Graduate Institute of Chinese Medical Science

Taichung, Taiwan

Graduate Institute of Chinese Medical Science

Taichung, Taiwan
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Chiang J.,Chinese Culture University | Chen Y.-Y.,National Taiwan Sport University | Akiko T.,Chinese Culture University | Huang Y.-C.,China Medical University at Taichung | And 3 more authors.
Immunological Investigations | Year: 2010

Dendritic cells, the most potent antigen-presenting cells linking innate and adoptive immunity, are thought to be important targets of immune modulators such as exercise. We examined the effect of Tai Chi Chuan (TCC) on dendritic cells. TCC practitioners were further divided to high-level practitioners (TCC-H) and low-level practitioners (TCC-L). The quantities of myeloid and plasmacytoid dendritic cells were estimated by flow cytometry. We examined parameters including age, body weight, body length, body fat, and serum albumin level, in the controls, TCC-H and TCC-L, which did not differ significantly. The mean peak (volume of O2 utilization) of the TCC-H group was greater than that of the sedentary control group. White blood cell (WBC) count in the entire TCC group was greater than that of the controls. The quantity of myeloid dendritic cells was significantly greater in the TCC group, whereas the quantity of plasmacytoid dendritic cells was similar for both groups. Among the TCC subgroups, the quantity of myeloid dendritic cells, but not plasmacytoid dendritic cells, in the TCC-H group was greater than that of TCC-L practitioners. TCC could increase the number of circulating myeloid dendritic cells, but not plasmacytoid dendritic cells, in a performance level-dependent manner. © 2010 Informa Healthcare USA, Inc.


Chen Y.W.,Graduate Institute of Basic Medical Science | Huang C.F.,Graduate Institute of Chinese Medical Science | Yang C.Y.,National Taiwan University Hospital | Yen C.C.,Chung San Medical University | And 2 more authors.
Toxicology and Applied Pharmacology | Year: 2010

Mercury is a well-known highly toxic metal. In this study, we characterize and investigate the cytotoxicity and its possible mechanisms of inorganic mercury in pancreatic β-cells. Mercury chloride (HgCl2) dose-dependently decreased the function of insulin secretion and cell viability in pancreatic β-cell-derived HIT-T15 cells and isolated mouse pancreatic islets. HgCl2 significantly increased ROS formation in HIT-T15 cells. Antioxidant N-acetylcysteine effectively reversed HgCl2-induced insulin secretion dysfunction in HIT-T15 cells and isolated mouse pancreatic islets. Moreover, HgCl2 increased sub-G1 hypodiploids and annexin-V binding in HIT-T15 cells, indicating that HgCl2 possessed ability in apoptosis induction. HgCl2 also displayed several features of mitochondria-dependent apoptotic signals including disruption of the mitochondrial membrane potential, increase of mitochondrial cytochrome c release and activations of poly (ADP-ribose) polymerase (PARP) and caspase 3. Exposure of HIT-T15 cells to HgCl2 could significantly increase both apoptotic and necrotic cell populations by acridine orange/ethidium bromide dual staining. Meanwhile, HgCl2 could also trigger the depletion of intracellular ATP levels and increase the LDH release from HIT-T15 cells. These HgCl2-induced cell death-related signals could be significantly reversed by N-acetylcysteine. The intracellular mercury levels were markedly elevated in HgCl2-treated HIT-T15 cells. Taken together, these results suggest that HgCl2-induced oxidative stress causes pancreatic β-cell dysfunction and cytotoxicity involved the co-existence of apoptotic and necrotic cell death. © 2009 Elsevier Inc. All rights reserved.


