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Ho M.,China Medical University Beigang Hospital | Cheng S.-Y.,China Medical University Beigang Hospital
Obstetrics and Gynecology | Year: 2010

Objective: To compare titrated oral misoprostol to intravenous oxytocin for labor augmentation among women at 36 to 42 weeks of gestation with spontaneous onset of active labor. Methods: Women meeting the general selection criteria with regular contractions and an effaced cervix dilated between 3 and 9 cm, and who had inadequate uterine contractions (two or fewer contractions every 10 minutes) during the first stage of labor, were randomly assigned to titrated oral misoprostol or intravenous oxytocin. Augmentation-to-vaginal delivery interval and vaginal delivery within 12 or 24 hours were the primary outcomes. The data were analyzed by intention to treat. Results: Of the 231 women, 118 (51.1%) were randomized to titrated oral misoprostol and 113 (48.9%) to titrated intravenous oxytocin. The median interval from the start of augmentation to vaginal delivery was 5.22 hours (3.77-8.58 hours, 25th-75th percentile) in the misoprostol group, and 5.20 hours (3.23-6.50 hours, 25th-75th percentile) in the intravenous oxytocin group (P=.019). Complete vaginal delivery occurred within 12 hours for 92 women (78.0%) in the misoprostol group and for 97 women (85.8%) in the oxytocin group (P=.121; relative risk 0.91, 95% confidence interval 0.80-1.03). There were no significant differences between the two groups who delivered vaginally within 24 hours. Side effects and neonatal outcomes also did not differ between the two groups. Conclusion: Labor augmentation with titrated oral misoprostol or intravenous oxytocin resulted in similar rates of vaginal delivery within 12 and 24 hours. © 2010 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams &Wilkins.

Chen C.Y.-C.,China Medical University Beigang Hospital | Chen C.Y.-C.,China Medical University at Taichung | Chen C.Y.-C.,Asia University, Taiwan
Journal of Biomolecular Structure and Dynamics | Year: 2012

Mutant oncogene DJ1 L166P has been linked to a familial form of early-onset Parkinson's disease (PD). The DJ1 mutant deformed C-terminal helices and prevented the formation of a functional DJ1 dimer. Intriguingly, chaperon modulator, BCL2-associated athanogene (BAG1), has been shown to repair DJ1 mutant and restore its functions. Molecular simulation techniques were employed to elucidate protein-protein interactions between BAG1 and DJ1. Interaction of BAG1 with DJ1 showed recovery of disrupted alpha helix structures and H-bonds stabilizing the functional site Cys106. The His126-Pro184 H-bond (hydrogen-bond) critical to maintaining dimer interfaces was also restored and led to the restoration of dimer formation. High conformational to functional DJ1 dimer was confirmed root mean square deviation = 0.74 Å). Results of this suggest several molecular insights on BAG1-DJ1 repair mechanism and may have an impact on advancing PD treatments. Copyright © 2012 Taylor & Francis.

Tou W.I.,China Medical University at Taichung | Chen C.Y.-C.,China Medical University at Taichung | Chen C.Y.-C.,Asia University, Taiwan | Chen C.Y.-C.,China Medical University Beigang Hospital | Chen C.Y.-C.,Massachusetts Institute of Technology
Drug Discovery Today | Year: 2014

Insomnia is a self-reported disease where patients lose their ability to initiate and maintain sleep, leading to daytime performance impairment. Several drug targets to ameliorate insomnia symptoms have been discovered; however, these drug targets lead to serious side effects. Thus, we characterize the structural properties of these sleep-related receptors and the clock complex and discuss a possible drug design that will reduce side effects. Computational prediction shows that disordered property is shared. Over 30% of the structure of CLOCK, PER1/2/3, BMAL-1, muscarinic acetylcholine receptor-M1, melatonin receptor and casein kinase I are structurally disordered (the remaining proteins represent <30%). Investigations support the principle that the failures of insomnia drugs might be closely related to the protein architecture. © 2013 Elsevier Ltd.

