452 results on '"Chang, Deh-Ming"'
Search Results
152. Triggering of DC migration by dengue virus stimulation of COX-2-dependent signaling cascades in vitro highlights the significance of these cascades beyond inflammation.
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Wu, Wan-Lin, Ho, Ling-Jun, Chang, Deh-Ming, Chen, Chen-Hung, and Lai, Jenn-Haung
- Abstract
A term 'bone-breaking fever' is used in Chinese medicine to describe the symptoms of patients infected with dengue virus (DV). We examined the significance of the COX-prostaglandin pathway in human DC infected by DV. We show that DV infection induced the expression of COX-2 and the production of prostaglandin E (PGE) in DC, and stimulated the DNA binding of NF-κB and the kinase activity of both IκBα kinase (IKK) α and β. DV infection also activated MAPK and AP-1 signaling. Both IκBα kinase-NF-κB and MAPK-AP-1 were upstream of COX-2 activation. Our investigation into the significance of COX-2-PGE pathway also revealed that DV infection enhances DC migration by inducing CC chemokine receptor 7 (CCR7) expression, and that blocking COX-2 or MAPK activity suppresses DV-induced DC migration. Our data also suggest that PGE can induce CCR7 expression on DC and that antagonists of the PGE receptors EP2 and EP4 suppress DV-induced DC migration. We further show that the increased CCR7 expression was observed in both DV-infected and bystander DC, suggesting the presence of secondary effects in inducing CCR7 expression. Collectively, this study reveals not only the pathways involved in COX-2 synthesis in DV-infected DC but also the autocrine action of PGE on the migration of DV-infected DC. [ABSTRACT FROM AUTHOR]
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- 2009
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153. Human monocytes produce IL-1 and an inhibitor of IL-1 in response to two different signals
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Schur, Peter H., primary, Chang, Deh-Ming, additional, Baptiste, Paul, additional, Uhteg, Lawrence C., additional, and Hanson, Douglas C., additional
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- 1990
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154. Plant alkaloid tetrandrine downregulates IkappaBalpha kinases-IkappaBalpha-NF-kappaB signaling pathway in human peripheral blood T cell.
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Ho, Ling-Jun, Juan, Ting-Yi, Chao, Ping, Wu, Wan-Lin, Chang, Deh-Ming, Chang, Sun-Yran, and Lai, Jenn-Haung
- Abstract
Plant alkaloid tetrandrine (Tet), purified from Chinese herb Han-Fang Chi, is a potent immunomodulator used to treat rheumatic disorders, silicosis and hypertension in mainland China. We previously demonstrated that Tet effectively suppresses cytokine production and proliferation of CD28-costimulated T cells. In the present study, we investigated the possible involvement of nuclear factor kappa B (NF-kappaB) transcription factors, critical in CD28 costimulation, in Tet-mediated immunosuppression in human peripheral blood T cells. We showed that Tet inhibited NF-kappaB DNA-binding activities induced by various stimuli, including CD28 costimulation. At equal molar concentrations, Tet was as strong as methotrexate in suppressing CD28-costimulated NF-kappaB activities. Since Tet itself did not affect NF-kappaB binding to its corresponding DNA sequence, the results suggested that Tet might regulate NF-kappaB upstream signaling molecules. Further studies demonstrated that Tet could prevent the degradation of IkappaBalpha and inhibit nuclear translocation of p65 by blocking IkappaBalpha kinases alpha and beta activities. In addition, the activation of mitogen-activated protein kinases such as c-jun N-terminal kinase, p38 and extracellular signal-regulated kinase and activator protein-1 DNA-binding activity were all downregulated by Tet. Transfection assays performed in purified human peripheral blood T cells also confirmed the inhibition of NF-kappaB transcriptional activity by Tet. When four Tet analogues were readily compared, dauricine appeared to preserve the most potent inhibition on CD28-costimulated but not on H(2)O(2)-induced NF-kappaB DNA-binding activities. Our results provide the molecular basis of immunomodulation of Tet for being a potential disease-modifying antirheumatic drug in the therapy of autoimmune disorders like rheumatoid arthritis. [ABSTRACT FROM AUTHOR]
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- 2004
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155. Plant alkaloid tetrandrine downregulates IκBα kinases-IκBα- NF-κB signaling pathway in human peripheral blood T cell.
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Ling-Jun Ho, Juan, Ting-Yi, Chao, Ping, Wu, Wan-Lin, Chang, Deh-Ming, Chang, Sun-Yran, and Lai, Jenn-Haung
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RHEUMATOID arthritis ,IMMUNOSUPPRESSIVE agents ,AUTOIMMUNE diseases ,GENETIC transformation ,IMMUNOREGULATION ,PROTEIN kinases ,TRANSCRIPTION factors ,LYMPHOCYTES - Abstract
1 Plant alkaloid tetrandrine (Tet), purified from Chinese herb Han-Fang Chi, is a potent immunomodulator used to treat rheumatic disorders, silicosis and hypertension in mainland China. 2 We previously demonstrated that Tet effectively suppresses cytokine production and proliferation of CD28-costimulaied T cells. In the present study, we investigated the possible involvement of nuclear factor kappa B (NF-κB) transcription factors, critical in CD28 costimulation, in Tet-mediated immunosuppression in human peripheral blood T cells. 3 We showed that Tel inhibited NF-κB DNA-binding activities induced by various stimuli, including CD28 costimulation. At equal molar concentrations, Tet was as strong as methotrexate in suppressing CD28-costimulated NF-κB activities. Since Tet itself did not affect NF-κB binding lo its corresponding DNA sequence, the results suggested that Tet might regulate NF-κB upstream signaling molecules. 4 Further studies demonstrated that Tet could prevent the degradation of IκBα and inhibit nuclear translocation of p65 by blocking IκBα kinases α and β activities. In addition, the activation of mitogen-activated protein kinases such as c-jun N-terminal kinase, p38 and extracellular signalregulated kinase and activator protein-1 DNA-binding activity were all downregulated by Tet. Transfection assays performed in purified human peripheral blood T cells also confirmed the inhibition of NF-κB transcriptional activity by Tet. 5 When four Tel analogues were readily compared, dauricine appeared to preserve the most potent inhibition on CD28-coslimulaled but not on H
2 O2 -induced NF-κB DNA-binding activities. 6 Our results provide the molecular basis of immunomodulation of Tet for being a potential diseasemodifying antirheumalic drug in the therapy of autoimmune disorders like rheumatoid arthritis. [ABSTRACT FROM AUTHOR]- Published
- 2004
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156. Carvedilol, a new antioxidative β-blocker, blocks in vitro human peripheral blood T cell activation by downregulating NF-κB activity
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Yang, Shih-Ping, Ho, Ling-Jun, Lin, Yi-Ling, Cheng, Shu-Meng, Tsao, Tien-Ping, Chang, Deh-Ming, Hsu, Yu-Lin, Shih, Chin-Yi, Juan, Ting-Yi, and Lai, Jenn-Haung
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NF-kappa B ,ATHEROSCLEROSIS ,T cells - Abstract
Objective: The activation of T lymphocytes contributes to the inflammatory process of atherosclerosis. Here we examined the effects of carvedilol, a new β-blocker containing an antioxidative property, on the activation of T cells. Methods: Human peripheral blood T cells were negatively selected from whole blood. Cytokines were measured by ELISA. The NF-κB and related protein activity was determined by electrophoretic mobility shift assays, Western blotting, kinase assays and transfection assays. Results: Carvedilol was nontoxic at concentrations ≦10 μM, however, higher dosages (⩾20 μM) induced T cell apoptosis. We demonstrated that carvedilol inhibited cytokine production from various stimuli-activated T cells. Carvedilol also suppressed the expression of T cell activation markers, including CD25, CD69 and CD71. Molecular investigation indicated that carvedilol specifically downregulated NF-κB but not activator protein 1 DNA-binding activity in activated T cells. The inhibitory effect was likely due to its antioxidative property. Meanwhile, carvedilol prevented stimuli-induced IκBα degradation. Such an effect was mediated through the inhibition of IκBα kinase activity. The inhibitory specificity on NF-κB by carvedilol was also demonstrated in transfection assays. Conclusions: Our results demonstrated a novel therapeutic mechanism of carvedilol in atherosclerosis, namely the inhibition of T cell activation via downregulating NF-κB activity. [Copyright &y& Elsevier]
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- 2003
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157. Aspirin differentially regulates endotoxin-induced IL-12 and TNF-alpha production in human dendritic cells.
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Ho, Ling-Jun, Chang, Deh-Ming, Shiau, Hen-Yih, Chen, Chen-Hung, Hsieh, Tsai-Yuan, Hsu, Yu-Lin, Wong, Chih-Shung, Lai, Jenn-Haung, Ho, L J, Chang, D M, Shiau, H Y, Chen, C H, Hsieh, T Y, Hsu, Y L, Wong, C S, and Lai, J H
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ASPIRIN , *DENDRITIC cells , *PHYSIOLOGY , *BIOCHEMISTRY , *CELL culture , *COMPARATIVE studies , *DOCUMENTATION , *DOSE-effect relationship in pharmacology , *INTERLEUKINS , *PHENOMENOLOGY , *RESEARCH methodology , *MEDICAL cooperation , *NUCLEOTIDES , *POLYMERASE chain reaction , *REFERENCE values , *RESEARCH , *TUMOR necrosis factors , *EVALUATION research , *REVERSE transcriptase polymerase chain reaction , *LIPOPOLYSACCHARIDES , *PHARMACODYNAMICS - Abstract
Objective: In the development of autoimmune diseases, dendritic cells (DC) play critical roles. Here, we examined the effect of aspirin on lipopolysaccharide (LPS)-induced DC activation.Methods: The monocyte-derived DC were established. The cytokine production was measured by ELISA, reverse transcriptase/polymerase chain reaction, or intracellular staining analyzed by flow cytometry. The expression of cell surface molecules was determined by flow cytometry.Results: Aspirin inhibited LPS-induced DC maturation and costimulatory molecules expression. Aspirin, at therapeutic concentrations, also decreased LPS-induced IL-12 and IL-10 production. In contrast, the LPS-induced TNF-alpha production was enhanced by aspirin. The differential effects of aspirin on IL-12 and TNF-alpha production may not be due to down-regulation of cyclooxygenase activities.Conclusion: The various effects of aspirin on LPS-stimulated DC may influence the understanding of the diverse immunomodulatory mechanisms of this anti-inflammatory drug. [ABSTRACT FROM AUTHOR]- Published
- 2001
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158. Production Of Interleukin-L (Il-L) And Il-L Inhibitor By Human Monocytes Exposed To Dengue Virus.
