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通过混合天然人类气道黏液样本使盐分含量正常化可使样本流变学正常化。

Normalizing salt content by mixing native human airway mucus samples normalizes sample rheology.

作者信息

Markovetz Matthew R, Hibbard Jacob E, Plott Lucas M, Bacudio Lawrence G, Kissner William J, Ghio Andrew, Kumar Priya A, Arora Harendra, Hill David B

机构信息

Marsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.

National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Chapel Hill, NC, United States.

出版信息

Front Physiol. 2023 Mar 10;14:1111647. doi: 10.3389/fphys.2023.1111647. eCollection 2023.

Abstract

Across the globe, millions of people are affected by muco-obstructive pulmonary diseases like cystic fibrosis, asthma, and chronic obstructive pulmonary disease. In MOPDs, the airway mucus becomes hyperconcentrated, increasing viscoelasticity and impairing mucus clearance. Research focused on treatment of MOPDs requires relevant sources of airway mucus both as a control sample type and as a basis for manipulation to study the effects of additional hyperconcentration, inflammatory milieu, and biofilm growth on the biochemical and biophysical properties of mucus. Endotracheal tube mucus has been identified as a prospective source of native airway mucus given its several advantages over sputum and airway cell culture mucus such as ease of access and production that includes surface airway and submucosal gland secretions. Still, many ETT samples suffer from altered tonicity and composition from either dehydration, salivary dilution, or other contamination. Herein, the biochemical compositions of ETT mucus from healthy human subjects were determined. Samples were characterized in terms of tonicity, pooled, and restored to normal tonicity. Salt-normalized ETT mucus exhibited similar concentration-dependent rheologic properties as originally isotonic mucus. This rheology agreed across spatial scales and with previous reports of the biophysics of ETT mucus. This work affirms previous reports of the importance of salt concentration on mucus rheology and presents methodology to increase yield native airway mucus samples for laboratory use and manipulation.

摘要

在全球范围内,数以百万计的人受到诸如囊性纤维化、哮喘和慢性阻塞性肺疾病等黏液阻塞性肺部疾病的影响。在黏液阻塞性肺部疾病中,气道黏液变得高度浓缩,增加了黏弹性并损害了黏液清除功能。针对黏液阻塞性肺部疾病治疗的研究需要相关的气道黏液来源,既作为对照样本类型,又作为进行操作的基础,以研究额外的高浓度、炎症环境和生物膜生长对黏液生物化学和生物物理特性的影响。气管内插管黏液已被确定为天然气道黏液的一个潜在来源,因为它相对于痰液和气道细胞培养黏液具有多个优势,例如易于获取,并且其产生包括气道表面和黏膜下腺的分泌物。然而,许多气管内插管样本仍存在因脱水、唾液稀释或其他污染导致的张力和成分改变的问题。在此,我们测定了健康人类受试者气管内插管黏液的生物化学组成。对样本进行了张力表征、合并,并恢复到正常张力。盐标准化的气管内插管黏液表现出与原始等渗黏液相似的浓度依赖性流变学特性。这种流变学在不同空间尺度上是一致的,并且与先前关于气管内插管黏液生物物理学的报道相符。这项工作证实了先前关于盐浓度对黏液流变学重要性的报道,并提出了提高用于实验室使用和操作的天然气道黏液样本产量的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d4/10036356/4f369096bf13/fphys-14-1111647-g001.jpg

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