全國中小學科展

醫學與健康科學

利用 Verapamil 引發斑馬魚胚胎心衰竭模式並探討臨床心衰竭用藥 Dapagliflozin 和 Valsartan 之成效與機制

本研究利用 Verapamil 誘導斑馬魚胚胎心衰竭模式,並探討 Dapagliflozin 對斑馬魚胚胎表皮離子細胞的調控機制,以加深對 SGLT2 inhibitors 機制的了解。受精後第四天的斑馬魚在暴露於Verapamil 24小時後,除了抑制卵黃囊吸收以及造成心包膜水腫以外,對心臟整體功能(HR, EDV,ESV, SV, EF, CO)具負面影響。以粒線體染劑標記離子細胞,發現Verapamil使其密度上升,使用掃描式電子顯微鏡觀察,則可看到離子細胞頂端開口有明顯的萎縮,影響到正常功能。以抗體標記染色的方式檢測不同離子細胞亞型,顯示 Dapagliflozin 使富含 Na⁺-K⁺ ATPase 的 HR 細胞和富含 H⁺-ATPase 的 NaR 細胞密度上升。同時,心臟功能診斷標誌物的 mRNA 水平(naap, nppb,gata4, vmhc)暴露於Verapamil後上升,促進離子細胞代償性上調。

探討肝癌細胞中動力蛋白抑制對於癌症轉移的影響

肝細胞癌 (HCC) 為全球導致高死亡率的癌症之一,第一線標靶治療藥物 Sorafenib 雖能延長患者存活期,但其療效有限且伴隨嚴重副作用。在癌症中,中心體異常所導致的染色體變異是腫瘤發展的關鍵因素,而動力蛋白已知參與中心體裝配,且前人研究結果表明動力蛋白與肺癌、 HCC 等多種癌症有關連 。故本研究先透過基因表現資料庫分析,發現 HCC患者中的動力蛋白重鍊基因表現量大致顯著高於一般,後以 Ciliobrevin D 抑制三種 HCC 細胞株 Hep3B、HepG2、Huh-7 中的動力蛋白,並藉細胞存活率分析、遷移試驗與西方墨點法,探討抑制動力蛋白與 HCC 的關聯。據實驗結果,抑制動力蛋白後, Huh-7 的遷移速率減緩, 蛋白質表現量亦隨抑制劑濃度升高而降低。這表示抑制動力蛋白具有抑制肝癌細胞轉移的潛力,期未來能成為肝癌新的治療靶點。

Natural resources utilization for the in-house production of fluorescence lipid nanoparticles

Nanotechnology, a transformative force, has steadily gained traction across multiple scientific disciplines, including physics, chemistry, engineering, and biology. It offers unprecedented capabilities, especially in the realm of nanoscale particles, ushering in new paradigms in various applications. One of the most revolutionary applications of nanotechnology is in the pharmaceutical sector. Here, nanoparticles have transformed drug and vaccine delivery systems, offering both efficacy and precision. Among these nanoparticles, lipid nanoparticles (LNPs) have stood out, especially for their role in delivering nucleic acid-based drugs and vaccines. These LNPs are intricate assemblies composed of lipids and nucleic acid complexes, offering an amalgamation of stability and deliverability. Such properties have rendered LNPs as invaluable tools in enhancing therapeutic efficacy while minimizing off-target side effects. The myriad of nanoparticles available includes the likes of silver, gold, and lipid nanoparticles. However, the emphasis of this research lies with lipid nanoparticles, given their widespread success in the pharmaceutical arena. LNPs have showcased their potential in delivering drugs with low therapeutic indices, emphasizing their capability to act as versatile platforms for novel drug development. Recent advances have further expanded the horizons of LNPs, paving the way for novel antisense oligonucleotides, innovative vaccines, and complex lipid nanoparticle formations. Characterizing these nanoparticles is paramount, not only for the development of novel drugs but also to comprehend their in vivo behavior. Their multifaceted nature, stemming from their unique excipients, core-bilayer design, and varying sizes, makes their characterization a critical step in the research and development pipeline.

KidneyLifePlus+ : Retinal Imaging Analysis for Kidney Disease Risk Assessment

Chronic kidney disease (CKD) represents a significant public health challenge, often referred to as a “silent disease” due to its asymptomatic progression during early stages (1–2). Consequently, most diagnoses occur during advanced stages (3 and beyond), where treatment options are more complex and outcomes are less favorable. Globally, CKD affects over 850 million individuals, with 434.3 million cases in Asia alone. Despite its prevalence, early-stage awareness remains alarmingly low, with only 5% of affected individuals aware of their condition. Existing screening methods are predominantly hospital-based, expensive, and time-intensive, limiting their accessibility, particularly in resource-constrained settings. This underscores an urgent need for more accessible and efficient diagnostic tools to enable early intervention. In response to this critical problem, we developed KidneyLifePlus+, an AI-powered platform that leverages advanced machine learning models, including U-net, ResNet-50, and YOLO v8, to analyze retinal images for early CKD detection. These models are integrated to ensure high screening accuracy by identifying subtle biomarkers indicative of CKD progression. Complementing the software, we designed proprietary hardware capable of capturing high-resolution retinal images, delivering performance comparable to hospital-grade equipment. By ensuring affordability and ease of use, the system extends screening capabilities beyond clinical environments, making it suitable for deployment in community healthcare settings. KidneyLifePlus+ addresses key limitations of traditional methods by offering a rapid, cost-effective, and highly accurate diagnostic solution. The platform’s potential to enhance early detection rates could significantly improve clinical outcomes and quality of life for CKD patients. Furthermore, this innovation contributes to global efforts to reduce the burden of CKD by promoting equitable access to diagnostic services, particularly in underserved regions.

