Institute of Biology and Anatomy

Taipei, Taiwan

Institute of Biology and Anatomy

Taipei, Taiwan
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Shyu H.-Y.,Section of Neurology | Shyu H.-Y.,Institute of Biology and Anatomy | Chen M.-H.,Section of Neurology | Chen M.-H.,Tri Service General Hospital | And 5 more authors.
PLoS ONE | Year: 2017

Endothelial nitric oxide synthase (eNOS) is localized in caveole and has important effects on caveolar coordination through its interaction with caveolin-1 (Cav-1), which supports normal functioning of vascular endothelial cells. However, the relationship between genotypic polymorphisms of e-NOS and Cav-1 genes and ischemic stroke (IS) remains lesser reported. This hospital-based case-control study aimed to determine the genetic polymorphisms of the eNOS (Glu298Asp) and Cav-1 (G14713A and T29107A) genes in association with susceptibility risk in patients who had suffered from a large artery atherosclerotic (LAA) stroke. Genotyping determination for these variant alleles was performed using the TaqMan assay. The distributions of observed allelic and genotypic frequencies for the polymorphisms were in Hardy-Weinberg equilibrium in healthy controls. The risk for an LAA stroke in the Asp298 variant was 1.72 (95% CI = 1.09±2.75) versus Glu298 of the eNOS. In the GA/AA (rs3807987) variant, it was 1.79 (95% CI = 1.16±2.74) versus GG and in TA/AA (rs7804372) was 1.61 (95% CI = 1.06±2.43) versus TT of the Cav-1, respectively. A tendency toward an increased LAA stroke risk was significant in carriers with the eNOS Glu298Asp variant in conjunction with the G14713 A and T29107A polymorphisms of the Cav-1 (aOR = 2.03, P-Trend = 0.002). A synergistic effect between eNOS and Cav-1 polymorphisms on IS risk elevation was significantly influenced by alcohol drinking, heavy cigarette smoking (P-Trend<0.01), and hypercholesterolemia (P-Trend < 0.001). In conclusion, genotypic polymorphisms of the eNOS Glu298Asp and Cav-1 14713A/29107A polymorphisms are associated with the elevated risk of LAA stroke among Han Chinese in Taiwan. © 2017 Shyu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Huang W.-C.,Neurological Institute | Huang W.-C.,Graduate Institute of Medical science | Huang W.-C.,National Yang Ming University | Kuo W.-C.,Neurological Institute | And 8 more authors.
Neuroscience Letters | Year: 2010

Chondroitin sulfate proteoglycan (CSPG) is a major component of glial scar to restrict axonal regeneration in the lesion site after spinal cord injury (SCI). Chondroitinase ABC (ChABC), a bacteria enzyme, which has been demonstrated to digest the glycosaminoglycan (GAG) side chain of CSPG to promote axonal re-growth across the injured site. Our previous study suggested that long-term delivery of ChABC (1 U/ml, injection volume 0.6 μl for one animal) via intrathecal catheter could decrease the inhibitory effect of limiting axonal re-growth after SCI. The functional behavior has been shown to improve following ChABC treatment. Little axons re-grow across the lesion site of the spinal cord but not enough to support axon innervations to targets. In this article, we show that ChABC administration combining olfactory mucosa progenitor cell (OMPC) transplantation can promote axonal re-growth across the lesion site and enhance the consistency of stepping in spinally transected rats. These OMPCs generated NG2+ cell lineages after transplanting into the spinal cord parenchyma, and OMPCs were found to spread and migrate toward the lesion region of spinal cord. Moreover, the spatial and temporal characteristics of the step cycle in rats that receive a complete spinal cord transaction following continuous ChABC supply and OMPC transplantation. The gait characteristics of treated rats on a treadmill were consistent and approached that of intact rats. In future, the mechanism of restoring the injured spinal cord will be further investigated. © 2010 Elsevier Ireland Ltd. All rights reserved.


