生物醫學研究所

棘阿米巴原蟲相關研究

棘阿米巴角膜炎是由棘阿米巴原蟲造成的角膜損傷疾病,臨床中發現大部分的棘阿米巴角膜炎患者多長期配戴隱形眼鏡。棘阿米巴角膜炎會造成的症狀包含:眼睛畏光、視力模糊、眼睛異物感以及失明等，感染嚴重者需進行摘除眼球手術。隱形眼鏡配戴除棘阿米巴角膜炎外，細菌性感染也時常發生，細菌性角膜炎使用抗生素作為主要治療手段,但常用的眼用抗生素對於棘阿米巴並不具殺滅效果，而棘阿米巴有攜帶致病性細菌的能力並造成嚴重角膜炎，臨床案例也指出多重感染性角膜炎較難被治癒且嚴重性較高。過去研究已經發現棘阿米巴具有多種藥物耐受相關基因，而在我們的藉由細菌表達系統以及抗生素敏感性實驗，我們證實棘阿米巴中的β-內酰胺酶對於數種β-內酰胺類抗生素具有干擾效果。除了抗藥性相關基因導致棘阿米巴相關角膜炎治療效果不佳之外，臨床案例報告指出葡萄糖酸氯己定(chlorhexidine digluconate, CHG) 雖然為治療棘阿米巴角膜炎的第一線藥物，然而在部分案例中發現 CHG 無法有效治癒棘阿米巴相關角膜炎。因此，在本研究中我們想要了解為何體外試驗證實CHG有良好的殺滅棘阿米巴效果而在臨床使用卻無法有效控制棘阿米巴感染。我們的研究成果將提供棘阿米巴用藥的參考,並提升臨床藥物對於棘阿米巴感染症治療的效果。

口腔鞭毛蟲相關研究

口腔鞭毛蟲是一種有鞭毛的厭氧原生動物，被認為是人類口腔中的共生生物，主要存在於牙周袋、牙齦縫隙和牙菌斑內。研究顯示它與口腔衛生不良和牙周炎有關。儘管先前的研究表明口腔鞭毛蟲會引起細胞損傷併吞噬宿主上皮細胞，但其對牙齦細胞的病理作用仍不清楚。而且，在患有肺部疾病的個體的支氣管肺泡灌洗液（Bronchoalveolar lavage fluid, BALF）中也檢測到了它的存在。因此，我們的首要目的是確定口腔鞭毛蟲對牙齦和肺細胞系的細胞毒性和免疫作用。我們的結果證實，口腔鞭毛蟲可以引起牙齦細胞的細胞毒性，破壞細胞連接，並誘導牙齦和肺細胞系產生介白素-6。

接下來我們想要解析口腔鞭毛蟲在肺炎中的潛在作用，因此闡明寄生蟲與疾病之間的關係十分重要。我們與嘉義基督教醫院胸腔科合作採用巢式聚合酶鍊式反應檢測肺炎相關病患的BALF，並分析肺炎患者中與口腔鞭毛蟲感染相關的臨床因素。研究中納入了2022年8月至 2023 年8月期間在成大醫院接受肺支氣管鏡檢查的61名肺炎患者。我們的數據顯示，口腔鞭毛蟲的檢出與細菌感染、高肺炎嚴重程度指數(PSI)評分、鼻胃管餵食和肺部併發症之間存在顯著關聯。邏輯迴歸分析也顯示，口腔鞭毛蟲與肺炎患者的這些臨床因素之間有強烈的相關性。這些結果顯示肺炎中的口腔鞭毛蟲感染伴隨細菌感染和嚴重的臨床表現。

除了肺炎之外，我們也與成功大學附設醫院胸腔科合作檢測口腔鞭毛蟲於肺癌患者的流行率。肺癌是全世界最常見的惡性腫瘤之一。我們的研究結果進一步顯示口腔鞭毛蟲的感染導致致癌相關的路徑的顯著上調，其中包括細胞增殖、遷移和抗藥性基因的表達。

1. Chun-Hsien Chen; Jian-Ming Huang; Yu-Jen Wang; Chih-Ming Tsai; Wei-Chen Lin (2025, Apr). Recent in vitro advances in the ocular antimicrobial agents against Acanthamoeba. International Journal for Parasitology: Drugs and Drug Resistance.

2. Chun-Hsien Chen, Wei-Hung Cheng, Ling-Shan Syue, Ming-Chi Li, ChinShiang Tsai (2024, Dec). Entamoeba histolytica and Cryptosporidium coinfections in an HIV-infected, viral suppressed patient with a normal CD4 count. Journal of Microbiology, Immunology and Infection.

3. Chun-Hsien Chen, Jenn-Wei Chen, Chao-Han Lai, Chih-Ming Tsai , Chien-Chin Chen, Wei-Chen Lin, Po-Chuan Chen (2024, Oct). Antibiotic cocktail followed by Clostridium butyricum (CBM588) supplementation improves colonic anastomotic healing in mice. Journal of Functional Foods, 121. NSTC 112-2320-B-006-051.

