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      • KCI등재

        Cis-3-O-p-hydroxycinnamoyl Ursolic Acid Induced ROS-Dependent p53-Mediated Mitochondrial Apoptosis in Oral Cancer Cells

        Ching-Ying Wang,Chen-Sheng Lin,Chun-Hung Hua,Yu-Jen Jou,Chi-Ren Liao,Yuan-Shiun Chang,Lei Wan,Su-Hua Huang,Mann-Jen Hour,Cheng-Wen Lin 한국응용약물학회 2019 Biomolecules & Therapeutics(구 응용약물학회지) Vol.27 No.1

        Cis-3-O-p-hydroxycinnamoyl ursolic acid (HCUA), a triterpenoid compound, was purified from Elaeagnus oldhamii Maxim. This traditional medicinal plant has been used for treating rheumatoid arthritis and lung disorders as well as for its anti-inflammation and anticancer activities. This study aimed to investigate the anti-proliferative and apoptotic-inducing activities of HCUA in oral cancer cells. HCUA exhibited anti-proliferative activity in oral cancer cell lines (Ca9-22 and SAS cells), but not in normal oral fibroblasts. The inhibitory concentration of HCUA that resulted in 50% viability was 24.0 μM and 17.8 μM for Ca9-22 and SAS cells, respectively. Moreover, HCUA increased the number of cells in the sub-G1 arrest phase and apoptosis in a concentrationdependent manner in both oral cancer cell lines, but not in normal oral fibroblasts. Importantly, HCUA induced p53-mediated transcriptional regulation of pro-apoptotic proteins (Bax, Bak, Bim, Noxa, and PUMA), which are associated with mitochondrial apoptosis in oral cancer cells via the loss of mitochondrial membrane potential. HCUA triggered the production of intracellular reactive oxygen species (ROS) that was ascertained to be involved in HCUA-induced apoptosis by the ROS inhibitors YCG063 and N-acetyl-L-cysteine. As a result, HCUA had potential antitumor activity to oral cancer cells through eliciting ROS-dependent and p53-mediated mitochondrial apoptosis. Overall, HCUA could be applicable for the development of anticancer agents against human oral cancer.

      • KCI등재

        The role of the genomic mutation signature and tumor mutation burden on relapse risk prediction in head and neck squamous cell carcinoma after concurrent chemoradiotherapy

        Wang Hui-Ching,Moi Sin-Hua,Chan Leong-Perng,Wu Chun-Chieh,Du Jeng-Shiun,Liu Pei-Lin,Chou Meng-Chun,Wu Che-Wei,Huang Chih-Jen,Hsiao Hui-Hua,Pan Mei-Ren,Chen Li-Tzong 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

        Personalized genetic profiling has focused on improving treatment efficacy and predicting risk stratification by identifying mutated genes and selecting targeted agents according to genetic testing. Therefore, we evaluated the role of genetic profiling and tumor mutation burden (TMB) using next-generation sequencing in patients with head and neck squamous cell carcinoma (HNSC). The relapse mutation signature (RMS) and chromatin remodeling mutation signature (CRMS) were explored to predict the risk of relapse in patients with HNSC treated with concurrent chemoradiotherapy (CCRT) with platinum-based chemotherapy. Patients in the high RMS and CRMS groups showed significantly shorter relapse-free survival than those in the low RMS and CRMS groups, respectively (p < 0.001 and p = 0.006). Multivariate Cox regression analysis showed that extranodal extension, CCRT response, and three somatic mutation profiles (TMB, RMS, and CRMS) were independent risk predictors for HNSC relapse. The predictive nomogram showed satisfactory performance in predicting relapse-free survival in patients with HNSC treated with CCRT.

      • KCI등재

        Three-step in vitro digestion model for evaluating and predicting fecal odor emission from growing pigs with different dietary protein intakes

        Lo Shih-Hua,Chen Ching-Yi,Wang Han-Tsung 아세아·태평양축산학회 2022 Animal Bioscience Vol.35 No.10

