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9. Renal function is associated with 1-month and 1-year mortality in patients with ischemic stroke

Author

Liu, Chung-Hsiang, Tsai, Chon-Haw, Huang, Wei-Shih, Lu, Chung-Ta, Tsai, Tzung-Chang, Tseng, Chun-Hung, Lin, Kang-Hsu, Shyu, Woei-Cherng, Yang, Yu-Wan, Liu, Yen-Liang, Cho, Der-Yang, Chen, Chun-Chung, Jeng, Jiann-Shing, Tang, Sung-Chun, Tsai, Li-Kai, Yeh, Shin-Joe, Chen, Chih-Hao, Tsai, Hsin-Hsi, Li, Jie-Yuan, Chen, Han-Jung, Lu, Kan, Hsu, Shih-Pin, Kuo, Hung-Chang, Tsou, Jung-Chi, Wang, Yan-Tang, Tai, Yi-Cheng, Hsieh, Meng-Tsang, Liliang, Po-Chao, Liang, Cheng-Loong, Wang, Hao-Kuang, Tsai, Yu-Tun, Wang, Kuo-Wei, Chen, Jui-Sheng, Chen, Po-Yuan, Wang, Yi-Ching, Chen, Chih-Hung, Sung, Pi-Shan, Hsieh, Han-Chieh, Su, Hui-Chen, Chiu, Hou-Chang, Lien, Li-Ming, Chen, Wei-Hung, Bai, Chyi-Huey, Huang, Tzu-Hsuan, Lau, Chi-Ieong, Wu, Ya-Ying, Yeh, Hsu-Ling, Chang, Anna, Lin, Ching-Huang, Yen, Cheng-Chang, Lin, Ruey-Tay, Chen, Chun-Hung, Khor, Gim-Thean, Chao, A-Ching, Lin, Hsiu-Fen, Huang, Poyin, Lin, Huey-Juan, Ke, Der-Shin, Chang, Chia-Yu, Yeh, Poh-Shiow, Lin, Kao-Chang, Cheng, Tain-Junn, Chou, Chih-Ho, Yang, Chun-Ming, Shen, Hsiu-Chu, Chen, An-Chih, Tsai, Shih-Jei, Lu, Tsong-Ming, Kung, Sheng-Ling, Lee, Mei-Ju, Chou, Hsi-Hsien, Chang, Wei-Lun, Chiu, Pai-Yi, Hsu, Min-Hsien, Chan, Po-Chi, Pan, Chau-Hsiung, Shoung, Hai-Ming, Lo, Yi-Chen, Wang, Fu-Hwa, Chang, Wei-Chieh, Lai, Ta-Chang, Yin, Jiu-Haw, Wang, Chung-Jen, Wang, Kai-Chen, Chen, Li-Mei, Denq, Jong-Chyou, Sun, Yu, Lu, Chien-Jung, Lin, Cheng-Huai, Huang, Chieh-Cheng, Liu, Chang-Hsiu, Chan, Hoi-Fong, Lee, Siu-Pak, Sun, Ming-Hui, Ke, Li-Ying, Chen, Po-Lin, Lee, Yu-Shan, Sung, Sheng-Feng, Ong, Cheung-Ter, Wu, Chi-Shun, Hsu, Yung-Chu, Su, Yu-Hsiang, Hung, Ling-Chien, Lee, Jiunn-Tay, Lin, Jiann-Chyun, Hsu, Yaw-Don, Peng, Giia-Sheun, Hsu, Chang-Hung, Lin, Chun-Chieh, Yen, Che-Hung, Cheng, Chun-An, Sung, Yueh-Feng, Chen, Yuan-Liang, Lien, Ming-Tung, Chou, Chung-Hsing, Liu, Chia-Chen, Yang, Fu-Chi, Wu, Yi-Chung, Tso, An-Chen, Lai, Yu- Hua, Chiang, Chun-I., Tsai, Chia-Kuang, Liu, Meng-Ta, Lin, Ying-Che, Hsu, Yu-Chuan, Chiang, Tsuey-Ru, Huang, Pai-Hao, Liao, Pin-Wen, Lee, Mei-Ching, Chen, Jen-Tse, Lie, Sian-King, Sun, Mu-Chien, Hsiao, Pi-Ju, Chen, Wei-Liang, Chen, Ta-Cheng, Chang, Chen-Shu, Lai, Chien-Hsu, Chuang, Chieh-Sen, Chen, Yen-Yu, Lin, Shinn-Kuang, Su, Yu-Chin, Shiao, Jen-Lun, Yang, Fu-Yi, Liu, Chih-Yang, Chiang, Han-Lin, Chen, Guei-Chiuan, Hsu, Po-Jen, Chang, Chun-Yuan, Lin, I.-sheng, Chien, Chung-Hsien, Chang, Yang-Chuang, Chen, Ping-Kun, Hsiao, Yu-Jen, Fang, Chen-Wen, Chen, Yu-Wei, Lee, Kuo-Ying, Lin, Yun-Yu, Li, Chen-Hua, Tsai, Hui-Fen, Hsieh, Chuan-Fa, Yang, Chih-Dong, Liaw, Shiumn-Jen, Liao, How-Chin, Yeh, Shoou-Jeng, Wu, Ling-Li, Hsieh, Liang-Po, Lee, Yong-Hui, Chen, Chung-Wen, Hsu, Chih-Shan, Jhih, Ye-Jian, Zhuang, Hao-Yu, Pan, Yan-Hong, Shih, Shin-An, Chen, Chin-I., Sung, Jia-Ying, Weng, Hsing-Yu, Teng, Hao-Wen, Lee, Jing-Er, Huang, Chih-Shan, Chao, Shu-Ping, Yuan, Rey-Yue, Sheu, Jau-Jiuan, Yu, Jia-Ming, Ho, Chun-Sum, Lin, Ting-Chun, Yu, Shih-Chieh, Chen, Jiunn-Rong, Tsai, Song-Yen, Wei, Cheng-Yu, Hung, Chao-Hsien, Lee, Chia Fang, Yang, Sheng-Kung, Chen, Chih-Lin, Lin, Wei, Tseng, Hung-Pin, Liu, Chin-Hsiung, Lin, Chun-Liang, Lin, Hung-Chih, Chen, Pi-Tzu, Hu, Chaur-Jong, Chan, Lung, Chi, Nai-Fang, Chern, Chang-Ming, Lin, Chun-Jen, Wang, Shuu-Jiun, Hsu, Li-Chi, Wong, Wen-Jang, Lee, I-Hui, Yen, Der-Jen, Tsai, Ching-Piao, Kwan, Shang-Yeong, Soong, Bing-Wen, Chen, Shih-Pin, Liao, Kwong-Kum, Lin, Kung-Ping, Chen, Chien, Shan, Din-E., Fuh, Jong-Ling, Wang, Pei-Ning, Lee, Yi-Chung, Yu, Yu-Hsiang, Huang, Hui-Chi, Tsai, Jui-Yao, Wu, Ming-Hsiu, Chiang, Szu-Yi, Wang, Chiung-Yao, Hsu, Ming-Chin, Chen, Chien-Chung, Yeh, Po-Yen, Tsai, Yu-Tai, Wang, Ko-Yi, Chen, Tsang-Shan, Hsieh, Cheng-Yang, Chen, Wei-Fen, Yip, Ping-Keung, Wang, Vinchi, Wang, Kaw-Chen, Tsai, Chung-Fen, Chen, Chao-Ching, Liu, Yi-Chien, Chen, Shao-Yuan, Zhao, Zi-Hao, Wei, Zhi-Peng, Wu, Shey-Lin, Liu, Ching-Kuan, Lin, Ryh-Huei, Chu, Ching-Hua, Yan, Sui-Hing, Lin, Yi-Chun, Chen, Pei-Yun, Hsiao, Sheng-Huang, Yip, Bak-Sau, Tsai, Pei-Chun, Chou, Ping-Chen, Kuo, Tsam-Ming, Lee, Yi-Chen, Chiu, Yi-Pin, Tsai, Kun-Chang, Liao, Yi-Sheng, Tsai, Ming-Jun, Kao, Hsin-Yi, Wang, I-Kuan, Yen, Tzung-Hai, Tsai, I-Ju, Sung, Fung-Chang, and Hsu, Chung Y.

