Browsing by Author "Lin, Kuan-Hao"

Now showing 1 - 4 of 4

Differences in texture evolution from low-entropy to high-entropy face-centered cubic alloys during tension test
(2020-03-01)
Lin, Kuan-Hao
;
Chang, Shou-Yi
;
Lo, Yu-Chieh
;
Wang, Chun-Chieh
;
Lin, Su-Jien
Texture evolution during tension test was investigated on three face-centered cubic (FCC) metals, namely, Ni (unary), equiatomic CrFeNi (ternary), and equiatomic CoCrFeMnNi (quinary) with small and large grain sizes of similar to 20 and similar to 100 mu m, respectively. The microtextures for 18%, 36% and 54% engineering strains of a tension-interrupted specimen were characterized on the same area. The three metals exhibited a similar texture evolution, which the fraction of {001}//ND remains constant However, the fraction of {011}//ND decreases, whereas that of {111}//ND increases. On the other hand, the fraction of <001>//RD also remains constant, that of <011>//RD decreases, and that of <111>//RD increases. However, the several differences still were found during plastic deformation. Fine-grained Ni initiated a significantly crystallographic rotation (CRo) at the lower strain, increased with strain and then remained nearly unchanged as strain was higher than 18%. Coarse-grained Ni delayed this rotation and slowly developed the trend at large strains. As for CrFeNi, the comparison between fine-grained and coarse-grained structure does not have obvious difference. As for fine-grained CoCrFeMnNi, it can be seen that an obvious CRo develops under 36% strain, and maintains constant over 36% strain. But the coarse-grained CoCrFeMnNi reveals that the significant CRo develops continuously from 0% to 54% strain. The mechanisms for the effects of number of element and grain size in the present study are elucidated.
Identification of Novel Anti-Liver Cancer Small Molecules with Better Therapeutic Index Than Sorafenib via Zebrafish Drug Screening Platform
(2019-06-01)
Lin, Han-Syuan
;
Huang, Yi-Luen
;
Wang, Yi-Rui Stefanie
;
Hsiao, Eugene
;
Hsu, Tsu-An
Hepatocellular carcinoma (HCC) ranks as the fourth leading cause of cancer-related deaths worldwide. Sorafenib was the only U.S. Food and Drug Administration (FDA) approved drug for treating advanced HCC until recently, so development of new target therapy is urgently needed. In this study, we established a zebrafish drug screening platform and compared the therapeutic effects of two multiple tyrosine kinase inhibitors, 419S1 and 420S1, with Sorafenib. All three compounds exhibited anti-angiogenesis abilities in immersedflil:EGFP transgenic embryos and the half inhibition concentration (IC50) was determined. 419S1 exhibited lower hepatoxicity and embryonic toxicity than 420S1 and Sorafenib, and the half lethal concentration (LC50) was determined. The therapeutic index (LC50/IC50) for 419S1 was much higher than for Sorafenib and 420S1. The compounds were either injected retro-orbitally or by oral gavage to adult transgenic zebrafish with HCC. The compounds not only rescued the pathological feature, but also reversed the expression levels of cell-cycle-related genes and protein levels of a proliferation marker. Using a patient-derived-xenograft assay, we found that the effectiveness of 419S1 and 420S1 in preventing liver cancer proliferation is better than that of Sorafenib. With integrated efforts and the advantage of the zebrafish platform, we can find more effective and safe drugs for HCC treatment and screen for personalized medicine.
Low Molecular Weight Fucoidan Prevents Radiation-Induced Fibrosis and Secondary Tumors in a Zebrafish Model
(2020-06-01)
Wu, Szu-Yuan
;
Yang, Wan-Yu
;
Cheng, Chun-Chia
;
Hsiao, Ming-Chen
;
Tsai, Shin-Lin
Radiotherapy often causes unwanted side effects such as radiation-induced fibrosis and second malignancies. Fucoidan, a sulfated polysaccharide extracted from brown seaweed, has many biological effects including anti-inflammation and anti-tumor. In the present study, we investigated the radioprotective effect of Oligo-Fucoidan (OF) using a zebrafish animal model. Adult zebrafish of wild-type and transgenic fish with hepatocellular carcinoma were orally fed with Oligo-Fucoidan before irradiation. Quantitative PCR, Sirius red stain, hematoxylin, and eosin stain were used for molecular and pathological analysis. Whole genomic microarrays were used to discover the global program of gene expression after Oligo-Fucoidan treatment and identified distinct classes of up- and downregulated genes/pathways during this process. Using Oligo-Fucoidan oral gavage in adult wild-type zebrafish, we found Oligo-Fucoidan pretreatment decreased irradiation-induced fibrosis in hepatocyte. Using hepatitis B virus X antigen (HBx), Src and HBx, Src, p53-/+ transgenic zebrafish liver cancer model, we found that Oligo-Fucoidan pretreatment before irradiation could lower the expression of lipogenic factors and enzymes, fibrosis, and cell cycle/proliferation markers, which eventually reduced formation of liver cancer compared to irradiation alone. Gene ontology analysis revealed that Oligo-Fucoidan pretreatment increased the expression of genes involved in oxidoreductase activity in zebrafish irradiation. Oligo-Fucoidan also decreased the expression of genes involved in transferase activity in wild-type fish without irradiation (WT), nuclear outer membrane-endoplasmic reticulum membrane network, and non-homologous end-joining (NHEJ) in hepatocellular carcinoma (HCC) transgenic fish. Rescue of those genes can prevent liver cancer formation. Conclusions: Our results provide evidence for the ability of Oligo-Fucoidan to prevent radiation-induced fibrosis and second malignancies in zebrafish.
Transcriptomically Revealed Oligo-Fucoidan Enhances the Immune System and Protects Hepatocytes via the ASGPR/STAT3/HNF4A Axis
(2020-06-01)
Cheng, Chun-Chia
;
Yang, Wan-Yu
;
Hsiao, Ming-Chen
;
Lin, Kuan-Hao
;
Lee, Hao-Wei
Oligo-fucoidan, a sulfated polysaccharide extracted from brown seaweed, exhibits anti-inflammatory and anti-tumor effects. However, the knowledge concerning the detailed mechanism of oligo-fucoidan on liver cells is obscure. In this study, we investigate the effect of oligo-fucoidan in normal hepatocytes by transcriptomic analysis. Using an oligo-fucoidan oral gavage in wild-type adult zebrafish, we find that oligo-fucoidan pretreatment enhances the immune system and anti-viral genes in hepatocytes. Oligo-fucoidan pretreatment also decreases the expression of lipogenic enzymes and liver fibrosis genes. Using pathway analysis, we identify hepatocyte nuclear factor 4 alpha (HNF4A) to be the potential driver gene. We further investigate whether hepatocyte nuclear factor 4 alpha (HNF4A) could be induced by oligo-fucoidan and the underlying mechanism. Therefore, a normal hepatocyte clone 9 cell as an in vitro model was used. We demonstrate that oligo-fucoidan increases cell viability, Cyp3a4 activity, and Hnf4a expression in clone 9 cells. We further demonstrate that oligo-fucoidan might bind to asialoglycoprotein receptors (ASGPR) in normal hepatocytes through both in vitro and in vivo competition assays. This binding, consequently activating the signal transducer and activator of transcription 3 (STAT3), increases the expression of the P1 isoform of HNF4A. According to our data, we suggest that oligo-fucoidan not only enhances the gene expression associated with anti-viral ability and immunity, but also increases P1-HNF4A levels through ASGPR/STAT3 axis, resulting in protecting hepatocytes.