天狗現形劑-研發分辨四型登革病毒之抗原快篩試劑

登革熱(Dengue Fever)俗稱天狗熱,由登革病毒(Dengue virus; DENV)透過埃及斑蚊(Aedes aegypti)和白線斑蚊(Aedes albopictus)傳播並於熱帶及溫帶地區肆虐。每年全球約有五千萬至一億人感染登革病毒,約有五十萬人因登革出血熱(Dengue Hemorrhagic Fever; DHF)而住院。登革熱主要流行於熱帶及亞熱帶地區,尤其是與台灣頻繁往來的東南亞國家,其中一型與二型在東南亞國家病例數較高。當不同血清型登革病毒交錯感染容易引發登革出血熱以及登革休克症候群(Dengue Shock Syndrome),對公共衛生構成重大挑戰。因此研發可快速辨識四型登革病毒之檢驗試劑將有助於提升臨床診斷與後續治療。本報告的研究結果有三項,(1)四型登革病毒NS1 (Nonstructural Protein 1)蛋白的表達與純化:利用分子生物技術成功構建載體並純化四型NS1蛋白,作為免疫原蛋白用於小鼠免疫;(2)單株抗體的篩選與親和性測試:經三次免疫後,利用小鼠脾臟細胞與骨髓瘤細胞進行融合,篩選並生產針對NS1蛋白的單株抗體(monoclonal antibody, mAb),並通過酵素結合免疫吸附法(Enzyme-linked immunosorbent assay, ELISA)驗證抗體的專一性及親和力;(3)快篩試劑的開發與性能測試:運用側向流體免疫層析法(lateral flow immunoassay)設計並組裝快篩試劑,先以重組蛋白進行初步測試,隨後將使用去活性病毒進行性能驗證,確保試劑的靈敏度與準確性。期望這些研究成果有助於台灣登革熱防疫且為臨床治療提供參考。

運用細胞水膠化技術製作微流道晶片進行抗原專一性T細胞之篩選 Flow-induced Mechanical Screening of Antigen Specific T cells with Biomimetic Microfluidic Chip

積極發展癌症相關治療策略極為重要,其中T細胞免疫療法(adaptive T cell therapy)是一深具臨床價值的選項。即是將T細胞自體內取出後並增殖到一定數量,而後將其回輸病人體內使得T細胞攻擊癌細胞。此方式關鍵的步驟在於必須要能夠篩選出足量的抗原專一性T細胞。現行主要的篩選方法雖然方便,但會誤捕不相關抗原專一性T細胞,降低治療效率。為解決此問題,本研究將利用水膠細胞技術,運用其完整保存生物膜的特性,模仿細胞膜之免疫突觸現象,搭配微流控晶片可控制流速改變沖刷力的特性,成功開發一可篩選親和力較高之T細胞微流道晶片。已在晶片內建立可置換任意抗原之水膠細胞單層,並以SIINFEKEL抗原作為模擬,達到極高之置換率。預期能在未來的研究中提升篩選專一性與數量,進而提升其臨床價值。

天狗現形劑-研發分辨四型登革病毒之抗原快篩試劑

登革熱(Dengue Fever)俗稱天狗熱,由登革病毒(Dengue virus; DENV)透過埃及斑蚊(Aedes aegypti)和白線斑蚊(Aedes albopictus)傳播並於熱帶及溫帶地區肆虐。每年全球約有五千萬至一億人感染登革病毒,約有五十萬人因登革出血熱(Dengue Hemorrhagic Fever; DHF)而住院。登革熱主要流行於熱帶及亞熱帶地區,尤其是與台灣頻繁往來的東南亞國家,其中一型與二型在東南亞國家病例數較高。當不同血清型登革病毒交錯感染容易引發登革出血熱以及登革休克症候群(Dengue Shock Syndrome),對公共衛生構成重大挑戰。因此研發可快速辨識四型登革病毒之檢驗試劑將有助於提升臨床診斷與後續治療。本報告的研究結果有三項,(1)四型登革病毒NS1 (Nonstructural Protein 1)蛋白的表達與純化:利用分子生物技術成功構建載體並純化四型NS1蛋白,作為免疫原蛋白用於小鼠免疫;(2)單株抗體的篩選與親和性測試:經三次免疫後,利用小鼠脾臟細胞與骨髓瘤細胞進行融合,篩選並生產針對NS1蛋白的單株抗體(monoclonal antibody, mAb),並通過酵素結合免疫吸附法(Enzyme-linked immunosorbent assay, ELISA)驗證抗體的專一性及親和力;(3)快篩試劑的開發與性能測試:運用側向流體免疫層析法(lateral flow immunoassay)設計並組裝快篩試劑,先以重組蛋白進行初步測試,隨後將使用去活性病毒進行性能驗證,確保試劑的靈敏度與準確性。期望這些研究成果有助於台灣登革熱防疫且為臨床治療提供參考。