Published
2018
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12. Cholesterol Levels Are Associated with 30-day Mortality from Ischemic Stroke in Dialysis Patients

Author

Liu, Chung-Hsiang, Tsai, Chon-Haw, Huang, Wei-Shih, Lu, Chung-Ta, Tsai, Tzung-Chang, Tseng, Chun-Hung, Lin, Kang-Hsu, Shyn, Woei-Cherng, Yang, Yu-Wan, Liu, Yen-Liang, Cho, Der-Yang, Chen, Chun-Chung, Jeng, Jiann-Shing, Tang, Sung-Chun, Tsai, Li-Kai, Yeh, Shin-Joe, Hsu, Shih-Pin, Chen, Han-Jung, Chang, Cheng-Sen, Kuo, Hung-Chang, Lee, Lian-Hui, Tsui, Huan-Wen, Tsou, Jung-Chi, Wang, Yan-Tang, Tai, Yi-Cheng, Tsai, Kun-Chang, Chen, Yen-Wen, Lu, Kan, Liliang, Po-Chao, Tsai, Yu-Tun, Liang, Cheng-Loong, Wang, Kuo-Wei, Wang, Hao-Kuang, Chen, Jui-Sheng, Chen, Po-Yuan, Chye, Cien-Leong, Tzeng, Wei-Jie, Wu, Pei-Hua, Chen, Chih-Hung, Sung, Pi-Shan, Hsieh, Han-Chieh, Su, Hui-Chen, Chiu, Hou-Chang, Lien, Li-Ming, Chen, Wei-Hung, Bai, Chyi-Huey, Huang, Tzu-Hsuan, Lau, Chi-Ieong, Wu, Ya-Ying, Yeh, Hsu-Ling, Chang, Anna, Lin, Ching-Huang, Yen, Cheng-Chang, Lin, Ruey-Tay, Chen, Chun-Hung, Khor, Gim-Thean, Chao, A-Ching, Lin, Hsiu-Fen, Huang, Poyin, Lin, Huey-Juan, Ke, Der-Shin, Chang, Chia-Yu, Yeh, Poh-Shiow, Lin, Kao-Chang, Cheng, Tain-Junn, Chou, Chih-Ho, Yang, Chun-Ming, Shen, Hsiu-Chu, Chen, An-Chih, Tsai, Shih-Jei, Lu, Tsong-Ming, Kung, Sheng-Ling, Lee, Mei-Ju, Chou, Hsi-Hsien, Chi, Hsin-Yi, Pan, Chou-Hsiung, Chan, Po-Chi, Hsu, Min-Hsien, Chang, Wei-Lun, Huang, Zhi-Zang, Shoung, Hai-Ming, Lo, Yi-Chen, Wang, Fu-Hwa, Lai, Ta-Chang, Yin, Jiu-Haw, Wang, Chung-Jen, Wang, Kai-Chen, Chen, Li-Mei, Denq, Jong-Chyou, Sun, Yu, Lu, Chien-Jung, Lin, Cheng-Huai, Huang, Chieh-Cheng, Liu, Chang-Hsiu, Chan, Hoi-Fong, Lee, Siu-Pak, Sun, Ming-Hui, Ke, Li-Ying, Chen, Po-Lin, Lee, Yu-Shan, Sung, Sheng-Feng, Ong, Cheung-Ter, Wu, Chi-Shun, Hsu, Yung-Chu, Su, Yu-Hsiang, Hung, Ling-Chien, Lee, Jiunn-Tay, Lin, Jiann-Chyun, Hsu, Yaw-Don, Peng, Giia-Sheun, Hsu, Chang-Hung, Lin, Chun-Chieh, Yen, Che-Hung, Cheng, Chun-An, Sung, Yueh-Feng, Chen, Yuan-Liang, Lien, Ming-Tung, Chou, Chung-Hsing, Liu, Chia-Chen, Yang, Fu-Chi, Wu, Yi-Chung, Tso, An-Chen, Lai, Yu-Hua, Chiang, Chun-I, Tsai, Chia-Kuang, Liu, Meng-Ta, Lin, Ying-Che, Hsu, Yu-Chuan, Chiang, Tsuey-Ru, Lee, Mei-Ching