Lin Y.-M.,Changhua Christian Hospital | Su C.-C.,Anatomic Pathology Buddhist Dalin Tzu Chi General Hospital | Su C.-C.,Tzu Chi University | Su W.-W.,Changhua Christian Hospital | And 11 more authors.
Chinese Journal of Physiology | Year: 2012

The role of protein kinase C (PKC) in the carcinogenesis of human breast tissue has been studied at the molecular level for more than two decades. In this study, we employed Western blotting to determine the presence of PKC isoforms in cancerous and normal breast tissues. The results indicate significant expression of a conventional PKC (PKCα) and two atypical PKCs (PKC ζ and λ/ι) in both breast tumors and adjacent normal breast tissue. For the α, ζ and λ/ι isoforms, the expression of individual isoforms was higher in the breast tumors than in the adjacent normal breast tissue. Although the correlation coefficient was low, significant linear correlation was found among the activities of the isoforms. The data suggest a potential new direction in cancer chemotherapy, namely the blockage of the signal transduction pathway of specific PKC isoforms. © 2012 by The Chinese Physiological Society and Airiti Press Inc.


Lo J.-F.,National Yang Ming University | Lo J.-F.,Taipei Veterans General Hospital | Yu C.-C.,National Yang Ming University | Yu C.-C.,Chung Shan Medical University | And 11 more authors.
Cancer Research | Year: 2011

Cancer-initiating cells (CIC) comprise a rare subpopulation of cells in tumors that are proposed to be responsible for tumor growth. Starting from CICs identified in head and neck squamous cell carcinomas (HNSCC), termed head and neck cancer-initiating cells (HN-CIC), we determined as a candidate stemnessmaintaining molecule for HN-CICs the proinflammatory mediator S100A4, which is also known to be an inducer of epithelial-mesenchymal transition. S100A4 knockdown in HN-CICs reduced their self-renewal capability and their stemness and tumorigenic properties, both in vitro and in vivo. Conversely, S100A4 overexpression in HNSCC cells enhanced their stem cell properties. Mechanistic investigations indicated that attenuation of endogenous S100A4 levels in HNSCC cells caused downregulation of Notch2 and PI3K (phosphoinositide 3-kinase)/pAKT along with upregulation of PTEN, consistent with biological findings. Immunohistochemical analysis of HNSCC clinical specimens showed that S100A4 expression was positively correlated with clinical grading, stemness markers, and poorer patient survival. Together, our findings reveal a crucial role for S100A4 signaling pathways in maintaining the stemness properties and tumorigenicity of HN-CICs. Furthermore, our findings suggest that targeting S100A4 signaling may offer a new targeted strategy for HNSCC treatment by eliminating HN-CICs. ©2010 AACR.


Chen S.Y.,Genetic Center | Chen S.Y.,Graduate Institute of Chinese Medical Science | Wan L.,Genetic Center | Wan L.,Graduate Institute of Chinese Medical Science | And 11 more authors.
Journal of Applied Genetics | Year: 2010

Rheumatoid arthritis (RA) is a chronic autoimmune disease and can lead to deformities and severe disabilities, due to irreversible damage of tendons, joints, and bones. A previous study indicated that a DNA repair system was involved in the development of RA. In this study, we investigated the association of four N-methylpurine-DNA glycosylase (MPG) gene polymorphisms (rs3176364, rs710079, rs2858056, and rs2541632) with susceptibility to RA in 384 Taiwanese individuals (192 RA patients and 192 control subjects). Our data show a statistically significant difference in genotype frequency distributions at rs710079 and rs2858056 SNPs between RA patients and control groups (P = 0.040 and 0.029, respectively). Our data also indicated that individuals with the GG genotype at rs2858056 SNP may have a higher risk of developing RA. In addition, compared with the haplotype frequencies between case and control groups, individuals with the GCGC haplotype appeared to be at a greater risk of RA progression (P = 0.003, OR = 1.75; 95% CI = 1.20-1.55). Our results suggest that rs710079 and rs2858056 polymorphisms and the GCGC haplotype in the MPG gene are associated with the risk of RA progression, and thus may be used as molecular markers of RA if they are confirmed by further research.