Lan H.-C.,Institute of Biology and Anatomy | Wu K.-Y.,Institute of Biology and Anatomy | Lin I.-W.,Institute of Biology and Anatomy | Yang Z.-J.,Institute of Biology and Anatomy | And 2 more authors.
Chemosphere | Year: 2017

Bisphenol A (BPA) is a well-known endocrine disrupting chemical (EDC) that is used to manufacture plastic consumer products. It is well known that exposure to BPA can induce defects in gonad development and negatively influences reproductive function in both males and females. In this study, we assessed the effects of BPA on hormone production in Leydig cells, which secrete hormones in the testes and support male fertility. We examined two steroidogenic enzymes, CYP11A1 and CYP19 that involved in sex hormone synthesis in mouse MA-10 Leydig cells. We found that BPA activated CYP gene in both mRNA and protein levels then resulted in alteration of the normal sex hormone ratio. Furthermore, we found that BPA induced c-Jun phosphorylation and contributed to CYP gene expression. Similar results were observed in an animal study. In conclusion, BPA disrupts the hormone environment in testis via steroidogenic gene activation through the JNK/c-Jun signaling pathway. © 2017 Elsevier Ltd


Pao L.-H.,National Defense Medical Center | Lu S.-W.,Tri Service General Hospital | Sun G.-G.,National Defense Medical Center | Chiou S.-H.,Taipei Veterans General Hospital | Ma K.-H.,Institute of Biology and Anatomy
Journal of Ethnopharmacology | Year: 2012

Ethnopharmacological relevance: The present study investigated whether Chinese herbal medicines (CHMs) could reverse the effects of chronic mild stress (CMS) in a depression-like mouse model. Materials and methods: The effects of three Chinese herbals, Rhizome Chuanxiong, Radix Scutellaria and Radix Phellodendri on promoting neuroproliferation were evaluated in vitro first and followed by in vivo study of mice which were received by an experimental setting of CMS for 14 days. The effects of the three CHMs on depression were evaluated using a behavioral test, named a forced swimming test (FST). The possible anti-depressive mechanisms of these three CHMs, including the modulation of HPA axis and promoting the hippocampal precursor cell proliferation, were evaluated by measuring plasma corticosterone levels and BrdU incorporation. Results: The in vitro results of MTS assay showed that Rhizome Chuanxiong, Radix Scutellaria and Radix Phellodendri could promote the proliferation of neural stem cells (NSCs) in a concentration-dependent manner. The oral administration of these three CHMs for 14 days reversed not only the elevation of plasma corticosterone levels and body weight loss, but also the decreasing of hippocampal precursor cell proliferation and abnormal behavior in the CMS induced depression-like mouse model. Conclusion: These results indicated that Rhizome Chuanxiong, Radix Scutellaria and Radix Phellodendri have the potential to ameliorate depression. The possible mechanisms were the inhibition of HPA axis hyperactivity and the increasing of hippocampal precursor cell proliferation. These findings supported the multicomponent and multitargeted approach of Chinese herbal medicine.


Huang W.-C.,Taipei Veterans General Hospital | Huang W.-C.,Graduate Institute of Medical science | Huang W.-C.,National Yang Ming University | Kuo H.-S.,Taipei Veterans General Hospital | And 13 more authors.
Journal of Gene Medicine | Year: 2011

Background: Following spinal cord injury, the delivery of neurotrophic factors to the injured spinal cord has been shown to promote axonal regeneration and functional recovery. In previous studies, we showed that acidic fibroblast growth factor (aFGF) is a potent neurotrophic factor that promotes the regeneration of axotomized spinal cord or dorsal root ganglion neurones. Methods: We constructed a recombinant adeno-associated virus (AAV) vector to express human aFGF and evaluated aFGF expression and function in AAV-aFGF-infected PC12 cells. We analyzed AAV-green fluorescent protein (GFP) tropism and AAV-mediated aFGF expression in contused spinal cords. Animals received behavioural testing to evaluate the functional recovery. Results: Overexpression of aFGF was shown in AAV-aFGF-infected PC12 cells in a dose-dependent manner. Concurrently, neurite extension and cell number were significantly increased in AAV-aFGF infected cells. AAV-mediated GFP expression persisted for at least 5 weeks in contused spinal cords, and the most prominently transduced cells were neurones. Contusive injury reduced endogenous aFGF expression in spinal cords. Overexpression of aFGF was demonstrated in AAV-aFGF transduced spinal cords compared to AAV-GFP transduced spinal cords at 3 and 14 days post-injury. Evaluation of motor function revealed that the improvement of AAV-aFGF-treated rats was prominent. Both AAV-aFGF- and recombinant human aFGF-treated rats revealed significantly better recovery at 5 weeks post-injury, compared to vehicle- and AAV-GFP-treated rats. Conclusions: These data suggest that supplement of aFGF improve the functional recovery of spinal cord-contused rats and that AAV-aFGF-mediated gene transfer could be a clinically feasible therapeutic approach for patients after nervous system injuries. © 2011 John Wiley & Sons, Ltd.


