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      • The HCV-Associated Hepatocarcinogenesis in Intracellular Low Viral Load Cells

        ( Chia-yen Dai ),( Shu-chi Wang ),( Chung-feng Huang ),( Wang-long Chung ),( Ming-lung Yu ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

        Aims: There are differential viral load distribution in HCV infected liver tissues. We conduct the present study aimed to dissect the different viral load cells to investigate the viral-host resistance on the HCV asssoicated hepatocarcinogenesis. Methods: The study was performed using a replicated in vitro HCV-fluorescence infection model to discuss HCV-high viral load (HVL) cells and the HCV-low viral load (LVL) cells by Flow sort system. The next generation RNA sequence and miRNA array were used to explore the gene profiles and miRNA expression on different HCV-viral load cell populations. Results: The ROS indicator shows that the ROS abundantly in low viral load cells. The RNA-Seq analysis showed that significant enrichment in Cancer (P=5.00E-02 - 2.76E-04; 40 molecules) and a network of the Cellular Movement, Immune Cell Trafficking, Inflammatory Response (Score: 18) by IPA analysis. Protein analysis results confirmed the GADD45A and iNOS overexpression in the LVL cells which verified the oxidative stress qPCR array data in LVL cells. We also found the up-regulated Src oncoprotein expression and down-regulated E-cadherin expression in LVL cells. The miRNA array showed that miR-194, miR-192/215 and miR-10a were preferentially expressed in low viral load cells. Conclusions: With our established cell sorting system, this study provided the gene network between viral and host cells resistance by different viral load cells. The findings show the activated oxidative stress related-gene expression in hepatocytes is associated with the HCV-infected epithelial-to-mesenchymal transition (EMT), providing an important link between HCV viral load and liver cancer. The miRNA-gene intergraded dada need further studies.

      • The Different Expression of Gene Profiles on Hepatocellular Carcinoma Cells with Different Intracellular Hepatitis C Viral Load

        ( Chia-yen Dai ),( Shu-chi Wang ),( Meng-hsuan Hsieh ),( Cheng-fu Yang ),( Ching-i Huang ),( Chung-feng Huang ),( Ming-lun Yeh ),( Jee-fu Huang ),( Wang-long Chung ),( Ming-lung Yu ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

        Aims: The different hepatitis C virus (HCV) replication has been reported among individual hepatocytes in chronic HCV infection by identifying hepatocytes with different HCV RNA levels. We have previously established a fluorescence-activated cell sorting (FACS) protocol to study the effects of different intracellular viral loads in HCV-infected cells. The present study aimed to further study the gene expression on different hepatocellular carcinoma (HCC) cells with different HCV viral load. Methods: The JFH1-EYFP viral florescence intensity was used to sort the high and low viral load cells after 5 days infection in vitro which has been shown in our previous study that infected cells efficiently and accurately discriminated between high- and low-viral load cell populations. The next generation sequence-RNA sequence was used to clarify the mRNA and miRNA gene network between HCV-high and HCV-low infected cells of the HCC cell line. Venn diagram summarizing the probe sets that were differentially expressingbetween the Huh7.5.1 versus each differential viral load cell population and miRDB and miRTar databases were used to predict HVL and LVL/S2 unique miRNA target genes. Results: By analyzing the NGS dataset and miRNA microarray dataset, of the significant transcripts, three miRNA were unique for the LVL/S2 cells and nine miRNA unique for the HVL. Twenty-three miRNA were common for all 3 viral load groups. We verified them by q-PCR and data confirmed the array data expression level. We found that high viral loads were associated with cell inflammation- and cell death-associated pathway; and the low viral loads were associated many stress response- and cell adhesion molecular (CAMs)-related genes. Conclusions: With the established cell sorting protocol, we have demonstrated that different gene network between HCV-high and HCV-low infected cells in JFH1-EYFP infectious cells exists. Our results may provide a boarder gene regulation map between high and low viral load cell populations.

