Graduate Institute of Integrated Medicine

Integrated, Taiwan

Graduate Institute of Integrated Medicine

Integrated, Taiwan
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Lin C.-P.,National Yang Ming University | Lin C.-P.,Institute of Biotechnology in Medicine | Huang P.-H.,Taipei Veterans General Hospital | Huang P.-H.,National Yang Ming University | And 7 more authors.
Journal of Pharmacy and Pharmacology | Year: 2011

Objectives Inflammation is associated with atherosclerosis. Cholestin (Monascus purpureus-fermented rice) contains a naturally occurring statin, which has lipid-modulating, anti-inflammatory and antioxidative effects. This study aimed to investigate the effects of Cholestin extract on the expression of matrix metalloproteinase (MMP)-2 and MMP-9 by tumor necrosis factor (TNF)-α-treated human aortic smooth muscle cells (HASMCs). Methods Zymography, reverse transcription polymerase chain reaction and immunoblot analyses were used for analysis of MMP expression of TNF-α-stimulated HASMCs. Gel shift assay was used for analysis of transcription factor nuclear factor-κB (NF-κB) activation. Intracellular reactive oxygen species (ROS) generation was also analysed. Key findings The supplement of HASMCs with Cholestin extract significantly suppresses enzymatic activities of MMP-2 and MMP-9 in TNF-α-stimulated HASMCs. RT-PCR and immunoblot analyses show that Cholestin extract significantly attenuates TNF-α-induced mRNA and protein expressions of MMP-2 and MMP-9. Gel shift assays show that Cholestin treatment reduces TNF-α-activated NF-κB. Furthermore, Cholestin also attenuates intracellular ROS generation in TNF-α-treated HASMCs. The supplement with an ROS scavenger N-acetyl-cysteine (glutathione precursor) gives similar results to Cholestin. Conclusions Cholestin reduces TNF-α-stimulated MMP-2 and MMP-9 expression as well as downregulating NF-κB activation and intracellular ROS formation in HASMCs, supporting the notion that the natural compound Cholestin may have potential application in clinical atherosclerosis disease. © 2011 The Authors.

Chang C.-M.,Taipei Veterans General Hospital | Chang C.-M.,Chang Gung University | Wu P.-C.,China Medical University at Taichung | Chiang J.-H.,China Medical University at Taichung | And 11 more authors.
Journal of Ethnopharmacology | Year: 2017

Ethnopharmacological relevance Evidence on alleviating the risk of lupus nephritis by integrative therapy with conventional medicine (CM) and herbal medicine (HM) had not been addressed. Aim of the study We investigated the integrative effect associated the risk by a retrospective Systemic Lupus Erythematosus (SLE) cohort from Taiwan National Health Insurance Research Database (NHIRD). Materials and methods SLE patients with a catastrophic illness certificate (CIC) were retrospectively enrolled from the SLE cohort of the Taiwan NHIRD between 1997 and 2011. The patients were divided into an integrative medicine (IM: integrated CM plus HM) and a non-IM (CM only) group with 1:1 propensity score matching. Cox proportional regression model and the Kaplan-Meier method were conducted to estimate the hazard ratio (HR) for lupus nephritis in the cohort. Results Among 16,645 newly diagnosed SLE patients holding a CIC (SLE/CIC), 1933 had received HM and 1571 had received no HM treatment. After propensity score matching, there were 273 patients with lupus nephritis-120 in the IM group and 153 in the non-IM group. The adjusted HR (0.68, 95% confidence interval [CI]: 0.54–0.87, p<0.01) for lupus nephritis was lower in the IM group than in the non-IM group. The adjusted HR (0.69, 95% CI: 0.54–0.88, p<0.001) for lupus nephritis was also lower in the group of patients who had received CM plus HM than in the group that received CM only. The core pattern of HM prescriptions, which were integrated with CM for preventing lupus nephritis, was “Sheng-Di-Huang” (raw Rehmannia glutinosa Libosch.), “Mu-Dan-Pi” (Paeonia suffruticosa Andr.), “Dan-Shan” (Salvia miltiorrhiza Bge.), “Zhi-Bo-Di-Huang-Wan.”, and “Chi-Shao” (Paeoniae lactiflorae Rubra). Conclusion Integrative therapy decreased the risk of lupus nephritis among SLE patients in Taiwan. Further investigation of the pharmacological mechanism and clinical efficacy are warranted. © 2016

