Analytical and Bioanalytical Chemistry ( IF 3.8 ) Pub Date : 2023-12-02 , DOI: 10.1007/s00216-023-05061-3 Rama Ballouze 1 , Mohd Nazri Ismail 2 , Nur Sofiah Abu Kassim 3 , Salizawati Muhamad Salhimi 1 , Irfan Mohamad 4 , Nor Shahida Abd Mutalib 5 , Ahmad Anuar Hassim 1 , Siti Sarah Fazalul Rahiman 1
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Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent inflammation of the sinonasal mucosa. CRSwNP treatments are associated with inconsistent efficacy and recurrence of symptoms. Dynorphin 1-17 (DYN 1-17) and its fragments have been shown to modulate the immune response in various inflammatory conditions. This study aimed to investigate the effect of different pH and degrees of inflammation on DYN 1-17 metabolism in human CRSwNP tissues. DYN 1-17 was incubated with grade 3 and grade 4 inflamed tissues of CRSwNP patients at pH 5.5 and pH 7.4 over a range of incubation periods. The resulting fragments were identified using an ultra-performance liquid chromatography (UPLC) system coupled to quadrupole-time of flight (QTOF) mass spectrometry based on their accurate mass. The rate of DYN 1-17 fragmentation was slower at pH 5.5 in comparison to pH 7.4. The extent and rate of metabolism of DYN 1-17 were much lower in grade 3 inflamed tissue (31–32 fragments) than in grade 4 (34–41 fragments). N-Terminal fragments (DYN 1-15, 1-11, 1-10, and 1-6) were metabolized slower at pH 5.5 as compared to pH 7.4. DYN 1-12, 1-8, 2-10, 4-10, 5-10, and 8-14 were only observed under the inflammatory pH while DYN 5-17 and 6-17 were only identified upon incubation with grade 4 CRSwNP tissues. DYN 1-17 metabolism was significantly affected by the pH level and the severity of the inflammation of CRSwNP tissues, indicating the potential roles of DYN 1-17 and its fragments in modulating the inflammatory response and their avenue as therapeutics in future studies.
Graphical Abstract
中文翻译：
UPLC-QTOF-MS 检测人鼻息肉中强啡肽 1-17 生物转化片段
慢性鼻窦炎伴鼻息肉（CRSwNP）是鼻窦粘膜的持续性炎症。 CRSwNP 治疗与疗效不一致和症状复发有关。强啡肽 1-17 (DYN 1-17) 及其片段已被证明可以调节各种炎症条件下的免疫反应。本研究旨在探讨不同pH值和炎症程度对人CRSwNP组织中DYN 1-17代谢的影响。 DYN 1-17 与 CRSwNP 患者的 3 级和 4 级炎症组织在 pH 5.5 和 pH 7.4 下孵育一系列孵育期。使用超高效液相色谱 (UPLC) 系统结合四极杆飞行时间 (QTOF) 质谱法根据其精确质量对所得片段进行鉴定。与 pH 7.4 相比，DYN 1-17 断裂速率在 pH 5.5 时更慢。 3 级炎症组织（31-32 个碎片）中 DYN 1-17 代谢的程度和速率远低于 4 级（34-41 个碎片）。与 pH 7.4 相比，N 端片段（DYN 1-15、1-11、1-10 和 1-6）在 pH 5.5 下代谢较慢。 DYN 1-12、1-8、2-10、4-10、5-10 和 8-14 仅在炎症 pH 条件下观察到，而 DYN 5-17 和 6-17 仅在与 4 级 CRSwNP 一起孵育后才被识别组织。 DYN 1-17 代谢受到 pH 水平和 CRSwNP 组织炎症严重程度的显着影响，表明 DYN 1-17 及其片段在调节炎症反应中的潜在作用及其在未来研究中作为治疗的途径。
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