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Chang, Deh-Ming and Shaio, Men-Fang
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- 1994
159. Increased Monocyte Chemoattractant Protein-1 in Knee Joints of Rats with Adjuvant-Induced Arthritis: In Vivo Microdialysis
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Liu, Shao-Hsiang, Wong, Chih-Shung, and Chang, Deh-Ming
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OBJECTIVE: Imbalance of inflammatory and antiinflammatory cytokines plays a critical role in the pathogenesis of rheumatoid arthritis (RA). Precise determination of these cytokines would lead to better understanding of the progression of RA. METHODS: We developed an in vivo microdialysis technique to directly monitor cytokine profiles in knee joints of rats with adjuvant-induced arthritis (AIA). Microdialysates drained from knee joints of rats with AIA and controls were collected and cytokine concentrations were measured by ELISA. Pathological changes of the knee joints and the source of monocyte chemoattractant factor–1 (MCP-1) secretion were also determined by histology and immunohistochemistry. RESULTS: MCP-1 expression in knee joints was significantly higher in AIA rats with erosive changes in their ankles than in normal rats, while interleukin 6 (IL-6) levels were similar in both cases. IL-1β and interferon-g were not detectable in the microdialysates. Increased synovial proliferation and mononuclear inflammatory infiltrates were observed. Synovial cells and mononuclear inflammatory cells expressed both MCP-1 and its receptor, CCR2. CONCLUSION: Our results indicate that the in vivo microdialysis technique is capable of detecting cytokines in the knee joints of rats. Increased expression of MCP-1 and CCR2 in knee joints of AIA rats suggests a role for this cytokine in triggering the mechanisms involved in the pathogenesis of knee joint after ankle erosion.
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- 2005
160. Pleural Effusion as a Manifestation of Lyme Disease
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Chen, Hsiang-Cheng, Shih, Chien-Ming, Lai, Jenn-Haung, Chao, Li-Lian, Kuo, San-Yuan, and Chang, Deh-Ming
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- 2004
161. The 11th Asia-Pacific League of Associations for Rheumatology Congress (APLAR 2004): JCR Sponsored Symposium “Efficacy and Safety of TNF-alpha Blockers in Rheumatoid Arthritis” September 12 (Sunday), 2004, 14:00-15:30, Jeju, Korea 1. Efficacy and safety of infliximab in the treatment of Japanese rheumatoid arthritis patients 2. Expression profile analysis by microarray to predict responders to anti-TNF biologics in rheumatoid arthritis 3. Biologicals in India - postmarketing surveillance: problems and prospects 4. Infliximab: the experience in Hong Kong 5. Postmarketing surveillance of etanercept in Australia up to June 2004 6. The open-label evaluation of the efficacy and safety of etanercept in patients with active rheumatoid arthritis and ankylosing spondylitis
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Miyasaka, Nobuyuki, Takeuchi, Tsutomu, Itoh, Satoru, Pispati, Prakash K., Gavin, Lee Ka-Wing, de Jager, Julien P., Chou, Chung-Tei, Tsai, Jaw-Ji, Cheng, Tien-Tsai, Liou, Lieh-Bang, Chang, Cheng-Pi, Huang, Chung-Ming, Chen, Chung-Jen, Lee, Chyou-Shen, Yu, Chia-Li, Chang, Deh-Ming, and Cheng, He-Hsiung
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TUMOR necrosis factors ,RHEUMATOID arthritis ,BIOLOGICALS ,ETANERCEPT - Abstract
Presents several abstracts related to the efficacy and safety of tumor necrosis factor (TNF)-alpha blockers in rheumatoid arthritis. Expression profile analysis by microarray to predict responders to anti-TNF biologics in rheumatoid arthritis; Postmarketing surveillance of etanercept in Australia; Open-label evaluation of the efficacy and safety of etanercept in patients with active rheumatoid arthritis and ankylosing spondylitis.
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- 2004
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162. Tuberculosis of skeletal muscle in a case of polymyositis: CASE REPORT.
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Huang, Kun-Lun, Chang, Deh-Ming, and Lu, Jang-Jih
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POLYMYOSITIS , *MUSCULOSKELETAL system diseases , *PATIENTS - Abstract
We describe a patient with polymyositis receiving corticosteroid therapy, who presented with persistent fever and mass lesion at the left thigh. Surgical exploration and mycobacterial culture proved to be Mycobacterium Tuberculosis infection involving the semitendinous muscle of the left thigh. Suitable surgical debridement, anti-TB medications, and sufficient corticosteroid administration resulted in a good control of both polymyositis and the tuberculous infection. [ABSTRACT FROM AUTHOR]
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- 1999
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163. Peripheral Arthritis Caused by Mycobacterium avium-intracellularein a Patient With Ankylosing Spondylitis
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Yang, Deng-Ho, Chang, Wei-Chou, Cheng, Ming-Fang, Lai, Jenn-Haung, Chang, Deh-Ming, and Chen, Chen-Hung
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- 2009
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164. Acute Gouty Inflammation of a Cystic Tophaceous Lesion of a Leg Muscle Associated with "Urate Milk"
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Huang, Guo-Shu, CHANG, DEH-MING, CHANG, WEI-CHOU, KAO, HUNG-WEN, HSU, YI-CHIH, and CHEN, CHENG-YU
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- 2005
165. An unrecognized cause of oedema in a patient with lupus nephritis: protein losing enteropathy.
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Wu, Chia-Chao, Lin, Shih-Hua, Chu, Pauling, Lai, Jenn-Haung, Chang, Deh-Ming, and Lin, Yuh-Feng
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- 2004
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166. Di‐(2‐ethylhexyl) phthalate exposure links to inflammation and low bone mass in premenopausal and postmenopausal females: Evidence from ovariectomized mice and humans.
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Lai, Chien‐Chih, Liu, Fei‐Lan, Tsai, Chang‐Youh, Wang, Shu‐Li, and Chang, Deh‐Ming
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POSTMENOPAUSE , *BONE density , *TUMOR necrosis factors , *OSTEITIS , *CANCELLOUS bone , *BONE densitometry , *HAIR analysis - Abstract
Objective: Phthalates induce inflammation and are ubiquitously used in daily life. We aim to study the impact of di‐(2‐ethylhexyl) phthalate (DEHP) exposure on inflammation and osteoporosis in premenopausal and postmenopausal females. Methods: Female 8‐week‐old C57BL/6JNarl mice received an ovariectomy (OVX) or a sham operation and were fed with DEHP or vehicle by oral gavage for 4 or 8 weeks. Their femurs were isolated for micro‐computed tomography, and their serum was collected for inflammatory cytokine assays. Correlations between urinary phthalate metabolites and the lumbar spine bone mineral density (BMD) in premenopausal and postmenopausal volunteers were performed. Results: Among the OVX mice treated for 4 weeks, significant lower bone volume, bone volume/tissue volume, and trabecular number but significant higher trabecular bone pattern factor and structure model index were identified in the mice treated with DEHP than with vehicle. The OVX mice treated with DEHP for 4 weeks had significantly higher serum interleukin (IL)‐1β, IL‐10, IL‐17A, interferon (IFN)‐γ, tumor necrosis factor (TNF)‐α, and Dickkopf‐1 levels than those treated with vehicle. The sham mice treated with DEHP for 8 weeks showed an impaired femur trabecular microstructure and had significantly higher serum IL‐1β, IL‐6, IL‐10, IL‐17A, IFN‐γ, and TNF‐α than those treated with vehicle. DEHP metabolites were inversely correlated with the BMD of premenopausal women and the T‐score of postmenopausal women. Conclusion: DEHP treatment in OVX and sham mice results in osteoporosis and impairs the microstructure of the femur trabecula through inflammation. Phthalate exposure negatively affects the bone mass in both premenopausal and postmenopausal women. Thus, long‐term avoidance is suggested. [ABSTRACT FROM AUTHOR]
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- 2022
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167. TACE-dependent amphiregulin release is induced by IL-1β and promotes cell invasion in fibroblast-like synoviocytes in rheumatoid arthritis.
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Liu, Fei-Lan, Wu, Cheng-Chi, and Chang, Deh-Ming
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- 2014
168. Design, synthesis and evaluation of telomerase inhibitory, hTERT repressing, and anti-proliferation activities of symmetrical 1,8-disubstituted amidoanthraquinones
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Lee, Chia-Chung, Huang, Kuo-Feng, Chang, Deh-Ming, Hsu, Jung-Jung, Huang, Fong-Chun, Shih, Kai-Ning, Chen, Chun-Liang, Chen, Tsung-Chih, Chen, Ruei-Huei, Lin, Jing-Jer, and Huang, Hsu-Shan
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TELOMERASE , *DRUG design , *DRUG synthesis , *CELL proliferation , *ANTHRAQUINONES , *CELL-mediated cytotoxicity - Abstract
Abstract: A series of symmetrical disubstituded 1,8-diamidoanthraquinones were synthesized and evaluated for anti-proliferation, telomerase inhibitory by TRAP assay, and hTERT expression by SEAP assay. All of the compounds tested, except for compounds 3a and 3s were selected by the NCI screening system. In addition, compounds 4e and 4k exhibited inhibitory effects on telomerase activity. Taken together, our findings indicated that the analysis of cytotoxicity and telomerase inhibition might provide information applicable for further developing potential telomerase targeting strategy. [Copyright &y& Elsevier]
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- 2012
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169. MRI contributes to accurate and early diagnosis of non-radiographic HLA-B27 negative axial spondyloarthritis.
