Hsin-Yi Chen

Asia University, 臺中市, Taiwan, Taiwan

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Publications (65)129.5 Total impact

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    ABSTRACT: Background: To date, the relationship between zolpidem use and subsequent risk of glaucoma in a Taiwanese population has not been assessed.Methods: We used data from the National Health Insurance system to investigate whether zolpidem use was related to glaucoma risk. A 1:4 matched case-control study was conducted. The cases were patients newly diagnosed with glaucoma from 2001 to 2010. The controls were randomly selected non-glaucoma subjects matched by sex and age (±5 years). Zolpidem exposure and/or the average dosage of zolpidem used (mg/year) were evaluated. Medical comorbidities were considered as confounding factors. Multiple logistic regression models were used to evaluate the potential risk of zolpidem exposure on glaucoma with/without adjustment for the effects of confounding variables.Results: The exposure rate of zolpidem use in the glaucoma group was significantly higher than that of the control group (2.8% vs. 2.0%, P < 0.0001). The adjusted odds ratio (OR) of the risk of glaucoma for those with zolpidem use vs. those without was 1.19 (95% confidence interval [CI], 1.02-1.38). Compared to non-zolpidem users, zolpidem users with an average dose of more than 200 mg/year had significantly increased risk of glaucoma (OR 1.31, 95% CI 1.03-1.68).Conclusions: This study suggests that the use of zolpidem might increase the risk of subsequent glaucoma. Further confirmatory studies are recommended to clarify this important issue.
    Journal of Epidemiology 08/2014; · 2.11 Impact Factor
  • Hsin-Yi Chen, Yue-Cune Chang
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    ABSTRACT: To evaluate the diagnostic accuracy of glaucoma in different stages, different types of glaucoma, and different ethnic groups using Stratus optical coherence tomography (OCT).
    Optometry and vision science: official publication of the American Academy of Optometry 07/2014; · 1.53 Impact Factor
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    ABSTRACT: Superoxide dismutase type 1 (SOD1) mutations cause protein aggregation and decrease protein stability, which are linked to amyotrophic lateral sclerosis (ALS) disease. This research utilizes the world's largest traditional Chinese medicine (TCM) database to search novel inhibitors of mutant SOD1, and molecular dynamics (MD) simulations were used to analyze the stability of protein that interacted with docked ligands. Docking results show that hesperidin and 2,3,5,4'-tetrahydroxystilbene-2-O- β -D-glucoside (THSG) have high affinity to mutant SOD1 and then dopamine. For MD simulation analysis, hesperidin and THSG displayed similar value of RMSD with dopamine, and the migration analysis reveals stable fluctuation at the end of MD simulation time. Interestingly, distance between the protein and ligand has distinct difference, and hesperidin changes the position from initial binding site to the other place. In flexibility of residues analysis, the secondary structure among all complexes does not change, indicating that the structure are not affect ligand binding. The binding poses of hesperidin and THSG are similar to dopamine after molecular simulation. Our result indicated that hesperidin and THSG might be potential lead compound to design inhibitors of mutant SOD1 for ALS therapy.
    Evidence-based Complementary and Alternative Medicine 01/2014; 2014:156276. · 1.72 Impact Factor
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    ABSTRACT: Nowadays, obesity becomes a serious global problem, which can induce a series of diseases such as type 2 diabetes mellitus, cancer, cardiovascular disease, metabolic syndrome, and stoke. For the mechanisms of diseases, the hedgehog signaling pathway plays an important role in body patterning during embryogenesis. For this reason, smoothened homologue (Smo) protein had been indicated as the drug target. In addition, the small-molecule Smo inhibitor had also been used in oncology clinical trials. To improve drug development of TCM compounds, we aim to investigate the potent lead compounds as Smo inhibitor from the TCM compounds in TCM Database@Taiwan. The top three TCM compounds, precatorine, labiatic acid, and 2,2'-[benzene-1,4-diylbis(methanediyloxybenzene-4,1-diyl)]bis(oxoacetic acid), have displayed higher potent binding affinities than the positive control, LY2940680, in the docking simulation. After MD simulations, which can optimize the result of docking simulation and validate the stability of H-bonds between each ligand and Smo protein under dynamic conditions, top three TCM compounds maintain most of interactions with Smo protein, which keep the ligand binding stable in the binding domain. Hence, we propose precatorine, labiatic acid, and 2,2'-[benzene-1,4-diylbis(methanediyloxybenzene-4,1-diyl)]bis(oxoacetic acid) as potential lead compounds for further study in drug development process with the Smo protein.
