Browsing by Author "Chen, Chun-Ming"

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A visual observation of the air flow pattern for the high speed nozzle applicable to high power laser cutting and welding
(2013-12-01)
Tseng, Chi-Shan
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Chen, Chun-Ming
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Wang, Chi-Chuan
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工學院
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College of Engineering
In this study, the flow pattern and pressure variation of the nozzles applicable to high power laser cutting and welding were studied. A total of five nozzles are made and tested with nozzle diameter ranging from 0.8 to 4 mm. The depth of focus and the width of focus are measured based on the flow visualization. It is found that the depth of focus is increased with the rise of exit Mach number while the width of focus is increased with the nozzle diameter. The visual results indicate that the supersonic nozzle reveals a more concentrated jet flow pattern even the flow has passed through the depth of focus. On the other hand, appreciate deviation of the flow pattern is observed for the subsonic nozzle after the depth of focus. As far as more concentrated air flow pattern is concerned, a supersonic nozzle with an exit diameter less than 3.0 mm is recommended. The total pressure decreasing tremendously with the exit Mach number is encountered while moderate decline of the static and dynamic pressure for supersonic nozzles is seen. However, its corresponding dynamic pressure is still higher than that of the subsonic nozzle. (C) 2013 Elsevier Ltd. All rights reserved.
DDX3 Represses Stemness by Epigenetically Modulating Tumor-suppressive miRNAs in Hepatocellular Carcinoma
(2016-06-27)
Li, Hao-Kang
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Mai, Ru-Tsun
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Huang, Hsien-Da
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Chou, Chih-Hung
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Chang, Yi-An
Studies indicate that the presence of cancer stem cells (CSCs) is responsible for poor prognosis of hepatocellular carcinoma (HCC) patients. In this study, the functional role of DDX3 in regulation of hepatic CSCs was investigated. Our results demonstrated that reduced DDX3 expression was not only inversely associated with tumor grade, but also predicted poor prognosis of HCC patients. Knockdown of DDX3 in HCC cell line HepG2 induced stemness gene signature followed by occurrence of self-renewal, chemoreisistance, EMT, migration as well as CSC expansion, and most importantly, DDX3 knockdown promotes tumorigenesis. Moreover, we found positive correlations between DDX3 level and expressions of tumor-suppressive miR-200b, miR-200c, miR-122 and miR-145, but not miR-10b and miR-519a, implying their involvement in DDX3 knockdown-induced CSC phenotypes. In addition, DDX3 reduction promoted up-regulation of DNA methyltransferase 3A (DNMT3A), while neither DNMT3B nor DNMT1 expression was affected. Enriched DNMT3A binding along with hypermethylation on promoters of these tumor-suppressive miRNAs reflected their transcriptional repressions in DDX3-knockdown cells. Furthermore, individual restoration of these tumor-suppressive miRNAs represses DDX3 knockdown-induced CSC phenotypes. In conclusion, our study suggested that DDX3 prevents generation of CSCs through epigenetically regulating a subset of tumor-suppressive miRNAs expressions, which strengthens tumor suppressor role of DDX3 in HCC.
