非靶向代谢组学揭示了根尖牙周炎病变的大小依赖性代谢差异。

IF 5.5 2区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of dentistry Pub Date : 2025-09-09 DOI:10.1016/j.jdent.2025.106096

Mengchen Tang , Yilin Zhang , Huang Fang , Zihan Li , Lijia Huang , Lisha Gu

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引用次数: 0

摘要

目的：本研究旨在通过比较不同大小的牙周炎（AP）病变，探讨代谢差异与疾病严重程度的关系。方法：在根尖显微手术中采集无全系统疾病患者的根尖组织标本12份，其中大病变（大于1000mm³）6份，小病变（小于1000mm³）6份。采用液相色谱-质谱法分析不同大小AP病变的代谢谱。主成分分析和正交偏最小二乘判别分析用于表征病变大小相关的代谢差异。随后，采用差异表达代谢物（DEMs）筛选和富集分析来阐明与AP病变大小异质性相关的代谢途径。结果：在检测到的2431种代谢物中，鉴定出21种dem。大病变表现为α-亚麻酸、二十碳四烯酸等11种代谢物上调，主要富集于“α-亚麻酸代谢”和“不饱和脂肪酸生物合成”。小病变显示胆碱、2′-脱氧肌苷等10种代谢物上调，“嘌呤代谢”、“甘氨酸、丝氨酸、苏氨酸代谢”、“甘油磷脂代谢”、“谷胱甘肽代谢”等相关通路富集。结论：不同状态的AP存在不同的代谢特征。大病变显示脂肪酸衍生物水平升高，暗示不饱和脂肪酸的生物合成增强。相反，小病变显示氮基和氨基酸衍生物上调，提示嘌呤和谷胱甘肽相关通路失调。不同的代谢物谱表明它们在疾病严重程度和疗效优化方面的生物标志物潜力。临床意义：在大小病变之间观察到的差异表达的代谢物和途径表明它们可能作为生物标志物作为进一步机制研究的靶点。

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Untargeted-metabolomics reveals size-dependent metabolic disparities of apical periodontitis lesions

Aim

This study aimed to investigate the variations in metabolic differences associated with the disease severity of apical periodontitis (AP) by comparing lesions of different sizes.

Methods

Twelve apical tissue samples were collected during apical microsurgery from patients without systemic diseases, comprising 6 large lesions (greater than 1000 mm³) and 6 small lesions (<1000 mm³). Liquid chromatography-mass spectrometry was conducted to analyze the metabolic profiles of AP lesions with different sizes. Principal component analysis and orthogonal partial least squares discriminant analysis were utilized to characterize lesion size-dependent metabolic disparities. Subsequently, differentially expressed metabolites (DEMs) screening and enrichment analysis was employed to clarify metabolic pathways that correlate with AP lesion size heterogeneity.

Results

Among the 2431 detected metabolites, 21 DEMs were identified. Large lesions exhibited the upregulation of 11 metabolites (e.g., α-linolenic acid, eicosatetraenoic acid), which were predominantly enriched in “α-linolenic acid metabolism” and “unsaturated fatty acid biosynthesis”. Small lesions showed the upregulation of 10 metabolites (e.g., choline, 2′-deoxyinosine), which were enriched in pathways related to “purine metabolism”, “glycine, serine and threonine metabolism”, “glycerophospholipid metabolism” and “glutathione metabolism”.

Conclusion

There are distinct metabolic profiles characterize between different states of AP. Large lesions exhibited elevated levels of fatty acid derivatives, implicating enhanced unsaturated fatty acid biosynthesis. Conversely, small lesions showed upregulation of nitrogenous bases and amino acid derivatives, suggesting dysregulation in purine and glutathione-related pathways. The distinct metabolite profiles indicate their biomarker potential for disease severity and efficacy optimization.

Clinical significance

The differential-expressed metabolites and pathways observed between large and small lesions suggests their potential role as biomarkers for as targets for further mechanistic investigation.

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来源期刊

Journal of dentistry 医学-牙科与口腔外科

CiteScore

7.30

自引率

11.40%

发文量

349

审稿时长

35 days

期刊介绍： The Journal of Dentistry has an open access mirror journal The Journal of Dentistry: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. The Journal of Dentistry is the leading international dental journal within the field of Restorative Dentistry. Placing an emphasis on publishing novel and high-quality research papers, the Journal aims to influence the practice of dentistry at clinician, research, industry and policy-maker level on an international basis. Topics covered include the management of dental disease, periodontology, endodontology, operative dentistry, fixed and removable prosthodontics, dental biomaterials science, long-term clinical trials including epidemiology and oral health, technology transfer of new scientific instrumentation or procedures, as well as clinically relevant oral biology and translational research. The Journal of Dentistry will publish original scientific research papers including short communications. It is also interested in publishing review articles and leaders in themed areas which will be linked to new scientific research. Conference proceedings are also welcome and expressions of interest should be communicated to the Editor.