      • THE EFFECT OF RESTAURANT INNOVATIVENESS ON CUSTOMER ADVOCACY

        Chang-Hua Yen,Hui-Hsuan Yen,Shu-Chin Wu,Ko-Yu Chang 글로벌지식마케팅경영학회 2023 Global Marketing Conference Vol.2023 No.07

        This study supplements the literature by determining how restaurant innovativeness is linked to customer advocacy as well as considering self-image congruity as mediator of this relationship. A questionnaire survey of 385 restaurant customers was conducted in Taiwan. The results indicated that restaurant innovativeness is positively related to customers’ self-image congruity and customer advocacy. Customers’ self-image congruity is positively associated with customer advocacy. In addition, self-image congruity mediates the relationship between restaurant innovativeness and customer advocacy. The research contributes to literature by extend the relationships between restaurant innovativeness, self-image congruity, and customer advocacy. Restaurant managers should adopt approaches (e.g. innovativeness-related activities) for enhancing self-image congruity in customers.

      • THE EFFECT OF RESTAURANT INNOVATIVENESS ON CUSTOMER ADVOCACY

        Chang-Hua Yen,Hui-Hsuan Yen,Shu-Chin Wu,Ko-Yu Chang 글로벌지식마케팅경영학회 2023 Global Marketing Conference Vol.2023 No.07

        This study supplements the literature by determining how restaurant innovativeness is linked to customer advocacy as well as considering self-image congruity as mediator of this relationship. A questionnaire survey of 385 restaurant customers was conducted in Taiwan. The results indicated that restaurant innovativeness is positively related to customers’ self-image congruity and customer advocacy. Customers’ self-image congruity is positively associated with customer advocacy. In addition, self-image congruity mediates the relationship between restaurant innovativeness and customer advocacy. The research contributes to literature by extend the relationships between restaurant innovativeness, self-image congruity, and customer advocacy. Restaurant managers should adopt approaches (e.g. innovativeness-related activities) for enhancing self-image congruity in customers.

      • KCI등재

        Epidemiological trend in inflammatory bowel disease in Taiwan from 2001 to 2015: a nationwide population-based study

        Hsu-Heng Yen,Meng-Tzu Weng,Chien-Chih Tung,Yu-Ting Wang,Yuan Ting Chang,Chin-Hao Chang,Ming-Jium Shieh,Jau-Min Wong,Shu-Chen Wei 대한장연구학회 2019 Intestinal Research Vol.17 No.1

        Background/Aims: Incidences of inflammatory bowel disease (IBD), ulcerative colitis (UC), and Crohn’s disease (CD), havebeen increasing in Asia. In this study, we report the relevant clinical characteristics and determined the epidemiological trend ofIBD in Taiwan from 2001 to 2015. Methods: A retrospective study was conducted to analyze data recorded from January 2001through December 2015 in the registered database compiled by the National Health Insurance and provided by the Ministry ofHealth and Welfare, Taiwan. Results: A total of 3,806 patients with catastrophic IBD illness were registered from 2001 to 2015 inTaiwan (CD, 919; UC, 2,887). The crude incidence of CD increased from 0.17/100,000 in 2001 to 0.47/100,000 in 2015, whereasthat of UC increased from 0.54/100,000 in 2001 to 0.95/100,000 in 2015. The prevalence of CD increased from 0.6/100,000 in2001 to 3.9/100,000 in 2015, whereas that of UC increased from 2.1/100,000 in 2001 to 12.8/100,000 in 2015. The male-to-femaleratio in the study sample was 2.19 for CD and 1.62 for UC. The median age of those registered with CD was lower than that ofthose registered for UC: 38.86 and 44.86 years, respectively. A significantly greater increase in CD incidence rate was identifiedamong 20 to 39-year-old compared with other age groups. Conclusions: Using Taiwan’s nationwide insurance database, we determinedthat the number of patients with CD increased more rapidly during the study period than the number of patients withUC, especially among age 20 to 39-year-old, resulting in a decreased UC-to-CD ratio. (Intest Res 2019;17:54-62)

      • KCI등재

        Impact of microbiota in colorectal carcinogenesis: lessons from experimental models

        Linda Chia-Hui Yu,Shu-Chen Wei,Yen-Hsuan Ni 대한장연구학회 2018 Intestinal Research Vol.16 No.3

