Chang Gung Memorial Hospital Chiayi Branch

Chiayi, Taiwan

Chang Gung Memorial Hospital Chiayi Branch

Chiayi, Taiwan
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Hwang S.-L.,Chang Gung University | Hwang S.-L.,Chang Gung Memorial Hospital Chiayi Branch | Lin Y.-C.,Chang Gung Memorial Hospital Chiayi Branch | Lin Y.-C.,Chang Gung University | And 2 more authors.
Environmental Science and Pollution Research | Year: 2017

This population-based study evaluated the short-term association between fine particulate matter (PM2.5) concentrations and its constituents and hospital emergency room visits (ERVs) for asthma in southern Taiwan during the period 2008–2010. Data on hospital ERVs for asthma and ambient PM2.5 levels and its constituents were obtained from the National Health Insurance Research database and the Environmental Protection Administration, respectively. The quasi-Poisson generalized additive model was used to explore the associations between PM2.5 and hospital ERVs for asthma. During the study period, the average daily number of ERVs for asthma and mean 24-h average level of PM2.5 was 20.0 and 39.4 μg m−3, respectively. The estimated effects of PM2.5 on asthma ERVs fluctuated with increasing tendencies after adjusting for O3 and attenuating tendencies after adjusting for NO2, SO2, and CO. Children were more susceptible than other age groups to the effects of PM2.5 exposure on asthma ERVs, with the relative risks (RRs) for every 10 μg m−3 increase in PM2.5 being 1.016 [95% confidence interval (CI) = 1.002–1.030] and 1.018 (95% CI = 1.002–1.034), respectively, at a lag 0 day (i.e., no lag days) and lag 0–1 days. The effect of PM2.5 concentrations on asthma ERVs was similar in male and female. Furthermore, asthma ERVs was significantly associated with concentrations of nitrate (NO3 −), with the RR for each 1 μg m−3 increase in NO3 − concentrations being 1.004 (95% CI = 1.001–1.007) at lag 0 day. In conclusion, both PM2.5 concentrations and its chemical constituents are associated with ERVs for asthma; moreover, children were more susceptible to the effects of PM2.5 in southern Taiwan. PM2.5 constituent, nitrate, is more closely related to ERVs for asthma. © 2017 Springer-Verlag Berlin Heidelberg

Wang W.-H.,Chang Gung University | Kuo C.-W.,Chang Gung University | Chang L.-K.,National Taiwan University of Science and Technology | Hung C.-C.,Chang Gung University | And 3 more authors.
Journal of Virology | Year: 2015

The Epstein-Barr virus (EBV) capsid contains a major capsid protein, VCA; two minor capsid proteins, BDLF1 and BORF1; and a small capsid protein, BFRF3. During the lytic cycle, these capsid proteins are synthesized and imported into the host nucleus for capsid assembly. This study finds that EBV capsid proteins colocalize with promyelocytic leukemia (PML) nuclear bodies (NBs) in P3HR1 cells during the viral lytic cycle, appearing as nuclear speckles under a confocal laser scanning microscope. In a glutathione S-transferase pulldown study, we show that BORF1 interacts with PML-NBs in vitro. BORF1 also colocalizes with PML-NBs in EBV-negative Akata cells after transfection and is responsible for bringing VCA and the VCA-BFRF3 complex from the cytoplasm to PML-NBs in the nucleus. Furthermore, BDLF1 is dispersed throughout the cell when expressed alone but colocalizes with PML-NBs when BORF1 is also present in the cell. In addition, this study finds that knockdown of PML expression by short hairpin RNA does not influence the intracellular levels of capsid proteins but reduces the number of viral particles produced by P3HR1 cells. Together, these results demonstrate that BORF1 plays a critical role in bringing capsid proteins to PMLNBs, which may likely be the assembly sites of EBV capsids. The mechanisms elucidated in this study are critical to understanding the process of EBV capsid assembly. © 2015, American Society for Microbiology.

PubMed | Chang Gung Memorial Hospital Chiayi Branch, National Chiayi University, National Yang Ming University, Taipei Veterans General Hospital and Chang Gung University
Type: Journal Article | Journal: PloS one | Year: 2015

Bone morphogenetic proteins (BMPs) play positive roles in cartilage development, but they can barely be detected in healthy articular cartilage. However, recent evidence has indicated that BMPs could be detected in osteoarthritic and damaged cartilage and their precise roles have not been well defined. Extremely high amounts of leptin have been reported in obese individuals, which can be associated with osteoarthritis (OA) development. The aim of this study was to investigate whether BMPs could be induced in human primary chondrocytes during leptin-stimulated OA development and the underlying mechanism. We found that expression of BMP-2 mRNA, but not BMP-4, BMP-6, or BMP-7 mRNA, could be increased in human primary chondrocytes under leptin stimulation. Moreover, this BMP-2 induction was mediated through transcription factor-signal transducer and activator of transcription (STAT) 3 activation via JAK2-ERK1/2-induced Ser727-phosphorylation. Of note, histone deacetylases (HDACs) 3 and 4 were both involved in modulating leptin-induced BMP-2 mRNA expression through different pathways: HDAC3, but not HDAC4, associated with STAT3 to form a complex. Our results further demonstrated that the role of BMP-2 induction under leptin stimulation is to increase collagen II expression. The findings in this study provide new insights into the regulatory mechanism of BMP-2 induction in leptin-stimulated chondrocytes and suggest that BMP-2 may play a reparative role in regulating leptin-induced OA development.

