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已发表论文
代谢组学分析揭示了伴或不伴抑郁症的痤疮患者血浆代谢特征的差异
Authors Chen SY, Wang ZQ, Tang Q, Xu Y, Rao Y, Lei Z, Xiong X, Liu ZJL, Li CQ
Received 28 July 2025
Accepted for publication 16 October 2025
Published 5 November 2025 Volume 2025:18 Pages 2923—2937
DOI https://doi.org/10.2147/CCID.S556629
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Monica K. Li
Si-Yu Chen,1,* Zheng-Qun Wang,2,* Qian Tang,1 Yang Xu,1 Yu Rao,1 Zheng Lei,1 Xia Xiong,1 Zong-Jun-Lin Liu,1 Chang-Qiang Li1,3
1Department of Dermatology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646099, People’s Republic of China; 2Department of Dermatology, The First People’s Hospital of Neijiang City, Neijiang, Sichuan, 641000, People’s Republic of China; 3Department of Dermatology, The Fourth Affiliated Hospital, Southwest Medical University, Meishan, Sichuan, 620564 People’s Republic of China
*These authors contributed equally to this work
Correspondence: Chang-Qiang Li, Department of Dermatology, The Fourth Affiliated Hospital of Southwest Medical University, Meishan, Sichuan, People’s Republic of China, Email lcq-1973@163.com Zong-Jun-Lin Liu, Department of Dermatology, The Affiliated Hospital of Southwest Medical University, No. 25 of Taiping Road, Luzhou, Sichuan, 646000, People’s Republic of China, Email 623921812@qq.com
Background: Acne vulgaris is common and often accompanied by depression, but their linking mechanisms remain unclear. Metabolomic profiling helps identify biomarkers and perturbed pathways, so this study explores metabolic associations/pathways in acne comorbid with depression via untargeted metabolomics.
Methods: Seventy-four acne patients were grouped by Patient Health Questionnaire-9 (PHQ-9) scores (≥ 10: depressive, n=21; < 10: non-depressive, n=53). Their plasma was pretreated with cold methanol/acetonitrile, analyzed via Agilent 1290 Ultra-High Performance Liquid Chromatography (UHPLC)-AB Triple TOF 6600 Liquid Chromatography-Mass Spectrometry (LC-MS). Data were processed by XCMS; metabolites annotated via Human Metabolome Database (HMDB)/METLIN. Principal Component Analysis (PCA), Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used.
Results: We identified differential metabolites using Fold Change (FC) analysis combined with statistical significance testing, defining those with FC > 1.5 (upregulated) or FC < 0.67 (downregulated) and p < 0.05 as significant. Volcano plots and hierarchical clustering heatmaps clearly visualize these metabolites, showing distinct clustering patterns that distinguish the two groups. OPLS-DA modeling further revealed 24 key differential metabolites (VIP > 1 and p < 0.05), including 16 in positive ion mode (eg, hypoxanthine, taurine, L-tryptophan) and 8 in negative ion mode (eg, L-ascorbic acid, palmitic acid). Notably, Clustering patterns aligned with these metabolites (eg, upregulated hypoxanthine, downregulated L-ascorbic acid), confirming reliable differences. KEGG annotated 41 core pathways, with protein digestion and absorption (lowest p-value, annotated with 7 key amino acids) as a top-ranked pathway. Five amino acid metabolism-related pathways were upregulated, indicating enhanced amino acid turnover in acne patients with depression; all metabolites in the protein digestion and absorption pathway were also upregulated in this group.
Conclusion: Hypoxanthine, taurine and branched-chain amino acids may be biomarkers for acne-depression comorbidity. Protein digestion/absorption could be a new prognostic marker/therapeutic target, with metabolic-neuroendocrine imbalance underlying the comorbidity.
Keywords: acne with comorbid depression, untargeted metabolomics, serum biomarkers, metabolic pathways
1Department of Dermatology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646099, People’s Republic of China; 2Department of Dermatology, The First People’s Hospital of Neijiang City, Neijiang, Sichuan, 641000, People’s Republic of China; 3Department of Dermatology, The Fourth Affiliated Hospital, Southwest Medical University, Meishan, Sichuan, 620564 People’s Republic of China
*These authors contributed equally to this work
Correspondence: Chang-Qiang Li, Department of Dermatology, The Fourth Affiliated Hospital of Southwest Medical University, Meishan, Sichuan, People’s Republic of China, Email lcq-1973@163.com Zong-Jun-Lin Liu, Department of Dermatology, The Affiliated Hospital of Southwest Medical University, No. 25 of Taiping Road, Luzhou, Sichuan, 646000, People’s Republic of China, Email 623921812@qq.com
Background: Acne vulgaris is common and often accompanied by depression, but their linking mechanisms remain unclear. Metabolomic profiling helps identify biomarkers and perturbed pathways, so this study explores metabolic associations/pathways in acne comorbid with depression via untargeted metabolomics.
Methods: Seventy-four acne patients were grouped by Patient Health Questionnaire-9 (PHQ-9) scores (≥ 10: depressive, n=21; < 10: non-depressive, n=53). Their plasma was pretreated with cold methanol/acetonitrile, analyzed via Agilent 1290 Ultra-High Performance Liquid Chromatography (UHPLC)-AB Triple TOF 6600 Liquid Chromatography-Mass Spectrometry (LC-MS). Data were processed by XCMS; metabolites annotated via Human Metabolome Database (HMDB)/METLIN. Principal Component Analysis (PCA), Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used.
Results: We identified differential metabolites using Fold Change (FC) analysis combined with statistical significance testing, defining those with FC > 1.5 (upregulated) or FC < 0.67 (downregulated) and p < 0.05 as significant. Volcano plots and hierarchical clustering heatmaps clearly visualize these metabolites, showing distinct clustering patterns that distinguish the two groups. OPLS-DA modeling further revealed 24 key differential metabolites (VIP > 1 and p < 0.05), including 16 in positive ion mode (eg, hypoxanthine, taurine, L-tryptophan) and 8 in negative ion mode (eg, L-ascorbic acid, palmitic acid). Notably, Clustering patterns aligned with these metabolites (eg, upregulated hypoxanthine, downregulated L-ascorbic acid), confirming reliable differences. KEGG annotated 41 core pathways, with protein digestion and absorption (lowest p-value, annotated with 7 key amino acids) as a top-ranked pathway. Five amino acid metabolism-related pathways were upregulated, indicating enhanced amino acid turnover in acne patients with depression; all metabolites in the protein digestion and absorption pathway were also upregulated in this group.
Conclusion: Hypoxanthine, taurine and branched-chain amino acids may be biomarkers for acne-depression comorbidity. Protein digestion/absorption could be a new prognostic marker/therapeutic target, with metabolic-neuroendocrine imbalance underlying the comorbidity.
Keywords: acne with comorbid depression, untargeted metabolomics, serum biomarkers, metabolic pathways