Induction of Forkhead Class box O3a and apoptosis by a standardized ginsenoside formulation, KG-135, is potentiated by autophagy blockade in A549 human lung cancer cells

Chih-Jung Yao,Jyh-Ming Chow,Shuang-En Chuang,Chia-Lun Chang,Ming-De Yan,Hsin-Lun Lee,I-Chun Lai,Pei-Chun Lin,Gi-Ming Lai 고려인삼학회 2017 Journal of Ginseng Research Vol.41 No.3

Background: KG-135, a standardized formulation enriched with Rk1, Rg3, and Rg5 ginsenosides, has been shown to inhibit various types of cancer cells; however, the underlying mechanisms are not fully understood. In this study, we explored its effects in A549 human lung cancer cells to investigate the induction of Forkhead Class box O3a (FOXO3a) and autophagy. Methods: Cell viability was determined by sulforhodamine B staining. Apoptosis and cell cycle distribution were analyzed using flow cytometry. The changes of protein levels were determined using Western blot analysis. Autophagy induction was monitored by the formation of acidic vesicular organelles stained with acridine orange. Results: KG-135 effectively arrested the cells in G1 phase with limited apoptosis. Accordingly, a decrease of cyclin-dependent kinase-4, cyclin-dependent kinase-6, cyclin D1, and phospho-retinoblastoma protein, and an increase of p27 and p18 proteins were observed. Intriguingly, KG-135 increased the tumor suppressor FOXO3a and induced the accumulation of autophagy hallmark LC3-II and acidic vesicular organelles without an increase of the upstream marker Beclin-1. Unconventionally, the autophagy adaptor protein p62 (sequestosome 1) was increased rather than decreased. Blockade of autophagy by hydroxychloroquine dramatically potentiated KG-135-induced FOXO3a and its downstream (FasL) ligand accompanied by the cleavage of caspase-8. Meanwhile, the decrease of Bcl-2 and survivin, as well as the cleavage of caspase-9, were also drastically enhanced, resulting in massive apoptosis. Conclusion: Besides arresting the cells in G1 phase, KG-135 increased FOXO3a and induced an unconventional autophagy in A549 cells. Both the KG-135-activated extrinsic FOXO3a/FasL/caspase-8 and intrinsic caspase-9 apoptotic pathways were potentiated by blockade of autophagy. Combination of KG- 135 and autophagy inhibitor may be a novel strategy as an integrative treatment for cancers.

대만 신종교의 문화콘텐츠 고찰 -자제기금회, 유심성교 그리고 일관도의 문화사업을 중심으로-

쩡쯔밍 ( Chih-ming Cheng ),이경원 ( Gyung-won Lee ),이수현 ( Su-hyun Lee ) 한국신종교학회 2018 신종교연구 Vol.39 No.-