Huang H.-J.,China Medical University at Taichung | Jian Y.-R.,China Medical University at Taichung | Chen C.Y.-C.,Asia University, Taiwan | Chen C.Y.-C.,China Medical University at Taichung | Chen C.Y.-C.,China Medical University Beigang Hospital
Journal of Biomolecular Structure and Dynamics | Year: 2014

Viral infection by human immunodeficiency virus (HIV) requires integration of viral DNA with host DNA which involves the binding of HIV integrase (IN) with its co-factor lens epithelium-derived growth factor (LEDGF/p75). Since disrupted binding of IN with LEDGF/p75 inhibits proliferation of HIV, inhibition or denaturation of IN is a possible method for inhibiting HIV replication. D77 is a known drug with demonstrated inhibition against HIV by binding to IN. Herein, we utilized D77 as a control to screen for traditional Chinese medicine (TCM) compounds that exhibit similar atomic-level characteristics. 9-Hydroxy-(10E)-octadecenoic acid and Beauveriolide I were found to have higher Dock Scores to IN than D77 through virtual screening. Multiple linear regression (R2 = 0.9790) and support vector machine (R2 = 0.9114) models consistently predicted potential bioactivity of the TCM candidates against IN. The 40 ns molecular dynamics simulation showed that the TCM compounds fulfilled the drug-like criteria of forming stable complexes with IN. Atomic-level investigations revealed that 9-hydroxy-(10E)-octadecenoic acid bound to an important residue A:Lys173, and Beauveriolide I formed stable interactions with the core LEDGF binding site and with Asn256 of the IN binding site on LEDGF. The TCM candidates also initiated loss of α-helices that could affect the functionality of IN. Taken together, the ability of 9-hydroxy-(10E)-octadecenoic acid and Beauveriolide I to (1) form stable interactions affecting IN-LEDGF binding and (2) have predicted bioactivity against IN suggests that the TCM candidates might be potential starting structures for developing compounds that may disrupt IN-LEDGF binding. An animated interactive 3D complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:40 © 2013 Taylor & Francis.

Yang S.-C.,China Medical University at Taichung | Chang S.-S.,China Medical University at Taichung | Chen H.-Y.,Asia University, Taiwan | Chen C.Y.-C.,China Medical University at Taichung | And 2 more authors.
PLoS Computational Biology | Year: 2011

Overexpression of epidermal growth factor receptor (EGFR) has been associated with cancer. Targeted inhibition of the EGFR pathway has been shown to limit proliferation of cancerous cells. Hence, we employed Traditional Chinese Medicine Database (TCM Database@Taiwan) (http://tcm.cmu.edu.tw) to identify potential EGFR inhibitor. Multiple Linear Regression (MLR), Support Vector Machine (SVM), Comparative Molecular Field Analysis (CoMFA), and Comparative Molecular Similarities Indices Analysis (CoMSIA) models were generated using a training set of EGFR ligands of known inhibitory activities. The top four TCM candidates based on DockScore were 2-O-caffeoyl tartaric acid, Emitine, Rosmaricine, and 2-O-feruloyl tartaric acid, and all had higher binding affinities than the control Iressa®. The TCM candidates had interactions with Asp855, Lys716, and Lys728, all which are residues of the protein kinase binding site. Validated MLR (r 2 = 0.7858) and SVM (r 2 = 0.8754) models predicted good bioactivity for the TCM candidates. In addition, the TCM candidates contoured well to the 3D-Quantitative Structure-Activity Relationship (3D-QSAR) map derived from the CoMFA (q 2 = 0.721, r 2 = 0.986) and CoMSIA (q 2 = 0.662, r 2 = 0.988) models. The steric field, hydrophobic field, and H-bond of the 3D-QSAR map were well matched by each TCM candidate. Molecular docking indicated that all TCM candidates formed H-bonds within the EGFR protein kinase domain. Based on the different structures, H-bonds were formed at either Asp855 or Lys716/Lys728. The compounds remained stable throughout molecular dynamics (MD) simulation. Based on the results of this study, 2-O-caffeoyl tartaric acid, Emitine, Rosmaricine, and 2-O-feruloyl tartaric acid are suggested to be potential EGFR inhibitors. © 2011 Yang et al.

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