4. Chun-Hsien Chen, Chin-Wei Kuo, Chih-Ming Tsai, Zih-Bin Hong , Ching-Han Lai, Tzu-Yi Chan, Wei-Chen Lin (2024, Aug). Detection of trichomonads in patients with lung cancer and transcription analysis on the response of human pulmonary epithelial cells to Trichomonas tenax invasion. Journal of Microbiology, Immunology and Infection , 57(4). NSTC 112-2320-B-006-051.

5. Ming-Der Shi,Ko-Chiang Sung,Jian-Ming Huang,Chun-Hsien Chen, Yu-Jen Wang (2024, Jun). Development of an Ex Vivo Porcine Eye Model for Exploring the Pathogenicity of Acanthamoeba. Microorganisms, 12(6), 1161.

6. Zih-Bin Hong, Yu-Ting Lai, Chun-Hsien Chen, Ching-Han Lai, Yi-Jen Chen, Chin-Wei Kuo, Tzu-Yi Chan, Pei-Chi Fang, Chien-Chin Chen, Wei-Chen Lin (2024, Jun). Prospective observational study of Trichomonas tenax infection in patients with pneumonia. Heliyon, 10(12). NSTC 112-2320-B-006-051.

7. Chun-Hsien Chen, Chen-Chieh Liao, Yu-Jen Wang, Fu-Chin Huang, Wei-Chen Lin (2023, Dec). A. castellanii and P. aeruginosa mutually exacerbate damage to corneal cells during coinfection. Microbiology Spectrum, 12(1). e0268323.NSTC 112-2320-B-006-051.

8. Chih-Ming Tsai, Chun-Hsien Chen, Wei-Hung Cheng, Foekje F Stelma, Sung-Chou Li, Wei-Chen Lin (2023, Jul). Homeostasis of cellular amino acids in Acanthamoeba castellanii exposed to different media under amoeba-bacteria coculture conditions. BMC Microbiology, 23,1 198.. NSTC 111-2628-B-006-003.

9. Chen-Chieh Liao, Chun-Hsien Chen, Jyh-Wei Shin, Wei-Chen Lin , Chien-Chin Chen, Chun-Ting Chu (2023, Jun). Lipid Accumulation in Blastocystis Increases Cell Damage in Co-Cultured Cells. Microorganisms,

11(6):1582. Chia-Yi Christian Hospital and National Cheng Kung University Hospital: NCKUCYCP11102-1-1.

10. Zih-Bin Hong, Yu-Ting Lai, Chun-Hsien Chen, Yi-Jen Chen 2, Chien-Chin Chen, Wei-Chen Lin (2023, May). Trichomonas tenax induces barrier defects and modulates the inflammatory cytotoxicity of gingival and pulmonary epithelial cells. Parasite, 30:7. Chia-Yi Christian Hospital and National Cheng Kung University Hospital: NCKUCYCP-11102-1-1.

11. Yu-Jen Wang, Chun-Hsien Chen, Jenn-Wei Chen, Wei-Chen Lin (2021, Dec). Commensals Serve as Natural Barriers to Mammalian Cells during Acanthamoeba castellanii Invasion. Microbiology spectrum, 9(3), e0051221. MOST 109-2628-B-006-022.

12. Jian-Ming Huang, Pin-Ju Ko, Chao-Li Huang, Po-Wei Wen, Chun-Hsien Chen, Min-Hsiu Shih, Wei-Chen Lin, Fu-Chin Huang (2021, Nov). Cytochrome P450 monooxygenase of Acanthamoeba castellanii participates in resistance to polyhexamethylene biguanide treatment. Parasite, 28, 77.

13. Yu-Ying Chen, Chun-Hsien Chen, Wei-Chen Lin, Chih-Wei Tung, Yung-Chia Chen, Shang-Hsun Yang, Bu-Miin Huang and Rong-Jane Chen (2021, Aug). The Role of Autophagy in Anti-Cancer and Health Promoting Effects of Cordycepin.

14. Molecules, 26(16), 4954. MOST 110-2628-B-006-032. 14. Chun-Hsien Chen, Yu-Jen Wang, Jian-Ming Huang, Fu-Chin Huang and WeiChen Lin (2021, May). Inhibitory effect of host ocular microenvironmental

factors on chlorhexidine digluconate activity. Antimicrobial Agents and Chemotherapy, 65(5), e02066-20. MOST 109-2628-B-006-022.

15. Chun-Hsien Chen, Hsin-Chun Chen, Wen-Te Chang, Meng-Shiou Lee, Yi-Chen Liu, Ming-Kuem Lin (2020, Apr). Magnoliae Flos Essential Oil as an Immunosuppressant in Dendritic Cell Activation and Contact Hypersensitivity Responses. The American Journal of Chinese Medicine, 48(3), 597-613. MOST 108-2320-B-039-019.