitated IFN‐γ signaling and its anticancer activity.
Szu-Yuan Wu; Chia‐Ling Chen; Po‐Chun Tseng; Chi‐Yun Chiu; Yung‐En Lin; Chiou‐Feng Lin. Fractionated ionizing radiation facilitates interferon‐γ signaling and anticancer activity in lung adenocarcinoma cells. Journal of Cellular Physiology 2019, 234, 16003 -16010.
AMA StyleSzu-Yuan Wu, Chia‐Ling Chen, Po‐Chun Tseng, Chi‐Yun Chiu, Yung‐En Lin, Chiou‐Feng Lin. Fractionated ionizing radiation facilitates interferon‐γ signaling and anticancer activity in lung adenocarcinoma cells. Journal of Cellular Physiology. 2019; 234 (9):16003-16010.
Chicago/Turabian StyleSzu-Yuan Wu; Chia‐Ling Chen; Po‐Chun Tseng; Chi‐Yun Chiu; Yung‐En Lin; Chiou‐Feng Lin. 2019. "Fractionated ionizing radiation facilitates interferon‐γ signaling and anticancer activity in lung adenocarcinoma cells." Journal of Cellular Physiology 234, no. 9: 16003-16010.