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Lu, Chun-Chi, Huang, Guo-Shu, Lee, Tony Szu-Hsien, Chao, En, Chen, Hsiang-Cheng, Guo, Yong-Si, Chu, Shi-Jye, Liu, Feng-Cheng, Kao, San-Yuan, Hou, Tsung-Yun, Chen, Chen-Hung, Chang, Deh-Ming, and Lyu, Sin-Yi
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MAGNETIC resonance imaging , *HLA-B27 antigen , *EARLY diagnosis , *HLA histocompatibility antigens , *RECEIVER operating characteristic curves - Abstract
Background: Nonradiographic axial spondyloarthropathies (nr-axSpA) are diagnosed by the absence of radiographic sacroiliitis and the presence of bone marrow edema (BME) on magnetic resonance imaging (MRI). According to the classification criteria of the international Assessment of Spondyloarthritis Society (ASAS), structural changes to sacroiliac joints (SIJs) on MRI cannot be used as criteria in the absence of BME. However, less than half the Asian patients with clinically active axSpA show BME. The incidence of human leukocyte antigen (HLA)-B27 is low in Asian populations, which makes it more difficult to identify nr-axSpA. We used MRI to evaluate the structural damage to SIJs in patients with nr-axSpA with and without BME with the aim of identifying the best methodology for accurate diagnosis, especially in populations with less common BME and HLA-B27.Methods: One hundred three patients with inflammatory back pain were included in this prospective study. No patient's radiograph met the definition of positive modified New York criteria. BME and structural damage to SIJ including sclerosis and erosion were assessed independently on coronal and axial short-tau inversion recovery and T1-weighted spin echo MRI scans by two well-trained musculoskeletal radiologists using the Spondyloarthritis Research Consortium of Canada (SPARCC) score. Demographics of patients were collected. Disease characteristics and structural damage were analyzed in patients with and without BME on SIJ MRI. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of structural damage.Results: All individuals in the cohort had at least one abnormal finding on SIJ MRI, including BME or structural damage; 36 of 103 patients had BME. We identified a significant positive correlation between SPARCC scores and severe erosion assessed by focal joint space widening (fJSW) (p = 0.001) in these 36 patients. Fifty-eight of the 103 enrolled patients fulfilled the ASAS criteria for nr-axSpA in the either absence or presence of BME. Of these 58 patients, 57 and 19 had erosions or fJSW, respectively, and the presence of BME was significantly correlated with fJSW (phi score of 0.319 and p = 0.015). We demonstrated a significant positive correlation between fJSW and either the presence or the severity of BME in patients with nr-axSpA who met the ASAS definition. There was a positive correlation between BME and fJSW across the whole study cohort (phi score of 0.389; p < 0.001). The area under the ROC curve (AUC) for fJSW on SIJ MRI was 0.736, p < 0.001. In both HLA-B27-positive and -negative groups, BME was more common in the presence of fJSW (phi scores of 0.370 and 0.377, p = 0.018 and 0.003, respectively) and SPARCC scores were higher in patients with fJSW (p < 0.001 and p = 0.005). We also identified a positive correlation between fJSW and BME in patients with nr-axSpA and normal serum levels of C-reactive protein (phi score of 0.362 and p = 0.001).Conclusion: Structural damage detected on SIJ MRI, sclerosis, erosions and fJSW may be present in patients without detectable inflammation on SIJ MRI. However, fJSW is significantly correlated with the severity of inflammation seen on SIJ MRI, which contributes to the accurate diagnosis of nr-axSpA, and it could be used as an alternative diagnostic test for nr-axSpA in the general population, especially for those who do not carry the HLA-B27 gene, Asian patients without BME, or patients with normal serum inflammatory biomarkers. [ABSTRACT FROM AUTHOR]- Published
- 2021
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170. SUMO-defective c-Maf preferentially transactivates Il21 to exacerbate autoimmune diabetes.
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Chao-Yuan Hsu, Li-Tzu Yeh, Shin-Huei Fu, Ming-Wei Chien, Yu-Wen Liu, Shi-Chuen Miaw, Deh-Ming Chang, Huey-Kang Sytwu, Hsu, Chao-Yuan, Yeh, Li-Tzu, Fu, Shin-Huei, Chien, Ming-Wei, Liu, Yu-Wen, Miaw, Shi-Chuen, Chang, Deh-Ming, and Sytwu, Huey-Kang
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AUTOIMMUNE diseases , *DIABETES , *MYC proteins , *T cell receptors , *CARRIER proteins , *IMMUNOLOGY - Abstract
SUMOylation is involved in the development of several inflammatory diseases, but the physiological significance of SUMO-modulated c-Maf in autoimmune diabetes is not completely understood. Here, we report that an age-dependent attenuation of c-Maf SUMOylation in CD4+ T cells is positively correlated with the IL-21-mediated diabetogenesis in NOD mice. Using 2 strains of T cell-specific transgenic NOD mice overexpressing wild-type c-Maf (Tg-WTc) or SUMOylation site-mutated c-Maf (Tg-KRc), we demonstrated that Tg-KRc mice developed diabetes more rapidly than Tg-WTc mice in a CD4+ T cell-autonomous manner. Moreover, SUMO-defective c-Maf preferentially transactivated Il21 to promote the development of CD4+ T cells with an extrafollicular helper T cell phenotype and expand the numbers of granzyme B-producing effector/memory CD8+ T cells. Furthermore, SUMO-defective c-Maf selectively inhibited recruitment of Daxx/HDAC2 to the Il21 promoter and enhanced histone acetylation mediated by CREB-binding protein (CBP) and p300. Using pharmacological interference with CBP/p300, we illustrated that CBP30 treatment ameliorated c-Maf-mediated/IL-21-based diabetogenesis. Taken together, our results show that the SUMOylation status of c-Maf has a stronger regulatory effect on IL-21 than the level of c-Maf expression, through an epigenetic mechanism. These findings provide new insights into how SUMOylation modulates the pathogenesis of autoimmune diabetes in a T cell-restricted manner and on the basis of a single transcription factor. [ABSTRACT FROM AUTHOR]
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- 2018
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171. Design, synthesis and SARs of novel salicylanilides as potent inhibitors of RANKL-induced osteoclastogenesis and bone resorption.
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Chen, Chun-Liang, Lee, Chia-Chung, Liu, Fei-Lan, Chen, Tsung-Chih, Ahmed Ali, Ahmed Atef, Chang, Deh-Ming, and Huang, Hsu-Shan
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DRUG design , *SALICYLANILIDES , *STRUCTURE-activity relationship in pharmacology , *TRANCE protein , *CHEMICAL synthesis , *OSTEOCLAST inhibition , *OSTEOCLASTOGENESIS , *CHROMOSOMAL translocation - Abstract
Inhibiting osteoclastogenesis is a promising therapeutic target for treating osteoclast-related diseases. Herein, we synthesized a series of modified salicylanilides and their corresponding 3-phenyl-2 H -benzo[ e ][1,3]oxazine-2,4(3 H )-dione and 10-phenyldibenzo[ b,f ][1,4]oxazepin-11(10 H )-one derivatives, and investigated the effects of such compounds on RANKL-induced osteoclast formation. Among them, a salicylanilide derivative ( A04) and its 3-phenyl-2 H -benzo[ e ][1,3]oxazine-2,4(3 H )-dione derivative ( B04 ) markedly suppressed RANKL-induced osteoclast differentiation and showed no significant cytotoxic effects at doses higher than that required to inhibit osteoclast formation. Both compounds reduced osteoclast formation and bone resorptive activity of osteoclasts in a dose-dependent manner. Further, the anti-osteoclastogenic effects of A04 and B04 may operate through reducing the RANKL-induced nuclear translocation of NFATc1. Accordingly, we present the potent anti-osteoclastogenic compounds A04 and B04 as promising candidates for further optimization as anti-resorptive agents. [ABSTRACT FROM AUTHOR]
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- 2016
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172. Novel inhibitors of RANKL-induced osteoclastogenesis: Design, synthesis, and biological evaluation of 6-(2,4-difluorophenyl)-3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-diones.
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Lee, Chia-Chung, Liu, Fei-Lan, Chen, Chun-Liang, Chen, Tsung-Chih, Liu, Feng-Cheng, Ahmed Ali, Ahmed Atef, Chang, Deh-Ming, and Huang, Hsu-Shan
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OSTEOCLASTOGENESIS , *OSTEOPROTEGERIN , *ORGANIC synthesis , *DRUG design , *OXAZINES , *ENZYME inhibitors , *CHEMICAL derivatives - Abstract
A series of novel 6-(2,4-difluorophenyl)-3-phenyl-2 H -benzo[ e ][1,3]oxazine-2,4(3 H )-dione derivatives were synthesized and evaluated for their inhibitory effects on osteoclast activities by using TRAP-staining assay. Among the tested compounds, 3d and 3h exhibited more potent osteoclast-inhibitory activities than the lead compound NDMC503 (a ring-fused structure of NDMC101), as reported in our previous study. Both 3d and 3h exhibited two-fold increase in activity compared to NDMC503. In addition, our biological results indicated that 3d and 3h could suppress RANKL-induced osteoclastogenesis-related marker genes, such as NFATc1 , c-fos , TRAP , and cathepsin K . Notably, 3d could significantly attenuate the bone-resorbing activity of osteoclasts in the pit formation assay. Thus, this study might provide a new class of lead structures that warrant further development as potential anti-resorptive agents. [ABSTRACT FROM AUTHOR]
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- 2015
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173. Discovery of 5-(2′,4′-difluorophenyl)-salicylanilides as new inhibitors of receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis.
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Lee, Chia-Chung, Liu, Fei-Lan, Chen, Chun-Liang, Chen, Tsung-Chih, Chang, Deh-Ming, and Huang, Hsu-Shan
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SALICYLANILIDES , *TRANCE protein , *OSTEOCLASTOGENESIS , *DRUG development , *LEAD compounds , *CATHEPSINS - Abstract
To improve the inhibitory potency of lead compound NDMC101 on RANKL-induced osteoclastogenesis, a series of new 5-(2′,4′-difluorophenyl)-salicylanilide derivatives were synthesized and evaluated for osteoclast inhibition by using TRAP-staining assay. Among them, both of compounds 6d and 6i showed three-fold increase in osteoclast–inhibitory activities compared to NDMC101 at half-inhibitory concentration. Further, the mechanistic study showed that 6d and 6i could suppress RANKL-induced osteoclastogenesis-related genes, such as NFATc1 , c-fos , TRAP , and cathepsin K . Their inhibitory activities were further confirmed by including specific inhibition of NF-κB and NFATc1 expression levels in nucleus. In addition, 6d and 6i also could significantly attenuate bone-resorbing activity of osteoclasts by performing pit formation assay. Thus, a new class of 5-(2′,4′-difluorophenyl)-salicylanilide derivatives may be considered as essential lead structures for the further development of anti-resorptive agents. [ABSTRACT FROM AUTHOR]
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- 2015
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174. Ring fusion strategy for the synthesis of anthra[2,3-d]oxazole-2-thione-5,10-dione homologues as DNA topoisomerase inhibitors and as antitumor agents.
