全國中小學科展

醫學與健康科學

Flavored Nanofiber Strips Loaded with Amoxicillin as an Alternative Method for Treating Bacterial Infections in Children

Semisynthetic penicillin, Amoxicillin, is a broad-spectrum antibiotic that is widely used to treat bacterial infections in children suffering ear, nose, and throat infections, genitourinary tract infections, skin infections, and lower respiratory tract infections1. This antibiotic works against both gram-positive and gram-negative bacteria, such as Listeria monocytogenes, Haemophilus influenza, Streptococcus pneumonia , Streptococcus pyogene and Escherichia coli1,2. It shows antibacterial activity by inhibiting dd-transpeptidase, which maintains the integrity of the bacterial cell wall which results in bacterial cell death due to a fragile cell wall3. Nonadherence to medication was associated with 50% of drug-related hospitalizations in children4. In order to improve adherence and influence clinical outcome, it is important to acknowledge the importance of drug palatability to children4–6. The currently available liquid suspension form of this antibiotic is administered to patients through oral/GI routes. It is also available in capsules or tablets for adults7–9. In the gastrointestinal tract, the drug has to withstand variable pH conditions and enzymatic degradation , mucus and mucosal barriers to survive resulting in limiting drug bioavailability10,11. In addition to conventional drug delivery formulations, nanofibers can be used to deliver drugs orally, topically, and through buccal or transdermal routes12. Drug-loaded nanofibers offer many advantages as a delivery system, including their porous structure and their efficient delivery of various drugs and bioactive molecules including hydrophobic and hydrophilic drugs12–14. Considering that amoxicillin palatability can affect children patients’ compliance and due to the advantages of both nanofiber drug delivery system and drug delivery through buccal routes, hence, this project aims to prepare flavored electrospun nanofibers loaded with amoxicillin to mask the unpleasant taste of the drug for treating children with bacterial infection. Nanofibers loaded with amoxicillin can be applied between the child's gum and cheek, allowing the fibers to dissolve in mucus and penetrate directly into the bloodstream.

Non-Invasive Vagus Nerve Stimulation as a Novel Therapy for Alzheimer’s Disease by Enhancing the Brain Clearance System(非侵入性迷走神經刺激術作為阿茲海默症的新療法—透過增強大腦清除系統)

阿茲海默症(AD)是導致失智症的主因,影響全球數千萬人。然而,AD目前的藥物大多昂貴且療效有限。目前已知腦內β類澱粉蛋白(Aβ)斑塊為AD的病理特徵,且大腦清除系統被認為對AD的治療具有重要性。先前研究發現非侵入性迷走神經刺激術(nVNS)增加腦脊髓液循環,但在神經退化疾病中的機制和應用尚不明確。本研究旨在探討nVNS增強大腦清除系統來作為AD新療法之成效,使用Aβ誘導之AD小鼠模型,利用巨視顯微鏡和免疫組織化學染色評估其膠淋巴系統功能,並以新奇事物測試評估認知功能。本研究發現於AD小鼠中,給予nVNS使大腦清除系統之水通道蛋白-4顯著增加、促進膠淋巴系統,進而改善認知功能。本研究首次發現nVNS可通過增強大腦清除系統功能,進而改善AD病理引起的失智症狀,支持nVNS作為AD新療法的可行性。

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。

YKT6與癌纖維母細胞的「泌」密關係

本研究以人類肺癌A549細胞株和纖維母細胞模擬體內腫瘤微環境,挖掘纖維母細胞如何促進癌細胞的生長。從病人的正常和癌組織提取癌相關纖維母細胞(cancer-associated fibroblasts, CAFs) 和 正常纖維母細胞(Normal Fibroblasts, NFs),經過基因序列一對對作分析,開發新的治療策略和潛在的靶點。利用核糖核酸定序(RNA-Seq)分析發現CAFs會比NFs分泌更多SNARE 蛋白 YKT6,而更深入地探究獲悉YKT6會透過活化YKT6+CAFs途徑促進肺癌A549細胞惡化,此惡化過程包括誘導及提升癌細胞的生殖(proliferation),轉移(migration)和入侵(invasion)能力。 此外,在 CAFs 中敲除 YKT6基因,減弱CAFs 的外泌體(exosome)釋放,從而調節了其對肺癌細胞A549的腫瘤促進作用。本研究發現靶向YKT6並抑制外泌體分泌,從而降低CAFs對肺腺癌細胞的腫瘤支援功能可以為肺癌治療提供一種新的策略。

Non-Invasive Vagus Nerve Stimulation as a Novel Therapy for Alzheimer’s Disease by Enhancing the Brain Clearance System(非侵入性迷走神經刺激術作為阿茲海默症的新療法—透過增強大腦清除系統)

阿茲海默症(AD)是導致失智症的主因,影響全球數千萬人。然而,AD目前的藥物大多昂貴且療效有限。目前已知腦內β類澱粉蛋白(Aβ)斑塊為AD的病理特徵,且大腦清除系統被認為對AD的治療具有重要性。先前研究發現非侵入性迷走神經刺激術(nVNS)增加腦脊髓液循環,但在神經退化疾病中的機制和應用尚不明確。本研究旨在探討nVNS增強大腦清除系統來作為AD新療法之成效,使用Aβ誘導之AD小鼠模型,利用巨視顯微鏡和免疫組織化學染色評估其膠淋巴系統功能,並以新奇事物測試評估認知功能。本研究發現於AD小鼠中,給予nVNS使大腦清除系統之水通道蛋白-4顯著增加、促進膠淋巴系統,進而改善認知功能。本研究首次發現nVNS可通過增強大腦清除系統功能,進而改善AD病理引起的失智症狀,支持nVNS作為AD新療法的可行性。

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。

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。

Analyzing Glucose Metabolism Connectivity in Huntington's Disease Using Dynamic Glucose-Enhanced MRI in zQ175 and R6/2 KI Mouse Models

亨丁頓舞蹈症為與認知功能障礙密切相關的神經退行性疾病。本研究首次應用動態葡萄糖強化磁振造影(DGE MRI)以了解葡萄糖代謝作為亨丁頓舞蹈症神經影像生物標記的可行性,以分析大腦中不同區域之間的代謝關係。 本研究對腦區間葡萄糖代謝關聯性進行分析,並針對訊號進行自動化分群,觀察特定訊號樣態之特徵。於zQ175 KI和R6/2 KI小鼠中不同的連接性變化模式中,發現紋狀體和齒狀回之間葡萄糖代謝連接性具顯著變化,與已知病理一致,顯示DGE MRI作為臨床生物標記之潛力,以利及時診斷和監測該疾病。 這項開創性的研究探索了使用DGE MRI作為亨丁頓舞蹈症影像標記可行性,並詳細分析腦區間葡萄糖代謝相關性,不僅進一步對該疾病之病理更加深入了解,同時提高早期診斷、疾病監測和精準醫療應用發展,說明可能有針對代謝紊亂的潛在治療策略。

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.