문화콘텐츠라는 용어가 한국사회에서 등장한 지는 그리 오래되지 않았다. 특히 종교문화콘텐츠는 오늘날 문화콘텐츠 조사 및 연구에서 빼놓을 수 없는 핵심분야가 되었다. 이에 신종교문화콘텐츠 연구도 그 관심과 다양한 연구가 필요한 상황이다. 그동안 학회에서 논의되어 온 한국 신종교의 문화콘텐츠 연구에 힘입어 그 연구의 외연을 넓히는 차원에서 가까운 외국의 사례를 조사하고 그 특징을 살펴보는 연구를 진행하고자 한다. 본 고는 대만 신종교의 사례를 중심으로 논의하되 특히 그 사회사업의 현황을 개괄하고 문화사업의 영역에서 나타난 문화콘텐츠의 측면을 다루고자 한다. 그 사례가 되는 종교는 자제기금회와 유심성교 그리고 일관도이다. 이 세가지 신종교의 경우 사회적으로 가장 두드러진 현상을 중심으로 문화콘텐츠의 요소들을 고찰해보고자 한다. 자제기금회의 경우 활발한 구호사업을 벌이고 있는 가운데 특히 인문사업의 분야에서 다양한 콘텐츠를 축적하고 있다. 자선인문, 의료인문, 교육인문의 3대분야에서 그 두각을 드러내고 있다. 유심성교는 종교활동 이외에도 예술과 문학을 중시하여 인간 본성의 진선미를 드러내고자 한다. 유심방송국, 출판사, 문화원, 합창단, 역경대학 등의 활동에서 많은 콘텐츠를 축적하고 있다. 일관도의 문화콘텐츠는 사회사업의 역사를 기반으로 탄생하였으며 현대 정보통신문명의 발전과 더불어 다양한 미디어콘텐츠들이 생산되었다. 특히 전국 각지에서 운용하고 있는 일관도 전문 서점에서는 각종 CD, DVD, VCD, 경전해설서, 일관도 교리서 등을 디지털로 제작하여 판매하고 있다. 이처럼 대만 신종교가 보여주는 활발한 사회활동과 문화콘텐츠는 한국 신종교연구자에게도 주목할 만한 일이다. Official use of the word ‘Cultural Contents’ (referring to creative works as a whole in use as digital content) in Korean society is a fairly recent development. ‘Cultural Contents of Religions’ became especially necessary in the field of research on cultural contents today. Furthermore the cultural contents of new religions also need more interest and various research. Encouraged by the results of research in Korean new religious cultural contents, we tried to expand the research area of cultural contents into foreign countries and collect several of their cases. In this paper we will focus on several Taiwanese new religions and introduce their social works in addition to their cultural works constituting their cultural contents. The main cases are Tzuchi, Weixin and Ikuandao. The content will be composed of current prominent records of these new religions in Taiwanese society. In the case of Tzuchi, they are accumulating cultural contents since they have expanded their relief works. They distinguish themselves in the fields of charitable humanity, medical humanity, and educational humanity. Weixin is trying to manifest human nature in truth, goodness, and beauty through taking a serious involvement in art and literature besides religious works. They accumulate cultural contents through the works of Weixin’s own broadcasting organization, publications, Institute of Culture, choral groups, Yijing college. IKuan-Dao cultural contents have been created based on various social works. Further, various media contents accompanying the development of a contemporary IT civilization have been produced. There are also many bookstores that specialize in IKuan-Dao and they sell many items like CD, DVD, VCD, books of scripture interpretation, and text books. All previous facts of energetic Taiwanese new religious movements are worthy of note to Korean researchers.

Induction of Forkhead Class box O3a and apoptosis by a standardized ginsenoside formulation, KG-135, is potentiated by autophagy blockade in A549 human lung cancer cells

Yao, Chih-Jung,Chow, Jyh-Ming,Chuang, Shuang-En,Chang, Chia-Lun,Yan, Ming-De,Lee, Hsin-Lun,Lai, I-Chun,Lin, Pei-Chun,Lai, Gi-Ming The Korean Society of Ginseng 2017 Journal of Ginseng Research Vol.41 No.3

Background: KG-135, a standardized formulation enriched with Rk1, Rg3, and Rg5 ginsenosides, has been shown to inhibit various types of cancer cells; however, the underlying mechanisms are not fully understood. In this study, we explored its effects in A549 human lung cancer cells to investigate the induction of Forkhead Class box O3a (FOXO3a) and autophagy. Methods: Cell viability was determined by sulforhodamine B staining. Apoptosis and cell cycle distribution were analyzed using flow cytometry. The changes of protein levels were determined using Western blot analysis. Autophagy induction was monitored by the formation of acidic vesicular organelles stained with acridine orange. Results: KG-135 effectively arrested the cells in G1 phase with limited apoptosis. Accordingly, a decrease of cyclin-dependent kinase-4, cyclin-dependent kinase-6, cyclin D1, and phospho-retinoblastoma protein, and an increase of p27 and p18 proteins were observed. Intriguingly, KG-135 increased the tumor suppressor FOXO3a and induced the accumulation of autophagy hallmark LC3-II and acidic vesicular organelles without an increase of the upstream marker Beclin-1. Unconventionally, the autophagy adaptor protein p62 (sequestosome 1) was increased rather than decreased. Blockade of autophagy by hydroxychloroquine dramatically potentiated KG-135-induced FOXO3a and its downstream (FasL) ligand accompanied by the cleavage of caspase-8. Meanwhile, the decrease of Bcl-2 and survivin, as well as the cleavage of caspase-9, were also drastically enhanced, resulting in massive apoptosis. Conclusion: Besides arresting the cells in G1 phase, KG-135 increased FOXO3a and induced an unconventional autophagy in A549 cells. Both the KG-135-activated extrinsic FOXO3a/FasL/caspase-8 and intrinsic caspase-9 apoptotic pathways were potentiated by blockade of autophagy. Combination of KG-135 and autophagy inhibitor may be a novel strategy as an integrative treatment for cancers.