DNA Damage, Liver Injury, and Tumorigenesis: Consequences of DDX3X Loss
(2019-02-01)
Chan, Chieh-Hsiang
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Chen, Chun-Ming
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Lee, Yan-Hwa Wu
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You, Li-Ru
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交大名義發表
The pleiotropic roles of DEAD-box helicase 3, X-linked (DDX3X), including its functions in transcriptional and translational regulation, chromosome segregation, DNA damage, and cell growth control, have highlighted the association between DDX3X and tumorigenesis. However, mRNA transcripts and protein levels of DDX3X in patient specimens have shown the controversial correlations of DDX3X with hepatocellular carcinoma (HCC) prevalence. In this study, generation of hepatocyte-specific Ddx3x-knockout mice revealed that loss of Ddx3x facilitates liver tumorigenesis. Loss of Ddx3x led to profound ductular reactions, cell apoptosis, and compensatory proliferation in female mutants at 6 weeks of age. The sustained phosphorylation of histone H2AX (gamma H2AX) and significant accumulation of DNA single-strand breaks and double-strand breaks in liver indicated that the replicative stress occurred in female mutants. Further chromatin immunoprecipitation analyses demonstrated that DDX3X bound to promoter regions and regulated the expression of DNA repair factors, DDB2 and XPA, to maintain genome stability. Loss of Ddx3x led to decreased levels of DNA repair factors, which contributed to an accumulation of unrepaired DNA damage, replication stress, and eventually, spontaneous liver tumors and DEN-induced HCCs in Alb-Cre/+Ddx3xflox/flox mice. Implications: These data identify an important role of DDX3X in the regulation of DNA damage repair to protect against replication stress in liver and HCC development and progression.
MicroRNA-122, a Tumor Suppressor MicroRNA that Regulates Intrahepatic Metastasis of Hepatocellular Carcinoma
(2009-05-01)
Tsai, Wei-Chih
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Hsu, Paul Wei-Che
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Lai, Tsung-Ching
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Chau, Gar-Yang
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Lin, Ching-Wen
MicroRNAs (miRNAs), which are inhibitors of gene expression, participate in diverse biological functions and in carcinogenesis. In this study, we show that liver-specific microRNA-122 (miR-122) is significantly down-regulated in liver cancers with intrahepatic metastastasis and negatively regulates tumorigenesis. Restoration of miR-122 in metastatic Mahlavu and SK-HEP-1 cells significantly reduced in vitro migration, invasion, and anchorage-independent growth as well as in vivo tumorigenesis, angiogenesis, and intrahepatic metastasis in an orthotopic liver cancer model. Because an inverse expression pattern is often present between an miRNA and its target genes, we used a computational approach and identified multiple miR-122 candidate target genes from two independent expression microarray datasets. Thirty-two target genes were empirically verified, and this group of genes was enriched with genes regulating cell movement, cell morphology, cell-cell signaling, and transcription. We further showed that one of the miR-122 targets, ADAM17 (a disintegrin and metalloprotease 17) is involved in metastasis. Silencing of ADAM17 resulted in a dramatic reduction of in vitro migration, invasion, in vivo tumorigenesis, angiogenesis, and local invasion in the livers of nude mice, which is similar to that which occurs with the restoration of miR-122. Conclusion: Our study suggests that miR-122, a tumor suppressor microRNA affecting hepatocellular carcinoma intrahepatic metastasis by angiogenesis suppression, exerts some of its action via regulation of ADAM17. Restoration of miR-122 has a far-reaching effect on the cell. Using the concomitant down-regulation of its targets, including ADAM17, a rational therapeutic strategy based on miR-122 may prove to be beneficial for patients with hepatocellular carcinoma. (HEPATOLOGY 2009;49:1571-1582.)
Targeted inactivation of murine Ddx3x: essential roles of Ddx3x in placentation and embryogenesis
(2016-07-15)
Chen, Chia-Yu
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Chan, Chieh-Hsiang
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Chen, Chun-Ming
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Tsai, Yin-Shuan
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Tsai, Tsung-Yuan
The X-linked DEAD-box RNA helicase DDX3 (DDX3X) is a multifunctional protein that has been implicated in gene regulation, cell cycle control, apoptosis, and tumorigenesis. However, the precise physiological function of Ddx3x during development remains unknown. Here, we show that loss of Ddx3x results in an early post-implantation lethality in male mice. The size of the epiblast marked by Oct3/4 is dramatically reduced in embryonic day 6.5 (E6.5) Ddx3x(-)/Y embryos. Preferential paternal X chromosome inactivation (XCI) in extraembryonic tissues of Ddx3x heterozygous (Ddx3x(-/+)) female mice with a maternally inherited null allele leads to placental abnormalities and embryonic lethality during development. In the embryonic tissues, Ddx3x exhibits developmental-and tissue-specific differences in escape from XCI. Targeted Ddx3x ablation in the epiblast leads to widespread apoptosis and abnormal growth, which causes embryonic lethality in the Sox2-cre/+; Ddx3x(flox)/Y mutant around E11.5. The observation of significant increases in gamma H2AX and p-p53(Ser15) indicates DNA damage, which suggests that loss of Ddx3x leads to higher levels of genome damage. Significant upregulation of p21(WAF1/Cip1) and p15(Ink4b) results in cell cycle arrest and apoptosis in Ddx3x-deficient cells. These results have uncovered that mouse Ddx3x is essential for both embryo and extraembryonic development.