    BioMed Research International 01/2014; 2014:873010. · 2.71 Impact Factor
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    ABSTRACT: A recent research of cancer has indicated that the mutant of isocitrate dehydrogenase 1 and 2 (IDH1 and 2) genes will induce various cancers, including chondrosarcoma, cholangiocarcinomas, and acute myelogenous leukemia due to the effect of point mutations in the active-site arginine residues of isocitrate dehydrogenase (IDH), such as IDH1/R132, IDH2/R140, and IDH2/R172. As the inhibition for those tumor-associated mutant IDH proteins may induce differentiation of those cancer cells, these tumor-associated mutant IDH proteins can be treated as a drug target proteins for a differentiation therapy against cancers. In this study, we aim to identify the potent TCM compounds from the TCM Database@Taiwan as lead compounds of IDH2 R140Q mutant inhibitor. Comparing to the IDH2 R140Q mutant protein inhibitor, AGI-6780, the top two TCM compounds, precatorine and abrine, have higher binding affinities with target protein in docking simulation. After MD simulation, the top two TCM compounds remain as the same docking poses under dynamic conditions. In addition, precatorine is extracted from Abrus precatorius L., which represents the cytotoxic and proapoptotic effects for breast cancer and several tumor lines. Hence, we propose the TCM compounds, precatorine and abrine, as potential candidates as lead compounds for further study in drug development process with the IDH2 R140Q mutant protein against cancer.
    BioMed Research International 01/2014; 2014:364625. · 2.71 Impact Factor
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    ABSTRACT: A recent research demonstrates that the inhibition of mammalian target of rapamycin (mTOR) improves survival and health for patients with Leigh syndrome. mTOR proteins can be treated as drug target proteins against Leigh syndrome and other mitochondrial disorders. In this study, we aim to identify potent TCM compounds from the TCM Database@Taiwan as lead compounds of mTOR inhibitors. PONDR-Fit protocol was employed to predict the disordered disposition in mTOR protein before virtual screening. After virtual screening, the MD simulation was employed to validate the stability of interactions between each ligand and mTOR protein in the docking poses from docking simulation. The top TCM compounds, picrasidine M and acerosin, have higher binding affinities with target protein in docking simulation than control. There have H-bonds with residues Val2240 and π interactions with common residue Trp2239. After MD simulation, the top TCM compounds maintain similar docking poses under dynamic conditions. The top two TCM compounds, picrasidine M and acerosin, were extracted from Picrasma quassioides (D. Don) Benn. and Vitex negundo L. Hence, we propose the TCM compounds, picrasidine M and acerosin, as potential candidates as lead compounds for further study in drug development process with the mTOR protein against Leigh syndrome and other mitochondrial disorders.
    BioMed Research International 01/2014; 2014:139492. · 2.71 Impact Factor
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    ABSTRACT: Protein phosphatase 2A (PP2A) is an important phosphatase which regulates various cellular processes, such as protein synthesis, cell growth, cellular signaling, apoptosis, metabolism, and stress responses. It is a holoenzyme composed of the structural A and catalytic C subunits and a regulatory B subunit. As an environmental toxin, okadaic acid, is a tumor promoter and binds to PP2A catalytic C subunit and the cancer-associated mutations in PP2A structural A subunit in human tumor tissue; PP2A may have tumor-suppressing function. It is a potential drug target in the treatment of cancer. In this study, we screen the TCM compounds in TCM Database@Taiwan to investigate the potent lead compounds as PP2A agent. The results of docking simulation are optimized under dynamic conditions by MD simulations after virtual screening to validate the stability of H-bonds between PP2A- α protein and each ligand. The top TCM candidates, trichosanatine and squamosamide, have potential binding affinities and interactions with key residues Arg89 and Arg214 in the docking simulation. In addition, these interactions were stable under dynamic conditions. Hence, we propose the TCM compounds, trichosanatine and squamosamide, as potential candidates as lead compounds for further study in drug development process with the PP2A- α protein.