PubMed | Chang Gung University, National Chiayi University, Taipei Veterans General Hospital and Chang Gung Memorial Hospital Chiayi Branch
Type: Journal Article | Journal: International journal of molecular sciences | Year: 2015

A high level of serum resistin has recently been found in patients with a number of cancers, including colorectal cancer (CRC). Hence, resistin may play a role in CRC development. Fulvic acid (FA), a class of humic substances, possesses pharmacological properties. However, the effect of FA on cancer pathophysiology remains unclear. The aim of this study was to investigate the effect of resistin on the endothelial adhesion of CRC and to determine whether FA elicits an antagonistic mechanism to neutralize this resistin effect. Human HCT-116 (p53-negative) and SW-48 (p53-positive) CRC cells and human umbilical vein endothelial cells (HUVECs) were used in the experiments. Treatment of both HCT-116 and SW-48 cells with resistin increases the adhesion of both cells to HUVECs. This result indicated that p53 may not regulate this resistin effect. A mechanistic study in HCT-116 cells further showed that this resistin effect occurs via the activation of NF-B and the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Co-treating cells with both FA and resistin revealed that FA significantly attenuated the resistin-increased NF-B activation and ICAM-1/VCAM-1 expression and the consequent adhesion of HCT-116 cells to HUVECs. These results demonstrate the role of resistin in promoting HCT-116 cell adhesion to HUVECs and indicate that FA might be a potential candidate for the inhibition of the endothelial adhesion of CRC in response to resistin.

PubMed | Chang Gung Memorial Hospital, Chang Gung Memorial Hospital Chiayi Branch, National formosa University and National Chiayi University
Type: | Journal: BMC complementary and alternative medicine | Year: 2016

Far-infrared ray (FIR) has been widely used in promoting health and has been shown to exert beneficial effects in vascular function. The non-thermal effect of FIR has been found to play a significant role in the protective effect on some vascular-related diseases, but its protective effects and use against hypertension have not been clearly presented.In the present study, by using a wooden board coated with FIR-irradiated materials, we evaluated the long-term antihypertensive effect on spontaneously hypertensive rats (SHRs) in the environment in contact with the FIR-irradiated wooden board. SHRs were placed on the wooden board with or without FIR radiation for 4 weeks.The systolic blood pressure (BP) of SHRs undergoing different treatments was measured weekly using a tail-cuff method. FIR radiation significantly reduced the systolic BP of the SHRs along with a decreasing plasma level of angiotensin II and an increasing plasma level of bradykinin. In addition, long-term contact of FIR did not significantly affect the BP in normotensive Wistar Kyoto rats (WKYs).Our results provided the evidence based on which FIR radiation could be considered an effective non-pharmacological choice for preventing hypertension.

PubMed | Chang Gung University, St Martin Of Porres Hospital, National Chiayi University and Chang Gung Memorial Hospital Chiayi Branch
Type: Journal Article | Journal: PloS one | Year: 2015

Beclin 1 and Beclin 2 are autophagy-related proteins that show similar amino acid sequences and domain structures. Beclin 1 established the first connection between autophagy and cancer. However, the role of Beclin 2 in cancer is unclear. The aims of this study were to analyze Beclin 1 and Beclin 2 expressions in oral cancer tissues and in cell lines, and to evaluate their possible roles in cancer progression.We investigated Beclin 1 and Beclin 2 expressions by immunohistochemistry in 195 cases of oral cancer. The prognostic roles of Beclin 1 and Beclin 2 were analyzed statistically. In vitro, overexpression and knockdown of Beclin proteins were performed on an oral cancer cell line, SAS. The immunofluorescence and autophagy flux assays confirmed that Beclin proteins were involved in autophagy. The impacts of Beclin 1 and Beclin 2 on autophagy and tumor growth were evaluated by conversion of LC3-I to LC3-II and by clonogenic assays, respectively.Oral cancer tissues exhibited aberrant expressions of Beclin 1 and Beclin 2. The cytoplasmic Beclin 1 and Beclin 2 expressions were unrelated in oral cancer tissues. In survival analyses, high cytoplasmic Beclin 1 expression was associated with low disease specific survival, and negative nuclear Beclin 1 expression was associated with high recurrent free survival. Patients with either high or low cytoplasmic Beclin 2 expression had significantly lower overall survival and disease specific survival rates than those with moderate expression. In oral cancer cells, overexpression of either Beclin 1 or Beclin 2 led to autophagy activation and increased clonogenic survival; knockdown of Beclin 2 impaired autophagy and increased clonogenic survival.Our results indicated that distinct patterns of Beclin 1 and Beclin 2 were associated with aggressive clinical outcomes. Beclin 1 overexpression, as well as Beclin 2 overexpression and depletion, contributed to tumor growth. These findings suggest Beclin proteins are associated with tumorigenesis.

