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人糖尿病伤口溃疡渗出液中生物胺和小分子代谢物的分析

Analysis of Biogenic Amines and Small Molecule Metabolites in Human Diabetic Wound Ulcer Exudate.

作者信息

Gould Lisa, Mahmoudi Morteza

机构信息

Warren Alpert Medical School of Brown University, Providence, Rhode Island02912, United States.

South Shore Health Center for Wound Healing, Weymouth, Massachusetts02189, United States.

出版信息

ACS Pharmacol Transl Sci. 2024 Sep 4;7(9):2894-2899. doi: 10.1021/acsptsci.4c00418. eCollection 2024 Sep 13.

Abstract

Diabetic foot ulcers (DFUs) pose a significant challenge in wound care due to their chronic nature and impaired healing processes. This study examines the biogenic amines and small molecule metabolites present in DFU wound exudates to identify their potential roles in wound healing. Under an IRB-approved protocol, wound fluid samples were collected from 25 diabetic patients and analyzed using ultrahigh-pressure liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry. The analysis identified 721 metabolites, with 402 confirmed through stringent criteria. Key metabolites significantly contributing to the wound exudates include betaine, lactic acid, carnitine, choline, creatine, and metformin (a widely used first-line treatment for type 2 diabetes). These molecules are known to influence wound healing processes, such as collagen synthesis, angiogenesis, inflammation modulation, and energy metabolism. Notably, the presence of drugs such as metformin and beclomethasone in the exudates suggests significant pharmacodynamic interactions that could influence wound healing. Specifically, we discovered that the combined use of insulin and metformin administered systemically significantly increased the concentration of metformin in the wound exudates (from 0.3% ± 0.0 to 3.1% ± 3.4; = 0.00 49). This study highlights the complexity of DFU exudate composition and underscores the potential for targeted metabolic profiling to develop personalized wound care strategies.

摘要

糖尿病足溃疡(DFUs)因其慢性性质和受损的愈合过程,在伤口护理方面构成了重大挑战。本研究检测了DFU伤口渗出液中存在的生物胺和小分子代谢物,以确定它们在伤口愈合中的潜在作用。在一项经机构审查委员会(IRB)批准的方案下,从25名糖尿病患者身上采集了伤口液体样本,并使用超高压液相色谱与电喷雾电离四极杆飞行时间串联质谱联用技术进行分析。分析确定了721种代谢物,其中402种通过严格标准得到确认。对伤口渗出液有显著贡献的关键代谢物包括甜菜碱、乳酸、肉碱、胆碱、肌酸和二甲双胍(一种广泛使用的2型糖尿病一线治疗药物)。已知这些分子会影响伤口愈合过程,如胶原蛋白合成、血管生成、炎症调节和能量代谢。值得注意的是,渗出液中存在二甲双胍和倍氯米松等药物表明存在可能影响伤口愈合的显著药效学相互作用。具体而言,我们发现全身联合使用胰岛素和二甲双胍可显著提高伤口渗出液中二甲双胍的浓度(从0.3%±0.0升至3.1%±3.4;P = 0.0049)。本研究突出了DFU渗出液成分的复杂性,并强调了进行靶向代谢谱分析以制定个性化伤口护理策略的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/786a/11406679/9dda49c8da84/pt4c00418_0001.jpg

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