, Huang, Pai-Hao, Lie, Sian-King, Liao, Pin-Wen, Chen, Jen-Tse, Sun, Mu-Chien, Lai, Tien-Pao, Chen, Wei-Liang, Chen, Yen-Chun, Chen, Ta-Cheng, Wang, Wen-Fu, Lee, Kwo-Whei, Chang, Chen-Shu, Lai, Chien-Hsu, Shih, Siao-Ya, Chuang, Chieh-Sen, Chen, Yen-Yu, Chen, Chien-Min, Lin, Shinn-Kuang, Su, Yu-Chin, Hsiao, Cheng-Lun, Yang, Fu-Yi, Liu, Chih-Yang, Chiang, Han-Lin, Chang, Chun-Yuan, Lin, I-sheng, Chien, Chung-Hsien, Chang, Yang-Chuang, Chen, Ping-Kun, Chiu, Pai-Yi, Hsiao, Yu-Jen, Fang, Chen-Wen, Chen, Yu-Wei, Lee, Kuo-Ying, Lin, Yun-Yu, Li, Chen-Hua, Tsai, Hui-Fen, Hsieh, Chuan-Fa, Yang, Chih-Dong, Liaw, Shiumn-Jen, Liao, How-Chin, Yeh, Shoou-Jeng, Wu, Ling-Li, Hsieh, Liang-Po, Lee, Yong-Hui, Chen, Chung-Wen, Hsu, Chih-Shan, Jhih, Ye-Jian, Zhuang, Hao-Yu, Pan, Yan-Hong, Shih, Shin-An, Chen, Chin-I, Sung, Jia-Ying, Weng, Hsing-Yu, Teng, Hao-Wen, Lee, Jing-Er, Huang, Chih-Shan, Chao, Shu-Ping, Yuan, Rey-Yue, Sheu, Jau- Jiuan, Yu, Jia-Ming, Ho, Chun-Sum, Lin, Ting-Chun, Yu, Shih-Chieh, Chen, Jiunn-Rong, Tsai, Song-Yen, Wei, Cheng-Yu, Yang, Chao-Nan, Hung, Chao-Hsien, Shih, Ian, Tseng, Hung-Pin, Liu, Chin-Hsiung, Lin, Chun-Liang, Lin, Hung-Chih, Chen, Pi-Tzu, Hu, Chaur-Jong, Chi, Nai-Fang, Chan, Lung, Chern, Chang-Ming, Lin, Chun-Jen, Wang, Shuu-Jiun, Hsu, Li-Chi, Wong, Wen-Jang, Lee, I-Hui, Yen, Der-Jen, Tsai, Ching-Piao, Kwan, Shang-Yeong, Soong, Bing-Wen, Chen, Shih-Pin, Liao, Kwong-Kum, Lin, Kung-Ping, Chen, Chien, Shan, Din-E, Fuh, Jong-Ling, Wang, Pei-Ning, Lee, Yi-Chung, Yu, Yu-Hsiang, Huang, Hui-Chi, Tsai, Jui-Yao, Wu, Ming-Hsiu, Chen, Shi-Cheng, Chiang, Szu-Yi, Wang, Chiung-Yao, Hsu, Ming-Chin, Chen, Chien-Chung, Yeh, Po-Yen, Tsai, Yu-Tai, Wang, Ko-Yi, Chen, Tsang-Shan, Yip, Ping-Keung, Wang, Vinchi, Wang, Kaw-Chen, Tsai, Chung-Fen, Chen, Chao-Ching, Chen, Chih-Hao, Liu, Yi-Chien, Chen, Shao-Yuan, Zhao, Zi-Hao, Wei, Zhi-Peng, Wu, Shey-Lin, Liu, Ching-Kuan, Lin, Ryh-Huei, Chu, Ching-Hua, Yan, Sui-Hing, Lin, Yi-Chun, Chen, Pei-Yun, Hsiao, Sheng-Huang, Yip, Bak-Sau, Tsai, Pei-Chun, Chou, Ping-Chen, Kuo, Tsam-Ming, Lee, Yi-Chen, Chiu, Yi-Pin, Liao, Yi-Sheng, Tsai, Ming-Jun, Kao, Hsin-Yi, Wang, I.-Kuan, Yen, Tzung-Hai, Muo, Chih-Hsin, Ma, Henry, Wen, Chi-Pang, Sung, Fung-Chang, and Hsu, Chung Y.

