全國中小學科展

醫學與健康科學

THE DESIGN OF MICROFLUIDIC PUMP (MFP) FOR MEDICAL FIELD

The ability of microfluidic (MF) device technologies to provide a lot of information with a small amount of sample, the opportunities it offers increases their use in the medical field in the bedside monitoring in drug delivery systems. Three-dimensional (3D) printer technologies provide advantages such as cost-effectiveness in the production of MF devices and quick and easy production in intricate designs. In our project, it is aimed to design microfluidic pumps (MFP) to be used in the medical field and conduct its production with 3D printer technologies. The developed MFP is intended to be at low cost, bio-compatible, adaptable, and portable to the drug, suitable flow properties as a pharmaceutical pump. First of all, MFP air channel, flow channel, etc. parts were designed and printed with the help of a 3D printer and on AutoCAD, one of the professional drawing programs. The poly(dimethylsiloxane) (PDMS) membrane that will enable MFP activation is produced in different thicknesses and glued to the air channel of MFP. The resistance to the applied pressure is observed, and the appropriate membrane thickness is determined as ~ 235µm. Liquid PDMS was applied to the inner surfaces of MFP's air and flow channel, PDMS membrane was placed between them, and the parts were assembled in the oven at 60ºC. MFP has been connected to the pneumatic valve system, where operation codes have been prepared with Arduino Uno, and flow properties have been examined. The flow rate of MFP is ~ 50 µL/min at a maximum of 15 Hz, and the backpressure is ~ 0.085 Pa under a maximum pressure of 3 bar. Also, values such as size, membrane thickness, and applied pressure for the possible models of MFP were supported by theoretical calculations. As a result, MFP, which is biocompatible, drug adaptable, portable, wearable technology application potential, and has suitable flow characteristics as a pharmaceutical pump, has been developed. MFP introduced a microfluidic pump system that can make life easier for the patient and contribute to the national economy through domestic production and can be used as a drug pump in the treatment of diseases such as diabetes and cancer.

Consensus-based Machine Learning Model in the Scoring for Hepatic Steatosis Severity

研究目的:脂肪肝的盛行率在全世界的現代化國家都在增加。病理醫師在評估脂肪肝的嚴重等級時,常缺乏參考意見以減少差異。許多地區也缺乏病理醫師。本研究旨在建立一個有效評估脂肪肝嚴重程度的病理組織學人工智慧模型。研究過程:本研究經由臺中榮民總醫院人體研究倫理審查委員會審核通過,篩選後取得病理資料庫中適合的肝臟組織切片,由兩位病理醫師獨立為肝組織中脂肪堆積的程度評分。再以病理醫師討論後的共識答案為分級標準,來訓練人工智慧模型。研究結果:在100個樣本的獨立測試中,人工智慧模型和病理專科醫師的評分,有71%完全相同、27%差異只有一個等級、2%差異2個等級、而沒有2個等級以上的差異。結論及應用:我們已初步建立一個可以評估脂肪肝嚴重程度的人工智慧模型。這模型可為將來人工智慧的臨床應用,建立一個良好的基礎。

探討組蛋白脫乙醯酶HDAC7對於癌細胞DNA損傷修復機制之影響

DNA損傷導致的基因體不穩定是癌症的共同特徵,而細胞依賴DNA損傷反應 (DDR) 來感知和修復受損的DNA,以維持基因體完整。DDR由DNA損傷傳感信號和修復網絡組成, DDR的活化可阻滯細胞週期並啟動DNA修復,是應對DNA損傷的關鍵步驟。其過程受許多因素調控,包括多種轉譯後修飾如乙醯化、脫乙醯化、小泛素化等。HDAC7是組蛋白脫乙醯酶,該家族成員有多個已被證實參與DDR且在多種癌細胞中常過量表現。最近研究發現HDAC7具小泛素蛋白E3連接酶活性,但相關研究甚少,因此欲探討HDAC7在DDR所扮演的角色。 本研究使用西方墨點法、免疫螢光染色、流式細胞儀分析、細胞存活率測試和細胞群落形成能力實驗,發現以RNAi技術將細胞的HDAC7基因沉默後會降低DNA損傷引起的ATR-Chk1及ATM-Chk2訊號強度,使不能有效率活化檢查點,並對DNA損傷藥物較敏感。由以上結果顯示,HDAC7有潛力做為抗癌藥物研發的新目標。

探討病毒配體與樹突細胞間的交互作用

由於新冠肺炎的影響,引發了世界的一陣恐慌,也促使我對於免疫系統及病毒之間的交互作用有了更濃厚的興趣。而在疾病的肆虐之下,疫苗儼然成為對抗病原體的重要武器。試想我們若能找到某些化合物,在未找到特定疾病的疫苗之前,能藉由化合物刺激增強人體免疫能力,進而達到對抗病毒的功效,或許會是未來萬用疫苗的首選。 目前已知一種配體R848在RNA病毒界具有一定的代表性,在動物實驗中對冠狀病毒的感染也有一定的功效,因此我希望進一步探究此配體在免疫系統中的作用。本研究以細胞株及小鼠骨髓細胞為材料,以R848、CpG等2種不同的配體刺激,發現R848濃度會影響細胞的分化種類及活性,而經過CpG再刺激的細胞將會被活化。且若於發育過程受到持續高濃度R848刺激,將會使細胞活性下降,進以避免自體免疫反應的發生。透過此研究,可初步了解R848影響免疫系統的途徑。