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Chen, Chun-Liang, Liu, Fei-Lan, Lee, Chia-Chung, Chen, Tsung-Chih, Chang, Wen-Wei, Guh, Jih-Hwa, Ahmed Ali, Ahmed Atef, Chang, Deh-Ming, and Huang, Hsu-Shan
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OXAZOLES , *DNA topoisomerases , *ANTINEOPLASTIC agents , *ANTHRAQUINONES , *CHEMICAL synthesis , *ENZYME inhibitors , *PHARMACEUTICAL chemistry - Abstract
The efficient synthesis of mono-substituted anthraquinones and ring fusion into anthra[2,3- d ]oxazole-2-thione-5,10-dione derivatives were developed, and all the compounds were tested for their cytotoxicity against PC-3 cancer cell lines. Compounds 8 , 14 , 17 and 23 were selected by the NCI and 12 , 17 and 19 were evaluated for topoisomerase I-mediated DNA relaxation. Among them, 17 appeared to be the most active compound of this series and not only showed higher inhibition when indicated from the low IC 50 values against PC-3 cancer cell line but also attenuated the in vitro topoisomerase I-mediated DNA relaxation at low micromolar concentrations. All test compounds exhibited different cytostatic and cytotoxic activities for further developing potential anticancer drugs. [ABSTRACT FROM AUTHOR]
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- 2014
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175. Decoy receptor 3 suppresses RANKL-induced osteoclastogenesis via down-regulating NFATc1 and enhancing cell apoptosis.
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Cheng, Chia-Pi, Sheu, Ming-Jen, Sytwu, Huey-Kang, and Chang, Deh-Ming
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- 2013
176. A Benzamide-linked Small Molecule NDMC101 Inhibits NFATc1 and NF-κB Activity: A Potential Osteoclastogenesis Inhibitor for Experimental Arthritis.
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Cheng, Chia-Pi, Huang, Hsu-Shan, Hsu, Yu-Chieh, Sheu, Ming-Jen, and Chang, Deh-Ming
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BENZAMIDE , *NF-kappa B , *OSTEOCLAST inhibition , *ARTHRITIS , *LIGANDS (Biochemistry) , *CELL differentiation , *IMMUNOLOGICAL adjuvants - Abstract
Purpose: Using receptor activator of NF-κB ligand (RANKL) induced osteoclast differentiation on RAW264.7 as a screening tool; we synthesize and identify small-molecule inhibitors preserving immunomodulatory effects as therapeutics for rheumatoid arthritis. Methods: Differentiation into osteoclast-like cells was examined by tartrate-resistant acid phosphatase (TRAP) staining and expression of osteoclast differentiation markers. Collagen-induced arthritis (CIA) mice were administered test articles by gavages to assess its efficacy. Then clinical, histological, and biochemical parameters were assessed to determine the effects of N-(4-chloro-2-fluorophenyl)-2-hydroxybenzamide (NDMC101) on synovial inflammation and bone erosion by hematoxlin and eosin staining and Enzyme-linked immunosorbent assay (ELISA). Results: NDMC101 markedly inhibited RANKL-induced formation of TRAP+ multinucleated cells in RAW264.7 and bone marrow macrophage cells (BMMs). Moreover, pit formation assay showed that NDMC101 significantly reduced the bone-resorbing activity of mature osteoclasts. In CIA mice, oral administration of NDMC101 reduced arthritic index and mitigated bone erosion. Serum TNF-α and IL-1β concentrations in these mice were decreased significantly at the higher dose of 62.5 mg/kg. Conclusions: Screening of our chemical library, our findings suggest that NDMC101 inhibits osteoclastogenesis which also ameliorates paw swelling and inflammatory bone destruction. Its efficacy is associated with the inhibition of such transcription factors as NF-κB and NFATc1 as well as multiple protein kinases, including p38, ERK, and JNK. There results guarantee further clinical tests of NDMC101 for its therapeutic potential in the treatment of inflammation-induced bone diseases. [ABSTRACT FROM AUTHOR]
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- 2012
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177. TNF-α inhibitor reverse the effects of human umbilical cord-derived stem cells on experimental arthritis by increasing immunosuppression.
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Wu, Cheng-Chi, Wu, Tzu-Chin, Liu, Fei-Lan, Sytwu, Huey-Kang, and Chang, Deh-Ming
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TUMOR necrosis factors , *UMBILICAL cord , *TREATMENT of arthritis , *IMMUNOSUPPRESSION , *MESENCHYMAL stem cells , *HISTOPATHOLOGY , *THERAPEUTICS - Abstract
To demonstrate the therapeutic potential for cartilage repair of mesenchymal stem cells derived from human umbilical cord (HUCSC), we studied the clinical and histopathological effects of intra-articular injection of HUCSCs in a collagen-induced arthritis (CIA) model. In our study, intra-articular injection of HUCSCs had no benefit in CIA mice; and accelerated the progression of arthritis in the presence of TNF-α. To determine the role of TNF-α, we injected the combination with HUCSCs and TNF inhibitor, showed reduced the disease signs in CIA mice. On exposure of TNF-α, stem cells significantly decreased the expression of CD90, HLA-G, and the levels of IL-10 in vitro and in vivo. Our data showed that TNF-α blocks the immunosuppressive effects of HUCSCs and that inhibition of TNF-α decreases cartilage destruction by suppressing the immunogenicity of HUCSCs. Injecting both a TNF inhibitor and HUCSCs may be a potential effective therapy for ameliorating the disease. [ABSTRACT FROM AUTHOR]
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- 2011
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178. Immunosuppressive Effects and Mechanisms of Leflunomide in Dengue Virus Infection of Human Dendritic Cells.
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Wu, Wan-Lin, Ho, Ling-Jun, Chen, Pei-Chih, Tsai, Yi-Ting, Hsu, Seng-Ting, Chang, Deh-Ming, and Lai, Jenn-Haung
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DENGUE , *IMMUNOSUPPRESSION , *LEFLUNOMIDE , *NF-kappa B , *IMMUNOREGULATION , *TREATMENT of arthritis , *DENDRITIC cells , *INFLAMMATION - Abstract
Background: Dengue virus (DENV) infection is a serious public health issue without specific treatment. We examined the potential immunomodulatory effects of leflunomide, a dihydroorotate dehydrogenase inhibitor commonly prescribed for arthritis, in DENV-stimulated monocyte-derived dendritic cells (mo-DCs). Methods: mo-DCs were prepared from purified monocytes. Cytokine and chemokine concentrations were determined by enzyme-linked immunosorbent assay. Expression of cell surface markers or viral E protein was measured by flow cytometry. The activation of transcription factors and kinases was determined by electrophoretic mobility shift assays, Western blotting, or immunoprecipitation kinase assays. Chemotaxis assays were used to determine cell migration. Results: Leflunomide at therapeutic concentrations inhibited cytokine and chemokine production from DENV-infected mo-DCs. Leflunomide suppressed mo-DC maturation by downregulating the expression of both CD80 and CD86. In addition, leflunomide inhibited DENV-induced mo-DC migration and mo-DC response to chemoattractants CCL19 and CCL21. Inhibition of mo-DC migration was likely due to the suppression of CCR7 expression on mo-DCs. These events were associated with the suppression of nuclear factor kappa B and activator protein-1 signaling pathways by leflunomide. Conclusions: Leflunomide preserves immunosuppressive effects, inhibiting activation of DENV-stimulated mo-DCs. Leflunomide may be helpful in the development of therapeutics for DENV infection. [ABSTRACT FROM AUTHOR]
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- 2011
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179. A Benzamide-Linked Small Molecule HS-Cf Inhibits TNF-α-Induced Interferon Regulatory Factor-1 in Porcine Chondrocytes: A Potential Disease-Modifying Drug for Osteoarthritis Therapeutics.
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Liu, Feng-Cheng, Huang, Hsu-Shan, Huang, Chuan-Yueh, Yang, Ro, Chang, Deh-Ming, Lai, Jenn-Haung, and Ho, Ling-Jun
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OSTEOARTHRITIS treatment , *BENZAMIDE , *DRUG development , *TUMOR necrosis factors , *CARTILAGE cells , *INTERFERONS , *IMMUNOREGULATION , *LABORATORY swine - Abstract
Background: Using tumor necrosis factor-alpha (TNF-α)-activated porcine chondrocytes as a screening tool, we aim to synthesize and identify small-molecule inhibitors preserving immunomodulatory effects as therapeutics for osteoarthritis (OA). Methods: Chondrocytes were isolated from pig joints. A minilibrary of 300 benzamide-linked small molecules was established. The levels of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) were measured by Western blot and Griess reaction, respectively. Proteoglycan degradation in cartilage explants was determined by histochemistry analysis. The activation of transcription factors and protein kinases was determined by electrophoretic mobility shift assays or Western blots. Zymography and real-time reverse transcriptase-polymerase chain reaction were used to determine enzyme activity and expression of matrix metalloproteinases (MMPs) and aggrecanases, respectively. Results: Bioassay screening of benzamide-linked small molecules revealed that 2-hydroxy- N-[3-(trifluoromethyl)phenyl]benzamide (HS-Cf) was a potent inhibitor of NO production and iNOS expression in TNF-α-stimulated porcine chondrocytes. HS-Cf suppressed TNF-α-induced activity of MMP-13 and expressions of several aggrecanases and prevented TNF-α-mediated reduction of collagen II. Histochemistry analysis confirmed that HS-Cf could prevent TNF-α-induced degradation and release of proteoglycan/aggrecan in cartilage explants. Such effects by HS-Cf were likely through suppressing TNF-α-induced interferon regulatory factor-1 (IRF-1) but not nuclear factor-kappaB signaling. The significance of IRF-1 was further confirmed by short hairpin knockdown studies. Conclusions: In a minilibrary containing 300 small molecules, we identified a benzamide-linked small molecule, HS-Cf, that through down-regulating TNF-α-induced IRF-1 activity suppressed chondrocyte activation and prevented cartilage destruction. HS-Cf might be a potential disease-modifying drug for OA therapeutics. [ABSTRACT FROM AUTHOR]
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- 2011
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180. Association of PPP2CA polymorphisms with systemic lupus erythematosus susceptibility in multiple ethnic groups.
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Tan, Wenfeng, Sunahori, Katsue, Zhao, Jian, Deng, Yun, Kaufman, Kenneth M., Kelly, Jennifer A., Langefeld, Carl D., Williams, Adrienne H., Comeau, Mary E., Ziegler, Julie T., Marion, Miranda C., Bae, Sang-Cheol, Lee, Joo Hyun, Lee, Ji-Seon, Chang, Deh-Ming, Song, Yeong Wook, Yu, Chack-Yung, Kimberly, Robert P., Edberg, Jeffrey C., and Brown, Elizabeth E.
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SYSTEMIC lupus erythematosus , *AUTOANTIBODIES , *COMPUTER software , *CONFIDENCE intervals , *EPIDEMIOLOGY , *GENES , *GENETIC polymorphisms , *POLYMERASE chain reaction , *RESEARCH funding , *DATA analysis , *CASE-control method , *REVERSE transcriptase polymerase chain reaction , *GENETICS - Abstract
Objective T cells from patients with systemic lupus erythematosus (SLE) express increased amounts of PP2Ac, which contributes to decreased production of interleukin-2 (IL-2). Because IL-2 is important in the regulation of several aspects of the immune response, it has been proposed that PP2Ac contributes to the expression of SLE. This study was designed to determine whether genetic variants of PPP2AC are linked to the expression of SLE and specific clinical manifestations and account for the increased expression of PP2Ac. Methods We conducted a trans-ethnic study of 8,695 SLE cases and 7,308 controls of 4 different ancestries. Eighteen single-nucleotide polymorphisms (SNPs) across PPP2CA were genotyped using an Illumina custom array. PPP2CA expression in SLE and control T cells was analyzed by real-time polymerase chain reaction. Results A 32-kb haplotype comprising multiple SNPs of PPP2CA showed significant association with SLE in Hispanic Americans, European Americans, and Asians, but not in African Americans. Conditional analyses revealed that SNP rs7704116 in intron 1 showed consistently strong association with SLE across Asian, European American, and Hispanic American populations (odds ratio 1.3 [95% confidence interval 1.14-1.31], meta-analysis P = 3.8 × 10−7). In European Americans, the largest ethnic data set studied, the risk A allele of rs7704116 was associated with the presence of renal disease, anti-double-stranded DNA, and anti-RNP antibodies. PPP2CA expression was ∼2-fold higher in SLE patients carrying the rs7704116 AG genotype than those carrying the GG genotype ( P = 0.007). Conclusion Our data provide the first evidence of an association between PPP2CA polymorphisms and elevated PP2Ac transcript levels in T cells, which implicates a new molecular pathway for SLE susceptibility in European Americans, Hispanic Americans, and Asians. [ABSTRACT FROM AUTHOR]
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- 2011
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181. Phytoestrogen bavachin mediates anti-inflammation targeting IκB kinase-IκBα-NF-κB signaling pathway in chondrocytes in vitro
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Cheng, Cheng-Chung, Chen, Yi-Hsin, Chang, Wen-Liang, Yang, Shih-Ping, Chang, Deh-Ming, Lai, Jenn-Haung, and Ho, Ling-Jun
- Subjects
- *
PHYTOESTROGENS , *INFLAMMATORY mediators , *ANTI-inflammatory agents , *PROTEIN kinases , *OSTEOARTHRITIS treatment , *CELLULAR signal transduction , *CARTILAGE cells , *NF-kappa B - Abstract
Abstract: The pro-inflammatory cytokine interleukin-1beta (IL-1β) plays critical roles in pathogenesis of osteoarthritis. Although estrogen is protective for cartilage in osteoarthritis patients, it also potentially increases the risk of stroke and cancer. Phytoestrogens acting as natural estrogen receptor modulators may serve as alternatives. This study aimed to identify medicinal phytoestrogens that preserve anti-inflammatory property and may function as potential chondro-protective compounds. Both human chondrocytes and chondrocytic cell line CHON-002 were used for this study. Protein concentrations or expressions were measured by ELISA or Western blot, respectively. The DNA-binding activity and transcriptional activity of transcription factors were evaluated by electrophoretic mobility shift assay and dual-luciferase reporter assay, respectively. Cell migration was analyzed by chemotaxis assays. We found that among screened phytoestrogens, bavachin could potently decrease IL-1β-induced nuclear factor-kappa B (NF-κB) but not activator protein-1 (AP-1) DNA-binding activity. Bavachin also inhibited IκBα degradation, increased nuclear translocation of p65 and p50 as well as decreased IκBα kinase (IKK) activity. Furthermore, bavachin inhibited IL-1β-induced chemokine production that resulted in reduced migration of THP-1 monocytic cells. Our results suggest that through decreasing IL-1β-induced activation of IKK-IκBα-NF-κB signaling pathway, bavachin potentially protects cartilage from inflammation-mediated damage in joints of osteoarthritis patients. [Copyright &y& Elsevier]
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- 2010
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182. GDF-5 is suppressed by IL-1β and enhances TGF-β3-mediated chondrogenic differentiation in human rheumatoid fibroblast-like synoviocytes
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Liu, Fei-Lan, Lin, Li-Hsiang, Sytwu, Huey-Kang, and Chang, Deh-Ming
- Subjects
- *
INTERLEUKIN-1 , *FIBROBLASTS , *CHONDROGENESIS , *CELL differentiation , *GENE expression , *CARTILAGE cells , *TRANSFORMING growth factors , *RHEUMATOID arthritis - Abstract
Abstract: Objective: To investigate the expression of growth differentiation factor-5 (GDF-5) in chondrocytes (HC) and fibroblast-like synoviocytes (FLS) from humans with rheumatoid arthritis (RA) when stimulated with proinflammatory cytokines and to explore whether GDF-5 plays a role in regulating the differentiation of FLS-RA into chondrocytes. Methods: Expression of GDF-5 in synovium and cartilage in RA and osteoarthritis (OA) was assessed by immunohistochemistry. GDF-5 production in FLS-RA and HC-RA was examined through real-time quantitative RT-PCR (Q-PCR) and western blotting. Expressions of GDF-associated receptors on FLS-RA were determined by semiquantitative-PCR, and MTT assay was used to study the effects on FLS-RA proliferation. Effect of GDF-5 and TGF-β3 on in vitro chondrogenic ability of FLS-RA was investigated using pellet-culture system, Q-PCR and histological analysis. Results: Immunohistochemical analysis demonstrated that GDF-5 expression in the synovium and cartilage from joints of RA patients was much lower than that of OA patients. Addition of IL-1β or TNF-α appeared to downregulate the expression of GDF-5 in HC-RA and FLS-RA. Inhibition of GDF-5 expression by IL-1β in RA-FLS was attenuated by pretreatment with MEK1/2 inhibitor. GDF-5-associated receptors were expressed in FLS-RA, but GDF-5 had no effect on FLS-RA proliferation. GDF-5 had a strong chondrogenic-promoting effect on TGF-β3-induced chondrocyte differentiation in FLS-RA. Conclusions: GDF-5 is expressed in FLS-RA and HC-RA, and its expression is strongly downregulated by proinflammatory cytokines. MEK-ERK pathway is a negative regulator of GDF-5 expression in FLS-RA. In FLS-RA, synergy between GDF-5 and TGF-β3 enhances chondrogenesis. Anti-inflammatory drugs combined with GDF-5 might be a new therapeutic treatment for RA. [Copyright &y& Elsevier]
- Published
- 2010
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183. Glutamine attenuates hyperoxia-induced acute lung injury in mice.
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Perng, Wann-Cherng, Huang, Kun-Lun, Li, Min-Hui, Hsu, Ching-Wang, Tsai, Shih-Hung, Chu, Shi-Jye, and Chang, Deh-Ming
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- *
LUNG injury treatment , *LABORATORY mice , *GLUTAMINE , *HYPEROXIA , *PHYSIOLOGICAL effects of oxygen , *TUMOR necrosis factors - Abstract
1. Glutamine is an amino acid that is used to treat various diseases. Glutamine has been reported to have protective effects in human pulmonary epithelia-like cells exposed to hyperoxia. However, the effects of glutamine in hyperoxia-induced lung injury have not been investigated in vivo. 2. Mice treated with saline or glutamine [(750 mg/kg) intravenously] were randomly exposed to hyperoxia for 48 or 72 h. Control mice treated with saline or glutamine were exposed to room air. Cytokine levels in bronchoalveolar lavage fluid (BALF), heat shock protein (HSP) 70, the wet/dry (W/D) weight ratio, malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity and pathoglogical findings in lung tissue were evaluated to determine the effects of glutamine on acute lung injury. In addition, survival was monitored. 3. Lung expression of HSP70 was significantly enhanced in both the control (room air) and 48 and 72 h hyperoxic glutamine-treated mice. The W/D ratio, BALF concentrations of tumour necrosis factor-α and interleukin-6, MDA levels, MPO activity, neutrophil infiltration and interstitial oedema in lung tissue were significantly lower at 48 and 72 h of hyperoxia in glutamine-treated mice compared with saline-treated mice. 4. In a separate series of experiments evaluating survival, after 96 h continuous exposure to hyperoxia, all saline-treated mice died. In contrast, all glutamine-treated mice died after 108 h exposure to hyperoxia. 5. The data suggest that glutamine administered to mice during hyperoxia has a protective effect against hyperoxia-induced acute lung injury and improves survival. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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184. Decoy receptor 3 ameliorates experimental autoimmune encephalomyelitis by directly counteracting local inflammation and downregulating Th17 cells
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Chen, Shyi-Jou, Wang, Yen-Lin, Kao, Jen-Hsin, Wu, Shu-Feng, Lo, Wen-Tsung, Wu, Chia-Cho, Tao, Pao-Luh, Wang, Chih-Chien, Chang, Deh-Ming, and Sytwu, Huey-Kang
- Abstract
Abstract: To investigate the therapeutic potential of decoy receptor 3 (DcR3) in multiple sclerosis (MS), we used intrathecal (IT) administration of DcR3 into C57/BL6 mice with experimental autoimmune encephalomyelitis (EAE). DcR3 significantly ameliorated EAE symptoms as shown by a lower clinical score and less inflammation in the spinal cord. The expression of TNF-α, IFN-γ, and IL-17 was lower in the spinal cord in IT DcR3-treated mice. Flow cytometry showed a drastic reduction in IL-17-producing CD4 T cells, slightly fewer IFN-γ producing CD4 T cells and more IL-4-producing CD4 T cells isolated from the central nervous system (CNS) of IT DcR3-treated mice than of controls. Myelin oligodendrocyte glycoprotein (MOG)-specific T cell proliferation was significantly inhibited in DcR3-treated mice. The IL-17 concentration was lower and the IL-4 concentration higher in the supernatants of MOG-stimulated splenocytes from DcR3-treated mice. An adoptive transfer study showed that splenocytes from DcR3-treated mice retained this disease-inhibiting ability. Our data suggest that DcR3 has potential as a suppressor of CNS inflammation in EAE, which may be attributed to either direct inhibition of CNS inflammation or suppression of encephalitogenic Th17 cells. In conclusion, we demonstrate a therapeutic effect of DcR3 in EAE, suggesting its potential for treating human MS. [Copyright &y& Elsevier]
- Published
- 2009
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185. Differential effects of triptolide and tetrandrine on activation of COX-2, NF-κB, and AP-1 and virus production in dengue virus-infected human lung cells
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Liou, Jun-Ting, Chen, Zih-Yan, Ho, Ling-Jun, Yang, Shih-Ping, Chang, Deh-Ming, Liang, Chun-Chin, and Lai, Jenn-Haung
- Subjects
- *
LIVER cells , *TRANSCRIPTION factors , *PROSTAGLANDINS , *DENDRITIC cells - Abstract
Abstract: Most virus infections induce cycloxygenase-2 (COX-2) expression and subsequent prostaglandin E2 (PGE2) production in cells, an inflammatory response that might be detrimental to virus replication and pathogenesis. This response in dengue virus infection remains to be elucidated. Triptolide and tetrandrine, compounds derived from two commonly used Chinese herbs, both demonstrate anti-inflammatory and immunosuppressive effects partly through modulation of COX-2 expression and, hence, may have antiviral effects. In this study, we examined, firstly, the immune response to dengue virus infection with respect to COX-2 expression and PGE2 production in human lung cells (A549), liver cells (HepG2) and dendritic cells. Secondly, we assessed the potential antiviral effects of triptolide and tetrandrine on dengue virus infection vis-à-vis expression of COX-2, PGE2, transcription factors, as well as virus production. We found that dengue virus infection enhanced COX-2 expression and PGE2 production in A549 cells, similarly to the response in dendritic cells, but not in HepG2 cells. In dengue virus-infected A549 cells, nuclear factor κB (NF-κB) and activator protein 1 (AP-1) were also activated, and both were dose-dependently inhibited by triptolide (0.5–4 ng/ml). Tetrandrine (1–10 μM) had no similar immunosuppressive effects and, moreover, at higher concentrations, enhanced NF-κB and AP-1 activity, COX-2 expression and PGE2 production. However, unexpectedly, tetrandrine, but not triptolide, dose-dependently suppressed dengue virus production in A549 cells, independent of PGE2 level. Our findings imply that triptolide and tetrandrine may attenuate dengue virus infection in human lung cells, but through distinct pathways. [Copyright &y& Elsevier]
- Published
- 2008
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186. Protective role of programmed death 1 ligand 1 (PD-L1)in nonobese diabetic mice: the paradox in transgenic models.
