研究專長 (Research Specialties)

神經生理病理學 (Neurophysiological Pathology)、細胞訊號傳遞 (Cellular Signal Transduction)、藥物效用評估與開發 (Drug Efficacy Evaluation and Development)

研究概要 (Research Summary)

本實驗室研究之目標在探討腦部發炎相關細胞病變之致病原因及其訊號機轉，以中樞神經系統(腦部)細胞如腦星狀細胞(astrocytes)、小神經膠細胞(microglia)及神經細胞(neurons)等為材料，陸續發現許多發炎因子如緩激肽(bradykinin)、內毒素(LPS)及高血糖等可藉由誘發腦星狀細胞之胞內訊號活化致使發炎反應生成，最終導致神經細胞死亡，其中發現活性氧分子(ROS)及基質金屬蛋白酶(MMPs)扮演著極重要的角色，此亦是導致神經退化或死亡之重要因素。為進一步了解此部分，實驗室與臨床醫師合作探討失智症相關之腦部神經病變，期能結合實驗室研究成果與臨床案例，解開在臨床相關腦病變之原因，作為保健或治療之依據。此外，實驗室近幾年陸續發現許多中草藥及天然物具有抗氧化或抗神經發炎之潛力，期能開發其具神經保護功效之成分。迄今，實驗室研究成果已在各相關領域之國際期刊發表90篇研究論文。
(The goal of this laboratory's research is to investigate the pathogenic causes and signaling mechanisms of brain inflammation-related cellular pathologies. Using central nervous system (brain) cells such as astrocytes, microglia, and neurons as materials, we have successively discovered that many inflammatory factors like bradykinin, endotoxin (LPS), and hyperglycemia can induce intracellular signaling activation in astrocytes, leading to inflammatory responses and ultimately neuronal cell death. Among these, reactive oxygen species (ROS) and matrix metalloproteinases (MMPs) play extremely important roles, which are also critical factors leading to neurodegeneration or cell death. To further understand this, the laboratory collaborates with clinicians to explore brain neuropathies related to dementia, hoping to combine laboratory research findings with clinical cases to unravel the causes of clinically relevant brain pathologies, serving as a basis for health maintenance or treatment. Additionally, in recent years, the laboratory has successively discovered that many traditional Chinese medicines and natural products possess antioxidant or anti-neuroinflammatory potential, aiming to develop their neuroprotective components. To date, the laboratory's research achievements have been published in 90 research papers in international journals across various related fields.)

研究方向 (Research Directions)

1. 探討中樞神經系統炎症及病變發生之機轉 (Investigating the Mechanisms of Central Nervous System Inflammation and Pathogenesis)
2. 探討糖尿病併發中樞神經系統病變之機轉 (Investigating the Mechanisms of Central Nervous System Complications in Diabetes)
3. 探究神經發炎退化及老化之機轉 (Exploring the Mechanisms of Neuroinflammatory Degeneration and Aging)
4. 中草藥活性成分對中樞神經系統保護作用之評估與開發 (Evaluation and Development of Traditional Chinese Medicine Active Ingredients for Neuroprotective Effects on the Central Nervous System)

學會或專業認證或得獎事蹟 (Societies, Professional Certifications, or Awards)

一、學會 (I. Societies)

• 台灣自由基學會 (Society for Free Radical Research-Taiwan)
• 中華天然藥物學會 永久會員 (Permanent Member, Chinese Society of Pharmacognosy)
• 台灣藥理學會 (The Pharmacological Society in Taiwan)
• 中國生理學會 會員 (Member, Chinese Physiological Society)

二、得獎事蹟 (II. Awards)