Influence of Residential Environment and Lifestyle on Multiple Primary Malignancies in Taiwan

Chang, Chih-Chun,Chung, Yi-Hua,Liou, Ching-Biau,Lee, Yi-Chen,Weng, Wei-Ling,Yu, Yun-Chieh,Yen, Tzung-Hai,Wu, Jiann-Ming Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.8

Background: Multiple primary malignancies (MPM) have become increasingly prevalent worldwide. This investigation was aimed at establishing the clinicopathological characteristics of MPM patients and evaluating the impact of the living environment on MPM in the Taiwanese population. Materials and Methods: From January 2009 to December 2013, a total of 8,268 cancer patients were identified in our institutional center. Of these, 125 were diagnosed as MPM and thus enrolled. Data for clinicopathological features and treatment approaches for these MPM patients living in urban or suburb zone were obtained. Findings for the air pollution status in Taiwan were also collected. Results: The most common cancer match of MPM was esophageal cancer with hypopharyngeal cancer (12.8%), followed by colorectal cancer with gastric cancer (6.4%) and colorectal cancer with breast cancer (5.6%). The air quality was significantly worse in the urban than in the suburban zone and there was a remarkably higher portion of MPM patients in the urban zone suffering from grade III and IV post-chemotherapeutic neutropenia (30.8% vs 15.1%, P=0.036). Conclusions: The tumor frequency and site distribution should be taken into the clinical evaluation because there is a relatively high risk of developing MPM. This study also highlighted the potential influence of environmental factors on post-chemotherapeutic neutropenia for patients with MPM.

Impact of Peri-Operative Anemia and Blood Transfusions in Patients with Gastric Cancer Receiving Gastrectomy

Chang, Chih-Chun,Sun, Jen-Tang,Chen, Jing-Yuan,Chen, Yi-Ting,Li, Pei-Yu,Lee, Tai-Chen,Su, Ming-Jang,Wu, Jiann-Ming,Yen, Tzung-Hai,Chu, Fang-Yeh Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.3

Background: Potential disadvantages of blood transfusion during curative gastrectomy for gastric cancer have been reported, and the role of peri-operative transfusions remains to be ascertained. Thus, the aim of our study was to survey its impact in patients with gastric cancer undergoinging gastrectomy. Materials and Methods: Clinical data of patients receiving curative gastrectomy at Far Eastern Memorial Hospital were obtained. Findings for pre-operative anemia states, pre-, peri- and post-operative transfusion of red blood cell (RBC) products as well as post-operative complication events were collected for univariate analysis. Results: A total of 116 patients with gastric cancer received gastrectomy at Far Eastern Memorial Hospital from 2011 to 2014. Both pre-operative and intra- and post-operative transfusion of RBC products were markedly associated with post-operative infectious events (OR: 3.70, 95% CI: 1.43-9.58, P=0.002; OR: 8.20, 95% CI: 3.11-22.62, P<0.001, respectively). In addition, peri- and post-operative RBC transfusion was significantly associated with prolonged hospital stay from admission to discharge (OR: 8.66, 95% CI: 1.73-83.00, P=0.002) and post-operative acute renal failure (OR: 19.69, 95% CI: 2.66-854.56, P<0.001). Also, the overall survival was seemingly decreased by peri-operative RBC transfusion in our gastric cancer cases (P=0.078). Conclusions: Our survey indicated that peri-operative RBC transfusion could increase the risk of infectious events and acute renal failure post curative gastrectomy as well as worsen the overall survival in gastric cancer cases. Hence, unnecessary blood transfusion before, during and after curative gastrectomy should be avoided in patients with gastric cancer.

Creatine Kinase (CK)-MB-to-Total-CK Ratio: a Laboratory Indicator for Primary Cancer Screening