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Wang CJ, Chou FC, Chu CH, Wu JC, Lin SH, Chang DM, Sytwu HK, Wang, Chia-Jen, Chou, Feng-Cheng, Chu, Chi-Hong, Wu, Jen-Chine, Lin, Shih-Hua, Chang, Deh-Ming, and Sytwu, Huey-Kang
- Abstract
Objective: Coinhibitory signals mediated via programmed death 1 (PD-1) receptor play a critical role in downregulating immune responses and in maintaining peripheral tolerance. Programmed death 1 ligand 1 (PD-L1), the interacting ligand for PD-1, widely expressed in many cell types, acts as a tissue-specific negative regulator of pathogenic T-cell responses. We investigated the protective potential of PD-L1 on autoimmune diabetes by transgenically overexpressing PD-L1 in pancreatic beta-cells in nonobese diabetic (NOD) mice.Research Design and Methods: We established an insulin promoter-driven murine PD-L1 transgenic NOD mouse model to directly evaluate the protective effect of an organ-specific PD-L1 transgene against autoimmune diabetes. Transgene expression, insulitis, and diabetic incidence were characterized in these transgenic NOD mice. Lymphocyte development, Th1 cells, and regulatory T-cells were analyzed in these transgenic mice; and T-cell proliferation, adoptive transfer, and islet transplantation were performed to evaluate the PD-L1 transgene-mediated immune-protective mechanisms.Results: The severity of insulitis in these transgenic mice is significantly decreased, disease onset is delayed, and the incidence of diabetes is markedly decreased compared with littermate controls. NOD/SCID mice that received lymphocytes from transgenic mice became diabetic at a slower rate than mice receiving control lymphocytes. Moreover, lymphocytes collected from recipients transferred by lymphocytes from transgenic mice revealed less proliferative potential than lymphocytes obtained from control recipients. Transgenic islets transplanted in diabetic recipients survived moderately longer than control islets.Conclusions: Our results demonstrate the protective potential of transgenic PD-L1 in autoimmune diabetes and illustrate its role in downregulating diabetogenic T-cells in NOD mice. [ABSTRACT FROM AUTHOR]- Published
- 2008
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187. Retinoic acid blocks pro-inflammatory cytokine-induced matrix metalloproteinase production by down-regulating JNK-AP-1 signaling in human chondrocytes
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Ho, Ling-Jun, Lin, Leou-Chyr, Hung, Li-Feng, Wang, Shyu-Jye, Lee, Chian-Her, Chang, Deh-Ming, Lai, Jenn-Haung, and Tai, Tong-Yuan
- Subjects
- *
CARTILAGE cells , *CELLULAR immunity , *DNA polymerases , *CYTOKINES - Abstract
Abstract: The development of osteoarthritis (OA) has recently been implicated as a result of immune-mediated damage of chondrocytes and their supporting matrixes. Pro-inflammatory cytokines like interleukin (IL)-1 and tumor necrosis factor alpha (TNF-α) play pivotal roles in immunopathogenesis of OA. Because vitamins preserving anti-oxidative effects are suggested to provide protection in OA patients from joint damage, in the present study, we examined the effects and mechanisms of all-trans retinoic acid (t-RA) in suppressing pro-inflammatory cytokine-induced matrix metalloproteinases (MMPs) production in human chondrocytes. Chondrocytes were prepared from cartilage specimens of OA patients receiving total hip or total knee replacement. The protein concentration was measured by ELISA, the mRNA expression by reverse transcriptase-polymerase chain reaction, the protein expression by Western blotting, the transcription factor DNA-binding activity by electrophoretic mobility shift assay and the protein kinase activity by kinase assay. We showed that both MMP-1 and MMP-13 mRNA expression, protein production and enzyme activity induced by either IL-1 or TNF-α were suppressed by t-RA or different retinoid derivatives. The molecular investigation revealed that the t-RA-mediated suppression was likely through blocking p38 kinase and c-Jun N-terminal kinase-activator protein-1 signaling pathways. In contrast, t-RA had no effect on extracellular signal-regulated kinase activity, nuclear factor kappaB (NF-κB) DNA-binding activity and IκBα degradation. Furthermore, we showed that t-RA could reduce IL-1-induced TNF-α production in chondrocytes. Our results suggest that vitamin A may protect OA patients from pro-inflammatory cytokine-mediated damage of chondrocytes and their supporting matrixes. [Copyright &y& Elsevier]
- Published
- 2005
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188. A spontaneous intercostal artery hemorrhage in systemic lupus erythematosus.
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Lu, Chun-Chi, Chen, Chen-Hung, Yeh, Song-Feng, Lai, Jenn-Haung, and Chang, Deh-Ming
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- *
SYSTEMIC lupus erythematosus , *ANTIPHOSPHOLIPID syndrome , *PHOSPHOLIPID antibodies , *DISSEMINATED intravascular coagulation , *THERAPEUTIC embolization - Abstract
Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that can lead to damage to several vital organs. Antiphospholipid syndrome (APS), manifesting as vascular thromboembolic events and morbidities of pregnancy in the presence of antiphospholipid antibodies (aPL), has been described in patients with SLE. Catastrophic antiphospholipid syndrome (CAPS), in contradistinction to APS, is defined as three or more organs affected by thrombotic microangiopathy in patients demonstrating aPL and can result in mortality up to 50%. We describe a unique SLE patient who was diagnosed with recurrent APS presented with axillary venous thrombosis and subsequent superficial edema and compartment syndrome. The CAPS followed and revealed thromboses over liver, spleen, and acute pancreatitis. The spontaneous hemorrhage of left fourth intercostal artery (ICA) and left axillary artery occured at the same time without vasculitis or severe trauma. Though emergency transcatheter arterial embolization (TAE) of the left fourth ICA was successfully accomplished by the radiologist. The repeated computed tomography angiogram of chest demonstrated remission of ruptured ICA. Nevertheless, the patient died of diffuse alveolar hemorrhage and respiratory failure and shock. Both disseminated intravascular coagulation (DIC) and CAPS share similar characteristics encompassing thrombotic microangiopathy, bleeding, thromboembolism, and multiple organ dysfunction. It is difficult to distinguish between them, especially in cases such as our uremic SLE patient with a calamitous disease progression. The emphasis of treatment for DIC is on platelet and fresh plasma transfusion, in contrast with anti-coagulant for CAPS. To the best of our knowledge, this is the first report describing ICA hemorrhage in an SLE patient without vasculitis or aneurysm. The lupus flare initiated a pathological immunological cascade and resulted in the CAPS and the vascular damage. [ABSTRACT FROM AUTHOR]
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- 2012
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189. Formation of numerous rice bodies: an unusual finding of adult-onset Still’s disease.
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Lin, Kang-Min, Lai, Jenn-Haung, Chang, Chi-Ching, Lin, Chih-Kung, Chang, Deh-Ming, and Chen, Chen-Hung
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- *
ARTHRITIS , *OLDER men , *JOINTS (Anatomy) , *FEVER , *SHOULDER - Abstract
Adult-onset Still’s disease (AOSD) is an inflammatory disorder characterized by high-spiking fever, arthritis, and an evanescent rash. The pattern of chronic arthritis is a universal feature of AOSD. However, chronic bursitis with the formation of numerous rice bodies is a very rare presentation in a patient with AOSD. To our knowledge, no case of formation of numerous rice bodies in AOSD has been reported thus far. We describe the case of a 28-year-old man with AOSD with rice bodies in his left shoulder joint. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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190. Arthrite àListeria monocytogenes associée à l’acupuncture chez un patient atteint de polyarthrite rhumatoïde
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Tien, Chiung-Hsi, Huang, Guo-Shu, Chang, Chi-Ching, Chang, Deh-Ming, and Lai, Jenn-Haung
- Subjects
- *
LISTERIA monocytogenes , *ACUPUNCTURE , *RHEUMATOID arthritis , *ULTRASONIC imaging , *SYNOVIAL fluid , *TREATMENT of arthritis , *PATIENTS - Abstract
Résumé: L’arthrite septique est une complication rare de l’acupuncture. Nous rapportons l’observation d’un patient atteint de polyarthrite rhumatoïde qui a développé une arthrite septique du genou droit après des séances hebdomadaires d’acupuncture pendant trois semaines consécutives. L’infection a été localisée par une échographie de l’articulation et une IRM, avec une mise en culture du liquide synovial ponctionné dans l’articulation contenant Listeria monocytogenes. Le patient a bien répondu au traitement par antibiotique et a retrouvé la mobilité de l’articulation. Le processus infectieux doit être présent à l’esprit pour un diagnostic et un traitement rapide des infections articulaires associées à l’acupuncture chez les patients atteints de polyarthrite rhumatoïde qui représente un risque infectieux supplémentaire. [Copyright &y& Elsevier]
- Published
- 2008
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191. IgG4-related tubulointerstitial nephritis.