探討胞外基質軟硬度對神經突生長發育的影響

文獻指出若神經導管能針對不同組織調整適切軟硬度,將更有效協助神經再生,因此,了解胞外基質軟硬度對神經細胞的影響和其感知路徑非常重要。本研究以神經母細胞瘤Neuro-2a進行研究,分析不同軟硬度基質上N2a細胞面積、神經突長度。結果顯示分化後N2a細胞在100 KPa基質上面積大且神經突較長,說明N2a細胞能偵測基質軟硬度並進行生長調控。同時,advillin、paxillin、myosin IIa和pFAK等細胞骨架蛋白於細胞本體表現量在不同軟硬度基質上有所差異,但未與神經突長度相關。生長錐上細胞骨架蛋白表現量於不同軟硬度基質上具有差異,且與神經突長度趨勢吻合,說明神經細胞透過調控advillin和細胞骨架蛋白在生長錐上的表現量影響神經突生長長度。未分化N2a細胞轉染pAdvillin-IRES-hrGFP和pS1S3-HP-FLAG後長出神經突,且根據基質軟硬度生長情形不同,但轉染pS1S3-HP-FLAG長出的神經突長度較短,說明advillin的nucleation功能在神經突生長扮演重要角色。

香杉芝誘導黑色素癌細胞凋亡與自噬性死亡

香杉芝(Antrodia salmonea)是台灣特有的食藥用菇,具抗血癌、抗發炎及抗動脈硬化的功能。我們研究發現,香杉芝發酵液會誘導人類黑色素癌(A2058/A375)細胞毒性;比較香杉芝抗癌活性發現毒殺A2058強於A375細胞。我們亦發現,香杉芝作用黑色素癌(A2058)細胞,會誘導晚期凋亡(Annexin V-PI 雙染法)、Caspase-3增加及PARP裂解;產生自噬酸性囊泡(AVO)、促自噬蛋白LC3-II增加。加入細胞凋亡抑制劑 Z-VAD-FMK及自噬抑制劑3-MA/CQ可保護香杉芝誘導癌細胞死亡。此外,香杉芝會誘導黑色素癌細胞Bax/Bcl-2及Beclin-1/Bcl-2比例增加。推論,香杉芝可同時誘發黑色素癌細胞凋亡(Apoptosis)及自噬性死亡(Autophagy)。香杉芝會誘導黑色素癌細胞活性氧化物(ROS)生成;抗氧化劑N-acetylcysteine可減緩香杉芝對黑色素癌細胞毒殺。推測,香杉芝是透過ROS來殺死黑色素癌細胞。我們亦發現,香杉芝可與抗癌藥物Paclitaxe對黑色素癌細胞產生協同作用(CI<1)。總結,香杉芝發酵液具抗黑色素癌功效,可開發成抗癌的藥品/保健食品。

HOST TARGET PROTEINS OF SPIKE PROTEIN OF SARS-COV-2

Coronavirus Disease 2019 (COVID-19) is a newly emerged infectious disease caused by the new severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV-2). In less than one year, the virus has spread around the entire world, killing millions of people and disrupting travel and business worldwide. During infection, the virus uses its Spike protein to dock onto the Ace2 protein on the surface of its human host cell. Spike is 1273 amino acids long and only a short fragment of Spike (319-541) is sufficient to bind Ace2. We hypothesized that the remaining protein sequences of Spike might have functions for viral replication beyond the binding of Ace2. We have performed Split-Ubiquitin protein-protein interaction screens to isolate human proteins by their ability to bind to Spike, and we have identified Annexin2A2 and Cytochrome b as novel human protein interaction partners of Spike. Annexin2A2 is involved in both endocytosis and exocytosis, and the protein interaction with Spike might help the virus to enter and exit its host cell. The presence of the mitochondrial Cytochrome b protein inside the cytosol promotes apoptosis, and the protein interaction with Spike could speed up sapoptosis of the infected human cell. The Nub cDNA libraries that we have generated also allowed us to screen for synthetic peptides that interact with Spike. We have isolated two synthetic peptides, FL1a and FL7a, derived from the non-coding parts of human mRNAs by their ability to interact with Spike. We found that both FL1a and FL7a interact with the C-terminal half of the Spike protein. We also found that FL7a is able to block the Spike-Spike self-interaction at the C-terminal half of the Spike protein and we think that this could block the reassembly of the Spike protein in the host cell during viral reassembly. We hope that those synthetic peptides could be used as drugs due to their ability to block protein-protein interactions of Spike with human host proteins that are essential for viral replication.

