全國中小學科展

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醫學與健康科學

探討環形 RNA circACTN4 在非小細胞肺癌中的特性及功能

肺癌是世界上死亡率第一的癌症。根據近期研究發現,環形RNA (circular RNA;circRNA)比一般的線狀 mRNA穩定,並且會調控癌細胞。但circRNA於肺癌中的調控機制仍不清楚,因此我們決定挑選一個circRNA作為研究對象。首先,我們從 GEO 公開資料庫中篩選肺癌病人中差異表現的 circRNA,經 qPCR在肺癌細胞株驗證後,最終找到circACTN4 進行後續的研究。實驗結果顯示 circACTN4 在肺癌細胞株中確實為環狀結構,內生性表現量上升,且大都分布在細胞質。使用siRNA降低 circACTN4 表現量後,會增加細胞停留在細胞週期之G1期的數量,且 CDK4 和 CCND1 蛋白量也會降低。因此我們推測 circACTN4 可以促進肺癌細胞增殖的效果。更進一步的研究揭示,circACTN4能與LRPPRC蛋白結合,這種相互作用可能是circACTN4在肺癌中發揮調控作用的關鍵機制。總上所述,circACTN4 會促進肺癌細胞的生長,盼未來能作為預後的指標,並發展為治療肺癌的新標的。

Utilizing Flavonoids From the Invasive Species Pilea Melastomoides and Daucus Carota as Well as the Protein PTK-2 to Create a Skin Gel Aimed for Burn Wound Healing.

Burns are a major global health concern especially in developing countries like 印尼, where southeast asian women experience the highest burn incidents globally. Burns can cause severe physical and psychological impacts, with treatments that are critical to reduce complications. This study focuses on the development of organic, cost-effective burn gels using flavonoid compounds which are Quercetin and Myrecetin which are taken from pilea melastomoides leaves, a wild 印尼n plant and carrot (Daucus Carota). These skin extracts aim to accelerate wound healing, minimize pain and prevent infection. The gel formation involves extracting active compounds using 96% ethanol as it has been effectively used for extracting a wide range of bioactive compounds to preserve their quality by preventing microbial contamination, and ensures a high yield of active ingredients suitable for topical applications. Then it goes through a process of Phytochemical screening to confirm the presence of flavonoids by using the Shinoda test. The formulation process included dissolving the HPC-m (Hydroxypropyl Cellulose) as a gelling agent, then adding plant extracts (pilea melastomoides leaves and carrot), as well as combining other ingredients such as propylene glycol, sodium benzoate, sodium metabisulfite, and disodium EDTA. The gel was stirred thoroughly to ensure uniformity and left at room temperature for 48 hours to attain the required consistency. The gel that was formatted went under various quality assessments, first being organoleptic testing. This test is used to evaluate its physical characteristics which includes color aroma, and consistency which confirms a stable dark green appearance and a natural strong scent from the plant extracts. The homogeneity test is used to verify the uniformity distribution of active compounds across the gel, to ensure a consistent efficacy. The pH test showed the gel’s acidity level which remained the safe range for skin application. Additionally, the spreading ability test demonstrated the gel’s excellent application properties, with consistent results across trials. Subsequently, the in silico analysis was conducted to predict the behaviour of specific flavonoid compounds used which is the myricetin and quercetin, highlighting their potential anti-inflammatory and antimicrobial activities. Further bacterial contamination tests confirmed the gel’s antimicrobial efficacy, reducing the risk of infection in wounds. This study demonstrates that the gel, formulated with pilea melastomoides leaves and carrot skin extracts, effectively utilizes flavonoids and other phytochemicals to reduce inflammation, promote tissue regeneration and retain moisture, which fosters an optimal condition for wound healing. This organic and sustainable burn treatment utilizes locally sourced ingredients, providing a natural solution that speeds up recovery, reduces pain and prevents infections. The results highlight its significant potential for wider healthcare use, especially in resource-limited environments.

探討環形 RNA circACTN4 在非小細胞肺癌中的特性及功能

肺癌是世界上死亡率第一的癌症。根據近期研究發現,環形RNA (circular RNA;circRNA)比一般的線狀 mRNA穩定,並且會調控癌細胞。但circRNA於肺癌中的調控機制仍不清楚,因此我們決定挑選一個circRNA作為研究對象。首先,我們從 GEO 公開資料庫中篩選肺癌病人中差異表現的 circRNA,經 qPCR在肺癌細胞株驗證後,最終找到circACTN4 進行後續的研究。實驗結果顯示 circACTN4 在肺癌細胞株中確實為環狀結構,內生性表現量上升,且大都分布在細胞質。使用siRNA降低 circACTN4 表現量後,會增加細胞停留在細胞週期之G1期的數量,且 CDK4 和 CCND1 蛋白量也會降低。因此我們推測 circACTN4 可以促進肺癌細胞增殖的效果。更進一步的研究揭示,circACTN4能與LRPPRC蛋白結合,這種相互作用可能是circACTN4在肺癌中發揮調控作用的關鍵機制。總上所述,circACTN4 會促進肺癌細胞的生長,盼未來能作為預後的指標,並發展為治療肺癌的新標的。