Lan H.-C.,Academia Sinica, Taiwan | Lan H.-C.,Institute of Biology and Anatomy | Wu C.-F.,Academia Sinica, Taiwan | Wu C.-F.,National Yang Ming University | And 3 more authors.
Journal of Biological Chemistry | Year: 2012

SF-1 is a key transcription factor for all steroidogenic genes. It up-regulates the expression of the steroidogenic Cyp11a1 gene in the adrenal in a pathway stimulated by cAMP through HIPK3-mediated JNK/c-Jun phosphorylation. In the present study, we have investigated the factors mediating cAMP-dependent HIPK3 action to potentiate the activity of SF-1 for Cyp11a1 transcription in mouse adrenocortical Y1 cells. We found Daxx, a HIPK kinase substrate in the apoptosis pathway, was phosphorylated by HIPK3 at Ser-669 in response to cAMP stimulation. Daxx participated in SF-1-dependent Cyp11a1 expression as shown by experiments involving both overexpression and down-regulation via a dominant negative Daxx mutant. The S669A mutant of Daxx, which could not be phosphorylated by HIPK3, lost the ability to potentiate SF-1 activity for Cyp11a1 expression. The enhancement of SF-1 activity by Daxx required JNK and c-Jun phosphorylation. Thus, Daxx functioned as a signal transducer linking cAMP-stimulated HIPK3 activity with JNK/c-Jun phosphorylation and SF-1-dependent Cyp11a1 transcription for steroid synthesis. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.


Huang K.-H.,Taipei Medical University | Pai M.-H.,Taipei Medical University | Wu C.-H.,Institute of Biology and Anatomy | Liu J.-J.,Taipei Medical University | Yeh S.-L.,Taipei Medical University
e-SPEN | Year: 2010

Background & aims: Arginine (Arg) was shown to have immunomodulatory effect and inhibits advanced glycation end product (AGE) formation in in vitro studies. This study investigated the effects of dietary Arg supplementation on renal receptor of AGE (RAGE) expressions and oxidative damage in diabetic rats. Methods: There were 1 normal control (NC) group and 2 diabetic groups in this study. Rats in the NC group were fed with a chow diet. One diabetic group (DM) was fed a common semipurified diet, while the other diabetic group received a diet in which part of the casein was replaced by Arg (DM-Arg) for 8 wk. Diabetes was induced by an intraperitoneal injection of nicotinamide followed by streptozotocin. Rats with blood glucose levels exceeding 180 mg/dL were considered diabetic. Blood samples were collected at the baseline and 8 wk. Kidneys of the animals were harvested at the end of the study for further analysis. Results: Plasma fructosamine contents were significantly higher in the diabetic groups than in the NC group. The DM group had higher fructosamine than the DM-Arg group. Kidney nitrotyrosine concentrations and nuclear factor-κB p65 protein expressions were significantly lower in the DM-Arg group than in the DM group. The result of immunohistochemical staining also showed that the expressions of RAGE in the kidneys were significantly lower in the DM-Arg group than in the DM group. Conclusions: These results suggest that dietary Arg supplementation may decrease renal RAGE expressions and oxidative damage in rats with type 2 diabetes. © 2010 European Society for Clinical Nutrition and Metabolism.


Lan H.-C.,Institute of Biology and Anatomy | Lin I.-W.,Institute of Biology and Anatomy | Yang Z.-J.,Institute of Biology and Anatomy | Lin J.-H.,Institute of Biology and Anatomy
Toxicological Sciences | Year: 2015

Certain commonly used compounds that interfere with the functions of the endocrine system are classified as endocrine-disrupting chemicals (EDCs). Bisphenol A (BPA) is an EDC that is widely used in food containers. BPA levels in human sera are commonly observed to be approximately 1-100 nM. Compared with the effects of BPA on the gonads, its effects on the adrenal gland are poorly understood. To investigate the influence of BPA on steroidogenesis, we examined the activity of the steroidogenic gene Cyp11a1 and its regulatory pathways in mouse Y1 adrenal cortex cells. Treatment with BPA at < 100 μM did not cause cell death. However, increased promoter activity and protein expression of Cyp11a1 were induced by low doses of BPA (10-1000 nM). Moreover, BPA induced c-Jun phosphorylation, and a specific inhibitor of c-Jun N-terminal kinase (JNK) significantly suppressed BPA-induced steroidogenesis. Thus, treatment of adrenal cells with low doses of BPA activated Cyp11a1 and increased corticosterone production through the JNK/c-Jun signaling pathway. Identical results were observed in rats after BPA injection. The abnormal induction of hormone synthesis by BPA in the adrenal gland might be linked to human metabolic defects and neuropsychiatric disorders. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.