        A role of gut microbiota in colorectal cancer (CRC) growth was first suggested in germ-free rats almost 50 years ago, and the existence of disease-associated bacteria (termed pathobionts) had becoming increasingly evident from experimental data of fecal transplantation, and microbial gavage or monoassociation. Altered bacterial compositions in fecal and mucosal specimens were observed in CRC patients compared to healthy subjects. Microbial fluctuations were found at various cancer stages; an increase of bacterial diversity was noted in the adenoma specimens, while a reduction of bacterial richness was documented in CRC samples. The bacterial species enriched in the human cancerous tissues included Escherichia coli, Fusobacterium nucleatum, and enterotoxigenic Bacteroides fragilis. The causal relationship of gut bacteria in tumorigenesis was established by introducing particular bacterial strains in in situ mouse CRC models. Detailed experimental protocols of bacterial gavage and the advantages and caveats of different experimental models are summarized in this review. The microbial genotoxins, enterotoxins, and virulence factors implicated in the mechanisms of bacteria-driven tumorigenesis are described. In conclusion, intestinal microbiota is involved in colon tumorigenesis. Bacteria-targeting intervention would be the next challenge for CRC.

      • KCI등재

        Evaluation of Malignancy Risk of Ampullary Tumors Detected by Endoscopy Using 2-[18F]FDG PET/CT

        Chuang Pei-Ju,Wang Hsiu-Po,Tien Yu-Wen,Chin Wei-Shan,Hsieh Min-Shu,Chen Chieh-Chang,Hong Tzu-Chan,Ko Chi-Lun,Wu Yen-Wen,Cheng Mei-Fang 대한영상의학회 2024 Korean Journal of Radiology Vol.25 No.3

        Objective: We aimed to investigate whether 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) can aid in evaluating the risk of malignancy in ampullary tumors detected by endoscopy. Materials and Methods: This single-center retrospective cohort study analyzed 155 patients (79 male, 76 female; mean age, 65.7 ± 12.7 years) receiving 2-[18F]FDG PET/CT for endoscopy-detected ampullary tumors 5–87 days (median, 7 days) after the diagnostic endoscopy between June 2007 and December 2020. The final diagnosis was made based on histopathological findings. The PET imaging parameters were compared with clinical data and endoscopic features. A model to predict the risk of malignancy, based on PET, endoscopy, and clinical findings, was generated and validated using multivariable logistic regression analysis and an additional bootstrapping method. The final model was compared with standard endoscopy for the diagnosis of ampullary cancer using the DeLong test. Results: The mean tumor size was 17.1 ± 7.7 mm. Sixty-four (41.3%) tumors were benign, and 91 (58.7%) were malignant. Univariable analysis found that ampullary neoplasms with a blood-pool corrected peak standardized uptake value in earlyphase scan (SUVe) ≥ 1.7 were more likely to be malignant (odds ratio [OR], 16.06; 95% confidence interval [CI], 7.13–36.18; P < 0.001). Multivariable analysis identified the presence of jaundice (adjusted OR [aOR], 4.89; 95% CI, 1.80–13.33; P = 0.002), malignant traits in endoscopy (aOR, 6.80; 95% CI, 2.41–19.20; P < 0.001), SUVe ≥ 1.7 in PET (aOR, 5.43; 95% CI, 2.00–14.72; P < 0.001), and PET-detected nodal disease (aOR, 5.03; 95% CI, 1.16–21.86; P = 0.041) as independent predictors of malignancy. The model combining these four factors predicted ampullary cancers better than endoscopic diagnosis alone (area under the curve [AUC] and 95% CI: 0.925 [0.874–0.956] vs. 0.815 [0.732–0.873], P < 0.001). The model demonstrated an AUC of 0.921 (95% CI, 0.816–0.967) in candidates for endoscopic papillectomy. Conclusion: Adding 2-[18F]FDG PET/CT to endoscopy can improve the diagnosis of ampullary cancer and may help refine therapeutic decision-making, particularly when contemplating endoscopic papillectomy.

