全國中小學科展

醫學與健康科學

探討半乳糖凝集素-4在腸道沙門氏菌感染中扮演的角色

此研究旨在探討當腸道沙門氏菌感染人類腸道上皮細胞(HT-29)時半乳糖凝集素-4(galectin-4)所扮演的角色。我們用野生型(wild-type)以及半乳糖凝集素-4 剔除(galectin-4 knockout)的HT-29細胞進行沙門氏菌感染。我們首先經由CFU計數探討galectin-4對細胞內細菌量的影響,並檢測細胞釋出的LDH及IL-18和mature caspase-1的量,以此研究galectin-4是否會活化發炎體(inflammasome)。結果發現, wild type HT-29 cells相較galectin-4 knockout cells有較少的活細菌,釋出的LDH,IL-18也較少。但在經過wortmannin(一種自噬抑制劑)treatment後,wildtype HT-29 cells釋出較多的LDH,IL-18,並且也釋出了mature caspase-1。這些研究結果顯示galectin-4能夠降低細胞內活細菌的量,且能夠活化inflammasome。

肝未人生,肝緊治療-利用端粒酶轉基因斑馬魚斑馬魚模式研究三種藥物的組合抗肝癌作用

癌症為台灣國人十大死因之首,在台灣地區肝癌在十大癌症死因排名第二。雖然有第一線以及第二線藥物,但是頂多只能延長病人13個月的壽命,所以急需開發有效抑制肝癌的新藥。斑馬魚屬於脊椎動物,斑馬魚基因與人類基因的相似度達到87%,且繼代快成本低,對於研究人類的疾病或篩選藥物助益極大。在肝癌病患當中具有高達百分之六十的人,在肝癌中發現了端粒酶逆轉錄酶(TERT)啟動子的突變,這項突變會導致在肝癌細胞中端粒酶的過量表現並促進癌細胞的生長。先前在研究員實驗室建立了端粒酶轉基因斑馬魚,在15天有顯著增加細胞增殖相關基因以及b-catenin下游基因的表現,並且利用HE染色細胞組織病理學分析,有絲分裂以及三核的比例也大大增加。我們這個研究就是利用端粒酶轉基因斑馬魚研究三種藥物(小分子褐藻醣膠,鯽魚複合配方,麩胺酸螯合鈷)單獨使用跟組合使用抗肝癌的作用。我們發現使用三種藥物混合能有效抑制肝癌,未來可廣泛運用在醫學。

上皮細胞黏附因子(EpCAM)對腫瘤增生影響之機制探討

上皮細胞黏附因子 (EpCAM) 參與了細胞的黏附、信息傳遞、增殖及分化等功能,並在惡性腫瘤組織中大量表達。另外抗EpCAM中和性抗體可以阻斷EpCAM訊息傳遞,進而引起癌細胞PD-L1的表現量降低並促進T細胞的毒殺活性。為了觀察EpCAM是否會對癌細胞的增生、轉移以及侵入能力造成影響,我們將細胞分為野生型 (wild type) 和EpCAM基因剔除細胞株 (EpCAM knockout) 進行實驗。首先,我們以Western-blotting和qRT-PCR確認EpCAM基因剔除組的EpCAM基因有確實被剔除,再進一步利用細胞存活率及細胞群落實驗證實EpCAM會促進癌細胞的增生能力,並分別藉由EGFR的抑制劑Afatinib與HGFR的抑制劑Crizotinib對於癌細胞存活率的實驗證實EpCAM 對於EGFR與HGFR的訊息傳遞扮演重要角色。接著分析EpCAM對癌細胞轉移及侵入能力的影響,γ-secretase和ADAM17皆為裁剪EpCAM進行訊息傳遞的重要酵素,實驗中的癌細胞分別以γ-secretase和ADAM17的抑制劑DAPT和TAPI-1處理,證實EpCAM的訊息傳遞與癌細胞轉移與侵入能力有關。接著我們以EpCAM中和性抗體處理癌細胞後,證實EpCAM中和性抗體確實會促使癌細胞凋亡。最後我們利用Western blotting分析EpCAM對於不同激酶磷酸化的蛋白質表現量之影響,找出EpCAM下游訊息傳遞的完整路徑,期望能找到治療癌症的關鍵。

基因突變與骨硬化症之相關

本研究由骨硬化症(osteosclerosis)個案報告開始,進行基因變異的探查,先針對骨生成主要調控機制WNT pathway上的SOST、LRP5、LRP6基因,進行基因定序與分析。在此3個基因沒有發現異常位點後,轉而以全外顯子組定序(whole exome sequencing),進行次世代基因定序(next generation sequencing)。結果顯示病患帶有CTNNB1 c.1982G>A (p.Arg661Gln)之異合子(heterozygous)誤義變異(missense mutation),並證實是CTNNB1基因的原發突變(de novo mutation),該突變影響後續蛋白質表現,影響了ICAT對WNT/beta-catenin訊息傳遞鏈的抑制,繼而穩定beta-catenin,造成骨質異常增生、並導致全身骨硬化。此案例為全世界第二例、亞洲首例的CTNNB1基因功能增強突變(gain-of-function mutation)的病例報告。

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.

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.

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.

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.

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.