Ke W.-J.,Chang Gung University | Hsueh Y.-H.,Yuan Ze University | Cheng Y.-C.,Chang Gung University | Wu C.-C.,Chang Gung University | And 2 more authors.
Frontiers in Microbiology | Year: 2015

Many Bacillus subtilis strains swarm, often forming colonies with tendrils on agar medium. It is known that B. subtilis swarming requires flagella and a biosurfactant, surfactin. In this study, we find that water surface tension plays a role in swarming dynamics. B. subtilis colonies were found to contain water, and when a low amount of surfactin is produced, the water surface tension of the colony restricts expansion, causing bacterial density to rise. The increased density induces a quorum sensing response that leads to heightened production of surfactin, which then weakens water surface tension to allow colony expansion. When the barrier formed by water surface tension is breached at a specific location, a stream of bacteria swarms out of the colony to form a tendril. If a B. subtilis strain produces surfactin at levels that can substantially weaken the overall water surface tension of the colony, water floods the agar surface in a thin layer, within which bacteria swarm and migrate rapidly. This study sheds light on the role of water surface tension in regulating B. subtilis swarming, and provides insight into the mechanisms underlying swarming initiation and tendril formation. © 2015 Ke, Hsueh, Cheng, Wu and Liu.

PubMed | Chang Gung University and Chang Gung Memorial Hospital Chiayi Branch
Type: | Journal: International journal of environmental health research | Year: 2017

This study explored the effects of PM

PubMed | Chang Gung Memorial Hospital Chiayi Branch and National Yang Ming University
Type: Journal Article | Journal: Bioconjugate chemistry | Year: 2015

The design, preparation, as well as structural and functional characterizations of the recombinant fusion protein hVEGF-EGF as a dual-functional agent that may target both EGFR (R: receptor) and angiogenesis are reported. hVEGF-EGF was found to bind to EGFR more strongly than did EGF, and to bind to VEGFR similarly to VEGF. Mass spectrometry measurements showed that the sites of DTPA (diethylenetriaminepentaacetic acid) conjugated hVEGF-EGF (for radiolabeling) were the same as those of its parent hEGF and hVEGF proteins. All DTPA-conjugated proteins retained similar binding capacities to their respective receptors as compared to their respective parent proteins. In vitro cell binding studies using BAEC (a bovine aortic endothelial cell) and MDA-MB-231 (a human breast cancer) cells expressing both EGFR and VEGFR confirmed similar results. Treating BAEC cells with hVEGF-EGF induced remarkable phosphorylation of EGFR, VEGFR, and their downstream targets ERK1/2. Nevertheless, the radiolabeled (111)In-DTPA-hVEGF-EGF showed cytotoxicity against MDA-MB-231 cells. Pharmacokinetic studies using (111)In-DTPA-hVEGF-EGF in BALB/c nude mice showed that appreciable tracer activities were accumulated in liver and spleen. In all, this study demonstrated that the fusion protein hVEGF-EGF maintained the biological specificity toward both EGFR and VEGFR and may be a potential candidate as a dual-targeting moiety in developing anticancer drugs.

PubMed | Chang Gung Memorial Hospital Chiayi Branch and National Yang Ming University
Type: | Journal: Journal of biomedical science | Year: 2016

The enzyme-prodrug system is considered a promising tool for tumor treatment when conjugated with a targeting molecule. The asparagine-glycine-arginine (NGR) motif is a developing and interesting targeting peptide that could specifically bind to aminopeptidase N (APN), which is an NGR receptor expressed on the cell membrane of angiogenic endothelial cells and a number of tumor cells within the tumor tissues. The objective of this study was to develop a novel targeted enzyme-prodrug system using 5-fluorocytosine (5-FC) and an NGR-containing peptide fused with yeast cytosine deaminase (yCD), i.e. CNGRC-yCD fusion protein, to target APN-expressing cells within the tumor tissues and to convert 5-FC into 5-fluorouracil (5-FU) to kill tumors.Both yCD and CNGRC-yCD proteins were cloned into the pET28a vector and expressed by an Escherichia coli host. Both yCD and CNGRC-yCD proteins were purified and the yields were approximately 20 mg/L with over 95 % purity. The binding assay demonstrated that the CNGRC-yCD fusion protein had specific binding affinity toward purified APN recombinant protein and high-APN-expressing cells, including human endothelial cells (HUVECs) and various types of human tumor cell lines, but not low-APN-expressing tumor cell lines. Moreover, the enzyme activity and cell viability assay showed that the CNGRC-yCD fusion protein could effectively convert 5-FC into 5-FU and resulted in significant cell death in both high-APN-expressing tumor cells and HUVECs.This study successfully constructs a new targeting enzyme-prodrug system, CNGRC-yCD fusion protein/5-FC. Systematic experiments demonstrated that the CNGRC-yCD protein retained both the APN-binding affinity of NGR and the enzyme activity of yCD to convert 5-FC into 5-FU. The combined treatment of the CNGRC-yCD protein with 5-FC resulted in the significantly increased cell death of high-APN-expressing cells as compared to that of low-APN-expressing cells.

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