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夹心免疫分析法测定肾上腺髓质素前体及其实际应用。

Sandwich immunoassay for adrenomedullin precursor and its practical application.

机构信息

PAM Theragnostics GmbH, 16761, Hennigsdorf, Germany.

出版信息

Sci Rep. 2024 Nov 15;14(1):28091. doi: 10.1038/s41598-024-79542-5.

Abstract

Adrenomedullin (ADM) is a multifaceted peptide hormone involved in numerous physiological processes, including vascular stability, vasodilation, angiogenesis, and anti-inflammatory responses. The processing of ADM results in several fragments, including midregional proadrenomedullin (MR-proADM), and glycine-extended ADM (ADM-Gly) and bioactive ADM (bio-ADM). MR-proADM, the stable ADM fragment, and bio-ADM, the active form of ADM with a short half-life, have been shown to be potent biomarkers in a variety of pathologies. ADM-Gly, the direct precursor of bio-ADM, is a predominant form in human plasma, but remains less understood and least investigated. This study presents the development of a specific immunoluminometric assay for the quantification of ADM-Gly and offers a robust one-step approach for large-scale sample screening. Applied to human and rodent plasma, it elucidates the release kinetics and plasma half-life of ADM-Gly. Our findings confirm the predominance of ADM-Gly in healthy individuals and its significant release under pathological conditions. Our immunoluminometric assay enables precise measurement of ADM-Gly, advancing research into ADM-related pathophysiology and supporting its use as a biomarker and therapeutic target in various diseases.

摘要

肾上腺髓质素(ADM)是一种多功能肽激素,参与许多生理过程,包括血管稳定性、血管舒张、血管生成和抗炎反应。ADM 的加工产生几种片段,包括中区域原肾上腺髓质素(MR-proADM)、甘氨酸延伸 ADM(ADM-Gly)和生物活性 ADM(bio-ADM)。MR-proADM 是 ADM 的稳定片段,bio-ADM 是 ADM 的活性形式,半衰期短,已被证明是多种病理情况下的有效生物标志物。ADM-Gly 是 bio-ADM 的直接前体,是人类血浆中的主要形式,但了解较少,研究最少。本研究开发了一种用于定量测定 ADM-Gly 的特异性免疫发光分析方法,并提供了一种用于大规模样品筛选的稳健一步法。应用于人及啮齿动物血浆,阐明了 ADM-Gly 的释放动力学和血浆半衰期。我们的研究结果证实了 ADM-Gly 在健康个体中的优势及其在病理条件下的显著释放。我们的免疫发光分析方法能够精确测量 ADM-Gly,为 ADM 相关病理生理学的研究提供支持,并支持其作为各种疾病的生物标志物和治疗靶点的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cd1/11564509/ea09d2e94101/41598_2024_79542_Fig1_HTML.jpg

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