全國中小學科展

醫學與健康科學

探討miR-17-92透過調控T細胞分化影響腎纖維化

我國慢性腎病人口約 14%,大多患者會因藥物或免疫疾病而走向腎纖維化。根據文獻, miR-17-92 會影響 T 細胞分化,分化的差異則會造成不同程度的腎纖維化。 本研究取不同基因型小鼠的 CD4+T 細胞做體外分化。結果顯示含 miR-17-92 基因較多的 T 細胞分化成 Th1 比例較高、Treg 比例較少,但對 Th17 無顯著影響。將小鼠腎纖維化模式處理的細胞進行 RT-qPCR 和染色實驗,觀察剔除 miR-17-92 基因的小鼠(簡稱 KO)腎纖維化的情形,發現造成腎纖維化的纖維蛋白、膠原蛋白和其 mRNA 的表現量均減少。將WT 和 KO 小鼠腎臟進行染色後,發現 WT 小鼠腎中 Th1 的數量較多,Treg 則較少。綜合實驗結果推論,miR-17-92 可以增加腎中 Th1、降低 Treg 的數量,而 Th1 則會加重腎纖維化的情形。期盼本研究能對腎纖維化疾病有所貢獻。

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。

探討C1GALT1與IL-1受體醣基化在關節炎中的角色並尋找可能的治療藥物

C1GALT1為氧型醣基化的關鍵基因,若以 IL-1β與 TGF-β刺激 ATDC5細胞株模擬關節炎,C1GALT1 的mRNA 與蛋白質表現量增加,而這樣的趨勢在誘導關節炎的小鼠軟骨組織中也可以觀察到。抑制 C1GALT1 的mRNA 後,促炎基因-一氧化氮合酶(iNOS)與第二型膠原蛋白基因(Collagen II)的 mRNA 表現量下降,代表 C1GALT1 參與了促進發炎的調控路徑。透過以大數據為基礎的 NetOGlyc-4.0平台分析,我們發現小鼠和人類的 IL-1β受體上都含有可能的氧型醣基化位點,C1GALT1 可能透過醣基化 IL-1 受體以增加 iNOS 的表現,進而促進發炎。抑制 C1GALT1的mRNA會使 IL-1R1的蛋白質表現量下降,而抑制 C1GALT1的mRNA或是蛋白質皆可使 IL-1R1在核周內膜系統中的表現量減少,代表 C1GALT1所促進的醣基化修飾是調控 IL-1R1形成的關鍵,抑制 C1GALT1可能具有減緩關節炎的療效。伊曲康挫(Itraconazole)可抑制 C1GALT1 且對人體傷害極小,透過老藥新用,或許能夠應用於治療關節炎。

EIPCA : Electrocardiogram Interpretation Pattern for Cardiovascular Abnormalities Prediction

Cardiac Arrhythmia is one of the conditions in the group of heart and blood vessel diseases that can lead to sudden cardiac arrest (sudden death) and other conditions if not diagnosed quickly and accurately. According to research, heart and blood vessel diseases are the most common diseases and have a mortality rate of one-half of all non-communicable diseases. According to WHO statistics in 2012, it was found that there were 7.4 million deaths from heart and blood vessel diseases, and in 2017, the number of deaths increased to 177 million people, or about 94,444 people per day. Diagnosis of heart and blood vessel diseases can be done by measuring the electrical activity of the heart, and after the examination, a specialized physician will read and analyze the graph to find abnormal patterns. Currently, the shortage of qualified heart specialists to read the graph and screen for heart disease is a medical position shortage, which requires transferring data to hospitals with specialists, resulting in delays in diagnosis and treatment and even death. The project "EIPCA: Electrocardiogram Interpretation Pattern for Cardiovascular Abnormalities prediction" is an application program that assists in screening for fatal diseases that arise from abnormal heart rhythm. It employs artificial intelligence to aid in the screening and analysis of the electrical waveforms generated by an ECG machine, thus reducing diagnosis time and addressing the shortage of cardiology experts. EIPCA is comprised of two systems: (1) a system for screening and analyzing ECG waveforms using artificial intelligence to solve the problem of a shortage of specialized cardiology physicians, and (2) a system for risk assessment of fatal diseases by analyzing the ECG waveform data. The target group of the project is Rural hospitals, as well as health-related agencies. The project team hopes that the development of this project will significantly improve the efficiency and speed of screening for heart-related diseases, ultimately reducing the mortality rate from these diseases in the future.