Huang H.-C.,Chi Mei Medical Center | Su C.-M.,Chinese Institute of Basic Medical Sciences | Chen W.-C.,Graduate Institute of Integrated Medicine | Fong Y.-C.,China Medical University at Taichung | And 2 more authors.
Journal of Pharmacy and Pharmacology | Year: 2012

Objectives We investigated the effect of Cistanche deserticola Ma. (CD) on bone formation by cultured osteoblasts. Methods The mineralized nodule formation assay was used to examine the in-vitro effects of CD on bone formation. Alkaline phosphatase (ALP), bone morphogenetic proteins (BMP)-2 and osteopontin (OPN) mRNA expression was analysed by quantitative real-time polymerase chain reaction. The mechanism of action of CD extract was investigated using Western blotting. The in-vivo anti-osteoporotic effect of CD extract was assessed in ovariectomized mice. Key findings CD extract had no effect on the proliferation, migration or wound healing of cultured osteoblasts, but increased ALP, BMP-2 and OPN mRNA and bone mineralization. Mitogen-activated protein kinase (MAPK) or nuclear factor (NF)-κB inhibitors reduced CD extract-induced bone formation and ALP, BMP-2 and OPN expression. However, CD extract did not affect osteoclastogenesis. In addition, CD extract prevented the bone loss induced by ovariectomy in vivo. Conclusions CD may be a novel bone formation agent for the treatment of osteoporosis. © 2012 Royal Pharmaceutical Society.

Chou I.-C.,China Medical University at Taichung | Chou I.-C.,Graduate Institute of Integrated Medicine | Lin C.-C.,Data Management | Kao C.-H.,China Medical University at Taichung
Medicine (United States) | Year: 2015

Enterovirus (EV) infection is a major public health issue throughout the world with potential neurological complications. This study evaluated the relationship between attention deficit hyperactivity disorder (ADHD) and EV encephalitis in children. Data of reimbursement claims from the National Health Insurance Research Database of Taiwan were used in a population-based case-control design. The study comprised 2646 children with ADHD who were matched according to sex, age, urbanization level of residence, parental occupation, and baseline year, to people without ADHD at a ratio of 1:10. The index date of the ADHD group was the ADHD date of diagnosis. Histories of EV infections before the index dates were collected and recategorized according to the severity of infection. Compared with children without EV infection, the children with mild EV infection had a 1.16-fold increased risk of ADHD (odds ratio [OR]=1.16, 95% confidence interval [CI]=1.07-1.26), and the children with severe EV infection had a greater risk of ADHD (OR=2.82, 95% CI=1.05-7.57). The results also revealed a significant correlation between ADHD and the severity of EV infection (P for trend=0.0001). Patients with EV encephalitis have an increased risk of developing ADHD. Although most EV encephalitis in children has a favorable prognosis, it may be associated with significant long-term neurological sequelae, even in children considered fully recovered at discharge. Neuropsychological testing should be recommended for survivors of childhood EV encephalitis. The causative factors between EV encephalitis and the increased risk of ADHD require further investigation. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Hsieh M.-S.,Taipei Veterans General Hospital | Hsieh M.-S.,National Yang Ming University | Hsieh M.-S.,National Taiwan University | Chiu C.-S.,National Yang Ming University | And 18 more authors.
Medicine (United States) | Year: 2015