Published
2017
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14. The Transplantation of 3-Dimensional Spheroids of Adipose-Derived Stem Cells Promotes Achilles Tendon Healing in Rabbits by Enhancing the Proliferation of Tenocytes and Suppressing M1 Macrophages.

Author

Chen, Shih-Heng, Lee, Yun-Wei, Kao, Huang-Kai, Yang, Pei-Ching, Chen, Shih-Hsien, Liu, Shao-Wen, Lin, Yu-Jie, and Huang, Chieh-Cheng

Subjects
WOUND healing, IN vitro studies, IN vivo studies, ANIMAL experimentation, MACROPHAGES, RABBITS, FISHER exact test, ACHILLES tendon rupture, TREATMENT effectiveness, GENE expression, COMPARATIVE studies, FAT cells, CELL proliferation, ENZYME-linked immunosorbent assay, HEMATOPOIETIC stem cell transplantation, DATA analysis software
Abstract

Background: Tendons have limited regenerative potential, so healing of ruptured tendon tissue requires a prolonged period, and the prognosis is suboptimal. Although stem cell transplantation–based approaches show promise for accelerating tendon repair, the resultant therapeutic efficacy remains unsatisfactory. Hypothesis: The transplantation of stem cells preassembled as 3-dimensional spheroids achieves a superior therapeutic outcome compared with the transplantation of single-cell suspensions. Study Design: Controlled laboratory study. Methods: Adipose-derived stem cells (ADSCs) were assembled as spheroids using a methylcellulose hydrogel system. The secretome of ADSC suspensions or spheroids was collected and utilized to treat tenocytes and macrophages to evaluate their therapeutic potential and investigate the mechanisms underlying their effects. RNA sequencing was performed to investigate the global difference in gene expression between ADSC suspensions and spheroids in an in vitro inflammatory microenvironment. For the in vivo experiment, rabbits that underwent Achilles tendon transection, followed by stump suturing, were randomly assigned to 1 of 3 groups: intratendinous injection of saline, rabbit ADSCs as conventional single-cell suspensions, or preassembled ADSC spheroids. The tendons were harvested for biomechanical testing and histological analysis at 4 weeks postoperatively. Results: Our in vitro results demonstrated that the secretome of ADSCs assembled as spheroids exhibited enhanced modulatory activity in (1) tenocyte proliferation (P =.015) and migration (P =.001) by activating extracellular signal-regulated kinase (ERK) signaling and (2) the suppression of the secretion of interleukin-6 (P =.005) and interleukin-1α (P =.042) by M1 macrophages via the COX-2/PGE2/EP4 signaling axis. Gene expression profiling of cells exposed to an inflammatory milieu revealed significantly enriched terms that were associated with the immune response, cytokines, and tissue remodeling in preassembled ADSC spheroids. Ex vivo fluorescence imaging revealed that the engraftment efficiency of ADSCs in the form of spheroids was higher than that of ADSCs in single-cell suspensions (P =.003). Furthermore, the transplantation of ADSC spheroids showed superior therapeutic effects in promoting the healing of sutured stumps, as evidenced by improvements in the tensile strength (P =.019) and fiber alignment (P <.001) of the repaired tendons. Conclusion: The assembly of ADSCs as spheroids significantly advanced their potential to harness tenocytes and macrophages. As a proof of concept, this study clearly demonstrates the effectiveness of using ADSC spheroids to promote tendon regeneration. Clinical Relevance: The present study lays a foundation for future clinical applications of stem cell spheroid–based therapy for the management of tendon injuries. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Derivation and Validation of a Discharge Disposition Predicting Model after Acute Stroke