Lin P.-P.,China Medical University at Taichung | Lin P.-P.,Asia University, Taiwan | Lin P.-P.,Hungkuang University | Hsieh Y.-M.,Providence University | And 10 more authors.
International Journal of Molecular Medicine | Year: 2013

Apoptosis is recognized as a predictor of adverse outcomes in subjects with cardiac diseases. The aim of this study was to explore the effects of probiotic-fermented purple sweet potato yogurt (PSPY) with high γ-aminobutyric acid (GABA) content on cardiac apoptosis in spontaneously hypertensive rat (SHR) hearts. The rats were orally adminsitered with 2 different concentrations of PSPY (10 and 100%) or captopril, 15.6 mg/kg, body weight (BW)/day. The control group was administered distilled water. DAPI and TUNEL staining were used to detect the numbers of apoptotic cells. A decrease in the number of TUNEL-positive cardiac myocytes was observed in the SHR-PSPY (10 and 100%) groups. In addition, the levels of key components of the Fas receptor- and mitochondrial-dependent apoptotic pathways were determined by western blot analysis. The results revealed that the levels of the key components of the Fas receptor- and mitochondrial-dependent apoptotic pathway were significantly decreased in the SHR-captopril, and 10 and 100% PSPY groups. Additionally, the levels of phosphorylated insulin-like growth factor I receptor (p-IGF-IR) were increased in SHR hearts from the SHR-control group; however, no recovery in the levels of downstream signaling components was observed. In addition, the levels of components of the compensatory IGF-IR-dependent survival pathway (p-PI3K and p-Akt) were all highly enhanced in the left ventricles in the hearts form the SHR-10 and 100% PSPY groups. Therefore, the oral administration of PSPY may attenuate cardiomyocyte apoptosis in SHR hearts by activating IGF-IR-dependent survival signaling pathways.


Hsu T.-C.,Chung Shan Medical University | Lan J.-L.,National Yang Ming University | Kao S.-H.,Chung Shan Medical University | Li S.-L.,Chung Shan Medical University | And 5 more authors.
Chinese Journal of Physiology | Year: 2010

Antibodies against the proliferating cell nuclear antigen (PCNA) was first discovered in the sera of systemic lupus erythematosus (SLE) patients. However, the reactivity and specificity of anti-PCNA autoantibodies are still unclear. To investigate the property of anti-PCNA autoantibodies, we conducted an ELISA screening of the anti-PCNA autoantibodies in sera of SLE patients. Eighteen out of 191 SLE sera were found to be positive for anti-PCNA antibodies giving a frequency of nearly 10%. Among the positive sera, a sample with the highest titer of anti-PCNA autoantibody preferentially recognizes the wild-type PCNA as compared to the Y114A mutation which contains a single amino acid substitution at 114 and fails to form the toroidal structure. Moreover, the autoantibody purified from this serum identifies only the free PCNA in crude mammalian cell extracts but not other associated cellular components. This finding raises a possibility that immunostaining with the human anti-PCNA autoantibodies in previous studies might have only partially PCNAs in tissues. ©2010 by The Chinese Physiological Society.


Chen C.-T.,Graduate Institute of Chinese Medical Science | Lin J.-G.,Graduate Institute of Chinese Medical Science | Lu T.-W.,National Taiwan University | Tsai F.-J.,Graduate Institute of Chinese Medical Science | And 4 more authors.
American Journal of Chinese Medicine | Year: 2010

The present study provides in vitro and in vivo evaluations of earthworm (Pheretima aspergilum) on peripheral nerve regeneration. In the in vitro study, we found the earthworm (EW) water extracts caused a marked enhancement of the nerve growth factor-mediated neurite outgrowth from PC12 cells as well as the expressions of growth associated protein 43 and synapsin I. In the in vivo study, silicone rubber chambers filled with EW extracts were used to bridge a 10 mm sciatic nerve defect in rats. Eight weeks after implantation, the group receiving EW extracts had a much higher success percentage of regeneration (90%) compared to the control (60%) receiving the saline. In addition, quantitative histology of the successfully regenerated nerves revealed that myelinated axons in EW group at 31.25 μg/ml was significantly more than those in the controls (p < 0.05). These results showed that EW extracts can be a potential growth-promoting factor on regenerating peripheral nerves. © 2010 World Scientific Publishing Company Institute for Advanced Research in Asian Science and Medicine.

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