    Evidence-based complementary and alternative medicine : eCAM. 01/2014; 2014:436863.
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    ABSTRACT: Rheumatoid arthritis (RA) is a chronic inflammatory disease that will affect quality of life and, working efficiency, and produce negative thoughts for patients. Current therapy of RA is treated with disease-modifying antirheumatic drugs (DMARDs). Although most of these treatment methods are effective, most patients still have a pleasant experience either due to poor efficacy or side effects or both. Interleukin-6 receptor (IL6R) is important in the pathogenesis of RA. In this study, we would like to detect the potential candidates which inhibit IL6R against RA from traditional Chinese medicine (TCM). We use TCM compounds from the TCM Database@Taiwan for virtually screening the potential IL6R inhibitors. The TCM candidate compound, calycosin, has potent binding affinity with IL6R protein. The molecular dynamics simulation was employed to validate the stability of interaction in the protein complex with calycosin. The analysis indicates that protein complex with calycosin is more stable. In addition, calycosin is known to be one of the components of Angelica sinensis, which has been indicated to have an important role in the treatment of rheumatoid arthritis. Therefore, calycosin is a potential candidate as lead compounds for further study in drug development process with IL6R protein against rheumatoid arthritis.
    BioMed Research International 01/2014; 2014:528018. · 2.71 Impact Factor
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    ABSTRACT: It has been indicated that tumor necrosis factor receptor-associated factor-6 (TRAF6) will upregulate the expression of hypoxia-inducible factor-1α (HIF-1α) and promote tumor angiogenesis. TRAF6 proteins can be treated as drug target proteins for a differentiation therapy against cancers. As structural disordered disposition in the protein may induce the side-effect and reduce the occupancy for ligand to bind with target protein, PONDR-Fit protocol was performed to predict the disordered disposition in TRAF6 protein before virtual screening. TCM compounds from the TCM Database@Taiwan were employed for virtual screening to identify potent compounds as lead compounds of TRAF6 inhibitor. After virtual screening, the MD simulation was performed to validate the stability of interactions between TRAF6 proteins and each ligand. The top TCM compounds, tryptophan, diiodotyrosine, and saussureamine C, extracted from Saussurea lappa Clarke, Bos taurus domesticus Gmelin, and Lycium chinense Mill., have higher binding affinities with target protein in docking simulation. However, the docking pose of TRAF6 protein with tryptophan is not stable under dynamic condition. For the other two TCM candidates, diiodotyrosine and saussureamine C maintain the similar docking poses under dynamic conditions. Hence, we propose the TCM compounds, diiodotyrosine and saussureamine C, as potential candidates as lead compounds for further study in drug development process with the TRAF6 protein against cancer.
    BioMed Research International 01/2014; 2014:429486. · 2.71 Impact Factor
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    ABSTRACT: Apolipoprotein E4 (Apo E4) is the major genetic risk factor in the causation of Alzheimer's disease (AD). In this study we utilize virtual screening of the world's largest traditional Chinese medicine (TCM) database and investigate potential compounds for the inhibition of ApoE4. We present the top three TCM candidates: Solapalmitine, Isodesacetyluvaricin, and Budmunchiamine L5 for further investigation. Dynamics analysis and molecular dynamics (MD) simulation were used to simulate protein-ligand complexes for observing the interactions and protein variations. Budmunchiamine L5 did not have the highest score from virtual screening; however, the dynamics pose is similar to the initial docking pose after MD simulation. Trajectory analysis reveals that Budmunchiamine L5 was stable over all simulation times. The migration distance of Budmunchiamine L5 illustrates that docked ligands are not variable from the initial docked site. Interestingly, Arg158 was observed to form H-bonds with Budmunchiamine L5 in the docking pose and MD snapshot, which indicates that the TCM compounds could stably bind to ApoE4. Our results show that Budmunchiamine L5 has good absorption, blood brain barrier (BBB) penetration, and less toxicity according to absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction and could, therefore, be safely used for developing novel ApoE4 inhibitors.