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。

New Concept of Intelligent Wound Dressing

Substance losses, burns and injuries arising from various causes represent a constant problem encountered by homo sapiens throughout its existence. Rudimentary treatments, relatively effective and less effective, have left their mark on the way we perceive the presence and treatment of wounds caused by various factors. Searching through medical archives, we can trace the specific protocols for these medical conditions back to 2200 BC, when they were structured in three steps: 1) cleaning the skin lesion, 2) applying a dressing (from glue to various preparations) and 3 ) bandaging the skin lesion. Currently, the appearance of wounds on the skin is caused both by accidents in the performance of various activities and by certain diseases that manifest themselves through skin rashes or skin lesions. Their frequency is in the thousands, according to the latest statistics, affecting the majority of the population non-selectively. It is vital that skin lesions receive the necessary care and attention, commensurate with their severity. Being open wounds on the surface of the skin, it is essential that the treatment be meticulous and appropriate to their type, as skin lesions represent a threat to the patient's life. From infections to hydroelectrolytic imbalances specific to burns, the multitude of factors that influence healing highlight the need for a dressing that can be easily customized according to the specificity of the wound, the needs of the patient and that is affordable both from the point of view of production cost as well as its use, making death from skin lesions easily avoidable through an intelligent approach. One of the most complex biological processes and indispensable to humans is the healing of skin lesions. Healing involves a carefully regulated series of biochemical and cellular activities in tandem. Traditional therapies and substances of natural origin have been used to facilitate the regeneration process and accelerate the wound healing process, being applied with encouraging results. Despite the fact that these generally present a low cost, they can be more expensive than contemporary treatments and can be influenced by regional, seasonal factors, showing fluctuations from batch to batch, which could lead to unpredictable allergic reactions, side effects and inconsistent clinical findings. Currently, the standard of care for skin lesions is to clean the wound with antiseptic solutions to prevent infection, apply a dressing followed by bandaging to keep the dressing in place, and if necessary excision of the tissue that has become non-viable. In the case of diabetic ulcers, it is necessary to excise the tissue that has become non-viable and to maintain control over the level of glucose in the body.

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。

探討長片段非編碼RNA:IRX4-AS1在前列腺癌中的角色 Investigate the Role of Long Non-Coding RNA: IRX4-AS1 in Prostate Cancer

前列腺癌(PCa)是全球男性最常見的惡性腫瘤,雄性激素受體拮抗劑是常用的治療藥物,而其存在抗藥性演進問題。人類基因組有98%的基因未編碼蛋白質,許多研究證明這些非編 碼RNA在細胞中具重要功能,並與前列腺癌進程有關。 本研究藉由分析病人檢體資料,發現IRX4-AS1在前列腺癌細胞的表現量高於正常細胞,並且IRX4-AS1表現量較高的病人五年存活率較差。我們也在體外實驗發現,IRX4-AS1的202異構型主要表現在細胞核;203異構型則多在細胞質,兩者可能有不同作用機轉。相較於IRX 4,IRX4-AS1的穩定性較高,顯示其可能與蛋白質共同作用。在抗藥性細胞株中,IRX4-AS1表現量則低於正常細胞株。 未來將研究IRX4–AS1對前列腺癌惡化與抗藥性的影響,期待其能做為疾病診斷及預後的生物標誌物。

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。

維持粒線體功能的重要基因Rrm2b對於不同種類中樞神經細胞的調控與影響

老化造成的神經退化性疾病,與細胞內粒線體機能異常有重要的關聯性。已知核醣核苷酸還原酶 M2B (Rrm2b) 的主要負責協助粒線體的基因合成、修復以及功能維持。本研究以核醣體核酸干擾技術,使 Rrm2b 表現量降低,探討其對不同種類中樞神經細胞粒線體 DNA 含量、細胞形態及功能的影響。結果顯示,Rrm2b 表現量降低並不會對粒線體 DNA 含量造成影響,但會使呼吸作用的效率降低,以及讓神經細胞更易分化,甚至反分化。同時,星狀膠細胞中的水通道蛋白表現量增加 165%,葡萄糖轉運蛋白表現量增加 27%,麩胺醯胺合成酶表現量則降低 22%。因此,Rrm2b 的低表現量,使星狀膠細胞運輸功能變強,而麩胺醯胺的合成變慢,則氨的代謝減緩。這些星狀膠細胞異常可能是造成腦部功能受損的原因之一。

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。