The Role of Impaired SUV3 in Mitochondrial Dysfunction and Its Linkage to Insulin Resistance in Type 2 Diabetes

第二型糖尿病的主要致病機轉為胰島素阻抗性, 但胰島素阻抗性的機轉仍不清楚。以往研究發現胰島素阻抗性與粒線體功能異常高度相關,但是兩者➀間的關係及機轉目前仍有爭議。本研究以 SUV3來進行調控,SUV3為粒線體RNA分解體➀組成要件,負責粒線體RNA中的代謝及調控。小鼠SUV3缺失會引起粒線體DNA突變,粒線體功能下降,而這些表現型可以經由會由母系遺傳到下一代。我們發現這些經母系遺傳到粒線體DNA突變的小鼠,會產生葡萄糖不耐症與胰島素阻抗性,伴隨骨骼肌的磷酸化Akt表現量明顯下降。進一步的研究發現經母系遺傳到粒線體 DNA突變的小鼠會產生高游離脂肪酸血症及運動耐受性下降,間接卡洛里測定顯示脂肪酸燃燒的比例下降。影響胰島素信息傳遞途徑,因而引發胰島素阻抗性。這些研究結果將有助於糖尿病患者的臨床研究,並希望能夠幫助患者。

Establishment of a bacteria-based delivery approach in regulating mosquito development as a novel vector control strategy

登革熱是由埃及斑蚊傳播的疾病。近年其分布範圍不斷擴大,造成數百萬人死亡。病媒蚊控制對於防止疾病傳播至關重要,但目前尚無安全有效的疫苗以及治療藥物,過量倚賴殺蟲劑又造成病媒蚊抗藥性與環境問題,因此開發新型替代方案是當務之急。 本研究完成了一種 RNAi 新型殺蟲劑。以埃及斑蚊體內的 ADAM12d 作為標靶,由 qRT-PCR 評估,採用 RNAi 干擾的方式進行研究。經基因選殖後透過細菌載體,大量複製出 dsRNA,投放至埃及斑蚊二齡幼蟲的生活水域,抑制ADAM12d 表現。 結果顯示此 RNAi 殺蟲劑在發育過程使幼蟲出現蛻皮異常、生長緩慢、死亡率增加,達到減少病媒蚊的繁殖與孳生。亦已著手於實作層面研究。本研究結果將有助於確定 ADAM12d 的生物功能,也成功以 ADAM12d 基因作為一種新型的生物防治法。此 RNAi 的方式不會連帶殺死其他蚊蟲,也是完全針對有害病媒蚊蟲的,符合現行生態需求,有望成為有效新型藥物。

Toll-like受體3在慢性鼻竇炎合併鼻息肉吸菸患者之表現

慢性鼻竇炎是一種常見的鼻竇或鼻黏膜發炎性疾病,其特徵是經治療後症狀持續超過 12 週。香煙與多種呼吸道發炎疾病的發病機制有關,顯示吸煙可能與慢性鼻竇炎有一定關聯性。Toll-like 受體是一群會介入呼吸道發炎反應的蛋白質,會參與識別和回應體內的病原體和其他外來物質。本研究以免疫組織化學染色測定並比較三個組別:對照組、非吸煙 CRSwNP 患者(CRSwNP)與 CRSwNP 合併吸煙患者(CRSwNP+Smoker)的鼻黏膜組織中 TLR2 和 TLR3 的表現。結果顯示,TLR2 表現量在 CRSwNP 和CRSwNP+Smoker 組的上皮細胞中皆有增加。而與不吸煙的 CRSwNP 組相比,CRSwNP+Smoker 組的 TLR3 表現量較高,且顯著比 TLR2 強。此外,高達 80%比例 CRSwNP+Smoker 患者表現出非常強的 TLR3 IHC 強度。這項發現意味著吸菸、TLR3 表現與慢性鼻竇炎合併鼻息肉的發展或嚴重程度之間有潛在的相關性。對於理解該疾病的發病機制以及治療方法的開發可能具有重要意義。

Connectivity Analysis of Glucose Metabolism in Huntington’s Disease: A New Perspective Provided by Dynamic Glucose-Enhanced MRI

