Taipei Medical University Hospital
Taipei Medical University Hospital
Tang W.-C.,A-Life Medical |
Tang W.-C.,Academia Sinica, Taiwan |
Lin R.-J.,Taipei Medical University |
Lin R.-J.,Taipei Medical University Hospital |
And 3 more authors.
Journal of Virology | Year: 2014
Positive-sense RNA viruses, such as dengue virus (DENV), hijack the intracellular membrane machinery for their own replication. The Rab18 protein, a member of the Rab GTPase family, key regulators of membrane trafficking, is located on the organelles involved in DENV infection, such as the endoplasmic reticulum (ER) and lipid droplets (LDs). In this study, we addressed the potential involvement of Rab18 in DENV infection by using cells overexpressing the wild-type, GTP-bound active form, or GDP-bound inactive form of Rab18 and cells with Rab18 knockdown. DENV replication, measured by viral protein, viral RNA, and viral progeny production, as well as LD induction, was reduced in cells with inactive Rab18 and in cells deprived of Rab18 expression, suggesting a positive role of Rab18 in the DENV life cycle. Interestingly, the interaction of fatty acid synthase (FASN), a key lipogenic enzyme in lipid biosynthesis, with DENV NS3 protein relied on the conversion of the GDP-bound to the GTP-bound form of Rab18. Furthermore, the targeting of FASN to sites participating in DENV infection, such as the ER and LDs, depends on functional Rab18. Thus, Rab18-mediated membrane trafficking of FASN and NS3 facilitates DENV replication, probably by ensuring a sufficient and coordinated lipid supply for membrane proliferation and arrangement. © 2014, American Society for Microbiology.
Chen C.,National Yang Ming University |
Yang C.-Y.,Ming Chuan University |
Cheng Y.,National Yang Ming University |
Cheng Y.,Taipei Medical University Hospital
Social Neuroscience | Year: 2012
When perceiving imminent harm to others, quickly detecting potential hazards to oneself should be vital. In this case, mirroring the outcome of observed actions appears paradoxical. This study measured electroencephalographic/event-related potentials and mu suppression that were induced by dynamic animations; each animation was composed of three consecutive pictures depicting an individual being accidentally injured. The results indicated that the first picture evoked frontal N260 and central N360, the possible brain source of which is estimated in the dorsolateral prefrontal cortex, and the third picture elicited late positive potentials, the possible sources of which might be generated from the insular and mid-cingulate cortex. Differential mu suppression, in relation to the sensorimotor resonance of empathy for pain, is associated with the third picture containing the crucial affective valence, but not with the first picture. The masking procedure on the third picture attenuated this mu suppression. Mediation analysis further confirmed that sensorimotor resonance is not a significant mediator in predicting subjective unpleasantness for observed actions. The findings suggest that sensorimotor resonance is not a platform, but rather an outcome when anticipating harm to others. © 2012 Copyright 2012 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business.
Lee C.-C.,Taipei Medical University Hospital
Critical Care Medicine | Year: 2017
OBJECTIVES:: Use of calcium channel blockers has been found to improve sepsis outcomes in animal studies and one clinical study. This study determines whether the use of calcium channel blockers is associated with a decreased risk of mortality in patients with sepsis. DESIGN:: Population-based matched cohort study. SETTING:: National Health Insurance Research Database of Taiwan. PATIENTS:: Hospitalized severe sepsis patients identified from National Health Insurance Research Database by International Classification of Diseases, Ninth Revision, Clinical Modification codes. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: The association between calcium channel blocker use and sepsis outcome was determined by multivariate-adjusted Cox proportional hazard models and propensity score analysis. To examine the influence of healthy user bias, beta-blocker was used as an active comparator. Our study identified 51,078 patients with sepsis, of which, 19,742 received calcium channel blocker treatments prior to the admission. Use of calcium channel blocker was associated with a reduced 30-day mortality after propensity score adjustment (hazard ratio, 0.94; 95% CI, 0.89–0.99), and the beneficial effect could extend to 90-day mortality (hazard ratio, 0.95; 95% CI, 0.89–1.00). In contrast, use of beta-blocker was not associated with an improved 30-day (hazard ratio, 1.06; 95% CI, 0.97–1.15) or 90-day mortality (hazard ratio, 1.00; 95% CI, 0.90–1.11). On subgroup analysis, calcium channel blockers tend to be more beneficial to patients with male gender, between 40 and 79 years old, with a low comorbidity burden, and to patients with cardiovascular diseases, diabetes, or renal diseases. CONCLUSIONS:: In this national cohort study, preadmission calcium channel blocker therapy before sepsis development was associated with a 6% reduction in mortality when compared with patients who have never received calcium channel blockers. Copyright © by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Chen Y.-H.,Taipei Medical University |
