关键词: Mo4/3B2−x nanoscaffold amino acid and purine metabolism metabolomics scar removing wound healing

Mesh : Animals Wound Healing / drug effects Cicatrix / metabolism pathology drug therapy Mice Amino Acids / chemistry metabolism Purines / chemistry pharmacology Reactive Oxygen Species / metabolism Male

来  源:   DOI:10.1021/acsnano.4c06796

Abstract:
Wound rehabilitation is invariably time-consuming, scar formation further weakens therapeutic efficacy, and detailed mechanisms at the molecular level remain unclear. In this work, a Mo4/3B2-x nanoscaffold was fabricated and utilized for wound healing and scar removing in a mice model, while metabolomics was used to study the metabolic reprogramming of metabolome during therapy at the molecular level. The results showed that transition metal borides, called Mo4/3B2-x nanoscaffolds, could mimic superoxide dismutase and glutathione peroxidase to eliminate excess reactive oxygen species (ROS) in the wound microenvironment. During the therapeutic process, the Mo4/3B2-x nanoscaffold could facilitate the regeneration of wounds and removal of scars by regulating the biosynthesis of collagen, fibers, and blood vessels at the pathological, imaging, and molecular levels. Subsequent metabolomics study revealed that the Mo4/3B2-x nanoscaffold effectively ameliorated metabolic disorders in both wound and scar microenvironments through regulating ROS-related pathways including the amino acid metabolic process (including glycine and serine metabolism and glutamate metabolism) and the purine metabolic process. This study is anticipated to illuminate the potential clinical application of the Mo4/3B2-x nanoscaffold as an effective therapeutic agent in traumatic diseases and provide insights into the development of analytical methodology for interrogating wound healing and scar removal-related metabolic mechanisms.
摘要:
伤口康复总是耗时的,瘢痕形成进一步削弱了治疗效果,分子水平的详细机制尚不清楚。在这项工作中,Mo4/3B2-x纳米支架被制造并用于小鼠模型的伤口愈合和疤痕去除,而代谢组学用于在分子水平上研究治疗期间代谢组的代谢重编程。结果表明,过渡金属硼化物,叫做Mo4/3B2-x纳米支架,可以模拟超氧化物歧化酶和谷胱甘肽过氧化物酶,以消除伤口微环境中多余的活性氧(ROS)。在治疗过程中,Mo4/3B2-x纳米支架可以通过调节胶原蛋白的生物合成来促进伤口的再生和疤痕的去除,纤维,和病理血管,成像,和分子水平。随后的代谢组学研究表明,Mo4/3B2-x纳米支架通过调节ROS相关途径,包括氨基酸代谢过程(包括甘氨酸和丝氨酸代谢和谷氨酸代谢)和嘌呤代谢过程,有效改善了伤口和瘢痕微环境中的代谢紊乱。这项研究有望阐明Mo4/3B2-x纳米支架作为创伤疾病有效治疗剂的潜在临床应用,并为研究伤口愈合和疤痕去除相关代谢机制的分析方法的发展提供见解。
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