Author

Jeng, Jiann-Shing, Yeh, Shin-Joe, Tsai, Li-Kai, Chiu, Hou-Chang, Lien, Li-Ming, Chen, Wei-Hung, Bai, Chyi-Huey, Huang, Tzu-Hsuan, Lau, Chi-Ieong, Wu, Ya-Ying, Yuan, Rey-Yue, Hu, Chaur-Jong, Sheu, Jau-Jiuan, Yu, Jia-Ming, Ho, Chun-Sum, Chung, Wen-Ting, Sung, Jia-Ying, Chen, Chin-I, Weng, Hsing-Yu, Han, Yu-Hsuan, Huang, Chun-Ping, Lin, Huey-Juan, Ke, Der-Shin, Chang, Chia-Yu, Yeh, Poh-Shiow, Lin, Kao-Chang, Cheng, Tain-Junn, Chou, Chih-Ho, Yang, Chun-Ming, Lo, Yuk-Keung, Lin, Yu-Te, Lin, Ching-Hwung, Lin, Jiann-Chyun, Hsu, Yaw-Don, Denq, Jong-Chyou, Peng, Giia-Sheun, Lee, Jiunn-Tay, Hsu, Chang-Hung, Lin, Chun-Chieh, Yen, Che-Hung, Cheng, Chun-An, Sung, Yueh-Feng, Chen, Yuan-Liang, Lien, Ming-Tung, Chou, Chung-Hsing, Liu, Chia-Chen, Yang, Fu-Chi, Wu, Yi-Chung, Tso, An-Chen, Lai, Yu-Hua, Chiang, Chun-I, Tsai, Chia-Kuang, Liu, Meng-Ta, Lin, Ying-Che, Hsu, Yu-Chuan, Liu, Chung-Hsiang, Tsai, Chon-Haw, Huang, Wei-Shih, Lu, Chung-Ta, Tsai, Tzung-Chang, Tseng, Chun-Hung, Lin, Kang-Hsu, Shyn, Woei-Cherng, Yang, Yu-Wan, Liu, Yen-Liang, Cho, Der-Yang, Chen, Chun-Chung, Sun, Ming-Hui, Yu, Shih-Chieh, Ke, Li-Ying, Lai, Ming-Liang, Chen, Chih-Hung, Chen, Jiunn-Rong, Tsai, Song-Yen, Chiang, Tsuey-Ru, Lee, Mei-Ching, Lin, Shinn-Kuang, Tseng, Yuan-Fu, Lee, Jing-Er, Hsiao, Cheng-Lun, Liang, Jen-Feng, Chen, Chiu-Mei, Wu, Chao-Hsin, Chen, Yu-Wei, Lee, Kuo-Ying, Lin, Yun-Yu, Li, Chen-Hua, Smith, Eric E., Tsai, Hui-Fen, Hsieh, Chuan-Fa, Yang, Chih-Dong, Liaw, Shiumn-Jen, Liao, How-Chin, Hu, Han-Hwa, Wong, Wen-Jang, Luk, Yun-On, Chern, Chang-Ming, Hsu, Li-Chi, Chung, Chih-Ping, Sun, Mu-Chien, Wu, Shey-Lin, Tseng, Hung-Pin, Liu, Chin-Hsiung, Lin, Chun-Liang, Lin, Hung-Chih, Lai, Ta-Chang, Yin, Jiu-Haw, Wang, Chung-Jen, Wang, Kai-Chen, Chen, Li-Mei, Chan, Lung, Lee, Siu-Pak, Sun, Yu, Huang, Chieh-Cheng, Liu, Chang-Hsiu, Lin, Cheng-Huai, Lu, Chien-Jung, Yeh, Shoou-Jeng, Wu, Ling-Li, Hsieh, Liang-Po, Lee, Yong-Hui, Chen, Chung-Wen, Chen, Po-Lin, Lee, Yu-Shan, Chen, Shu-Yi, Chen, Han-Jung, Hsu, Shih-Pin, Chang, Cheng-Sen, Kuo, Hung-Chang, Wu, Shu-Lung, Tsui, Huan-Wen, Tsou, Jung-Chi, Chou, Feng-Hsiung, Lin, Pei-Jung, Tung, Chin-Sung, Lu, Kan, Liliang, Po-Chou, Tsai, Yu-Duan, Liang, Cheng-Loong, Wang, Kuo-Wei, Wang, Hao-Kuang, Chen, Te-Yuan, Hsin, Yue-Loong, Lin, Chih-Yuan, Yip, Bak-Sau, Tsai, Pei-Chun, Chou, Ping-Chen, Kuo, Tsam-Ming, Lee, Yi-Chen, Chiu, Yi-Pin, Tsai, Kun-Chang, Lin, Ruey-Tay, Chen, Chun-Hung, Khor, Gim-Thean, Chao, A-Ching, Lin, Hsiu-Fen, Lin, I-Sheng, Yan, Sui-Hing, Lin, Yi-Chun, Chen, Pei-Yun, Hsiao, Sheng-Huang, Po, Helen L., Lin, Ya-Ju, Tu, Hao-Chieh, Tang, Sung-Chun, Lin, Fu-Yu, Chen, Ping-Kun, Chiu, Pai-Yi, Yip, Ping-Keung, Wang, Vin-Chi, Wang, Kaw-Chen, Tsai, Chung-Fen, Chen, Chao-Ching, Chen, Chih-Hao, Liu, Yi-Chien, Yeh, Chung-Hsin, Pan, Chou-Hsiung, Jih, Shin-Yi, Chan, Po-Chi, Hsu, Min-Hsien, Shoung, Hai-Ming, Lo, Yi-Chen, Wang, Fu-Hwa, Wei, Cheng-Yu, Lee, Jun-Yu, Lin, Ryh-Huei, Chu, Ching-Hua, Hsu, Ming-Chin, Lin, Feng-Jenq, Chen, Pi-Tzu, Mou, Chih-Hsin, Chang, Chun-Yuan, Chen, An-Chih, Hsiao, Yu-Jen, Lin, Ching-Huang, Hsu, Chung-Y., and Sung, Fung-Chang

Published
2015
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32. Strontium Peroxide-Loaded Composite Scaffolds Capable of Generating Oxygen and Modulating Behaviors of Osteoblasts and Osteoclasts.