        Objective: The objective of this study was to select an effective in vitro digestion–fermentation model to estimate the effect of decreasing dietary crude protein (CP) on odor emission during pig production and to suggest potential prediction markers through in vitro and in vivo experiments. Methods: In the in vitro experiment, three diet formulations with different CP contents (170 g/kg, 150 g/kg, and 130 g/kg) but containing the same standardized ileal digestible essential amino acids (SID-EAA) were assessed. Each diet was evaluated by two different in vitro gastric-intestinal phase digestion methods (flask and dialysis), combined with fresh pig feces-ferment inoculation. Eighteen growing barrows (31.9±1.6 kg) were divided into three groups: control diet (180 g CP/kg, without SID-EAA adjustment), 170 g CP/kg diet, and 150 g CP/kg diet for 4 weeks. Results: The in vitro digestion results indicated that in vitro digestibility was affected by the gastric-intestinal phase digestion method and dietary CP level. According to the gas kinetic and digestibility results, the dialysis method showed greater distinguishability for dietary CP level adjustment. Nitrogen-related odor compounds (NH3-N, indole, p-cresol, and skatole) were highly correlated with urease and protease activity. The feeding study indicated that both EAA-adjusted diets resulted in a lower odor emission especially in p-cresol and skatole. Both protease and urease activity in feces were also closely related to odor emissions from nitrogen metabolism compounds. Conclusion: Dialysis digestion in the gastric-intestinal phase followed by fresh fecal inoculation fermentation is suitable for in vitro diet evaluation. The enzyme activity in the fermentation and the fecal samples might provide a simple and effective estimation tool for nitrogenrelated odor emission prediction in both in vitro and in vivo experiments. Objective: The objective of this study was to select an effective in vitro digestion–fermentation model to estimate the effect of decreasing dietary crude protein (CP) on odor emission during pig production and to suggest potential prediction markers through in vitro and in vivo experiments.Methods: In the in vitro experiment, three diet formulations with different CP contents (170 g/kg, 150 g/kg, and 130 g/kg) but containing the same standardized ileal digestible essential amino acids (SID-EAA) were assessed. Each diet was evaluated by two different in vitro gastric-intestinal phase digestion methods (flask and dialysis), combined with fresh pig feces-ferment inoculation. Eighteen growing barrows (31.9±1.6 kg) were divided into three groups: control diet (180 g CP/kg, without SID-EAA adjustment), 170 g CP/kg diet, and 150 g CP/kg diet for 4 weeks.Results: The in vitro digestion results indicated that in vitro digestibility was affected by the gastric-intestinal phase digestion method and dietary CP level. According to the gas kinetic and digestibility results, the dialysis method showed greater distinguishability for dietary CP level adjustment. Nitrogen-related odor compounds (NH<sub>3</sub>-N, indole, p-cresol, and skatole) were highly correlated with urease and protease activity. The feeding study indicated that both EAA-adjusted diets resulted in a lower odor emission especially in p-cresol and skatole. Both protease and urease activity in feces were also closely related to odor emissions from nitrogen metabolism compounds.Conclusion: Dialysis digestion in the gastric-intestinal phase followed by fresh fecal inoculation fermentation is suitable for in vitro diet evaluation. The enzyme activity in the fermentation and the fecal samples might provide a simple and effective estimation tool for nitrogen-related odor emission prediction in both in vitro and in vivo experiments.

      • KCI등재

        Ginsenoside compound K reduces the progression of Huntington's disease via the inhibition of oxidative stress and overactivation of the ATM/AMPK pathway

        Kuo-Feng Hua,A-Ching Chao,Ting-Yu Lin,Wan-Tze Chen,Yu-Chieh Lee,Wan-Han Hsu,Sheau-Long Lee,Hsin-Min Wang,Ding-I. Yang,Tz-Chuen Ju 고려인삼학회 2022 Journal of Ginseng Research Vol.46 No.4

        Background: Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion oftrinucleotide CAG repeat in the Huntingtin (Htt) gene. The major pathogenic pathways underlying HDinvolve the impairment of cellular energy homeostasis and DNA damage in the brain. The protein kinaseataxia-telangiectasia mutated (ATM) is an important regulator of the DNA damage response. ATM isinvolved in the phosphorylation of AMP-activated protein kinase (AMPK), suggesting that AMPK plays acritical role in response to DNA damage. Herein, we demonstrated that expression of polyQ-expandedmutant Htt (mHtt) enhanced the phosphorylation of ATM. Ginsenoside is the main and most effectivecomponent of Panax ginseng. However, the protective effect of a ginsenoside (compound K, CK) in HDremains unclear and warrants further investigation. Methods: This study used the R6/2 transgenic mouse model of HD and performed behavioral tests,survival rate, histological analyses, and immunoblot assays. Results: The systematic administration of CK into R6/2 mice suppressed the activation of ATM/AMPK andreduced neuronal toxicity and mHTT aggregation. Most importantly, CK increased neuronal density andlifespan and improved motor dysfunction in R6/2 mice. Conversely, CK enhanced the expression of Bcl2protected striatal cells from the toxicity induced by the overactivation of mHtt and AMPK. Conclusions: Thus, the oral administration of CK reduced the disease progression and markedlyenhanced lifespan in the transgenic mouse model (R6/2) of HD.