      • The Immunotyping Distribution of Serum Monoclonal Paraprotein and Environmental Impact on Multiple Myeloma (MM) and Monoclonal Gammopathy of Uncertain Significance (MGUS) in Taiwan: A Medical Center-Based Experience

        Chang, Chih-Chun,Su, Ming-Jang,Lee, Shu-Jene,Tsai, Yu-Hui,Kuo, Lin-Yin,Lin, I-Hsin,Huang, Hui-Ling,Yen, Tzung-Hai,Chu, Fang-Yeh Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.1

        Background: Whether ambient exposure to environmental pollutants leads to hematopoietic malignancies such as multiple myeloma (MM) remains to be ascertained. Therefore, we aimed to investigate the immunotyping distribution of serum monoclonal paraprotein and the environmental influence on MM and monoclonal gammopathy of uncertain significance (MGUS) in the Taiwanese population. Materials and Methods: Serum protein electrophoresis with immunosubtraction by the capillary zone electrophoresis method was performed as primary screening for MM and MGUS. Clinical, pathological, and residence data of patients were also obtained. Results: From August, 2013 to June, 2015, a total of 327 patients underwent serum protein electrophoresis with immunosubtraction. Among these, 281 demonstrated no remarkable findings or non-malignant oligoclonal gammopathy, 23 were detected to have MGUS, 18 were identified as MM, and a further 5 were found as other malignancies. The most frequent immunotyping distribution of serum monoclonal paraprotein was IgG kappa (54.3%, n=25), followed by IgA lambda (15.2%, n=7) and IgG lambda (10.9%, n=5) in subjects with gammopathy. Additionally, it was shown that the elderly (OR: 4.61, 95% CI: 1.88-11.30, P<0.01) and males (OR: 2.04, 95% CI: 1.04-4.02, P=0.04) had significantly higher risk of developing MM and MGUS. There was no obvious impact of environmental factors on the health risk of MM and MGUS evolution (OR: 0.77, 95% CI: 0.40-1.50, P=0.49). Conclusions: The most frequent immunotyping distribution of serum monoclonal paraprotein included IgG kappa, IgA lambda and IgG lambda in MM and MGUS in the Taiwanese population. The elderly and male subjects are at significantly higher risk of MM and MGUS development, but there was no obvious impact of environmental factors on risk.

      • KCI등재

        Dextromethorphan Protect the Valproic Acid Induced Downregulation of Neutrophils in Patients with Bipolar Disorder

        Ru-Band Lu,Yun-Hsuan Chang,Sheng-Yu Lee,Tzu-Yun Wang,Shu-Li Cheng,Po See Chen,Yen Kuang Yang,Jau-Shyong Hong,Shiou-Lan Chen 대한정신약물학회 2020 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.18 No.1

        Objective: Valproic acid (VPA) is an anticonvulsant and commonly long term used as a mood stabilizer for patients with mood disorders. However its chronic effects on the hematological changes were noticed and need to be further evaluated. In this study, we evaluated, in Taiwanese Han Chinese patients with bipolar disorders (BD), the chronic effects of VPA or VPA plus dextromethorphan (DM) on the hematological molecules (white blood cell [WBCs], red blood cells [RBCs], hemoglobin, hematocrit, and platelets). Methods: In a 12-week, randomized, double-blind study, we randomly assigned BD patients to one of three groups: VPA plus either placebo (VPA+P, n = 57) or DM (30 mg/day, VPA+DM30, n = 56) or 60 mg/day (VPA+DM60, n = 53). The Young Mania Rating Scale and Hamilton Depression Rating Scale were used to evaluate symptom severity, and the hematological molecules were checked. Results: Paired t test showed that the WBC, neutrophils, platelets and RBCs were significantly lowered after 12 weeks of VPA+P or VPA+DM30 treatment. VPA+DM60 represented the protective effects in the WBCs, neutrophils, and RBCs but not in the platelets. We further calculated the changes of each hematological molecules after 12 weeks treatment. We found that combination use of DM60 significantly improved the decline in neutrophils induced by the long-term VPA treatment. Conclusion: Hematological molecule levels were lower after long-term treatment with VPA. VPA+DM60, which yielded the protective effect in hematological change, especially in the neutrophil counts. Thus, DM might be adjunct therapy for maintaining hematological molecules in VPA treatment.

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