    BioMed Research International 01/2014; 2014:452625. · 2.71 Impact Factor
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    ABSTRACT: Recently, cardiovascular disease, also known as loop circulatory system diseases or disorders, is one of the serious diseases including heart disease, stroke, atherosclerosis, myocardial infarction, hypertension, hypotension, and thrombosis. Human pregnane X receptor, PXR, plays a crucial role in exogenous and endobiotic metabolism for rabbit, rat, mouse, and human. The PXR activation can protect the blood vessels from damage of hazardous substances. In this study we aim to investigate the potent lead compounds as PXR receptor agonist against cardiovascular disease. To improve drug development of TCM compounds, we aim to investigate the potent lead compounds as PXR agonists from the TCM compounds in TCM Database@Taiwan. The top three TCM compounds, bis(4-hydroxybenzyl) ether mono-β-D-glucopyranoside (BEMG), ixerisoside, and tangshenoside II, have displayed higher potent binding affinities than the positive control, PNU-142721, in the docking simulation. After MD simulations, which can optimize the result of docking simulation and validate the stability of H-bonds between each ligand and PXR protein under dynamic conditions, top TCM compounds, BEMG and tangshenoside II, maintain most of interactions with PXR protein, which keep the ligand binding stable in the binding domain. Hence, we propose BEMG and tangshenoside II as potential lead compounds for further study in drug development process with the PXR protein.
    BioMed Research International 01/2014; 2014:950191. · 2.71 Impact Factor
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    ABSTRACT: A recent research in cancer research demonstrates that tumor-specific pyruvate kinase M2 (PKM2) plays an important role in chromosome segregation and mitosis progression of tumor cells. To improve the drug development of TCM compounds, we aim to identify potent TCM compounds as lead compounds of PKM2 regulators. PONDR-Fit protocol was utilized to predict the disordered disposition in the binding domain of PKM2 protein before virtual screening as the disordered structure in the protein may cause the side effect and downregulation of the possibility of ligand to bind with target protein. MD simulation was performed to validate the stability of interactions between PKM2 proteins and each ligand after virtual screening. The top TCM compounds, saussureamine C and precatorine, extracted from Lycium chinense Mill. and Abrus precatorius L., respectively, have higher binding affinities with target protein in docking simulation than control. They have stable H-bonds with residues A:Lys311 and some other residues in both chains of PKM2 protein. Hence, we propose the TCM compounds, saussureamine C and precatorine, as potential candidates as lead compounds for further study in drug development process with the PKM2 protein against cancer.
    BioMed Research International 01/2014; 2014:189495. · 2.71 Impact Factor
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    ABSTRACT: Objective. To investigate if different treatment strategy of obstructive sleep apnea (OSA) was associated glaucoma risk in Taiwanese population. Methods. Population-based retrospective cohort study was conducted using data sourced from the Longitudinal Health Insurance Database 2000. We included 2528 OSA patients and randomly selected and matched 10112 subjects without OSA as the control cohort. The risk of glaucoma in OSA patients was investigated based on the managements of OSA (without treatment, with surgery, with continuous positive airway pressure (CPAP) treatment, and with multiple modalities). The multivariable Cox regression was used to estimate hazard ratio (HR) after adjusting for sex, age, hypertension, diabetes, hyperlipidemia, and coronary artery disease. Results. The adjusted HR of glaucoma for OSA patients was 1.88 (95% CI: 1.46-2.42), compared with controls. For patients without treatment, the adjusted HR was 2.15 (95% CI: 1.60-2.88). For patients with treatments, the adjusted HRs of glaucoma were not significantly different from controls, except for those with CPAP (adjusted HR = 1.65, 95% CI = 1.09-2.49). Conclusions. OSA is associated with an increased risk of glaucoma. However, surgery reduces slightly the glaucoma hazard for OSA patients.