Chang, Chih-Chun,Liou, Ching-Biau,Su, Ming-Jang,Lee, Yi-Chen,Liang, Chai-Ting,Ho, Jung-Li,Tsai, Huang-Wen,Yen, Tzung-Hai,Chu, Fang-Yeh Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Background: For the determination of creatine kinase (CK)-MB, the immunoinhibition method is utilized most commonly. However, the estimated CK-MB activity may be influenced by the presence of CK isoenzymes in some conditions like cancer. Thus, a CK-MB-to-total-CK ratio more than 1.0 could be found in such a situation. The study aimed to explore the relationship of cancer to high CK-MB-to-total-CK ratio. Materials and Methods: From January 2011 to December 2014, laboratory data on all CK-MB and total CK test requests were extracted at Far Eastern Memorial Hospital (88,415 requests). Patients with a CK-MB-to-total-CK ratio more than 1.0 were registered in this study. Clinical data including tumor location, tumor TNM stage and metastatic status were also collected. Results: A total of 846 patients were identified with a CK-MB-to-total-CK ratio more than 1.0. Of these, 339 (40.1%) were diagnosed with malignancies. The mean CK-MB-to-total-CK ratio was significantly higher in malignancy than in non-malignancy ($1.35{\pm}0.28$ vs $1.25{\pm}0.23$, p<0.001) groups. The most frequent malignancy with a CK-MB-to-total-CK ratio more than 1.0 was colorectal cancer ($1.42{\pm}0.28$, 16.5%, n=56), followed by lung cancer ($1.38{\pm}0.24$, 15.9%, n=54) and hepatocellular carcinoma (14.5%, n=49). Higher CK-MB-to-total-CK ratios in hematological malignancies ($1.44{\pm}0.41$)were also noted. Additionally, the CK-MB-to-total-CK ratio was markedly higher in advanced stage malignancy than in early stage ($1.37{\pm}0.26$ vs. $1.29{\pm}0.31$, p=0.014) and significantly higher in liver metastasis than in non-liver metastasis ($1.48{\pm}0.30$ vs. $1.30{\pm}0.21$, p<0.001). Conclusions: The CK-MB-to-total-CK ratio is an easily available indicator and could be clinically utilized as a primary screening tool for cancer. Higher ratio of CK-MB-to-total-CK was specifically associated with certain malignancies, like colorectal cancer, lung cancer and hepatocellular carcinoma, as well as some cancer-associated status factors such as advanced stage and liver metastasis.

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.

Group-based trajectory model to analyze the growth of students’ academic performance: a longitudinal investigation at one Taiwanese high school

Fu, Yuan Chih,Chen, Sheng Lee,Quetzal, Amelio Salvador,Lee, Hsiu Ming,Lin, Yi Hua 서울대학교 교육연구소 2022 Asia Pacific Education Review Vol.23 No.3

This study investigated the growth trajectory of academic achievement in Math and English among 519 students in a vocational senior high school in Taiwan. Covering the complete individual learning profile, our dataset included pre-enrollment variables, periodic test scores, and college entrance examination scores. We employed a group-based trajectory model that identified three homogenous subgroups with distinct trajectories of academic achievement in Math and English and demonstrated baseline predictive factors associated with these trajectories as well as relationships between different trajectories and students’ college entrance examination scores. Our analysis contributes to the literature in two ways. First, this study demonstrates that when school practices focus on improving or remediating the performance of students in the low-achievement group, the obvious decrease in performance of those in the middle is ignored. Such finding indicates the need for inclusive or specialized practices that enhance the performance of students in all groups. Second, our analysis reveals that pre-enrollment academic preparation appears to be a strong predictor of later academic performance as noted through the reproduction of pre-enrollment academic performance in students’ college entrance examination scores. Therefore, upon enrollment, schools should start interventions that reflect the needs of different groups of students.

Production performances and antioxidant activities of laying hens fed Aspergillus oryzae and phytase co-fermented wheat bran

Huang Chung Ming,Chuang Wen Yang,Lin Wei Chih,Lin Li Jen,Chang Sheng Chang,Lee Tzu Tai 아세아·태평양축산학회 2021 Animal Bioscience Vol.34 No.3