Author

Lin, Sheng-Ju and Huang, Chieh-Cheng

Subjects
*SOIL infiltration, *OSTEOBLASTS, *OSTEOCLASTS, *BONE substitutes, *STRONTIUM, *BIOACTIVE glasses, *TISSUE scaffolds, *BONE grafting
Abstract

The reconstruction of bone defects remains challenging. The utilization of bone autografts, although quite promising, is limited by several drawbacks, especially substantial donor site complications. Recently, strontium (Sr), a bioactive trace element with excellent osteoinductive, osteoconductive, and pro-angiogenic properties, has emerged as a potential therapeutic agent for bone repair. Herein, a strontium peroxide (SrO2)-loaded poly(lactic-co-glycolic acid) (PLGA)-gelatin scaffold system was developed as an implantable bone substitute. Gelatin sponges serve as porous osteoconductive scaffolds, while PLGA not only reinforces the mechanical strength of the gelatin but also controls the rate of water infiltration. The encapsulated SrO2 can release Sr2+ in a sustained manner upon exposure to water, thus effectively stimulating the proliferation of osteoblasts and suppressing the formation of osteoclasts. Moreover, SrO2 can generate hydrogen peroxide and subsequent oxygen molecules to increase local oxygen tension, an essential niche factor for osteogenesis. Collectively, the developed SrO2-loaded composite scaffold shows promise as a multifunctional bioactive bone graft for bone tissue engineering. [ABSTRACT FROM AUTHOR]

Published
2022
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34. Association of metallothionein 2A rs10636 with low mean corpuscular volume (MCV), low mean corpuscular haemoglobin (MCH) in healthy Taiwanese.

Author

Chen, Rong-Fu, Chen, Po-Ming, Pan, Chau-Shiung, Huang, Chieh-Cheng, and Chiang, En-Pei Isabel

Subjects
SINGLE nucleotide polymorphisms, GENE expression profiling, GENE expression, GENETIC variation, LIPOPROTEIN lipase, ERYTHROPOIETIN receptors
Abstract

Human metallothionein-2A (MT2A) protein participates in metal homeostasis, detoxification, oxidative stress reduction, and immune defense. It decreases heavy metal ions and reactive oxygen species (ROS) during injury of cells and tissues. The single nucleotide polymorphisms at the MT2A gene have been associated in various human diseases including cancer. The current study aimed to elucidate associations between MT2A genotypes with the clinical, biochemical, and molecular characteristics that potentially related to lowered MT2A ex-pression. One hundred and forty-one healthy Taiwanese subjects were enrolled from Changhua Show-Chwan Memorial Hospital. Clinical, biochemical and molecular characteristics including the frequent minor allele SNPs, rs28366003 and rs10636, within the MT2A gene were determined. The genotype distribution of MT2A rs10636 fits the Hardy–Weinberg equilibrium. The significant associations with gradually decline of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were identified with MT2A rs10636 and rs28366003 using analysis of variance (ANOVA) with Tukey's analysis as a post hoc test. We further validated the correlations between the expressions of genes in erythropoiesis, cholesterol synthesis, platelet synthesis, insulin with MT2A using the web-based Gene Expression Profiling Interactive Analysis (GEPIA) databases. The results revealed that hypoxia-inducible factor 1α (HIF-1α), erythropoietin (EPO), lipoprotein lipase (LPL), and lecithin-cholesterol acyltransferase (LCAT) mRNA ex-pression are significantly correlated with MT2A mRNA expression. In conclusion, these results suggested that genetic variations of MT2A rs10636 and rs28366003 might be an important risk factor for erythropoiesis in the Taiwanese general population. [ABSTRACT FROM AUTHOR]

Published
2022
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37. Injection of hybrid 3D spheroids composed of podocytes, mesenchymal stem cells, and vascular endothelial cells into the renal cortex improves kidney function and replenishes glomerular podocytes.

Author

Yang, Wen‐Yu, Chen, Li‐Chi, Jhuang, Ya‐Ting, Lin, Yu‐Jie, Hung, Pei‐Yu, Ko, Yi‐Ching, Tsai, Meng‐Yu, Lee, Yun‐Wei, Hsu, Li‐Wen, Yeh, Chih‐Kuang, Hsu, Hsiang‐Hao, and Huang, Chieh‐Cheng

Subjects
VASCULAR endothelial cells, KIDNEY cortex, MESENCHYMAL stem cells, KIDNEY physiology, INJECTIONS
Abstract

Podocytes are highly differentiated epithelial cells that are crucial for maintaining the glomerular filtration barrier in the kidney. Podocyte injury followed by depletion is the major cause of pathological progression of kidney diseases. Although cell therapy has been considered a promising alternative approach to kidney transplantation for the treatment of kidney injury, the resultant therapeutic efficacy in terms of improved renal function is limited, possibly owing to significant loss of engrafted cells. Herein, hybrid three‐dimensional (3D) cell spheroids composed of podocytes, mesenchymal stem cells, and vascular endothelial cells were designed to mimic the glomerular microenvironment and as a cell delivery vehicle to replenish the podocyte population by cell transplantation. After creating a native glomerulus‐like condition, the expression of multiple genes encoding growth factors and basement membrane factors that are strongly associated with podocyte maturation and functionality was significantly enhanced. Our in vivo results demonstrated that intrarenal transplantation of podocytes in the form of hybrid 3D cell spheroids improved engraftment efficiency and replenished glomerular podocytes. Moreover, the proteinuria of the experimental mice with hypertensive nephropathy was effectively reduced. These data clearly demonstrated the potential of hybrid 3D cell spheroids for repairing injured kidneys. [ABSTRACT FROM AUTHOR]

Published
2021
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38. Lysophosphatidic acid improves corneal endothelial density in tissue culture by stimulating stromal secretion of interleukin‐1β.