    Journal of ophthalmology. 01/2014; 2014:838912.
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    ABSTRACT: Insomnia is a prominent modern disease that affects an increasing population. Undesirable side effects of commercial drugs highlight the need to develop novel insomnia drugs. Virtual screening of traditional chinese medicine Database@Taiwan (TCM Database@Taiwan) identified 2-O-Caffeoyl tartaric acid (1), 2-O-Feruloyl tartaric acid (2), and Mumefural (3) as potential agonists for both gamma-amino butyric acid (GABA) or benzodiazepine (BZ) binding sites. The TCM candidates exhibited higher affinity than GABA and Zolpidem, a phenomenon that could be attributed to higher quantity of stabilizing H-bonds. Efficacy profiles using support vector machines and pharmacophore contour also suggest drug potential of the TCM candidates. Fragments added to the de novo derivatives 3a, 3b, 3c for GABA binding site, and 1a, 2a, and 3d for BZ binding site contributed to new binding sites and structural stability, further optimizing binding to GABA or BZ binding sites. Increased opening of the ion channel by candidate ligands provide strong support for their potential biological functions. The dual binding properties of the TCM candidates present a unique opportunity to develop twin-targeting drugs with less side effects. Derivative structures can be used as starting points for developing high affinity GABAA receptor agonists with specificity towards GABA binding site and BZ binding site.
    Journal of biomolecular structure & dynamics 06/2013; · 4.99 Impact Factor
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    ABSTRACT: To investigate the risk factors and comorbidities associated with ethambutol-induced optic neuropathy (EON). Using the Taiwan Longitudinal Health Insurance Database, we conducted a study within a nationwide representative cohort of patients treated with EMB. We identified 231 patients newly diagnosed with EON between 2000 and 2008, and 924 control subjects. Adjusted OR by estimating the risk of EON in relation to comorbidities and EMB prescription protocol was determined. Compared with the control group, EON patients were at risk with older age, hypertension (adjusted OR=1.62, 95% CI 1.16 to 2.26) and renal diseases (without end-stage renal diseases (ESRD), adjusted OR=2.11, 95% CI 1.02 to 4.35; with ESRD, adjusted OR=3.73, 95% CI 1.79 to 7.74). Patients with an EMB prescription duration longer than 3 months were not at elevated risk compared with those whose prescription less than 3 months (OR=1.35, 95% CI 0.99 to 1.83, adjusted for age, sex, hypertension and renal diseases). Patients whose average daily dose was greater than 1200 mg, compared with the other two groups (800∼1199 mg, less than 800 mg) were not at increased risk for EON. Age, hypertension and renal diseases are risk factors for EON in the Taiwanese population.
    The British journal of ophthalmology 09/2012; 96(11):1368-71. · 2.92 Impact Factor
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    ABSTRACT: PURPOSE:: To compare the glaucoma diagnostic power of Stratus and Cirrus optical coherence tomographies (OCTs) in a Taiwan Chinese population with different glaucoma types. PATIENTS AND METHODS:: One eye each was chosen from 21 ocular hypertension (OH) patients, 27 glaucoma-suspect (GS) patients, 35 primary open-angle glaucoma (POAG) patients, 26 primary angle-closure glaucoma (PACG) patients, and 52 normal subjects. Early glaucoma (EG) was identified among glaucomatous eyes on the basis of the visual field severity (better than -9 dB). All participants were imaged using 2 OCT units at the same visit. The area under the receiver operator characteristic (AROC) curve was used to differentiate normal eyes from OH, GS, POAG, PACG, and EG eyes, and the sensitivity and specificity of each parameter from internal normative classifications were analyzed. RESULTS:: For normal versus OH eyes, the best AROC value was the average thickness (Stratus, 0.693; Cirrus, 0.697). For normal versus GS eyes, the best AROC value was the average thickness (Stratus, 0.807; Cirrus, 0.776). For normal versus POAG eyes, the best AROC value was the average thickness (Stratus, 0.943; Cirrus, 0.930). For normal versus PACG eyes, the best AROC value was the 5-o'clock hour (Stratus, 0.830; Cirrus, 0.817). For normal versus EG eyes, the best AROC value was the average thickness with Stratus (0.868) and the 5-o'clock hour with Cirrus (0.876). All sensitivities in the 5 groups were fair on the basis of the internal normal classification database of both OCTs. CONCLUSIONS:: Cirrus and Stratus OCTs showed equal diagnostic power in EG, OH, GS, POAG, and PACG eyes in a Taiwan Chinese population. The utility of the current internal databases of both OCT units for the Chinese population is an interesting issue that needs to be addressed in the future.
