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Cheng C.-L.,National Taiwan Ocean University | Huang S.-J.,National Taiwan University | Wu C.-L.,Institute of Cellular and Organismic Biology | Gong H.-Y.,National Taiwan Ocean University | And 3 more authors.
Journal of Biomedical Science | Year: 2015

Background: Highly desaturated n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are synthesized by desaturases and elongase. They exert hepatoprotective effects to prevent alcoholic fatty liver syndrome or cholestatic liver injury. However, it is unclear how n-3 PUFAs improve immune function in liver. Vibrio vulnificus, a gram-negative bacterial pathogen, causes high mortality of aquaculture fishes upon infection. Humans can become infected with V. vulnificus through open wounds or by eating raw seafood, and such infections may result in systemic septicemia. Moreover, patients with liver diseases are vulnerable to infection, and are more likely than healthy persons to present with liver inflammation following infection. This study quantified n-3 PUFAs and their anti-bacterial effects in Fadsd6 and Elvol5a transgenic zebrafish. Results: Two transgenic zebrafish strains with strong liver specific expression of Fadsd6 and Elvol5a (driven by the zebrafish Fabp10 promoter) were established using the Tol2 system. Synthesis of n-3 PUFAs in these strains were increased by 2.5-fold as compared to wild type (Wt) fish. The survival rate in 24 h following challenge with V. vulnificus was 20 % in Wt, but 70 % in the transgenic strains. In addition, the bacteria counts in transgenic fish strains were significantly decreased. The expression levels of pro-inflammatory genes, such as TNF-aα, IL-1β, and NF-κB, were suppressed between 9 and 12 h after challenge. This study confirms the anti-bacterial function of n-3 PUFAs in a transgenic zebrafish model. Conclusions: Fadsd6 and Elvol5a transgenic zebrafish are more resistant to V. vulnificus infection, and enhance survival by diminishing the attendant inflammatory response. © 2015 Cheng et al.

Yu C.-Y.,Institute of Cellular and Organismic Biology | Kuo H.-C.,Institute of Cellular and Organismic Biology
Stem Cells | Year: 2016

The trans-spliced noncoding RNA RMST (tsRMST) is an emerging regulatory lncRNA in the human pluripotency circuit. Previously, we found that tsRMST represses lineage-specific transcription factors through the PRC2 complex and NANOG in human pluripotent stem cells (hESCs). Here, we demonstrate that tsRMST also modulates noncanonical Wnt signaling to suppress the epithelial-to-mesenchymal transition (EMT) and in vitro differentiation of embryonic stem cells (ESCs). Our results demonstrate that disruption of tsRMST expression in hESCs results in the upregulation of WNT5A, EMT, and lineage-specific genes/markers. Furthermore, we found that the PKC inhibitors Go6983 and Go6976 inhibited the effects of WNT5A, indicating that WNT5A promotes the EMT and in vitro differentiation although conventional and novel PKC activation in hESCs. Finally, we showed that either antiserum neutralization of WNT5A or Go6983 treatment in tsRMST knockdown cells decreased the expression of mesenchymal and lineage-specific markers. Together, these findings indicate that tsRMST regulates Wnt and EMT signaling pathways in hESCs by repressing WNT5A, which is a potential EMT inducer for promoting in vitro differentiation of hESCs through PKC activation. Our findings provide further insights into the role of trans-spliced RNA and WNT5A in hESC differentiation, in which EMT plays an important role. Stem Cells 2016. © 2016 AlphaMed Press.

Kapoor A.,Institute of Cellular and Organismic Biology | Kapoor A.,National Chung Hsing University | Wang B.-J.,Institute of Cellular and Organismic Biology | Wang B.-J.,National Taiwan University | And 5 more authors.
ACS Chemical Neuroscience | Year: 2013