亨丁頓症為神經退化性疾病,與認知功能障礙緊密相關。本研究首創應用 DGE MRI, 以探討葡萄糖代謝作為亨丁頓症神經影像生物標記的可行性,了解其腦區間代謝之關聯性。 本研究探討腦區間葡萄糖代謝關聯性與亨丁頓症病理之間的關係,在 zQ175 KI 和R6/2 KI 小鼠中不同的連接性變化模式,其中在紋狀體及齒狀迴之間之葡萄糖代謝關聯性發現顯著變化,與已知病理相符,說明 DGE MRI 用於臨床生物標記之潛力,助於及時診斷和監測。 本研究首創探討 DGE MRI 作為亨丁頓症影像生物標記之可行性,提供葡萄糖代謝行為於腦區間相互作用之分析,不僅可更加了該症病理,更可推動早期診斷、疾病監測和精準醫療應用之發展,說明可能有針對代謝紊亂的潛在治療策略。

In silico Screening of Forty Antiviral Phytochemicals as Inhibitors to the Envelope Protein of Dengue Virus Serotype 2 (DENV-2)

Infections by the Dengue virus (DENV) cause a disease amonghumansreferred to as Dengue fever, which causes thousands of fatalities globally. There is no existing treatment as of yet that successfully targets DENV. Among the factors thatdeterminetheentry of the virus and severity of the disease is the envelope(E) protein of DENV. This study aimed to examine forty antiviral phytochemicals enumeratedinpaststudiesaspossibleinhibitorstotheEprotein of DENV to provide candidates to aid in drug discovery against DENV. The phytochemicals were screened for their likelihood of inhibition of the E protein using AutoDock Suite and LigPlot+. Seven phytochemicals produced favorable binding affinities to the E protein, which are based on the interactions between the phytochemicals and amino acidsintheactivesiteoftheEprotein.Lipinski’s rule of 5 was then used to screen the seven phytochemicals for oral bioavailability. Glabridin has a binding affinity of -7.6 kcal/mol and was predicted to be orally bioavailable. This phytochemical interacts with amino acids in the E protein active site through hydrogen bonds to Asn355, andPhe337, as well as ten hydrophobic interactions. These interactions ensure that glabridin is able to specifically target and fit intotheactivesiteoftheEprotein, preventing its binding to the host cell and activating its viral proliferation. Glabridin is known to be found in the roots of licorice plants, providing anatural source for a possible cure for Dengue fever.

Sport specific assessment of inter-limb asymmetries: A way to reduce injuries

In recent years, lower inter-limb asymmetries have become a topic of increasing interest in sports research. Numerous studies have investigated the occurrence of between-limb differences in a variety of physical tests, ranging from strength, sprinting, and change of direction speed to jumping tasks. The main focus has been the association of asymmetries to either enhanced injury risk or reduced physical performance. Sport specific aspects and differences of lower limb asymmetries have not often been analysed. Additionally, most studies have been performed with male athletes. Women, however, present higher prevalence of lower limb asymmetries in strength, coordination, and postural control than men. These two aspects were therefore addressed in the present study. Female youth soccer (n=18, age: 16.7 ± 0.8 years) and floorball (n=18, age: 17.6 ± 0.9 years) players completed a test battery consisting of six unilateral jumping tasks in horizontal and lateral direction to detect sport specificity in inter-limb asymmetries. The test comprised the following hops: (1) Single Leg Hop for Distance and (2) a newly created version of it, (3) Single Leg Triple Hop, (4) Single Leg Crossover Hop, (5) Side Hop and (6) Single Leg 6-meters Timed Hop. The scores of every jump were calculated into Limb Symmetry Indexes for each participant. A linear mixed effect (LME) model (using function lmer in program R) was applied to evaluate the effects of sport and jump type on asymmetries. In terms of the whole test battery, there was a significantly higher magnitude of asymmetries in soccer compared to floorball (p=0.0067) with a mean difference of 1.9%. Three significant differences between the effects of different jump types were detected (5>2: p=0.027; 5>3: p6: p=0.014). Moreover, the results showed no significant effect on leg dominance. According to the findings of this study, soccer appears to be more asymmetric than floorball, leading to the suggestion that inter-limb asymmetries may not only be task-specific, but also sportspecific. Since no significant correlations were detected, this study suggests that inter-limb asymmetries are independent of leg dominance. Considering the possible reduction in athletic performance and increasing injury risk, strength and conditioning coaches are advised to assess athletes' inter-limb asymmetries using a broad, sport specific test battery and decrease them.