    Journal of glaucoma 05/2012; · 1.74 Impact Factor
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    ABSTRACT: To study the association between retinitis pigmentosa (RP) and the progression of diabetic retinopathy (DR). Using the Longitudinal Health Insurance Database 2000 of Taiwan, we identified individuals with an initial diagnosis for RP during the period of 1997-2008. A non-RP comparison group, 10-fold frequency matched by sex, age, index year and the year of diabetes diagnosed, were randomly selected from the same database. The occurrence of DR was observed for all subjects until the end of 2009. The Kaplan-Meier curves were used to illustrate the cumulative probability of developing DR for the RP group and comparison groups. The hazard ratio (HR) of DR for the RP group relative to the comparison group was estimated using Cox proportional hazards model after adjusting for potential confounders. The Kaplan-Meier curves were not statistically significant different between the RP group and the comparison group. However, the RP group had a higher cumulative probability of developing DR during the first six to seven years. The cumulative probability kept increasing and became higher in the comparison group but remained unchanged in the RP group. The HR for the RP patients comparing with the comparison group was 0.96 (95% confidence interval (CI) = 0.43-2.14). Stratified by severity, RP was associated with a non-statistically significant reduced risk of proliferative DR (PDR) (HR = 0.70, 95% CI = 0.16-3.14). The HR for non-proliferative DR (NPDR) was 1.08 (95% CI = 0.40-2.86). In this study, RP was not statistically significant associated with the incidence of DR.
    PLoS ONE 01/2012; 7(9):e45189. · 3.53 Impact Factor
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    ABSTRACT: PurposeTo study the correlation between Stratus optical coherence tomography (OCT) and scanning laser polarimetry (GDx VCC) in measuring retinal nerve fiber layer (RNFL) thickness in eyes with early glaucoma (EG), ocular hypertension (OH), and glaucoma suspect (GS) in a Taiwan Chinese population.Methods One eye each of 170 subjects (50 eyes with EG, 32 eyes with OH, 38 eyes with GS and 50 healthy eyes) was included. The RNFL thickness was measured by both technologies and three parameters (average, superior and inferior thickness) were correlated using the Pearson's correlation coefficient (r) in each group. Diagnostic capability of two instruments was evaluated in EG, OH and GS eyes based on the area under the receive operator characteristic (AROC) curve.ResultsIn healthy and EG eyes, three RNFL parameters were significantly correlated. In OH eye, there was no significant correlation in three parameters. In GS eye, there was significant correlation in inferior thickness only. For healthy vs EG eye, the best parameter with largest AROC was nerve fiber indicator (0.798) for GDx VCC and average thickness (0.787) for OCT. The diagnostic capability of two techniques is poor in OH (AROC, 0.510–0.645) and GS eyes (AROC, 0.510–0.689).Conclusion The RNFL thickness measured by OCT and GDx VCC was well correlated in EG and healthy eyes but poorly correlated in OH and GS eyes. When managing the case with OH or GS eye, we should be cautious in interpreting different imaging data.ResumenObjetivoEstudiar la correlación entre la tomografía de coherencia óptica (OCT) Stratus y la polarimetría láser de barrido (GDx VCC) en la medición del espesor de la capa de fibras nerviosas de la retina (CFNR) en ojos con glaucoma temprano (GT), hipertensión ocular (HO) y sospecha de glaucoma (SG) en una población de chinos taiwaneses.MétodosSe incluyeron 170 sujetos, un ojo de cada uno de ellos (50 ojos con GT, 32 ojos con HO, 38 ojos con SG y 50 ojos sanos). Se midió el espesor de la CFNR con ambas técnicas y se correlacionaron