      • DON’T BE A PASSING FAD: THE SUSTAINED COMPETITIVE ADVANTAGE OF HOTELS’ THEMING STRATEGY IN CHINESE MARKET

        Lee, Wen-Yin,Wang, Kuo-Ching,Wu, Ben,Chuang, Wan-Hua,Hsiao, Chia-Lin 글로벌지식마케팅경영학회 2018 Global Marketing Conference Vol.2018 No.07

        Theming has become a powerful strategy in hospitality industry to enhance customer engagement and to serve as a competitive advantage in a saturated market. Based on the resource-based theory (RBT) of sustained competitive advantage (SCA), this qualitative study is an exploratory attempt to investigate 10 hotels in Mainland China and Taiwan that have adopted the theming strategy. Introduction As hospitality industry is facing the increasingly intense competition and saturated markets, theming is continuously gaining importance of hotels strategy to survival and growth. In addition, strategy planning determines the future of firms and discover the method to achieve success (Yong & Oh, 2004). Holjevac (2003) predicted that at the beginning of the 21st century, hotels with themed strategy which characterized by a synthesis of esthetics, quality and functionality would become the future trend. Theming has created the differentiation in hospitality market, using the creation of experience-centric service. Pine & Gilmore (1999) once pointed out that the shaping of experience stems from simple and powerful thematic transmission. Moreover, experience marketing can bring preference to the product and service of the enterprise, which in turn leads to a positive value experience (Milman, 2013). The results of theming strategy will positively influence the satisfaction and return rate (Wu, M. Li, & T. Li, 2018). Theming strategy with the advantage of pursuing innovation and uniqueness was extensively used to firms in the competitive hospitality market, like hotels in Las Vegas and Macao. However, some scholars concerned about the sustainability for the strategy due to the high-capitalized cost and the customers sensitive taste (Wassler, Li, & Hung, 2015). Although hotels with themed strategy has flourished in Chinese market more than decade, market research has lagged behind to support the industry’s growth. Researchers still adopted a rather normative paradigm by either identifying the superficial issue focused on experiential market concept or pointing out problems without providing more sustainability related solutions (Zou & Peng, 2008; Xiao, Zhang, & Huang, 2013). Barney (2007) indicated that internal resources could lead to the competitive. Therefore, this study aims at understanding the factors that lead theming strategy to be sustainable in hotels, based on the resource-based theory of sustained competitive advantage. The article has the following structure. The first section establishes a theoretical foundation through a review of strategy literature on theming. The second section proposes a conceptualization of theming strategy’s sustained competitive advantage (SCA) consisting of firms intrinsic resources based on resource-based theory (RBT), also, describe the assessment of key sustainable factors of theming strategy through interview the superior manager of 10 hotels in Mainland China and Taiwan that have adopted the theming strategy. The final section discusses the study’s findings, implication, and suggests directions for future research. As this research is one of the first studies in the hospitality field that identifies the resources and capabilities of the hotels’ theming strategy from the inside viewpoint, the contribution of this study will, and can conceptualize and discover the key factors to sustain the competitive advantage of themed hotel managing strategy Literature review Theming strategy for hotels Theming is a complete and ubiquitous way of impressing consumers and improving brand awareness (Olson, 2004). From theme parks, casinos, department stores, aviation, restaurants to hotels, thematic construction has the dominant influence on most customer engagement (Mu?oz, Wood, & Solomon, 2006). Hotel theming strategy, based on the theme of cultural material (history, city story, etc.) either from surrounding area or develop within hotel, display the core value of theme from physical resources, as buildings and facilities, to invisible resources, as atmosphere and service, which would, in the end, create a valuable and unforgettable customer stay experience(Zins, 1998). Xiao, Zhang, & Huang (2013) noted that the distinctive consumer experience at the theme hotel can impress customers, and, ultimately enhances brand recognition, customer engagement and repurchase intention. On the other hand, Wassler, Li, and Hung (2015) has indicated the pros and cons for the China themed hotels, which are the uniqueness to create competitive advantages that are difficult to imitate. On the contrary, the gaining of customers’ sense of demand can lead to the difficulties to fulfill customers’ taste and the ingrained capital with the narrow development is hard to recapitalize once invested. Importance of sustainability for theming strategy. Due to the strong specific image of the themed hotels, some cases developed as a passing fad in the hospitality field. Although prior study has indicated the importance of theme selection for themed hotels (Xiao et al., 2013), seldom literature focus on the overall implementation and application within hotels’ ins and outs, also the SCA issue of hotels management. Xiao & O'Neill (2010) pointed out that the analysis of internal resource is enable manger to realize and build sources of competitive advantage, which is emanated from the resource-based view of strategy. In Resource Based Theory (RBT), scholars thought that resources and capabilities from firms could bring lasting competitive advantage to the organization, and companies that have SCA (Wernerfelt, 1984). Organization have SCAs can reach outstanding performance by constantly creating and delivering the core value through price, trust, aesthetics and functionality to its target markets (Barney, 1991). Thus, in order to observe the SCAs for themed hotels management, this research will employ on internal resource view based on RBT to explore the SCAs from the internal aspect of themed hotels. Methodology We illustrate the key factors and analyze the importance of internal resources for the SCA of hotels’ theming strategy by means of a qualitative study in which 10 hotels applied theming strategy in Mainland China and Taiwan were surveyed using semistructured interviews. For the research question, a qualitative approach offers the advantage to allow an adequate, in depth analysis of the complex relations between internal recourses and SCA of theming strategy. These 10 hotels adapted theming strategy are chosen by non-probability snowball sampling method, below Fig.1 is the hotels list for 10 interviews in Taiwan and Mainland China. In addition, because China with a vast territory is limited to cover all area, the research focuses on Zhejiang province and Shanghai city, which have well-developed economy and rich tourist resources. All interviewees of the hotels will be the superior manager who decides the core value and leads the hotel’s future. The interview will be three part to proceed. First, in warm-up period, interviewer will frame an informal and trust environment, first step is to confirm interviewees’ background. The second part will be identify period; there will be a questionnaire, which adopted Chuang (2000), whose survey to prioritize the 5 dimension of internal resources that essential to hotel theming strategy management. Finally, we will confirm the competency, competitive advantage, and the strategy to achieve the sustainability for hotels theming strategy. We present conclusions for research and practice, as well as deriving practical recommendations for hotels’ theming strategy in Chinese market based on our findings. Preliminary findings The preliminary findings of the research will base on the key themes that emerge from in-depth interview to understand perceptions of hotel managers regarding theming. The result will be presented and discussed in three period. First, based on the questionnaire result from the interviewees, we will recognize that what the priority degree about the five dimension of internal resources is regarding perception of theming in hotel strategy. Second, 10 interviews will transcribe from voice recordings to pages of text, then the text will go through the coding technique, in which the raw and efforts data will be identified as the themes and subthemes. All the analyzed process will be carried by expert triangulation. Finally, through the experts examining on the links of themes and quotations, we will create a view of framework that would explore the relationships between theming strategy and SCA, the result will find the formula for hotels adapted theming strategy to possess competitive advantage of being sustainable. Although space limitations of the conference preclude the detailed explanation of this research work, the authors believe this study will broaden the theoretical domains used in understanding internal resources and competency of hotels’ theming strategy and practical information can be observed from the findings.