Retinoic acid (RA)-elicited signaling has been shown to play critical roles in development, organogenesis, and the immune response. RA regulates expression of Alzheimer's disease (AD)-related genes and attenuates amyloid pathology in a transgenic mouse model. In this study, we investigated whether RA can suppress the production of amyloid-β (Aβ) through direct inhibition of γ-secretase activity. We report that RA treatment of cells results in significant inhibition of γ-secretase-mediated processing of the amyloid precursor protein C-terminal fragment APP-C99, compared with DMSO-treated controls. RA-elicited signaling was found to significantly increase accumulation of APP-C99 and decrease production of secreted Aβ40. In addition, RA-induced inhibition of γ-secretase activity was found to be mediated through significant activation of extracellular signal-regulated kinases (ERK1/2). Treatment of cells with the specific ERK inhibitor PD98059 completely abolished RA-mediated inhibition of γ-secretase. Consistent with these findings, RA was observed to inhibit secretase-mediated proteolysis of full-length APP. Finally, we have established that RA inhibits γ-secretase through nuclear retinoic acid receptor-α (RARα) and retinoid X receptor-α (RXRα). Our findings provide a new mechanistic explanation for the neuroprotective role of RA in AD pathology and add to the previous data showing the importance of RA signaling as a target for AD therapy. © 2013 American Chemical Society.

Chi J.R.,University of Taipei | Chi J.R.,Institute of Cellular and Organismic Biology | Chi J.R.,Food Industry Research and Development Institute | Huang C.-W.,National Taiwan Ocean University | And 2 more authors.
Journal of Aquaculture Research and Development | Year: 2014

Hybrid tilapia is a major aquaculture food fish species in developing countries. The development of molecular markers to characterize and trace tilapia species is necessary to improve tilapia quality and enhance the competitive advantage of the aquaculture industry. Microsatellite markers have been suggested to assist breeding, species identification, and traceability system for tilapia. We used six microsatellites markers located within growth-related genes to discriminate between several tilapia species. We found that a combination of two microsatellites markers located within the proximal promoter of the prolactin I (PRL I) gene, PRL I-MS01 and PRL I-MS02, were able to discriminate between five Oreochromis tilapia species (O. mossambicus, O. aureus, O. niloticus, O. hornorum and O. spilurus) and two O. niloticus strains that exhibit the distinctive growth traits. Furthermore, we found that PRL I-MS01 microsatellite marker was able to trace parental origin of hybrid tilapia. Thus, this marker is a potentially beneficial tool for a tilapia traceability system. We conclude that the GT tandem repeats in PRL I-MS01 and CA tandem repeats in PRL I-MS02 are useful genetic markers to characterize diverse tilapia species, assist in the genetic tracing and conventional breeding of superior strains and strengthen the management of the tilapia aquaculture industry. There was strong relationship between the cold and both temperature at death and cumulative degree hours represented by negative correlation coefficient for all tested fish. There was no correlation between cold tolerance and fish size for all tested fish. The cooling degree hours were significantly different between the selected and non-selected O. niloticus (P<0.005). The selected O. aureus exhibited greater cold tolerance than the non-selected and death began at 14.1°C, while non-selected occurred at 15.2°C. © 2014 Chi JR, et al.

Huang H.-P.,National Taiwan University Hospital | Chen P.-H.,Institute of Cellular and Organismic Biology | Chen P.-H.,A-Life Medical | Hwu W.-L.,National Taiwan University Hospital | And 13 more authors.
Human Molecular Genetics | Year: 2011

Pompe disease is caused by autosomal recessive mutations in the acid alpha-glucosidase (GAA) gene, which encodes GAA. Although enzyme replacement therapy has recently improved patient survival greatly, the results in skeletal muscles and for advanced disease are still not satisfactory. Here, we report the derivation of Pompe disease-induced pluripotent stem cells (PomD-iPSCs) from two patients with different GAA mutations and their potential for pathogenesis modeling, drug testing and disease marker identification. PomD-iPSCs maintained pluripotent features and had low GAA activity and high glycogen content. Cardiomyocyte-like cells (CMLCs) differentiated from PomD-iPSCs recapitulated the hallmark Pompe disease pathophysiological phenotypes, including high levels of glycogen and multiple ultrastructural aberrances. Drug rescue assessment showed that exposure of PomD-iPSC-derived CMLCs to recombinant human GAA reversed the major pathologic phenotypes. Furthermore, l-carnitine treatment reduced defective cellular respiration in the diseased cells. By comparative transcriptome analysis, we identified glycogen metabolism, lysosome and mitochondria-related marker genes whose expression robustly correlated with the therapeutic effect of drug treatment in PomD-iPSC-derived CMLCs. Collectively, these results demonstrate that PomD-iPSCs are a promising in vitro disease model for the development of novel therapeutic strategies for Pompe disease. © The Author 2011. Published by Oxford University Press. All rights reserved.

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