To investigate the association between iodinated contrast medium (ICM) exposure during computed tomography (CT) and the subsequent development of thyroid disorders in patients without known thyroid disease in Taiwan, an iodine-sufficient area. We conducted a population-based cohort study by using data from 1996 to 2012 in the Taiwan National Health Insurance Research Database. A total of 33,426 patients who underwent ICM-enhanced CT were included as the study cohort. To avoid selection bias, we used propensity score and matched for the index year (defined as the year of first ICM exposure) to retrieve 33,426 patients as the comparison cohort. No patients in the 2 cohorts had any known thyroid disease before the index year. Patients with a history of amiodarone treatment or coronary angiography and those with <1 year follow-up were excluded. Participants were followed until a new diagnosis of thyroid disorder or December 31, 2011. Hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated using the Cox proportional hazards regression. An association was identified between ICM exposure and the subsequent development of thyroid disorders after adjustment for potential confounders (adjusted HR=1.17; 95% CI:1.07-1.29; P=0.001). Male patients and patients' ages ≥40 years in the ICM-exposure cohort had a higher adjusted HR for developing thyroid disorders than did those in the non-ICM-exposure cohort. Hypothyroidism had the highest adjusted HR (HR=1.37; 95% CI:1.06-1.78; P<0.05) among all thyroid disorders and had a higher risk of development or detection during >0.5-year post-ICM exposure compared with that during ≤0.5-year post-ICM exposure (HR=1.26; 95% CI:1.01-1.58; P<0.05). Repeated ICM exposure increased the risk of thyroid disorders in patients who accepted >1 time of ICM per year on average compared with those who accepted ≤1 time per year on average (adjustedHR=3.04; 95%CI:2.47-3.73; P<0.001). © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Chen Y.-J.,I - Shou University | Chen Y.-J.,E DA Hospital | Chen H.-P.,E DA Hospital | Cheng Y.-J.,I - Shou University | And 10 more authors.
Life Sciences | Year: 2013

Aim Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. In this study, we explored the anti-cancer activity of WYC02-9, a synthetic protoapigenone, on human HCT116 CRC cells. Main methods The anti-cancer activity of WYC02-9 and its underlying mechanisms were analyzed using XTT cell proliferation assays, colony formation assays, FACS analysis, annexin V staining, immunoblotting analysis, reactive oxygen species (ROS) generation assays, soft agar assays, a nude mice xenograft study and immunohistochemistry assays. Key findings Data showed that WYC02-9 suppressed CRC cell growth by arresting cells at G2/M and inducing cell death via apoptotic pathways. Further analysis demonstrated that WYC02-9-induced apoptosis was mediated by the activation of a ROS-mediated MAPK14 pathway. An in vivo xenograft study revealed that WYC02-9 enhanced MAP2K3/6 and MAPK14 phosphorylation, induced apoptosis, and suppressed CRC tumor growth. Significance WYC02-9 exerts its anti-tumor effect via ROS/MAPK14-induced apoptosis and has the potential to be developed as a chemotherapeutic agent for CRC. © 2013 Elsevier Inc.

Chen H.-M.,E DA Hospital | Chen H.-M.,Graduate Institute of Natural Products | Chang F.-R.,Graduate Institute of Natural Products | Chang F.-R.,Kaohsiung Medical University | And 11 more authors.
Free Radical Biology and Medicine | Year: 2011