Author

Hsueh, Yi‐Jen, Meir, Yaa‐Jyuhn James, Lai, Jui‐Yang, Chen, Hung‐Chi, Ma, David Hui‐Kang, Huang, Chieh‐Cheng, Lu, Tsai‐Te, Cheng, Chao‐Min, and Wu, Wei‐Chi

Subjects
TISSUE culture, LYSOPHOSPHOLIPIDS, ENDOTHELIAL cells, SECRETION, STROMAL cells, VISUAL acuity
Abstract

The short supply of donor corneas is exacerbated by the unsuitability of donors with insufficient endothelial cell density. Few studies have investigated promoting corneal endothelial cell proliferation to increase the endothelial cell density. We hypothesize that pre‐transplantation treatment of proliferative tissue‐cultivated corneas may increase corneal endothelial cell density. We observed that the airlift cultures were superior to immersion cultures with respect to both transparency and thickness. In this tissue culture system, we observed that lysophosphatidic acid increased the rabbit corneal endothelial cell density, number of BrdU‐positive cells and improve wound healing. We also observed an indirect effect of lysophosphatidic acid on corneal endothelial cell proliferation mediated by the stimulation of interleukin‐1β secretion from stromal cells. Human corneal tissues treated with lysophosphatidic acid or interleukin‐1β contained significantly more Ki‐67‐positive cells than untreated group. The lysophosphatidic acid‐ or interleukin‐1β‐treated cultured tissue remained hexagon‐shaped, with ZO‐1 expression and no evidence of the endothelial‐mesenchymal transition. Our novel protocol of tissue culture may be applicable for eye banks to optimize corneal grafting. [ABSTRACT FROM AUTHOR]

Published
2020
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39. Enhancement of Subcutaneously Transplanted β Cell Survival Using 3D Stem Cell Spheroids with Proangiogenic and Prosurvival Potential.

Author

Yu, Chih‐Ping, Juang, Jyuhn‐Huarng, Lin, Yu‐Jie, Kuo, Ching‐Wen, Hsieh, Li‐Hung, and Huang, Chieh‐Cheng

Subjects
STEM cells, TYPE 1 diabetes, CORD blood, HUMAN stem cells, MESENCHYMAL stem cells
Abstract

Islet transplantation has been demonstrated to be a promising therapy for type 1 diabetes mellitus. Although it is a minimally invasive operating procedure and provides easy access for graft monitoring, subcutaneous transplantation of the islet only has limited therapeutic outcomes, owing to the poor capacity of skin tissue to foster revascularization in a short period. Herein, 3D cell spheroids of clinically accessible umbilical cord blood mesenchymal stem cells and human umbilical vein endothelial cells are formed and employed for codelivery with β cells subcutaneously. The 3D stem cell spheroids, which can secrete multiple proangiogenic and prosurvival growth factors, induce robust angiogenesis and prevent β cell graft death, as indicated by the results of in vivo bioluminescent tracking and histological analysis. These experimental data highlight the efficacy of the 3D stem cell spheroids that are fabricated using translationally applicable cell types in promoting the survival and function of subcutaneously transplanted β cells. [ABSTRACT FROM AUTHOR]

Published
2020
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40. Downregulation of Methionine Cycle Genes MAT1A and GNMT Enriches Protein-Associated Translation Process and Worsens Hepatocellular Carcinoma Prognosis.

Author

Chen, Po-Ming, Tsai, Cheng-Hsueh, Huang, Chieh-Cheng, Hwang, Hau-Hsuan, Li, Jian-Rong, Liu, Chun-Chi, Ko, Hsin-An, and Chiang, En-Pei Isabel

Subjects
CANCER prognosis, METHIONINE, RIBOSOMAL proteins, RIBOSOMES, GENES, GENE expression
Abstract

The major biological methyl donor, S-adenosylmethionine (adoMet) synthesis occurs mainly in the liver. Methionine adenosyltransferase 1A (MAT1A) and glycine N-methyltransferase (GNMT) are two key enzymes involved in the functional implications of that variation. We collected 42 RNA-seq data from paired hepatocellular carcinoma (HCC) and its adjacent normal liver tissue from the Cancer Genome Atlas (TCGA). There was no mutation found in MAT1A or GNMT RNA in the 42 HCC patients. The 11,799 genes were annotated in the RNA-Seq data, and their expression levels were used to investigate the phenotypes of low MAT1A and low GNMT by Gene Set Enrichment Analysis (GSEA). The REACTOME_TRANSLATION gene set was enriched and visualized in a heatmap along with corresponding differences in gene expression between low MAT1A versus high MAT1A and low GNMT versus high GNMT. We identified 43 genes of the REACTOME_TRANSLATION gene set that are powerful prognosis factors in HCC. The significantly predicted genes were referred into eukaryotic translation initiation (EIF3B, EIF3K), eukaryotic translation elongation (EEF1D), and ribosomal proteins (RPs). Cell models expressing various MAT1A and GNMT proved that simultaneous restoring the expression of MAT1A and GNMT decreased cell proliferation, invasion, as well as the REACTOME_TRANSLATION gene EEF1D, consistent with a better prognosis in human HCC. We demonstrated new findings that downregulation or defect in MAT1A and GNMT genes can enrich the protein-associated translation process that may account for poor HCC prognosis. This is the first study demonstrated that MAT1A and GNMT, the 2 key enzymes involved in methionine cycle, could attenuate the function of ribosome translation. We propose a potential novel mechanism by which the diminished GNMT and MAT1A expression may confer poor prognosis for HCC. [ABSTRACT FROM AUTHOR]

Published
2022
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41. Modulation of Inherent Niches in 3D Multicellular MSC Spheroids Reconfigures Metabolism and Enhances Therapeutic Potential.

