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理解可溶性蛋白和外泌体在基于尿液的子痫前期无创诊断中的作用。

Understanding the role of soluble proteins and exosomes in non-invasive urine-based diagnosis of preeclampsia.

机构信息

Department of Bionanotechnology, Graduate School, Hanyang University, Seoul, 04763, Korea.

Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.

出版信息

Sci Rep. 2024 Oct 15;14(1):24117. doi: 10.1038/s41598-024-75080-2.

DOI:10.1038/s41598-024-75080-2
PMID:39406891
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11482518/
Abstract

Preeclampsia is a hypertensive disorder of pregnancy that can lead to stillbirth and preterm birth if not treated promptly. Currently, the diagnosis of preeclampsia relies on clinical symptoms such as hypertension and proteinuria, along with invasive blood tests. Here, we investigate the role of soluble proteins and exosomes in noninvasive diagnosing preeclampsia non-invasively using maternal urine and urine-derived exosomes. We quantified the levels of particles and the presence of TSG101 and CD63 in urine and urinary exosomes via the biologically intact exosome separation technology (BEST) platform. Then, we obtained higher levels of soluble proteins such as fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) from urine as it was than urinary exosomes. Compared to commercial blood tests, the sensitivity of the sFlt-1/PlGF ratio was found to be 4.0 times higher in urine tests and 1.5 times higher in tests utilizing urine-derived exosomes. Our findings offer promising possibilities for the early and non-invasive identification of high-risk individuals at risk of preeclampsia, allowing for comprehensive preventive management.

摘要

子痫前期是一种妊娠高血压疾病,如果不及时治疗,可能导致死胎和早产。目前,子痫前期的诊断依赖于临床症状,如高血压和蛋白尿,以及侵入性血液检查。在这里,我们研究了使用母体尿液和尿液衍生的外泌体,通过可溶性蛋白和外泌体在非侵入性诊断子痫前期中的作用。我们通过生物完整外泌体分离技术(BEST)平台定量了尿液和尿外泌体中颗粒的水平和 TSG101 和 CD63 的存在。然后,我们从尿液中获得了更高水平的可溶性蛋白,如血管内皮生长因子受体 1(sFlt-1)和胎盘生长因子(PlGF)。与商业血液检查相比,尿液中 sFlt-1/PlGF 比值的灵敏度比血液检查高 4.0 倍,尿液衍生外泌体的灵敏度比血液检查高 1.5 倍。我们的研究结果为早期和非侵入性识别高危人群中可能患有子痫前期的个体提供了有希望的可能性,从而可以进行全面的预防管理。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11482518/597df6079d17/41598_2024_75080_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11482518/f957e2a91c33/41598_2024_75080_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11482518/a6019a13972e/41598_2024_75080_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11482518/a04449767cc7/41598_2024_75080_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11482518/597df6079d17/41598_2024_75080_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11482518/f957e2a91c33/41598_2024_75080_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11482518/a6019a13972e/41598_2024_75080_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11482518/a04449767cc7/41598_2024_75080_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11482518/597df6079d17/41598_2024_75080_Fig4_HTML.jpg

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本文引用的文献

1
Literature Review: The sFlt1/PlGF Ratio and Pregestational Maternal Comorbidities: New Risk Factors to Predict Pre-Eclampsia.文献综述:sFlt1/PlGF 比值与孕前母体合并症:预测子痫前期的新危险因素。
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Role of biomarkers (sFlt-1/PlGF) in cases of COVID-19 for distinguishing preeclampsia and guiding clinical management.生物标志物(sFlt-1/PlGF)在 COVID-19 病例中的作用,用于鉴别子痫前期并指导临床管理。
Pregnancy Hypertens. 2023 Mar;31:32-37. doi: 10.1016/j.preghy.2022.11.008. Epub 2022 Dec 5.
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miR-31-5p from placental and peripheral blood exosomes is a potential biomarker to diagnose preeclampsia.
胎盘和外周血外泌体中的 miR-31-5p 是诊断子痫前期的潜在生物标志物。
Hereditas. 2022 Sep 19;159(1):35. doi: 10.1186/s41065-022-00250-z.
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The association between maternal pre-pregnancy body mass index and pregnancy outcomes of preeclampsia.母亲孕前体重指数与子痫前期妊娠结局的关系。
Taiwan J Obstet Gynecol. 2022 May;61(3):441-446. doi: 10.1016/j.tjog.2022.03.008.
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Preeclampsia.子痫前期
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sFlt-1/PlGF ratio for prediction of preeclampsia in clinical routine: A pragmatic real-world analysis of healthcare resource utilisation.sFlt-1/PlGF 比值在临床常规预测子痫前期中的应用:医疗资源利用的实用真实世界分析。
PLoS One. 2022 Feb 24;17(2):e0263443. doi: 10.1371/journal.pone.0263443. eCollection 2022.
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Nature. 2022 Feb;602(7898):689-694. doi: 10.1038/s41586-022-04410-z. Epub 2022 Feb 9.
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Clinical tools and biomarkers to predict preeclampsia.预测子痫前期的临床工具和生物标志物。
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Clinical interpretation and implementation of the sFlt-1/PlGF ratio in the prediction, diagnosis and management of preeclampsia.sFlt-1/PlGF 比值在子痫前期预测、诊断和管理中的临床解读和应用。
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10
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Sci Rep. 2021 Oct 18;11(1):20613. doi: 10.1038/s41598-021-00152-6.