Project Description

Here shows why we choose this project, what we do and how to achieve our goal, as well as who is beneficial from our product.

 

  

Early warning AS by detecting Biomarker TMAO and miRNAs.


 

1. Why we choose this project ?

About 10 months ago, while our family was celebrating the 2023 Spring Festival together, my grandpa suddenly fainted, which terribly scared us all. After about 20 minutes, as the ambulance beeped further away, my grandpa was taken to the emergency room in a hospital.

Experiencing about 5 hours of rescue and surgery, my grandpa was out of danger, but his heart was placed with a stent. The doctor told us that he had a myocardial infarction caused by atherosclerosis (AS), and an arterial blood vessel was blocked more than 90%. Fortunately, my grandpa stayed in the hospital for two weeks before being discharged from hospital and returning home. However, another patient in the same ward was not so lucky, and he died of the same disease, and left his family during my grandpa was in the hospital. We all felt sad at his death (Fig.1).

 

Fig.1 The story of my grandpa.

 

I began to pay attention to the myocardial infarction and AS since then, before we started our program in this competition season, I wanted to do something using synthetic biology for those patients who are suffered from this disease. So, we discussed this topic in the brainstorm, and confirmed our determination.

 


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2. What we do for those patients ?

But what can we do for those patients? To clarify this problem, we interviewed Dr. Peng Jie who works in Jinan Cardiovascular and Cerebrovascular Disease (CCVD) Hospital (Fig.2). From the interview we knew that CCVD ranks the first in the various cause of death in China, and AS is the most risk factor for causing CCVD. Coronary AS can cause angina pectoris, myocardial infarction, arrhythmia and even sudden death. She told us that the current diagnosis of AS is usually when patients experience severe symptoms which is very danger and too late. If seeking early medical diagnosis, some death would be avoided. Early diagnostic warning of AS is crucial. So, we were going to focus on developing a testing method for AS early warning in our iGEM project.

 

Fig.2 We interviewed Dr. Peng Jie who works in Jinan Cardiovascular and Cerebrovascular Disease (CCVD) Hospital.

 


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3. How to achieve our goal ?

It is an opportunity and challenge. How do we develop a diagnostic method for early AS warning? To solve this problem, we searched and read lots of literatures, with consulting professor Wang of Shandong University (Fig.3), we designed our project to develop a filter paper biosensor used for early screening of AS by detecting biomarkers including trimethylamine N-oxide (TMAO) and microRNAs (miR-17-5p and miR-146a-5p), all of which were reported high concentration in the urine of patients. The detection of TMAO and miRNAs are based on TMAO receptor system and toehold switch, respectively, in cell free expression system (Fig.4).

 

Fig.3 We consulted professor Wang of Shandong University in TenCent Meeting.

 

Fig.4 Biomarkers in samples are detected in cell free system on the filter paper biosensor.

 


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4. Who is beneficial from our product ?

Since this early warning diagnosis of AS is mainly used for the middle aged and elderly, we conducted a survey and interviewed some elderly in community (Fig.5). With their suggestion and advices, we intended to develop a convenient hardware that can quantify the testing result of biomarkers (TMAO and miRNAs) in urine on the filter paper biosensor, which is used for early AS screening and warning (Fig.6).

 

Fig.5 We interviewed some elderly people in community, getting some suggestion and advices for developing hardware.

 

Due to its portability and convenience, our product facilitates the early screening of AS at home, providing an early warning followed by early intervention to avoid of CCVD caused by AS, which is the most risk factor for the elderly people health. It is very helpful and valuable!

 

Fig.6 With the hardware we developed, we hope we can help the elderly to perform the early AS screening and warning to maintain their health.

 

References

 

[1] Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med 2013; 368(17):1575-1584.

[2] Senthong V, Wang Z, Fan Y, Wu Y, Hazen SL, Tang WH. Trimethylamine N-Oxide and Mortality Risk in Patients With Peripheral Artery Disease. J Am Heart Assoc 2016; 5(10)

[3] Senthong V, Wang Z, Li XS, Fan Y, Wu Y, Tang WH, et al. Intestinal Microbiota-Generated Metabolite Trimethylamine-N-Oxide and 5-Year Mortality Risk in Stable Coronary Artery Disease: The Contributory Role of Intestinal Microbiota in a COURAGE-Like Patient Cohort. J Am Heart Assoc 2016; 5(6)

[4] Zhu Y, Li Q, Jiang H. Gut microbiota in atherosclerosis: focus on trimethylamine N-oxide. APMIS. 2020;128(5):353-366. doi:10.1111/apm.13038

[5] Moore JO, Hendrickson WA. An asymmetry-to-symmetry switch in signal transmission by the histidine kinase receptor for TMAO. Structure. 2012;20(4):729-741. doi:10.1016/j.str.2012.02.021

[6] Sharma AR, Sharma G, Bhattacharya M, Lee SS, Chakraborty C. Circulating miRNA in Atherosclerosis: A Clinical Biomarker and Early Diagnostic Tool. Curr Mol Med. 2022;22(3):250-262. doi:10.2174/1566524021666210315124438

[7] Chen J, Xu L, Hu Q, Yang S, Zhang B, Jiang H. MiR-17-5p as circulating biomarkers for the severity of coronary atherosclerosis in coronary artery disease. Int J Cardiol. 2015;197:123-124. doi:10.1016/j.ijcard.2015.06.037

[8] Quan X, Ji Y, Zhang C, et al. Circulating MiR-146a May be a Potential Biomarker of Coronary Heart Disease in Patients with Subclinical Hypothyroidism. Cell Physiol Biochem 2018; 45(1): 226-36.

[9] Wang T, Yang Y, Wang Z, Zhang X, Li D, Wei J. A SNP of miR-146a is involved in bladder cancer relapse by affecting the function of bladder cancer stem cells via the miR-146a signallings. J Cell Mol Med. 2020;24(15):8545-8556. doi:10.1111/jcmm.15480 [10] Sasaki H, Yoshiike M, Nozawa S, et al. Expression Level of Urinary MicroRNA-146a-5p Is Increased in Patients With Bladder Cancer and Decreased in Those After Transurethral Resection. Clin Genitourin Cancer. 2016;14(5):e493-e499. doi:10.1016/j.clgc.2016.04.002