JOURNAL OF NANOBIOTECHNOLOGY
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2025
·Vol. 23
·期 1
·1-22
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IF 12.6
Yang Chuan,Xie Langlang,Deng Zihan,Ai Hongbo,Xiang Tingwen,Yan Xiaojing,Ling Zhiguo,Xiao Shiyu,Tang Yong,Huang Gang,Luo Fei,Chen Yueqi
Dysbiosis of gut microbiota significantly exacerbates the progression of rheumatoid arthritis (RA). Targeting gut microbiota may present a promising therapeutic strategy for RA. Gold nanospheres (GNS), known for excellent biocompatibility, stability and minimal toxicity, have emerged as precise modulators of gut microbiota, reshaping intestinal environments to treat various inflammatory diseases. Our study found that oral administration of 60-nm GNS effectively ameliorated collagen-induced arthritis (CIA) in mice, with a marked reduction in disease severity and synovial inflammation. Specifically, GNS notably enriched the probiotic genus Ligilactobacillus while restoring intestinal barrier function by upregulating tight junction proteins Claudin-1 and ZO-1. Targeted metabolomics analysis revealed GNS substantially increased the production of indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA) in gut, which were shown to activate the aryl hydrocarbon receptor (AhR) pathway. Mechanistic studies demonstrated that the IPA/IAA mixture inhibited PTEN ubiquitination, stabilizing PTEN protein levels and suppressing NF-κB activation in synovial tissues. These changes correlated with reduced synovial hyperplasia and inflammatory infiltration. Our findings established GNS as an effective nanomodulator of the gut-joint axis, providing novel insights into microbiota-targeted therapies for RA and other inflammatory diseases. Graphical abstract
研究领域:
医学
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免疫学
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微生物学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2022
·Vol. 30
·期 5
·13739-13754
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IF 5.19
Wu Hao,Bao Yuling,Yan Tongtong,Huang Hui,Jiang Ping,Zhang Zhan,Li Lei,Wu Qian
Epidemiological studies have shown that PAHs may exert adverse effects on childhood asthma. However, the underlying molecular mechanism remains to be fully elucidated. This study aimed to investigate this process in view of metabolic pathways, especially one-carbon metabolism and tryptophan metabolism. Fifty asthmatic children and 50 control subjects were recruited for this study. Serum IgE and IL-17A levels were detected by ELISA. Serum PAH concentrations were measured by GC-MS. One-carbon-related metabolites and tryptophan metabolites were determined by UPLC-Orbitrap-MS. DNA methylation was analyzed by bisulfite sequencing PCR. ChIP assays were used to examine H3K4me3 enrichment on IL-17A gene. Multivariable linear regression was performed to evaluate the association between PAHs and childhood asthma mediated by intermediators. HE staining in lung tissue, IgE and IL-17A in BALF, metabolic profiles in urine, and Ahr , Il-17a , and Cyp1a1 gene expression were determined in PAH-exposed mice. Serum Fla level was associated with childhood asthma (OR = 1.380, 95% CI: 1.063–1.792), and had a great effect on one-carbon metabolites, especially SAH, SAM, and Ser, which exerted significant mediation effects on the relationship between the Fla concentration and asthma. Moreover, we did find significant mediation effects between serum Fla and asthma by LINE-1 DNA methylation and H3K4me3 levels in the IL-17A promoter region. The differential Trp metabolites, such as Trp, tryptamine, IA, IAA, indole, IAld, and IAAld, indicated that asthmatic children had increased indole-AhR pathway. Mediation analysis failed to show a mediator effect of Trp metabolites in the association between PAHs and childhood asthma. An animal study confirmed that PAH exposure increased methylation levels, and altered Trp metabolite-AhR-IL-17A axis, which may be influenced by gender. PAHs disturbed one-carbon metabolism to influence the methyl group refilling DNA methylation and histone methylation, and disturbed tryptophan metabolism to regulate Th17-cell differentiation, which may elevate serum IL-17A concentration in asthmatic children.
研究领域:
环境卫生
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免疫学
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分子生物学
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儿科
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2022
·
IF 5.714
Min Luo,Dan Luo,Jie Liu,Huailing Wang,Xiaoyu Liu,Min Yang,Fangfang Tian,Suofu Qin,Yuying Li
Probiotics are living bacteria that provide health benefits to the host when consumed in sufficient quantities. However, the protective effect of the bioactive peptides isolated from the probiotics against benzo(α)pyrene (BaP) induced gastrointestinal injury has never been investigated. The current work used a bio-assay guided technique to identify-four new cyclic peptides in BaP-induced Caco-2 cell culture and mouse colitis model. Lactobacillus rhamnosus cycle (Thr-His-Ala-Trp) peptide-1 (LRCP-1) effectively inhibited BaP-induced epithelial cytokine over-release and intracellular ROS over-production. Simultaneously, LRCP-1 attenuated BaP-induced NAD (P)H: oxidases (NOXs), Matrix metalloproteinases (MMPs) over-expression, respectively. Furthermore, increased NAD (P)H: quinone oxidoreductase 1 (NQO1)/heme oxygenase-1 (HO-1)/nuclear factor E2-related factor 2 (Nrf2) expression and aryl hydrocarbon receptor (AhR) pathway activation induced by the BaP-exposure were also inhibited after the LRCP-1 treatment. Notably, LRCP-1 is a promising agent protecting gastrointestinal epithelial cells from BaP-induced inflammatory and oxidative damages.
研究领域:
胃肠病学
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免疫学
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分子生物学
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毒理学
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DOI
PubMed
高影响因子
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