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Cheng C.-P.,Graduate Institute of Medical science | Sheu M.-J.,Chi Mei Medical Center | Sytwu H.-K.,Graduate Institute of Life science | Chang D.-M.,National Defense Medical Center
Rheumatology (United Kingdom) | Year: 2013

Objective. Decoy receptor 3 (DCR3) has been known to modulate immune functions of monocyte or macrophage. In the present study, we investigated the mechanism and the effect of DCR3 on RANK ligand (RANKL)-induced osteoclastogenesis.Methods. We treated cells with DCR3 in RANKL-induced osteoclastogenesis to monitor osteoclast formation by tartrate-resistant acid phosphatase (TRAP) staining. Osteoclast activity was assessed by pit formation assay. The mechanism of inhibition was studied by biochemical analysis such as RT-PCR and immunoblotting. In addition, cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis and apoptosis signalling were evaluated by immunoblotting and using flow cytometry.Results. DCR3 inhibited RANKL-induced TRAPplus multinucleated cells and inhibited RANKL-induced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) nuclear translocation in RAW264.7 cells. Also, DCR3 significantly inhibited the bone-resorbing activity of mature osteoclasts. Moreover, DCR3 enhanced RANKL-induced cell apoptosis and enhanced RANKL-induced Fas ligand expression. The mechanisms were mediated via the intrinsic cytochrome c and activated caspase 9 apoptosis pathway.Conclusion. We postulated that the inhibitory activity of DCR3 on osteoclastogenesis occurs via down-regulation of RANKL-induced NFATc1 expression and induction of cell apoptosis. Our results postulated DCR3 as a possible new remedy against inflammatory bone destruction. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. Source

Chang Y.-C.,Graduate Institute of Life science | Chen S.-F.,China Medical University at Heping | Jao S.-W.,Graduate Institute of Dental Science | Lin Y.-L.,Graduate Institute of Pathology | Fu E.,Graduate Institute of Dental Science
Histopathology | Year: 2010

Aims: To test the validity of an invasive pattern grading score (IPGS) developed for oral squamous cell carcinoma (OSCC) as a prognostic indicator and to elucidate the relationship between the IPGS and clinical parameters. Methods and results: The IPGS was applied to a total of 153 cases of OSCC. There were significant correlations between IPGS and distant metastasis (P = 0.01) or recurrence (P = 0.001). However, there were no significant correlations between IPGS and gender, age, size or extent, location, status of lymph node metastasis, clinical staging, or histological grading. Cases of OSCC with higher IPGS were associated with poor patient survival (P < 0.001) and higher probability of tumour recurrence (P = 0.001). Intraobserver ( = 0.74) and interobserver agreement ( = 0.67) were very satisfactory. Conclusions: Our study confirms the validity of the IPGS, an indicator that is simple and easy to use. IPGS not only provides histological assessment of biological behaviour, but also offers an independent prognostic factor that may influence the treatment of OSCC. © 2010 Blackwell Publishing Limited. Source

Shih T.-Y.,A-Life Medical | Young T.-H.,Cardinal Tien Hospital | Lee H.-S.,National Defense Medical Center | Hsieh C.-B.,National Defense Medical Center | Hu O.Y.-P.,Graduate Institute of Life science
AAPS Journal | Year: 2013

Isoniazid (INH) and rifampicin (RIF) are the first-line drugs for antituberculosis (anti-TB) chemotherapy. The levels of serum transaminases [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] are abnormal in 27% of patients undergoing INH and RIF treatments and in 19% of patients undergoing treatment with INH alone. Cytochrome P450 2E1 (CYP2E1) metabolizes many toxic substrates, including ethanol, carbon tetrachloride, and INH, which ultimately results in liver injury. The objective of this study was to screen for CYP2E1 inhibitors in vitro and investigate whether the selected compound could prevent INH/RIF-induced hepatotoxicity in vivo. We screened 83 known compounds from food and herbal medicines as inhibitors of CYP2E1. The hepatotoxic dose of INH/RIF was 50/100 mg kg-1 day-1. Hepatotoxicity was assessed using galactose single-point (GSP) method (a quantitative measurement of liver function), histopathological examination of the liver, malondialdehyde (MDA) assay, and measurement of AST and ALT activities. Kaempferol inhibited CYP2E1 activity in mice by 0.31- to 0.48-fold (p < 0.005). Mice with INH/RIF-induced hepatotoxicity showed significantly abnormal serum levels of AST and ALT, and GSP value, and these values could be decreased by the administration of kaempferol (p < 0.005). Kaempferol significantly reduced the depletion of hepatic glutathione and prevented the increase in MDA formation in mice. Furthermore, kaempferol did not affect the anti-TB effects of INH/RIF. To our knowledge, this is the first report of kaempferol's utility as an adjuvant for preventing CYP2E1-mediated hepatotoxicity induced by drugs such as INH and RIF. © 2013 American Association of Pharmaceutical Scientists. Source