• 99年度長庚技術學院優良教師 (2010 Chang Gung Institute of Technology Excellent Teacher Award)
• 99年度台灣藥理學會-杜聰明年輕學者獎 (2010 Taiwan Pharmacological Society - Tu Tsung-Ming Young Investigator Award)
• 101年度長科技大學優良教師研究類獎 (2012 Chang Gung University of Science and Technology Excellent Teacher (Research Category) Award)
• 教育部102年獎勵科技大學及技術學院教學卓越計畫補助經費支給特殊優秀人才彈性薪資 (2013 Ministry of Education Grant for Teaching Excellence Programs at Universities of Science and Technology and Institutes of Technology, Providing Flexible Salaries for Exceptionally Talented Individuals)
• 103年度長科技大學產學合作技術研發績優獎(優良教師研究獎) (2014 Chang Gung University of Science and Technology Industry-Academia Collaboration Technology R&D Excellence Award (Excellent Teacher Research Award))
• 104學年度長科技大學產學合作技術研發績優獎(優良教師研究獎) (2015 Chang Gung University of Science and Technology Industry-Academia Collaboration Technology R&D Excellence Award (Excellent Teacher Research Award))
• 107年度長科技大學產學合作技術研發績優獎(優良教師研究獎) (2018 Chang Gung University of Science and Technology Industry-Academia Collaboration Technology R&D Excellence Award (Excellent Teacher Research Award))
• 108學年度長科技大學產學合作技術研發績優銀獎 (2019 Chang Gung University of Science and Technology Industry-Academia Collaboration Technology R&D Excellence Silver Award)
• 110學年度長科技大學產學合作技術研發績優銀獎 (2021 Chang Gung University of Science and Technology Industry-Academia Collaboration Technology R&D Excellence Silver Award)
• 112學年度長科技大學產學合作技術研發績優金獎 (2023 Chang Gung University of Science and Technology Industry-Academia Collaboration Technology R&D Excellence Gold Award)

論文著作 (近五年) (Publications - Last Five Years)