Anti-bacterial Crab bio-bandages with Bio-dressings 2.0

Commercially available bandages such as hydrocolloid are neither biodegradable nor anti-bacterial. Chitin is known to be the second most naturally available polysaccharide which could be transformed to chitosan which is known to be anti-bacterial (Hasan, 2018) (Chao, 2019) and haemostatic (Okamoto, 2003) (Hu, 2018). Chitosan can be further converted to hydrogel which is bio-degradable and has good water absorbance. Anti-bacterial crab bio-bandages and crab bio-dressings should be bio-degradable as it took 42 days and a month for complete bio-degradation respectively, so they should be better than commercial bandages such as Nexcare Hydrocolloid as the disposal of anti-bacterial crab bio-bandages with bio-dressings would no longer pose burden to landfilling or threat to our environment. Anti-bacterial crab bio-bandages with bio-dressings are anti-bacterial with degree of deacetylation of DD% (measured using FTIR Spectrum II) 82.6% (due to the presence of chitosan) even without the application of other anti-bacterial agents and hence can provide complete protection of wounds from skin and soft tissues infections and haemostatic (due to the presence of chitosan). After testing and certification based on IS997:2004 and BS EN 13726-1, they should meet many requirements specified. Anti-bacterial crab bio-bandages should be eligible for marketing. Some results were as follows: 1.4 Anti-bacterial effect of crab hydrogels and roasted crab hydrogels Pure chitosan, crab chitosan, crab hydrogels and roasted crab hydrogels showed significant anti-bacterial effect. NO oral bacterial colonies were present in drinking water with crab hydrogels. Thus crab hydrogels could serve as effective anti-bacterial wound dressings. 1.6 Basing on IS997:2004 standard, the load per unit of area of anti-bacterial bio-bandages was 342g/m2 which met the minimum requirement of 36g/m2, the anti-bacterial bio-bandages had stronger tension strength (>20N both in dry and wet conditions) than commercial hydrocolloid. (2.7N dry 2.8N wet) which was comparable with that required (50-67N) and pH of about 7 which met the pH range of 4.5-8. 1.7 The FSA Free-Swell Absorbency of synthetic blood of crab hydrogel bio-dressings was 1.86g per 5cm x 5cm dressing which was much higher than that of commercial hydrocolloid (0.299g per 5cm x 5cm dressing) based on BS EN 13726-1.

尿液中不同物質對磷酸鈣、草酸鈣與尿酸結晶速率的影響

本研究主要研究人類尿液中,腎結石中的奈米細菌(nanobacteria)是礦物結晶或細菌成長作用,使用自製分光光度計,以OD值的差異劃分,結果顯示奈米細菌呈現礦物結晶特徵,成分分析亦證為磷酸鈣。之後研發腎結石抑制劑時,使用自製人工尿液,以磷酸鈣Ca3(PO4)2、草酸鈣CaC₂O₄和尿酸(C5H4N4O3)為主體,分別測試維他命C、(•OH)、模擬管壁發炎、模擬尿液pH值變化,並觀察其結晶型態變化,結果發現模擬管壁發炎OD值最高1.4,尿液pH值5時OD值 1.3次之。推斷腎結石主因與管壁發炎最密切,其次是pH值變化,偏酸與過鹼皆易產生結晶。最後以自製的結石抑制劑比較傳統C6H5K3O7(檸檬酸鉀) 抑制劑,本研究抑制劑OD值呈現較佳抑制效果。

HOST TARGET PROTEINS OF SPIKE PROTEIN OF SARS-COV-2

Coronavirus Disease 2019 (COVID-19) is a newly emerged infectious disease caused by the new severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV-2). In less than one year, the virus has spread around the entire world, killing millions of people and disrupting travel and business worldwide. During infection, the virus uses its Spike protein to dock onto the Ace2 protein on the surface of its human host cell. Spike is 1273 amino acids long and only a short fragment of Spike (319-541) is sufficient to bind Ace2. We hypothesized that the remaining protein sequences of Spike might have functions for viral replication beyond the binding of Ace2. We have performed Split-Ubiquitin protein-protein interaction screens to isolate human proteins by their ability to bind to Spike, and we have identified Annexin2A2 and Cytochrome b as novel human protein interaction partners of Spike. Annexin2A2 is involved in both endocytosis and exocytosis, and the protein interaction with Spike might help the virus to enter and exit its host cell. The presence of the mitochondrial Cytochrome b protein inside the cytosol promotes apoptosis, and the protein interaction with Spike could speed up sapoptosis of the infected human cell. The Nub cDNA libraries that we have generated also allowed us to screen for synthetic peptides that interact with Spike. We have isolated two synthetic peptides, FL1a and FL7a, derived from the non-coding parts of human mRNAs by their ability to interact with Spike. We found that both FL1a and FL7a interact with the C-terminal half of the Spike protein. We also found that FL7a is able to block the Spike-Spike self-interaction at the C-terminal half of the Spike protein and we think that this could block the reassembly of the Spike protein in the host cell during viral reassembly. We hope that those synthetic peptides could be used as drugs due to their ability to block protein-protein interactions of Spike with human host proteins that are essential for viral replication.