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Tsai MK, Chen YL, Chen HC, Liu FC, Chang DM, and Lu CC
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- Humans, Kidney, Immunoglobulin G, Nephritis, Interstitial
- Abstract
Competing Interests: Competing interests: None declared.
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- 2024
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192. Keratoderma blennorrhagica in a patient without arthritis.
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Tang H, Chang DM, and Chu CC
- Subjects
- Humans, Patients, Keratosis, Arthritis, Arthritis, Reactive
- Published
- 2023
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193. Risk factors for mortality in systemic lupus erythematosus patients: Analysis of adult and pediatric cohorts in Taiwan.
- Author
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Lai CC, Sun YS, Chen WS, Liao HT, Chen MH, Tsai CY, Huang DF, Chou CT, and Chang DM
- Subjects
- Adult, Humans, Female, Male, Child, Cohort Studies, Retrospective Studies, Taiwan epidemiology, Multivariate Analysis, Risk Factors, Proportional Hazards Models, Glucocorticoids therapeutic use, Lupus Erythematosus, Systemic complications, Lupus Erythematosus, Systemic drug therapy, Sepsis, Renal Insufficiency, Chronic, Hypertension
- Abstract
Background: Overall survival of systemic lupus erythematosus (SLE) patients significantly increased in recent decades, however, the relative risk of mortality is still high. Long-term survival outcome of pediatric SLE remains unclear. This study aims to explore the long-term survival rate and its predictors in patients with systemic lupus erythematosus (SLE)., Methods: A retrospective, hospital-based cohort study was performed between 2004 and 2018 in a tertiary referral medical center in Taiwan. Data on comorbidities, medications, and causes of admission were collected for risk factor analysis using time-dependent multivariate Cox proportional hazards models., Results: A total of 2392 adults and 115 pediatric SLE patients were enrolled (female, n = 2157 and 95, respectively). The 10-year survival rates were 93.2%, 90.2%, 98.9%, and 100% in adult women, adult men, girls, and boys with SLE, respectively. The overall mortality rate was 2.09 case/100 patient-years (PY) for male SLE and 1.39 case/100 PY for female SLE patients. Male SLE patients did not have a statistically significantly higher mortality rate than female SLE patients in each age stratification. Infectious disease (n = 119), heart failure (n = 21), and cerebrovascular accident (n = 14) were the leading causes of death in adult SLE patients. Advanced age (hazard ratio [HR]: 1.04, 95% confidence interval [CI]: 1.03-1.05), treatment with mean dosage of systemic glucocorticoid equivalent to >10 mg/d of prednisolone (HR: 1.71, 95% CI: 1.14-2.57), comorbidities with malignancy (HR: 1.94, 95% CI: 1.22-3.09), chronic kidney disease (HR: 1.86, 95% CI: 1.25-2.77), hypertension (HR: 1.42, 95% CI: 1.01-1.98), and admission due to bacterial pneumonia (HR: 1.92, 95% CI: 1.12-3.31) and sepsis (HR: 2.78, 95% CI: 1.51-5.13) were independent risk factors for mortality in SLE patients., Conclusion: SLE patients with advanced age, malignancy, chronic kidney disease, hypertension, treated with a higher average dosage of glucocorticoids, and admission due to bacterial pneumonia and sepsis have an increased risk of mortality., Competing Interests: Conflicts of interest: Dr. Chang-Youh Tsai and Dr. Deh-Ming Chang, editorial board members at Journal of the Chinese Medical Association, have no roles in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)
- Published
- 2022
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194. Thymoma-Related Paraneoplastic Syndrome Mimicking Reactive Arthritis.
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Liao CH, Lyu SY, Chen HC, Chang DM, and Lu CC
- Subjects
- Adult, Humans, Male, Neoplasm Recurrence, Local, Arthritis, Reactive, Myasthenia Gravis complications, Myasthenia Gravis diagnosis, Paraneoplastic Syndromes diagnosis, Thymoma complications, Thymoma diagnosis, Thymus Neoplasms complications, Thymus Neoplasms diagnosis
- Abstract
Background and Objectives : Thymomas are associated with a high frequency of paraneoplastic manifestations. Paraneoplastic syndrome (PNS) with thymoma presents a challenge to clinicians because of the need to decipher the association between the presenting symptoms and the underlying tumor. The condition most commonly noted in patients with PNS with thymoma is myasthenia gravis. Other common autoimmune diseases that may present as PNS include systemic lupus erythematosus, pure red cell aplasia, and Good syndrome. Seventy-six percent of patients with PNS-associated thymoma experience resolution of PNS after curing thymoma. Materials and Methods : A 37-year-old man with a two-month fever accompanied by polyarthritis accidently found thymoma after contrast computed tomography scans of his chest. He accepted Video assisted thoracoscopic surgery with resection of thymoma. Results : Fever and polyarthritis resolved after operation but recurred in five days due to cytomegalovirus viremia, which might be predisposed by previous antibiotics treatment before the diagnosis of thymoma. Conclusion : Patients with a thymoma also have a high frequency of PNS, and the most frequent condition found in patients with PNS-associated thymoma is myasthenia gravis. Fever with polyarthritis has been rarely reported as a symptom of PNS-associated thymoma. Here we reported an unusual case of PNS mimicking reactive arthritis with thymoma, as diagnosed based on the patient's clinical progression, imaging examination, and laboratory tests. The patient died of his comorbidities, and his death may have been related to long-term antibiotic use and consequent intestinal dysbiosis. This challenging case may help to inform clinicians of the need for detailed work-up of fever with unknown origin in the presence of chronic polyarthritis to prevent the overdiagnosis of inflammatory arthritis or rheumatic disease and avoid further comorbidities. Detailed work-up should include the patient's history of infections, inflammation, and malignant or nonmalignant tumors.
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- 2021
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- View/download PDF
195. Arecoline suppresses RANKL-induced osteoclast differentiation in vitro and attenuates LPS-induced bone loss in vivo.
- Author
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Liu FL, Chen CL, Lai CC, Lee CC, and Chang DM
- Subjects
- Animals, Bone Resorption metabolism, Bone Resorption pathology, Cell Differentiation drug effects, Cells, Cultured, Gene Expression Regulation drug effects, Genes, fos, Lipopolysaccharides toxicity, Macrophages drug effects, Male, Mice, Inbred DBA, NFATC Transcription Factors genetics, NFATC Transcription Factors metabolism, Osteoblasts drug effects, Osteoblasts physiology, Osteoclasts cytology, Osteoclasts physiology, Osteogenesis drug effects, Osteoporosis chemically induced, Osteoporosis drug therapy, RANK Ligand metabolism, RANK Ligand pharmacology, X-Ray Microtomography, Arecoline pharmacology, Bone Resorption drug therapy, Osteoclasts drug effects
- Abstract
Background: Areca nut has anti-inflammatory, antiparasitic, antihypertensive, and antidepressant properties. The pathological hallmarks of inflammatory joint diseases are an increased number of osteoclasts and impaired differentiation of osteoblasts, which may disrupt the bone remodeling balance and eventually lead to bone loss., Purpose: The present study assessed the effects of arecoline, the main alkaloid found in areca nut, on osteoclast and osteoblast differentiation and function., Method: M-CSF/RANKL-stimulated murine bone marrow-derived macrophages (BMMs) were incubated with several concentrations of arecoline, and TRAP staining and pit formation were assessed to monitor osteoclast formation. Quantitative real-time RT-PCR and western blot analyses were used to analyze the expression of osteoclast-associated genes and signaling pathways. The effects of arecoline on bone were investigated in an in vivo mouse model of lipopolysaccharide (LPS)-induced trabecular bone loss after oral administration of arecoline. Alizarin red S staining and assays to measure ALP activity and the transcription level of osteoblast-related genes were used to evaluate the effects of arecoline on osteoblast differentiation and bone mineralization., Results: In a dose-dependent manner, arecoline at concentrations of 50-100 μM reduced both the development of TRAP-positive multinucleated osteoclasts and the formation of resorption pits in M-CSF/RANKL-stimulated BMMs. In M-CSF/RANKL-stimulated BMMs, arecoline also suppressed the expression and translocation of c-Fos and NFATcl, and osteoclast differentiated-related genes via interference with the AKT, MAPK, and NF-kB activation pathways. Femur bone loss and microcomputed tomography parameters were recovered by oral administration of arecoline in the mouse LPS-induced bone loss model. Lastly, arecoline increased ALP activity, bone mineralization, and the expression of osteoblast differentiation-related genes, such as ALP and Runx2, in MC3T3-E1 cells., Conclusion: Our data suggest that arecoline may attenuate or prevent bone loss by suppressing osteoclastogenesis and promoting osteoblastogenesis. These findings provide evidence supporting arecoline's use as a potential therapeutic agent in bone-loss disorders and diseases., Competing Interests: Declaration of Competing Interest The authors have declared no conflicts of interest., (Copyright © 2020 Elsevier GmbH. All rights reserved.)
- Published
- 2020
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196. SUMO-defective c-Maf preferentially transactivates Il21 to exacerbate autoimmune diabetes.
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Hsu CY, Yeh LT, Fu SH, Chien MW, Liu YW, Miaw SC, Chang DM, and Sytwu HK
- Subjects
- Amino Acid Substitution, Animals, Benzimidazoles pharmacology, Binding Sites genetics, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Diabetes Mellitus, Type 1 genetics, Diabetes Mellitus, Type 1 metabolism, Epigenesis, Genetic, Interleukins biosynthesis, Isoxazoles pharmacology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, Knockout, Mice, SCID, Mice, Transgenic, Models, Biological, Mutant Proteins chemistry, Mutant Proteins genetics, Mutant Proteins metabolism, Promoter Regions, Genetic, Proto-Oncogene Proteins c-maf chemistry, Proto-Oncogene Proteins c-maf genetics, Transcriptional Activation, p300-CBP Transcription Factors antagonists & inhibitors, Diabetes Mellitus, Type 1 etiology, Interleukins genetics, Proto-Oncogene Proteins c-maf metabolism, Sumoylation
- Abstract
SUMOylation is involved in the development of several inflammatory diseases, but the physiological significance of SUMO-modulated c-Maf in autoimmune diabetes is not completely understood. Here, we report that an age-dependent attenuation of c-Maf SUMOylation in CD4+ T cells is positively correlated with the IL-21-mediated diabetogenesis in NOD mice. Using 2 strains of T cell-specific transgenic NOD mice overexpressing wild-type c-Maf (Tg-WTc) or SUMOylation site-mutated c-Maf (Tg-KRc), we demonstrated that Tg-KRc mice developed diabetes more rapidly than Tg-WTc mice in a CD4+ T cell-autonomous manner. Moreover, SUMO-defective c-Maf preferentially transactivated Il21 to promote the development of CD4+ T cells with an extrafollicular helper T cell phenotype and expand the numbers of granzyme B-producing effector/memory CD8+ T cells. Furthermore, SUMO-defective c-Maf selectively inhibited recruitment of Daxx/HDAC2 to the Il21 promoter and enhanced histone acetylation mediated by CREB-binding protein (CBP) and p300. Using pharmacological interference with CBP/p300, we illustrated that CBP30 treatment ameliorated c-Maf-mediated/IL-21-based diabetogenesis. Taken together, our results show that the SUMOylation status of c-Maf has a stronger regulatory effect on IL-21 than the level of c-Maf expression, through an epigenetic mechanism. These findings provide new insights into how SUMOylation modulates the pathogenesis of autoimmune diabetes in a T cell-restricted manner and on the basis of a single transcription factor.