Chien W.-C.,National Defense Medical Center | Chung C.-H.,Graduate Institute of Life science | Lai C.-H.,National Defense Medical Center | Chou C.-H.,National Defense Medical Center
International Journal of Injury Control and Safety Promotion | Year: 2014

The aim of the article was to investigate the injury types and medical utilisations among patients more than 65 years in Taiwan. The data used in this study were obtained from the years 1997 to 2008 of the National Health Insurance Research Database (NHIRD). The patients with the age of 65 years and older as well as with ICM-9-CM discharge injury principal diagnoses 800-959 were included in this study. SPSS 18.0 was used for data analysis. The results showed that there were 518,601 older adults hospitalised because of injuries in the period of study. The average age among them was 76.1 years old and 51.7% of them were females. The common causes of injury were falls and motor vehicle accident. The average number of operations that patients received was one, and the average length of stay was 9.1 days. The total medical expenditure was over NT$ 28.9 billion, and the average expenditure was NT$ 55,738. The factors associated with deaths were sex, ages, co-morbidity disease, level of care, number of operations, length of stay, expenditure of medical care, injury types and causes of injury. This study concludes that in order to decrease the incident of injuries in elder patients, the education of preventing falls and traffic safety should be promoted continuously among elders. © 2014 Copyright Taylor & Francis Group, LLC. Source

Huang S.-P.,Graduate Institute of Life science | Hsu C.-C.,Tri Service General Hospital | Chang S.-C.,National Defense Medical Center | Wang C.-H.,National Defense Medical Center | And 8 more authors.
Annals of Plastic Surgery | Year: 2012

INTRODUCTION: The promotion of wound healing using dermal substitutes has become increasingly widespread, but the outcomes of substitute-assisted healing remain functionally deficient. Adipose-derived stem cells (ASCs) have been investigated widely in regenerative medicine and tissue engineering, and they have the potential to enhance wound healing. In this study, we focused on investigating the effects and mechanism of ASCs combined with an acellular dermal matrix (ADM) to treat full-thickness cutaneous wounds in a murine model. METHODS: The ADM was prepared from the dorsal skin of nude mice by decellularization by treatment with trypsin followed by Triton X-100. The human ASCs were isolated and cultured from abdominal lipoaspirate. We created a rounded, 8-mm, full-thickness cutaneous wound in nude mice and divided the mice into the following 4 groups: silicon sheet cover only, silicon sheet with spreading ASCs, ADM only, and ASCs seeded on ADM. The granulation thickness was evaluated by histology after 7 days. Further comparisons between the ADM only and ASC-seeded ADM groups were undertaken by assessing the reepithelialization ratio and blood vessel density at postoperative days 9 and 14. Statistical analyses were conducted using Student 2-tailed t test. Immunofluorescent histology and ASC labeling were also performed to identify possible mechanisms. RESULTS: The ADM was successfully prepared, and the cytometry analysis and differentiation assay provided the characterization of the human ASCs. A marked improvement in granulation thickness was detected in the ADM-ASC group in comparison with other 3 groups. A significantly increased rate of reepithelialization in the ADM-ASC group (80 ± 6%) compared to the ADM only group (60 ± 7%) was noted on postoperative day 9. The blood vessel density was evidently increased in the ADM-ASC group (7.79 ± 0.40 vessels per field) compared to the ADM only group (5.66 ± 0.23 vessels) on day 14. Cell tracking experiments demonstrated that labeled ASCs were colocalized with staining for VEGF or endothelial cell maker vWF after the transplantation of ADM-ASCs on postoperative day 14. CONCLUSIONS: Adipose-derived stem cells seeded on an ADM can enhance wound healing, promote angiogenesis, and contribute to newly formed vasculature, and VEGF-expressing ASCs can be detected after transplantation. This model could be used to improve the other clinical applications of ASCs and to decipher the detailed mechanism by which ASCs interact with wound tissue. Copyright © 2012 by Lippincott Williams & Wilkins. Source

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