Objective: Wheat bran (WB) was co-fermented with Aspergillus oryzae and phytase (Phy) to determine whether co-fermentation improve WB phosphorus and fiber utilization in Isa-brown layers. Methods: A total of 112 Isa brown layer were randomly divided into 7 treatments with 8 replicates per a treatment and 2 hens per a replicate. The treatments included basal diet (control), basal diet supplemented with 250 unit/kg Phy (control+Phy), diet with 10% WB (10% WB), diet with 5% WB and 250 unit/kg Phy (5% WB+Phy) diet with 10% WB and 250 unit/kg Phy (10% WB+Phy), diet with 5% fermented WB supplemented with molasses and phy (PCFWH) and 125 unit/kg Phy (5% PCFWH), and diet with 10% PCFWH (10% PCFWH). The intestinal microbial population, intestinal morphology, serum antioxidant enzyme activities, and excreta phosphorus content were assessed. Results: In PCFWH, spore counts, protease activity, xylanase activity, and ferulic acid were 8.50 log/g dry matter (DM), 190 unit/g DM, 120 unit/g DM, and 127 μg/g, respectively. Xylobiose and xylotriose were released in PCFWH, while they were not detectable in WB. Antioxidant capacity was also enhanced in PCFWH compared to WB. The 10% WB+Phy and 10% PCFWH groups produced higher egg mass, but hens fed 5% WB+Phy had the lowest amount of feed intake. Eggs from 10% PCFWH had better eggshell weight, eggshell strength, and eggshell thickness. Birds fed with 10% PCFWH also had higher serum superoxide dismutase and catalase activities. Compare to control, 10% PCFWH significantly reduced excreta phosphorus content. Conclusion: Diet inclusion of 10% PCFWH improved egg quality, antioxidant status, and excreta phosphorus content of laying hens. Objective: Wheat bran (WB) was co-fermented with Aspergillus oryzae and phytase (Phy) to determine whether co-fermentation improve WB phosphorus and fiber utilization in Isa-brown layers.Methods: A total of 112 Isa brown layer were randomly divided into 7 treatments with 8 replicates per a treatment and 2 hens per a replicate. The treatments included basal diet (control), basal diet supplemented with 250 unit/kg Phy (control+Phy), diet with 10% WB (10% WB), diet with 5% WB and 250 unit/kg Phy (5% WB+Phy) diet with 10% WB and 250 unit/kg Phy (10% WB+Phy), diet with 5% fermented WB supplemented with molasses and phy (PCFWH) and 125 unit/kg Phy (5% PCFWH), and diet with 10% PCFWH (10% PCFWH). The intestinal microbial population, intestinal morphology, serum antioxidant enzyme activities, and excreta phosphorus content were assessed.Results: In PCFWH, spore counts, protease activity, xylanase activity, and ferulic acid were 8.50 log/g dry matter (DM), 190 unit/g DM, 120 unit/g DM, and 127 μg/g, respectively. Xylobiose and xylotriose were released in PCFWH, while they were not detectable in WB. Antioxidant capacity was also enhanced in PCFWH compared to WB. The 10% WB+Phy and 10% PCFWH groups produced higher egg mass, but hens fed 5% WB+Phy had the lowest amount of feed intake. Eggs from 10% PCFWH had better eggshell weight, eggshell strength, and eggshell thickness. Birds fed with 10% PCFWH also had higher serum superoxide dismutase and catalase activities. Compare to control, 10% PCFWH significantly reduced excreta phosphorus content.Conclusion: Diet inclusion of 10% PCFWH improved egg quality, antioxidant status, and excreta phosphorus content of laying hens.

Toward understanding of subscriber behabioral intention and risk assessment in adopting 3G value-added services from the secured handset enabler

Ke-Hwa Lee,Ming-Yu Zhang,Shih-Chih Chen 인하대학교 정석물류통상연구원 2009 인하대학교 정석물류통상연구원 학술대회 Vol.2009 No.10

Up to today, the third generation (3G) mobil services don’t perform as well as expectation than its business forecast a decade ago. Limited handset capability and availability are the one of roof causes to put the blame on operators’ optimistic 3G business model and overlook to subscriber behavioral intentions in various personal concerns. Secured handset enabler (SHE) comprises a series of remote software-controlled mechanism to protect the personal sensitive data and messages that stored in the Smartphone or PDA when the mobile device is mis-placed, lost, or stolen. This study discusses the possible alignment in innovating 3G value-added services (VAS) foundation toward understanding subscriber behavioral intentions and risk assessment. In the proposed modelling elements, perceived usefulness, perceived ease-of-use, subjective norms, and perceived behavioral, control directly influence the behavioral intention through mediation of attitude. The C-TAM-TPB model was utilized to examine those collected data from 233 interviewers in their perceptions of SHE application. Overall, the results revealed that the effect of satisfaction was significant importance, but those usefulness, subjective norms, and perceived behavioral control did not influence directly an individual’s continuance intentions. Moreover, perceived usefulness and perceived ease-of-use had influence indirectly the continuance intentions through mediation of satisfaction. The implications of this study were also discussed in this paper.