tres parámetros (espesor medio, superior e inferior) utilizando el coeficiente de correlación de Pearson (r) en cada grupo. Se evaluó la capacidad de diagnóstico de ambos instrumentos en ojos con GT, HO y SG basándose en el área bajo la curva de la característica operativa del receptor (AROC).ResultadosEn ojos sanos y con GT, se correlacionaron de manera significativa tres parámetros de CFNR. En los ojos con HO, no hubo correlación significativa en tres parámetros. En ojos con SG, hubo correlación significativa únicamente en el espesor inferior. Para ojos sanos frente a GT, el mejor parámetro con la mayor AROC fue el indicador de fibras nerviosas (0,798) en GDx VCC y el espesor medio (0,787) en OCT. La capacidad de diagnóstico de ambas técnicas es baja para ojos con HO (AROC: 0,510–0,645) y SG (AROC: 0,510–0,689).ConclusiónEl espesor de la CFNR medido por OCT y GDx VCC presentó una buena correlación en ojos con GT y sanos, pero muy baja en ojos con HO y SG. A la hora de tratar casos de ojos con HO o SG, deberemos ser prudentes al interpretar los diferentes datos de exploraciones por imagen.
    Journal of Optometry. 01/2012; 5(1):24–30.
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    ABSTRACT: 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 (r² = 0.7858) and SVM (r² = 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 (q² = 0.721, r² = 0.986) and CoMSIA (q² = 0.662, r² = 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.
    PLoS Computational Biology 10/2011; 7(10):e1002189. · 4.87 Impact Factor
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    ABSTRACT: Two nuclear plant disasters occurring within a span of 25 years threaten health and genome integrity both in Fukushima and Chernobyl. Search for remedies capable of enhancing DNA repair efficiency and radiation resistance in humans appears to be a urgent problem for now. XRCC4 is an important enhancer in promoting repair pathway triggered by DNA double-strand break (DSB). In the context of radiation therapy, active XRCC4 could reduce DSB-mediated apoptotic effect on cancer cells. Hence, developing XRCC4 inhibitors could possibly enhance radiotherapy outcomes. In this study, we screened traditional Chinese medicine (TCM) database, TCM Database@Taiwan, and have identified three potent inhibitor agents against XRCC4. Through molecular dynamics simulation, we have determined that the protein-ligand interactions were focused at Lys188 on chain A and Lys187 on chain B. Intriguingly, the hydrogen bonds for all three ligands fluctuated frequently but were held at close approximation. The pi-cation interactions and ionic interactions mediated by o-hydroxyphenyl and carboxyl functional groups respectively have been demonstrated to play critical roles in stabilizing binding conformations. Based on these results, we reported the identification of potential radiotherapy enhancers from TCM. We further characterized the key binding elements for inhibiting the XRCC4 activities.
    Journal of biomolecular structure & dynamics 10/2011; 29(2):325-37. · 4.99 Impact Factor

Publication Stats

610 Citations
129.50 Total Impact Points

Institutions

  • 2011–2014
    • Asia University
      • Department of Biomedical Informatics
      臺中市, Taiwan, Taiwan
    • Tamkang University
      • Department of Mathematics
      T’ai-pei, Taipei, Taiwan
  • 2004–2014
    • China Medical University Hospital
      • Department of Radiology
      臺中市, Taiwan, Taiwan
  • 2012
    • National Taiwan University
      • Graduate Institute of Epidemiology and Preventive Medicine
      Taipei, Taipei, Taiwan
    • National Taiwan University Hospital
      T’ai-pei, Taipei, Taiwan
  • 2010–2011
    • China Medical University (ROC)
      臺中市, Taiwan, Taiwan
  • 2005–2010
    • National Chin-Yi University of Technology
      Kinmen, Fukien, Taiwan