Author

Chen, Li-Chi, Wang, Hsin-Wen, and Huang, Chieh-Cheng

Subjects
STEM cell treatment, REGENERATIVE medicine, METABOLISM
Abstract

Multicellular spheroids show three-dimensional (3D) organization with extensive cell–cell and cell–extracellular matrix interactions. Owing to their native tissue-mimicking characteristics, mesenchymal stem cell (MSC) spheroids are considered promising as implantable therapeutics for stem cell therapy. Herein, we aim to further enhance their therapeutic potential by tuning the cultivation parameters and thus the inherent niche of 3D MSC spheroids. Significantly increased expression of multiple pro-regenerative paracrine signaling molecules and immunomodulatory factors by MSCs was observed after optimizing the conditions for spheroid culture. Moreover, these alterations in cellular behaviors may be associated with not only the hypoxic niche developed in the spheroid core but also with the metabolic reconfiguration of MSCs. The present study provides efficient methods for manipulating the therapeutic capacity of 3D MSC spheroids, thus laying solid foundations for future development and clinical application of spheroid-based MSC therapy for regenerative medicine. [ABSTRACT FROM AUTHOR]

Published
2021
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42. Cell-Penetrating Delivery of Nitric Oxide by Biocompatible Dinitrosyl Iron Complex and Its Dermato-Physiological Implications.

Author

Chen, Yu-Chieh, Chen, Yi-Hong, Chiu, Han, Ko, Yi-Hsuan, Wang, Ruei-Ting, Wang, Wei-Ping, Chuang, Yung-Jen, Huang, Chieh-Cheng, and Lu, Tsai-Te

Subjects
WOUND healing, NITRIC oxide, CHEMICAL biology, IRON, FIBROBLASTS, CELL proliferation, BIOCOMPATIBILITY
Abstract

After the discovery of endogenous dinitrosyl iron complexes (DNICs) as a potential biological equivalent of nitric oxide (NO), bioinorganic engineering of [Fe(NO)2] unit has emerged to develop biomimetic DNICs [(NO)2Fe(L)2] as a chemical biology tool for controlled delivery of NO. For example, water-soluble DNIC [Fe2(μ-SCH2CH2OH)2(NO)4] (DNIC-1) was explored for oral delivery of NO to the brain and for the activation of hippocampal neurogenesis. However, the kinetics and mechanism for cellular uptake and intracellular release of NO, as well as the biocompatibility of synthetic DNICs, remain elusive. Prompted by the potential application of NO to dermato-physiological regulations, in this study, cellular uptake and intracellular delivery of DNIC [Fe2(μ-SCH2CH2COOH)2(NO)4] (DNIC-2) and its regulatory effect/biocompatibility toward epidermal cells were investigated. Upon the treatment of DNIC-2 to human fibroblast cells, cellular uptake of DNIC-2 followed by transformation into protein-bound DNICs occur to trigger the intracellular release of NO with a half-life of 1.8 ± 0.2 h. As opposed to the burst release of extracellular NO from diethylamine NONOate (DEANO), the cell-penetrating nature of DNIC-2 rationalizes its overwhelming efficacy for intracellular delivery of NO. Moreover, NO-delivery DNIC-2 can regulate cell proliferation, accelerate wound healing, and enhance the deposition of collagen in human fibroblast cells. Based on the in vitro and in vivo biocompatibility evaluation, biocompatible DNIC-2 holds the potential to be a novel active ingredient for skincare products. [ABSTRACT FROM AUTHOR]

Published
2021
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43. Topical Ascorbic Acid Ameliorates Oxidative Stress-Induced Corneal Endothelial Damage via Suppression of Apoptosis and Autophagic Flux Blockage.

Author

Hsueh, Yi-Jen, Meir, Yaa-Jyuhn James, Yeh, Lung-Kun, Wang, Tze-Kai, Huang, Chieh-Cheng, Lu, Tsai-Te, Cheng, Chao-Min, Wu, Wei-Chi, and Chen, Hung-Chi

Subjects
VITAMIN C, ENDOTHELIAL cells, OXIDATIVE stress, CORNEAL opacity, APOPTOSIS
Abstract

Compromised pumping function of the corneal endothelium, due to loss of endothelial cells, results in corneal edema and subsequent visual problems. Clinically and experimentally, oxidative stress may cause corneal endothelial decompensation after phacoemulsification. Additionally, in vitro and animal studies have demonstrated the protective effects of intraoperative infusion of ascorbic acid (AA). Here, we established a paraquat-induced cell damage model, in which paraquat induced reactive oxygen species (ROS) production and apoptosis in the B4G12 and ARPE-19 cell lines. We demonstrate that oxidative stress triggered autophagic flux blockage in corneal endothelial cells and that addition of AA ameliorated such oxidative damage. We also demonstrate the downregulation of Akt phosphorylation in response to oxidative stress. Pretreatment with ascorbic acid reduced the downregulation of Akt phosphorylation, while inhibition of the PI3K/Akt pathway attenuated the protective effects of AA. Further, we establish an in vivo rabbit model of corneal endothelial damage, in which an intracameral infusion of paraquat caused corneal opacity. Administration of AA via topical application increased its concentration in the corneal stroma and reduced oxidative stress in the corneal endothelium, thereby promoting corneal clarity. Our findings indicate a perioperative strategy of topical AA administration to prevent oxidative stress-induced damage, particularly for those with vulnerable corneal endothelia. [ABSTRACT FROM AUTHOR]

Published
2020
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