Shyu H.-Y.,Armed Forces Taoyuan General Hospital | Shyu H.-Y.,Institute of Biology and Anatomy | Shieh J.-C.,Chung Shan Medical University | Lin J.-H.,Taipei General Hospital | And 2 more authors.
Journal of Atherosclerosis and Thrombosis | Year: 2012

Aim: Cigarette-smoking induced oxidative DNA damage to endothelial cells has been reported to play an etiological role in atherosclerosis development. Individual vulnerability to oxidative stress through smoking exposure and the ability to repair DNA damage, which plays a critical role in modifying the risk susceptibility of large artery atherosclerotic (LAA) stroke, is hypothesized. Thus, we examined the effect of genetic polymorphisms of DNA repair pathway genes and cigarette smoking in relation to risk susceptibility of LAA stroke. Methods: We enrolled 116 LAA stroke patients and 315 healthy controls from the Armed Forces Taoyuan General Hospital, Taoyuan, Taiwan. Genotyping of polymorphisms of the OGG1 (Ser326Cys), XRCC1 (Arg399Gln), ERCC2 (Lys751Gln), and ERCC5 (Asp1104His) genes was performed and used to evaluate LAA stroke susceptibility. Results: Of those non-synonymous polymorphisms, the ERCC2 Lys751Gln variant was found to be associated with LAA stroke risk (OR: 1.69, 95%CI: 1.02-2.86), and this association was more pronounced in smokers, manifesting a 2.73-fold increased risk of LAA stroke (p = 0.027). A joint effect on risk elevation of LAA stroke was seen in those patients with OGG1 and ERCC2 polymorphisms (OR: 2.75, 95%CI: 1.26-6.00). Moreover, among smokers carrying the OGG1 Ser326Cys polymorphism, there was a tendency toward an increased risk of LAA stroke in those patients who had a greater number of high-risk genotypes of XRCC1, ERCC2, and ERCC5 polymorphisms (p trend = 0.010). Conclusion: The susceptible polymorphisms of DNA repair pathway genes may have a modifying effect on the elevated risk of LAA stroke in smokers among ethnic Chinese in Taiwan.


Shyu H.-Y.,Armed Forces Taoyuan General Hospital | Shyu H.-Y.,Institute of Biology and Anatomy | Fong C.-S.,Buddhist Dalin Tzu Chi General Hospital | Fong C.-S.,Tzu Chi University | And 6 more authors.
Clinica Chimica Acta | Year: 2010

Background: γ-Glutamyl carboxylation, a reaction essential for the biosynthesis of vitamin K-dependent coagulation factors, requires the participation of the γ-glutamyl carboxylase (GGCX), vitamin K epoxide reductase (VKORC1), and NAD(P)H:quinone oxidoreductase (NQO1). We evaluated the role of these genotype polymorphisms in patients with large-artery atherosclerotic stroke. Methods: In this hospital-based case-control study, 117 patients who were categorized as having large-artery atherosclerotic stroke and 115 age- and gender-matched controls were recruited. Genotyping determination for the GGCX1 (Gln325Arg), NQO1 (Pro187Ser), and VKORC1 (rs9923231) polymorphisms was performed. The associations of genotype with ischemic stroke (IS) risk were examined. Results: A higher genotypic frequency of NQO1 C609T was found in the controls than in the patients, manifesting a 0.47-fold risk reduction in IS (95% CI=0.25-0.87). A tendency toward a reduced IS risk was statistically significant in those subjects who carried a greater number of the NQO1, GGCX, and VKORC1 polymorphisms (aOR=0.58, P trend=0.005). The synergistic effect of multiple genes on risk reduction was more significant in a subset of patients who were not alcoholics and who were non-smokers (P<0.05). Conclusions: Compartmentation of coagulation factor metabolism may account for the preferential role of NQO1, GGCX, and VKORC1 polymorphisms to lower the risk for large-artery atherosclerotic stroke. © 2010 Elsevier B.V.

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