上皮細胞黏附分子(EpCAM)與Dabrafenib對未分化性甲狀腺癌(ATC)進程機制之探討

上皮細胞黏附分子(EpCAM)與上皮細胞間黏附、信息傳導、增殖與分化等功能有密切關係,已被證實會在多種上皮癌細胞中大量表達,被視為一種可行的臨床標記。透過 細胞存活率、細胞群落、轉移與侵入試驗,觀察到EpCAM能增強未分化性甲狀腺癌(ATC)的細胞增殖、生長、轉移與侵入能力。 此外實驗發現dabrafenib小分子抗癌藥物處理的ATC,其細胞增殖、生長、轉移與侵入能力均有下降的趨勢,而細胞凋亡程度則有顯著的上升。此次研究藉由西方墨點法發現,磷酸化ERK蛋白的表現量隨dabrafenib濃度的上升而逐步下降,顯示dabrafenib能夠抑制ATC細胞訊息傳遞路徑中ERK蛋白的磷酸化,進而影響ATC的生長。若能深入了解EpCAM和dabrafenib在癌細胞中的作用機轉,EpCAM相關藥物與dabrafenib未來在臨床應用上,或許能為ATC患者提供另一種新的治療方式。

運用細胞水膠化技術製作微流道晶片進行抗原專一性T細胞之篩選 Flow-induced Mechanical Screening of Antigen Specific T cells with Biomimetic Microfluidic Chip

積極發展癌症相關治療策略極為重要,其中T細胞免疫療法(adaptive T cell therapy)是一深具臨床價值的選項。即是將T細胞自體內取出後並增殖到一定數量,而後將其回輸病人體內使得T細胞攻擊癌細胞。此方式關鍵的步驟在於必須要能夠篩選出足量的抗原專一性T細胞。現行主要的篩選方法雖然方便,但會誤捕不相關抗原專一性T細胞,降低治療效率。為解決此問題,本研究將利用水膠細胞技術,運用其完整保存生物膜的特性,模仿細胞膜之免疫突觸現象,搭配微流控晶片可控制流速改變沖刷力的特性,成功開發一可篩選親和力較高之T細胞微流道晶片。已在晶片內建立可置換任意抗原之水膠細胞單層,並以SIINFEKEL抗原作為模擬,達到極高之置換率。預期能在未來的研究中提升篩選專一性與數量,進而提升其臨床價值。

Automated Alternative Compression/Traction of Lower Extremities AACT as a Musculoskeletal Countermeasure to Mitigate Bone Loss and Muscle Atrophy in Microgravity

Space Medicine and relevant sciences are still considered a new era; the first humankind steps toward the space took place since less than 60 years. It has been noticed the adverse effects of microgravity on the human body in different aspects, our concern here is the musculoskeletal aspect. On the ground we didn’t notice how we can stand up, or how our muscles and bones of the lower limbs can keep us standing up right. This is by a complicated process including the bones, the equilibrium, and the anti-gravitational muscles of the lower limbs which occurred without thinking about it. The force of Earth gravity against our bones of the lower limbs makes them harder and makes the muscles stronger, because they are interfacing the earth gravitational force every moment we are standing up, as per Newton’s third law (for every action in nature there is an equal and opposite reaction), such forces are unavailable in space and its effect being obvious on arrival to earth after long stay space flights, so being unable to keep standing upright easily on their arrival. On return to earth the routine medical examinations revealed loss of astronaut muscle mass and bone density particularly of their lower extremities because they did not use them in space for a long time. Currently, astronauts on board of ISS (International Space Station) they accomplish daily tasks including resistive exercises ARED “Advanced Resistive Exercise Device” in form of treadmill, ergometer, and weightlifting machine, to decrease the loss of bone density and muscle mass of their lower limbs. Despite their discipline to those exercises they still lose 1-2% of the muscle mass and bone density that give importance to add some protective measures to keep their muscles and bones healthy. Through this article, the idea is to make a device such AACT (Automated Alternative Compression/Traction) to be applied daily to the astronauts lower limbs as part of their daily exercise during space flight to give push/traction forces to astronauts lower limbs to prevent or at least decrease such loss, by AACT we are mimicking the gravitational force of earth on astounds lower limbs during long space flights to let them be healthy till they come back.