- Published
- 2018
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197. Multidrug-resistance Acinetobacter baumannii pneumonia in a rheumatoid arthritis patient receiving tumor necrosis factor inhibitor: A case report.
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Lin SY, Huang ZH, Chen HC, Chang DM, and Lu CC
- Subjects
- Aged, Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents therapeutic use, Antirheumatic Agents therapeutic use, Arthritis, Rheumatoid diagnosis, C-Reactive Protein analysis, Cefoperazone administration & dosage, Cefoperazone therapeutic use, Drug Resistance, Multiple, Female, Humans, Pneumonia drug therapy, Pneumonia microbiology, Radiography methods, Sulbactam administration & dosage, Sulbactam therapeutic use, Tomography, X-Ray Computed methods, Treatment Outcome, Tumor Necrosis Factor-alpha antagonists & inhibitors, Tumor Necrosis Factor-alpha therapeutic use, Acinetobacter baumannii isolation & purification, Antirheumatic Agents adverse effects, Arthritis, Rheumatoid complications, Arthritis, Rheumatoid drug therapy, Pneumonia diagnostic imaging, Tumor Necrosis Factor-alpha adverse effects
- Abstract
Introduction: Multidrug-resistant Acinetobacter baumannii (MDRAB) pneumonia with severe sepsis in a patient with rheumatoid arthritis (RA), who is predisposed after treatment with tumor necrosis factor inhibitor (TNFI), is a rare severe infection and can be successfully treated with prompt antibiotics., Case Presentation: A 75-year-old woman was diagnosed with RA >30 years previously. After inadequate treatment responses to conventional disease-modifying antirheumatic drugs (DMARDs), she developed progressive RA, including swollen joints in both hands, and had a high disease activity score of 4.96 when presenting at our rheumatology clinic. She had started taking the TNFI, golimumab (50 mg/month), 3 years before and developed a productive cough 4 weeks before this admission. One week after admission, she developed fever, dyspnea, hypoxemia, tachycardia, and increased serum C-reactive protein level., Diagnosis: Chest plain film (CxR) and computed tomography of the chest showed hospital-acquired pneumonia; microbial examination of the sputum showed the presence of MDRAB., Therapeutics: She was prescribed a full course of antibiotics with cefoperazone sulbactam., Outcomes: CxR showed complete remission of pneumonia., Conclusion: Biological DMARDs, such as TNFI, act as a double-edged sword: these drugs are used to treat autoimmune diseases, but they increase the risk of infection. The trend toward antibiotic resistance and persistent environmental survival of MDRAB is an emerging problem in countries with high rates of antibiotic abuse. TNFI may affect intestinal immunity by inducing dysbiosis, which affects T helper 17-mediated mucosal immunity and can contribute to A baumannii colonization and the development of MDRAB in frequently hospitalized patients.
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- 2018
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198. Oxidative DNA and mitochondrial DNA change in patients with SLE.
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Lee HT, Wu TH, Lin CS, Lee CS, Pan SC, Chang DM, Wei YH, and Tsai CY
- Subjects
- 8-Hydroxy-2'-Deoxyguanosine, Antibodies, Antinuclear blood, Case-Control Studies, Chemokines blood, Cytokines blood, DNA, Mitochondrial genetics, Deoxyguanosine analogs & derivatives, Deoxyguanosine blood, Disease Progression, Female, Humans, Lupus Erythematosus, Systemic genetics, Lupus Erythematosus, Systemic immunology, Male, Sequence Deletion, DNA, Mitochondrial blood, Lupus Erythematosus, Systemic blood
- Abstract
We evaluated plasma IL-10, IFN-alpha, IL-23, IFN-gamma, IP-10, MCP-1, 8-OHdG, leukocyte mtDNA, serum anti-dsDNA antibodies and disease activity index (SLEDAI) in SLE patients. 93 patients (35 nephritis, 4 under dialysis, 5 under rituximab) and 50 healthy controls were recruited. Compared with healthy controls, SLE patients had higher IL-10, IFN-alpha, IL-23, IFN-gamma, IP-10 and MCP-1 ( p <0.05). High IFN-alpha ( p =0.031) and IP-10 ( p =0.026) correlated with high SLEDAI; high IFN-alpha ( p< 0.001), IL-23 ( p =0.023) and IP-10 ( p< 0.001) correlated with high anti-dsDNA. High IL-10 ( p =0.014), IL-23 ( p< 0.001), IFN-gamma ( p< 0.001) and MCP-1 ( p =0.002) correlated with high 8-OHdG and high IL-23 ( p <0.001), INF-gamma ( p <0.001), IP-10 ( p =0.023) and MCP-1 ( p =0.002) correlated with low leukocyte mtDNA. mtDNA 4977 deletion correlated with high mtDNA ( p =0.011) and low IL-10 ( p =0.009). MCP-1 ( p =0.043) decreased after rituximab therapy. 54 SLE patients without nephritis, 35 with nephritis but without dialysis, and 4 with nephritis under dialysis exhibited stepwise increases in IL-23 ( p =0.009) and MCP-1 ( p =0.015). These data suggest that oxidative DNA and mtDNA alterations and coordinate changes in cytokines/chemokines are implicated in progression of SLE and rituximab in amelioration of SLE.
- Published
- 2017
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199. Rituximab therapy in primary Sjögren's syndrome with interstitial lung disease: a retrospective cohort study.
- Author
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Chen MH, Chen CK, Chou HP, Chen MH, Tsai CY, and Chang DM
- Subjects
- Adult, Female, Humans, Lung diagnostic imaging, Lung Diseases, Interstitial diagnostic imaging, Lung Diseases, Interstitial etiology, Male, Middle Aged, Respiratory Function Tests, Retrospective Studies, Sjogren's Syndrome complications, Sjogren's Syndrome diagnostic imaging, Treatment Outcome, Antirheumatic Agents therapeutic use, Lung Diseases, Interstitial drug therapy, Rituximab therapeutic use, Sjogren's Syndrome drug therapy
- Abstract
Objectives: Interstitial lung disease (ILD) is one of the major systemic manifestations of primary Sjögren's syndrome (pSS). The aim of this study was to evaluate the therapeutic effect of rituximab on pSS patients with ILD., Methods: Pulmonary function test results, including diffusing capacity for carbon monoxide (DLCO) and DLCO/alveolar volume (Va) ratio, and high-resolution computed tomography (HRCT) findings/scores in ten pSS patients with ILD treated with rituximab were retrospectively investigated. Global disease, fatigue, dryness of eyes and mouth, shortness of breath, and cough were assessed by visual analogue scales (VAS, 0-100 mm)., Results: At 6 months after rituximab treatment, improvement in pulmonary function was observed (from 49.3±12.6 to 56.9±11.4% for DLCO, p=0.011; from 74.4±15.8 to 85.6±10.3% for DLCO/Va, p=0.021). Similarly, significant improvement of subjective symptoms were also noted after treatment (VAS global disease, from 62.0±11.4 to 26.0±10.8 mm, p<0.001; VAS fatigue, from 38.0±23.0 to 18.0±7.9 mm, p=0.006; VAS dryness of eyes, from 53.0±24.4 to 29.0±13.7 mm, p=0.004; VAS dryness of mouth, from 45.0±14.3 to 28.0±9.2 mm, p=0.001; VAS shortness of breath, from 64.0±16.5 to 31.0±16.0 mm, p<0.001; VAS cough, from 42.0±23.5 to 18.0±10.3 mm, p=0.011). The mean HRCT score decreased after rituximab therapy although to a lesser extent (from 8.7±4.1 to 7.6±4.6, p=0.419). An adverse event was observed in only one patient who had non-fatal pneumonia 4 months after rituximab infusion., Conclusions: Rituximab was effective in improving clinical symptoms and gas exchange, and in stabilising HRCT score in pSS patients with ILD.
- Published
- 2016
200. Genetic associations of leptin-related polymorphisms with systemic lupus erythematosus.
- Author
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Zhao J, Wu H, Langefeld CD, Kaufman KM, Kelly JA, Bae SC, Alarcón GS, Anaya JM, Criswell LA, Freedman BI, Kamen DL, Gilkeson GS, Jacob CO, James JA, Merrill JT, Gaffney PM, Sivils KM, Niewold TB, Petri MA, Song ST, Jeong HJ, Ramsey-Goldman R, Reveille JD, Scofield RH, Stevens AM, Boackle SA, Vilá LM, Chang DM, Song YW, Vyse TJ, Harley JB, Brown EE, Edberg JC, Kimberly RP, Hahn BH, Grossman JM, Tsao BP, and La Cava A
- Subjects
- Case-Control Studies, Genotype, Humans, Genetic Predisposition to Disease genetics, Leptin genetics, Lupus Erythematosus, Systemic genetics, Polymorphism, Single Nucleotide genetics
- Abstract
Leptin is abnormally elevated in the plasma of patients with systemic lupus erythematosus (SLE), where it is thought to promote and/or sustain pro-inflammatory responses. Whether this association could reflect an increased genetic susceptibility to develop SLE is not known, and studies of genetic associations with leptin-related polymorphisms in SLE patients have been so far inconclusive. Here we genotyped DNA samples from 15,706 SLE patients and healthy matched controls from four different ancestral groups, to correlate polymorphisms of genes of the leptin pathway to risk for SLE. It was found that although several SNPs showed weak associations, those associations did not remain significant after correction for multiple testing. These data do not support associations between defined leptin-related polymorphisms and increased susceptibility to develop SLE., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
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