The protoapigenone analogue WYC02-9, a novel synthetic flavonoid, has been shown to act against a variety of experimental tumors. However, its effects on prostate cancer and its mechanism of action are unknown. Thus, WYC02-9 was investigated for its cytotoxicity against DU145 prostate cancer cells, as was the underlying mechanisms by which WYC02-9 might induce DNA damage and apoptotic cell death through reactive oxygen species (ROS). WYC02-9 inhibited the cell growth of three prostate cancer cell lines, especially DU145 cells. In DU145 cells, WYC02-9 increased the generation of intracellular ROS, followed by induction of DNA damage and activation of the ATM-p53-H2A.X pathway and checkpoint-related signals Chk1/Chk2, which led to increased numbers of cells in the S and G2/M phases of the cell cycle. Furthermore, WYC02-9 induced apoptotic cell death through mitochondrial membrane potential decrease and activation of caspase-9, caspase-3, and PARP. The above effects were all prevented by the ROS scavenger N-acetylcysteine. Administration of WYC02-9 in a nude mouse DU145 xenograft model further identified the anti-cancer activity of WYC02-9. These findings therefore suggest that WYC02-9-induced DNA damage and mitochondria-dependent cell apoptosis in DU145 cells are mediated via ROS generation. © 2010 Elsevier Inc. All rights reserved.

Chen Y.-H.,Graduate Institute of Integrated Medicine | Chen Y.-H.,China Medical University at Taichung | Chen C.-J.,Graduate Institute of Integrated Medicine | Chen C.-J.,China Medical University at Taichung | And 12 more authors.
PLoS ONE | Year: 2014

Estrogen has various regulatory functions in the growth, development, and differentiation of the female urogenital system. This study investigated the roles of ERβ in stress urinary incontinence (SUI). Wild-type (ERβ+/+) and knockout (ERβ-/-) female mice were generated (aged 6-8 weeks, n=6) and urethral function and protein expression were measured. Leak point pressures (LPP) and maximum urethral closure pressure (MUCP) were assessed in mice under urethane anesthesia. After the measurements, the urethras were removed for proteomic analysis using label-free quantitative proteomics by nano-liquid chromatography-mass spectrometry (LC-MS/MS) analysis. The interaction between these proteins was further analysed using MetaCore. Lastly, Western blot was used to confirm the candidate proteins. Compared with the ERβ+/+ group, the LPP and MUCP values of the ERβ-/- group were significantly decreased. Additionally, we identified 85 differentially expressed proteins in the urethra of ERβ-/- female mice; 57 proteins were up-regulated and 28 were down-regulated. The majority of the ERβ knockout-modified proteins were involved in cell-matrix adhesion, metabolism, immune response, signal transduction, nuclear receptor translational regelation, and muscle contraction and development. Western blot confirmed the up-regulation of myosin and collagen in urethra. By contrast, elastin was down-regulated in the ERβ-/-mice. This study is the first study to estimate protein expression changes in urethras from ERβ-/- female mice. These changes could be related to the molecular mechanism of ERβ in SUI. © 2014 Chen et al.

Chang T.-N.,China Medical University at Taichung | Ho Y.-L.,Hungkuang University | Huang G.-J.,China Medical University at Taichung | Huang S.-S.,China Medical University at Taichung | And 5 more authors.
American Journal of Chinese Medicine | Year: 2011

The hepatoprotective potential of Crossostephium chinensis (L.) Makino water extract (CCW) on carbon tetrachloride (CCl4) induced liver damage was evaluated in preventive and curative rat models. Not only were indicators of hepatic damage including GPT, GOT, lipid peroxides and TBARS were examined, the activities of antioxidant enzymes (SOD, CAT, GPx) and GSH were examined as well. The results showed that CCW (0.1, 0.5 and 1.0 g/kg) significantly reduced the elevated levels of GPT and GOT by CCl4 administration (p < 0.05). TBARS level was dramatically reduced, and SOD, CAT, GPx and GSH activities were significantly increased. In addition, CCW decreased NO production and TNF-α activation in CCl4-treated rats. Therefore, we speculate that CCW protects against acute liver damage through its radical scavenging ability. CCW inhibited the expression of MMP-9 protein, indicating that MMP-9 played an important role in the development of CCl4-induced chronic liver damage in rats. In LC-MS-MS analysis, the chromatograms of CCW with good hepatoprotective activities were established. Scopoletin may be an important bioactive compound in CCW. © 2011 World Scientific Publishing Company & Institute for Advanced Research in Asian Science and Medicine.

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