      • KCI등재

        Health Care Utilization and Expenditures of Patients with Diabetes Comorbid with Depression Disorder: A National Population-Based Cohort Study

        Chun-Jen Huang,Hui-Min Hsieh,Herng-Chia Chiu,Peng-Wei Wang,Mei-Hsuan Lee,Chih-Yi Li,Ching-Hua Lin 대한신경정신의학회 2017 PSYCHIATRY INVESTIGATION Vol.14 No.6

        Objective: The study investigated to compare health care utilization and expenditures between diabetic patients with and without depression in Taiwan. Methods: Health care utilization and expenditure among diabetic patients with and without depression disorder during 2000 and 2004 were examined using Taiwan’s population-based National Health Insurance claims database. Health care utilization included outpatient visits and the use of inpatient services, and health expenditures were outpatient, inpatient, and total medical expenditures. Moreover, general estimation equation models were used for analyzing the factors associated with outpatient visits and expenditures. Multiple logistic regression analysis was applied for identifying the factors associated with hospitalization. Results: The average annual outpatient visits and annual total medical expenditures in the study period were 44.23–52.20; NT$87,496–133,077 and 30.75–32.92; NT$64,411–80,955 for diabetic patients with and without depression. After adjustment for covariates, our results revealed that gender and complication were associated with out-patient visits. Moreover, the time factor was associated with the total medical expenditure, and residential urbanization and complication factors were associated with hospitalization. Conclusion: Health care utilization and expenditures for diabetic patients with depression were significantly higher than those without depression. Sex, complications, time, and urbanization are the factors associated with health care utilization and expenditures.

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