Chen Y.-H.,Taipei Medical University Hospital |
Lin H.-C.,Taipei Medical University
Stroke | Year: 2011
Background and Purpose-Previous studies have identified an array of morbidities following traumatic bran injury (TBI), including certain neurological disorders. However, no direct evidence has been reported on the link between TBI and stroke. This population-based study was designed to estimate the risk of stroke during a period of 5 years following a TBI, compared with individuals who did not suffer TBI during the same period. Methods-Data were obtained from the Longitudinal Health Insurance Database 2000 (LHID 2000). A total of 23 199 patients receiving ambulatory or hospitalization care with a diagnosis of TBI were included, together with 69 597 non-TBI patients as our comparison group, matched by sex, age, and year of index use of health care. Each individual was followed for 5 years to identify subsequent occurrence of stroke. Cox proportional hazard regressions were performed for analysis. RESULTS-: During the 3-month follow-up period, 675 strokes (2.91%) occurred in TBI patients and in 207 patients (0.30%) in the non-TBI comparison cohort. A diagnosis of TBI was independently associated with a 10.21 (95% CI, 8.71-11.96), 4.61 (95% CI, 4.16-5.11), and 2.32 (95% CI, 2.17-2.47) times greater risk of stroke during 3-month, 1-year, and 5-year follow-up, respectively, after adjusting for sociodemographic characteristics and selected comorbidities. The risk of intracerebral hemorrhage was more noticeable among patients with TBI compared with those without a TBI. Conclusions-This is the first report showing an increased risk of stroke among individuals who have sustained a TBI. We suggest a need for more intensive medical monitoring and health education following TBI, especially during the first few months and years. © 2011 American Heart Association, Inc.
Chao K.-C.,Academia Sinica, Taiwan |
Yang H.-T.,Taipei Medical University Hospital |
Chen M.-W.,National Taiwan University
Journal of Cellular and Molecular Medicine | Year: 2012
The purpose of this study was to investigate how human umbilical cord mesenchymal stem cells (HUMSCs) affect breast cancer tumourigenesis. To observe the influence of HUMSCs on tumourigenesis in vitro, we performed a co-culture of MDA MB-231 breast cancer cells with HUMSCs, and a result of HUMSCs on tumourigenesis in vivo was achieved by injection of HUMSCs into nonobese diabetic/severe combined immunodeficient mice following tumour establishment with MDA-MB231. During the co-culture, apoptosis of MDA-MB231 was noted, which was driven either by binding with HUMSC through direct cell-cell contact or by formation of a novel cell-in-cell phenomenon after internalization of HUMSC. Also, treatment with HUMSC injection was efficacious in both in situ and metastatic breast cancers in the animal models. Since HUMSCs were proved to efficaciously suppress breast cancer tumourigenesis both in vitro and in vivo, it is our expectation that treatment with HUMSCs can be a viable therapy for breast cancer in the near future. In addition, we share a new point of view on the role of HUMSCs in foetal development during pregnancy. © 2012 The Authors. Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Leung T.K.,Taipei Medical University Hospital
The Chinese journal of physiology | Year: 2013
Previous biomolecular and animal studies have shown that a room-temperature far-infrared-rayemitting ceramic material (bioceramic) demonstrates physical-biological effects, including the normalization of psychologically induced stress-conditioned elevated heart rate in animals. In this clinical study, the Harvard step test, the resting metabolic rate (RMR) assessment and the treadmill running test were conducted to evaluate possible physiological effects of the bioceramic material in human patients. The analysis of heart rate variability (HRV) during the Harvard step test indicated that the bioceramic material significantly increased the high-frequency (HF) power spectrum. In addition, the results of RMR analysis suggest that the bioceramic material reduced oxygen consumption (VO2). Our results demonstrate that the bioceramic material has the tendency to stimulate parasympathetic responses, which may reduce resting energy expenditure and improve cardiorespiratory recovery following exercise.