1. Hsi-Lung Hsieh^†, Ming-Chin Yu^†, Yu-Chia Chang, Yi-Hsuan Wu, Kuo-Hsiung Huang, Ming-Ming Tsai*. (2024) Lonicera japonica Thunb. Ethanol Extract Exerts a Protective Effect on Normal Human Gastric Epithelial Cells by Modulating the Activity of Tumor-Necrosis-Factor-α-Induced Inflammatory Cyclooxygenase 2/Prostaglandin E2 and Matrix Metalloproteinase 9. Current Issues in Molecular Biology 46(7): 7303-7323.
2. Tsong-Hai Lee, Jiun-Liang Chen, Chuan-Hsin Chang, Ming-Ming Tsai, Hui-Ching Tseng, Yu-Chia Chang, Velayuthaprabhu Shanmugam, Hsi-Lung Hsieh*. (2024) A Brain-Protective Sterol from Soft Coral Inhibits Lipopolysaccharide-Induced Matrix Metalloproteinase-9-Mediated Astrocytic Migration. Biomedicines 12(1): 226.
3. Tsong-Hai Lee, Jiun-Liang Chen, Ming-Ming Tsai, Yi-Hsuan Wu, Hui-Ching Tseng, Li-Ching Cheng, Velayuthaprabhu Shanmugam, Hsi-Lung Hsieh*. (2023) Protective Effects of Sophoraflavanone G by Inhibiting TNF-α-Induced MMP-9-Mediated Events in Brain Microvascular Endothelial Cells. International Journal of Molecular Sciences 25(1): 283.
4. Yi-Hsuan Wu, Hsi-Lung Hsieh*. (2023) Effects of Redox Homeostasis and Mitochondrial Damage on Alzheimer's Disease. Antioxidants (Basel) 12(10):1816. (Review)
5. Hsi-Lung Hsieh, Shih-Hai Liu, Ya-Ling Chen, Chien-Yi Huang, Shu-Ju Wu. (2022) Astragaloside IV suppresses inflammatory response via suppression of NF-κB, and MAPK signalling in human bronchial epithelial cells. Archives of Physiology and Biochemistry 128(3):757-766.
6. Ming-Ming Tsai, Jiun-Liang Chen, Tsong-Hai Lee, Hsiuming Liu, Velayuthaprabhu Shanmugam, Hsi-Lung Hsieh*. (2022) Brain Protective Effect of Resveratrol via Ameliorating Interleukin-1β-Induced MMP-9-Mediated Disruption of ZO-1 Arranged Integrity. Biomedicines 10(6):1270.
7. Yi-Hsuan Wu, Hsi-Lung Hsieh*. (2022) Roles of Heme Oxygenase-1 in Neuroinflammation and Brain Disorders. Antioxidants (Basel) 11(5):923. (Review)
8. Hsi-Lung Hsieh, Ming-Chin Yu, Li-Ching Cheng, Mei-Yi Chu, Tzu-Hao Huang, Ta-Sen Yeh, Ming-Ming Tsai*. (2022) Quercetin exerts anti-inflammatory effects via inhibiting tumor necrosis factor-α-induced matrix metalloproteinase-9 expression in normal human gastric epithelial cells. World Journal of Gastroenterology 28(11):1139-1158.
9. Hsi-Lung Hsieh, Ming-Chin Yu, Li-Ching Cheng, Ta-Sen Yeh, Ming-Ming Tsai*.  (2022) Molecular mechanism of therapeutic approaches for human gastric cancer stem cells. World Journal of Stem Cells 14(1):76-91. (Review)
10. Hsi-Lung Hsieh, Ching-Chung Liang, Cheng-You Lu, Jen-Tsung Yang, Chiu-Yen Chung, Yu-Shien Ko, Tsong-Hai Lee. (2021) Induced pluripotent stem cells can improve thrombolytic effect of low-dose rt-PA after acute carotid thrombosis in rat. Stem Cell Research & Therapy 12(1):549.
11. Te-Chien Ku, Pin-Han Wang, Jhen-Ling Huang, Hsing-Yu Chen, Ji-Tseng Fang, Hsi-Lung Hsieh*, Jiun-Liang Chen. (2021) The survival outcome of nasopharyngeal cancer patients with traditional Chinese medicine external use: A hospital-based study. Journal of Ethnopharmacology 279:114380-114389.
12. Tong-Hong Wang, Chin-Chuan Chen, Yann-Lii Leu, Yun-Shien Lee, Jang-Hau Lian, Hsi-Lung Hsieh*, Chi-Yuan Chen. (2021) Palbociclib induces DNA damage and inhibits DNA repair to induce cellular senescence and apoptosis in oral squamous cell carcinoma. Journal of the Formosan Medical Association 120(9):1695-1705.
13. Tsong-Hai Lee, Pei-Shan Liu, Su-Jane Wang, Ming-Ming Tsai, Velayuthaprabhu Shanmugam and Hsi-Lung Hsieh*. (2021) Bradykinin, as a Reprogramming Factor, Induces Transdifferentiation of Brain Astrocytes into Neuron-Like Cells. Biomedicines 9(8): 923.
14. Kuei-Hung Lai, Po-Jen Chen, Chih-Chuan Chen, Sien-Hung Yang, Mohamed El-Shazly, Yu-Chia Chang, Yi-Hsuan Wu, Yi-Hsiu Wu, Yi-Hsuan Wang, Hsi-Lung Hsieh*, Tsong-Long Hwang. (2021) Lophatherum gracile Brongn. attenuates neutrophilic inflammation through inhibition of JNK and calcium. Journal of Ethnopharmacology 264:113224-113233.
15. Tsong-Hai Lee, Jiun-Liang Chen, Pei-Shan Liu, Ming-Ming Tsai, Su-Jane Wang, Hsi-Lung Hsieh*. (2020) The COX-2-derived PGE₂ autocrine contributes to bradykinin-induced matrix metalloproteinase-9 expression and astrocytic migration via STAT3 signaling. Cell Communication and Signaling 18(1):185-197.
16. Tsong-Hai Lee, Jiun-Liang Chen, Pei-Shan Liu, Ming-Ming Tsai, Su-Jane Wang, Hsi-Lung Hsieh*. (2020) Rottlerin, a natural polyphenol compound, inhibits up-regulation of matrix metalloproteinase-9 and brain astrocytic migration by reducing PKC-δ-dependent ROS signal. Journal of Neuroinflammation 17(1):177-189. 
17. Yu-Chia Chang, Kuei-Hung Lai, Sunil Kumar, Po-Jen Chen, Yi-Hsuan Wu, Ching-Long Lai, Hsi-Lung Hsieh*, Ping-Jyun Sung, Tsong-Long Hwang. (2020) ¹H NMR-Based Isolation of Anti-Inflammatory 9,11-Secosteroids from the Octocoral Sinularia leptoclados. Marine Drugs 18(5): 271-280.
18. Hsi-Lung Hsieh, Ming-Ming Tsai. (2019) Tumor progression-dependent angiogenesis in gastric cancer and its potential application. World Journal of Gastrointestinal Oncology 11(9): 686-704.
19. Chian-Jiun Liou, Chuen-Mao Yang, Tsong-Hai Lee, Pei-Shan Liu, Hsi-Lung Hsieh*. (2019) Neuroprotective Effects of Dehydroepiandrosterone Sulfate Through Inhibiting Expression of Matrix Metalloproteinase-9 from Bradykinin-Challengened Astroglia. Molecular Neurobiology 56(1):736-747.

實驗室活動剪影 (Laboratory Activities Snapshots)