Targeted inactivation of murine Ddx3x: essential roles of Ddx3x in placentation and embryogenesis
(2016-07-15)
Chen, Chia-Yu
;
Chan, Chieh-Hsiang
;
Chen, Chun-Ming
;
Tsai, Yin-Shuan
;
Tsai, Tsung-Yuan
The X-linked DEAD-box RNA helicase DDX3 (DDX3X) is a multifunctional protein that has been implicated in gene regulation, cell cycle control, apoptosis, and tumorigenesis. However, the precise physiological function of Ddx3x during development remains unknown. Here, we show that loss of Ddx3x results in an early post-implantation lethality in male mice. The size of the epiblast marked by Oct3/4 is dramatically reduced in embryonic day 6.5 (E6.5) Ddx3x(-)/Y embryos. Preferential paternal X chromosome inactivation (XCI) in extraembryonic tissues of Ddx3x heterozygous (Ddx3x(-/+)) female mice with a maternally inherited null allele leads to placental abnormalities and embryonic lethality during development. In the embryonic tissues, Ddx3x exhibits developmental-and tissue-specific differences in escape from XCI. Targeted Ddx3x ablation in the epiblast leads to widespread apoptosis and abnormal growth, which causes embryonic lethality in the Sox2-cre/+; Ddx3x(flox)/Y mutant around E11.5. The observation of significant increases in gamma H2AX and p-p53(Ser15) indicates DNA damage, which suggests that loss of Ddx3x leads to higher levels of genome damage. Significant upregulation of p21(WAF1/Cip1) and p15(Ink4b) results in cell cycle arrest and apoptosis in Ddx3x-deficient cells. These results have uncovered that mouse Ddx3x is essential for both embryo and extraembryonic development.
VBM reveals brain volume differences between Parkinson's disease and essential tremor patients
(2013-06-14)
Lin, Ching-Hung
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Chen, Chun-Ming
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Lu, Ming-Kuei
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Tsai, Chon-Haw
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Chiou, Jin-Chern
Symptoms of essential tremor (ET) are similar to those of Parkinsons disease (PD) during their initial stages. Presently, there are few stable biomarkers available on a neuroanatomical level for distinguishing between these two diseases. However, few investigations have directly compared the changes in brain volume and assessed the compensatory effects of a change in the parts of the brain associated with PD and with ET. To determine the compensatory and/or degenerative anatomical changes in the brains of PD and ET patients, the present study tested, via two voxel-based morphometry (VBM) approaches (Basic vs. DARTEL VBM processing), the anatomical brain images of 10 PD and 10 ET patients, as well as of 13 age-matched normal controls, obtained through a 3T magnetic resonance scanner. These findings indicate that PD and ET caused specific patterns of brain volume alterations in the brains examined. In addition, our observations also revealed compensatory effects, or self-reorganization, occurring in the thalamus and the middle temporal gyrus in the PD and ET patients, due perhaps in part to the enhanced thalamocortical sensorimotor interaction and the head-eye position readjustment, respectively, in these PD and ET patients. Such a distinction may lend itself to use as a biomarker for differentiating between these two diseases.