Su C.-M.,Taipei Medical University Hospital
Oncogene | Year: 2015
MicroRNAs (miRNAs) are small RNAs that suppress gene expression by their interaction with 3’untranslated region of specific target mRNAs. Although the dysregulation of miRNAs has been identified in human cancer, only a few of these miRNAs have been functionally documented in breast cancer. Thus, defining the important miRNA and functional target involved in chemoresistance is an urgent need for human breast cancer treatment. In this study, we, for the first time, identified a key role of miRNA 520h (miR-520h) in drug resistance. Through protecting cells from paclitaxel-induced apoptosis, expression of miR-520h promoted the drug resistance of human breast cancer cells. Bioinformatics prediction, compensatory mutation and functional validation further confirmed the essential role of miR-520h-suppressed Death-associated protein kinase 2 (DAPK2) expression, as restoring DAPK2 abolished miR-520h-promoted drug resistance, and knockdown of DAPK2 mitigated cell death caused by the depletion of miR-520h. Furthermore, we observed that higher level of miR-520h is associated with poor prognosis and lymph node metastasis in human breast cancer patients. These results show that miR-520h is not only an independent prognostic factor, but is also a potential functional target for future applications in cancer therapeutics.Oncogene advance online publication, 18 May 2015; doi:10.1038/onc.2015.168. © 2015 Macmillan Publishers Limited
Wu C.-H.,Taipei Medical University |
Lee C.-H.,Taipei Medical University |
Ho Y.-S.,Taipei Medical University |
Ho Y.-S.,Taipei Medical University Hospital
Clinical Cancer Research | Year: 2011
The nicotinic acetylcholine receptor (nAChR) was first characterized in 1970 as a membrane receptor of a neurotransmitter and an ion channel. nAChRs have been shown to be involved in smoking-induced cancer formation in multiple types of human cancer cells. In vitro and in vivo animal studies have shown that homopentameric nAChR inhibitors, such as methyllycaconitine and α-Bgtx, can attenuate nicotine-induced proliferative, angiogenic, and metastatic effects in lung, colon, and bladder cancer cells. Recent publications have shown that α9-nAChR is important for breast cancer formation, and in many in vivo studies, α9-nAChR-specific antagonists (e.g., α-ImI, α-ImI, Vc1.1, RgIA, and It14a) produced an analgesic effect. Vc1.1 functions in a variety of animal pain models and currently has entered phase II clinical trials. For cancer therapy, natural compounds such as garcinol and EGCG have been found to block nicotine- and estrogen-induced breast cancer cell proliferation through inhibition of the α9-nAChR signaling pathway. A detailed investigation of the carcinogenic effects of nAChRs and their specific antagonists would enhance our understanding of their value as targets for clinical translation. ©2011AACR.
Kang J.-H.,Taipei Medical University Hospital |
Lin H.-C.,Taipei Medical University Hospital
Journal of Neurotrauma | Year: 2012
The etiology of multiple sclerosis (MS) is still not well known. Previous data show conflicting results regarding the association between MS and prior brain trauma. This study aims to investigate the risk for MS following a traumatic brain injury (TBI) using a large-scale cohort study design. This study used data from the National Health Insurance Research Database. A total of 72,765 patients with TBI were identified and included as the study cohort, and 218,295 randomly selected subjects were matched with the study cohort by sex and age as controls. We traced each patient individually for a 6-year period from their index health care utilization to identify those who received a subsequent diagnosis of MS. We used the Kaplan-Meier method and the log-rank test to compare the difference in 6-year MS-free survival rates between the two groups. Stratified Cox proportional hazard regressions were computed to compare the risk of developing MS for these two cohorts. Patients with TBI had a higher incidence of MS during the 6-year period than the comparison group (0.055% versus 0.037%). After excluding cases who died from non-MS causes, stratifying for hospitalization of cases as a proxy for severity, and adjusting for monthly income and geographic region of the community in which the patient resided, the hazard ratio (HR) of MS for patients with hospital-treated TBI injuries was 1.97 (95% CI 1.31,2.93, p<0.01) that of patients without TBI during the 6-year follow-up period after index health care use. Our study concludes that patients with TBI are at higher risk for subsequent MS over a 6-year follow-up period. © 2012, Mary Ann Liebert, Inc.
Kang J.-H.,Taipei Medical University Hospital |
Chen Y.-H.,Taipei Medical University |
Lin H.-C.,Taipei Medical University
Annals of the Rheumatic Diseases | Year: 2010
Objective: Ankylosing spondylitis (AS) is a systemic inflammatory disease that can result in chronic pain and disability. This study aimed to analyse the prevalence and risk of medical comorbidities in patients with AS compared with the general population. Methods: 11 701 patients with AS and 58 505 matching controls were selected for analysis from the National Health Insurance Research Dataset (NHIRD) in Taiwan. The Elixhauser comorbidity index was used for selecting medical comorbidities. Pearson χ2 tests and conditional logistic regression a nalyses were performed to examine the prevalence and risk of comorbidities between these two groups. Results: Patients with AS were at increased risk for multiple systemic comorbidities including cardiovascular, neurological, pulmonary, gastrointestinal, endocrine, haematological and mental illness. The most prevalent comorbidities in patients with AS were hypertension (16.4%), peptic ulcers (13.9%) and headaches (10.2%). Conclusion: The results show that patients with AS have a higher prevalence of multiple comorbidities than the general population in Taiwan. These findings are consistent with previous studies done in Western populations. The results could be useful for both the clinical management of patients with AS and for researching the underlying pathological mechanisms.