Effects and mechanism of CYBB on the progression of multiple sclerosis: Evidence from bioinformatic analysis and experimental validation.

IF 2.7 3区生物学 Q2 GENETICS & HEREDITY

Gene Pub Date : 2026-10-09 DOI:10.1016/j.gene.2026.150441

Minli Lv, Hongen Wei, Jiajia Zhao, Man Li, Liansheng Ma, Huizhong Gao

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引用次数: 0

Abstract

Background: Neutrophil extracellular traps (NETs) are involved in the pathological progression of multiple sclerosis (MS), yet the intrinsic molecular mechanism by which NETs mediate the progression of MS remains unclear.

Methods: Differentially expressed genes were screened by integrating Gene Expression Omnibus (GEO) datasets and NETs-related genes, and candidate biomarker genes for MS were identified using machine learning algorithms and receiver operating characteristic (ROC) curve analysis. Gene Set Enrichment Analysis (GSEA), immune infiltration analysis, construction of competitive endogenous RNA (ceRNA) networks and drug-gene interaction networks were performed on these candidate biomarker genes. An experimental autoimmune encephalomyelitis (EAE) mouse model was established and intervened with cytochrome b-245 beta chain (CYBB) overexpression. Neurological scores, inflammatory factors (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β], interleukin-18 [IL-18], and monocyte chemoattractant protein-1 [MCP-1]), oxidative stress indicators (malondialdehyde [MDA], superoxide dismutase [SOD], and catalase [CAT]), pathological damage, and pyroptosis-related proteins (NOD-like receptor pyrin domain-containing 3 [NLRP3], apoptosis-associated speck-like protein containing a CARD [ASC], and Caspase-1) were evaluated.

Results: Four genes (CYBB, NF-kappa-B inhibitor alpha [NFKBIA], C-X-C motif chemokine receptor 4 [CXCR4], and IL1B) associated with MS were identified via bioinformatic analysis, among which CYBB exhibited the strongest immune-related correlation. The results of animal experiments revealed that EAE mice presented with weight loss, aggravated inflammation and oxidative stress, as well as elevated expression of pyroptosis-related proteins. CYBB overexpression significantly reversed these pathological alterations, suppressed proinflammatory cytokines and oxidative stress, and prevented the upregulation of pyroptosis-related proteins.

Conclusion: CYBB overexpression alleviated inflammation and oxidative stress, suppressed the expression of pyroptosis-related proteins, and was associated with the amelioration of EAE pathological symptoms.

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CYBB对多发性硬化症进展的影响和机制：来自生物信息学分析和实验验证的证据。

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来源期刊

Gene 生物-遗传学

CiteScore

6.10

自引率

2.90%

发文量

718

审稿时长

42 days

期刊介绍： Gene publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses.