Frontiers in Immunology
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2022
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IF 8.786
Hu Yu,Zhou Xuyue,Chen Lihao,Li Rong,Jin Shuang,Liu Lingxi,Ju Mei,Luan Chao,Chen Hongying,Wang Ziwei,Huang Dan,Chen Kun,Zhang Jiaan
Background: Keloids are a fibroproliferative disease characterized by unsatisfactory therapeutic effects and a high recurrence rate.Objective: This study aimed to investigate keloid-related circulating metabolic signatures.Methods: Untargeted metabolomic analysis was performed to compare the metabolic features of 15 keloid patients with those of paired healthy volunteers in the discovery cohort. The circulating metabolic signatures were selected using the least absolute shrinkage. Furthermore, the selection operators were quantified using multiple reaction monitoring-based target metabolite detection methods in the training and test cohorts.Results: More than ten thousand metabolic features were consistently observed in all the plasma samples from the discovery cohort, and 30 significantly different metabolites were identified. Four differentially expressed metabolites including palmitoylcarnitine, sphingosine, phosphocholine, and phenylalanylisoleucine, were discovered to be related to keloid risk in the training and test cohorts. In addition, using linear and logistic regression models, the respective risk scores for keloids based on a 4-metabolite fingerprint classifier were established to distinguish keloids from healthy volunteers.Conclusions: In summary, our findings show that the characteristics of circulating metabolic fingerprinting manifest phenotypic variation in keloid onset.
研究领域:
医学
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代谢组学
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皮肤病学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
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2020
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IF 2.09
Jiaxing Fan,Jianglu Zhou,Shenmin Su,Yunqiu Yu,Lihong Chen,Yunchen Le,Xiaopan Wang,Li Zhang,Jie Zheng,Xia Li
Psoriasis is a common chronic inflammatory skin disease which may exhibit a variety of skin clinical manifestations associated with multiple comorbidities. However, its pathogenesis associated with metabolism has not yet been understood. The metabolites of tricarboxylic acid (TCA) cycle and amino acids are interlinked with each other and involve many physiological processes. This study determined 32 metabolites of TCA cycle and amino acids in psoriasis using an improved GC-MS method. This one-pot derivatization applied silanization and oximation simultaneously for easy, quick and sensitive quantitative detection of 32 metabolites in serum of patients with psoriasis. Through the established GC-MS method, 32 metabolites in serum were detected in a single run. The result of this preliminary study showed that there were significant alterations of the metabolites in tricarboxylic acid (TCA) cycle and amino acids before and after treatment. A shift towards healthy controls of these metabolites after treatment was observed using principal component analysis (PCA) as well. Receiver operating-characteristic curve (ROC) analysis of the analyzed 32 metabolites filtered 5 potential biomarkers of the clinical efficacy of the treatment. This result suggested the importance of these metabolites in the pathogenesis of psoriasis. To our best know, this is the first targeted metabolomics work to study the changes of TCA cycle metabolites and amino acids in the background of treatment of psoriasis.
研究领域:
医学
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代谢组学
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产品关联
DOI
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2023
·Vol. 415
·期 17
·3475-3486
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IF 4.3
Li Jiawei,Zhang Kun,Yan Fei,Lang Chunhui
Tricarboxylic acid (TCA) metabolites in cancer cells show a marked difference from those in normal cells. Herein, we report a single-particle multiple-signal lanthanide/europium-based metal–organic framework (Tb/Eu MOF) sensor array for the detection of TCA metabolites and discrimination of cancer cells. In the presence of TCA metabolite, 6 characteristic peaks of Tb/Eu MOF showed dramatic changes due to host–guest interactions, allowing sensor array-based qualitative and quantitative detection to be performed. In the qualitative detection ability test, 18 TCA metabolites at 4 concentrations (50 μM, 100 μM, 200 μM, 300 μM) were accurately discriminated by the sensor array via linear discriminant analysis (LDA). Significantly, these 4 concentrations include the clinical detection criteria for most TCA metabolites. In the quantitative detection ability test, a good linear relationship between Euclidean distances and the concentrations of L-valine (Val) could be obtained in the range of 50 to 500 μM (R 2 = 0.9755). On this basis, the provided method was successfully applied for the classification of 2 normal cells and 5 cancer cells via principal components analysis (PCA), LDA and a radial basis function neural network (RBFN). What's more, by verifying the weight coefficient of each point, detection and discrimination results are proved as a trustworthy balanced evaluation of multiple factors. Depending on precise data processing, the experimental operation was simplified on the premise of ensuring accuracy, so our method is a meaningful exploration for array design.
研究领域:
生物化学
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分析化学
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医学诊断
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICAL VIROLOGY
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2024
·Vol. 96
·期 6
·e29723
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IF 6.8
Dekai Zheng,Changhao Cheng,Yanhua Tang,Zhixin Fang,Xuelian Gao,Yuchuan Chen,Qiuhong You,Kaifeng Wang,Heqi Zhou,Zhixian Lan,Jian Sun
Hepatitis B virus (HBV) can be completely suppressed after antiviral treatment; however, some patients with chronic hepatitis B (CHB) exhibit elevated alanine aminotransferase (ALT) levels and sustained disease progression. This study provides novel insights into the mechanism and potential predictive biomarkers of persistently elevated ALT (PeALT) in patients with CHB after complete viral inhibition. Patients having CHB with undetectable HBV DNA at least 12 months after antiviral treatment were enrolled from a prospective, observational cohort. Patients with PeALT and persistently normal ALT (PnALT) were matched 1:1 using propensity score matching. Correlations between plasma metabolites and the risk of elevated ALT were examined using multivariate logistic regression. A mouse model of carbon tetrachloride-induced liver injury was established to validate the effect of key differential metabolites on liver injury. Of the 1238 patients with CHB who achieved complete viral suppression, 40 (3.23%) had PeALT levels during follow-up (median follow-up: 2.42 years). Additionally, 40 patients with PnALT levels were matched as controls. Ser-Phe-Ala, Lys-Ala-Leu-Glu, 3-methylhippuric acid, 3-methylxanthine, and 7-methylxanthine were identified as critical differential metabolites between the two groups and independently associated with PeALT risk. Ser-Phe-Ala and Lys-Ala-Leu-Glu levels could be used to discriminate patients with PeALT from those with PnALT. Furthermore, N -acetyl- l -methionine (NALM) demonstrated the strongest negative correlation with ALT levels. NALM supplementation alleviated liver injury and hepatic necrosis induced by carbon tetrachloride in mice. Changes in circulating metabolites may contribute to PeALT levels in patients with CHB who have achieved complete viral suppression after antiviral treatment.
研究领域:
肝病学
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代谢组学
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药理学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2024
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IF 8.3
Tingjun Liu,Ziying You,Fangyuan Shen,Puying Yang,Junyu Chen,Shuhuai Meng,Chenglin Wang,Ding Xiong,Chengjia You,Zhenming Wang,Yu Shi,Ling Ye
Cranial bone defects remain a major clinical challenge, increasing patients’ life burdens. Tricarboxylic acid (TCA) cycle metabolites play crucial roles in facilitating bone tissue regeneration. However, the development of TCA cycle metabolite-modified biomimetic grafts for skull bone regeneration still needs to be improved. The mechanism underlying the release of TCA cycle metabolites from biomaterials in regulating immune responses and mesenchymal stem cell (MSC) fate (migration and differentiation) remains unknown. Herein, this work constructs biomimetic hydrogels composed of gelatin and chitosan networks covalently cross-linked by genipin (CGG hydrogels). A series of TCA cycle metabolite-coordinated CGG hydrogels with strong mechanical and antiswelling performances are subsequently developed. Remarkably, the citrate (Na3Cit, Cit)-coordinated CGG hydrogels (CGG-Cit hydrogels) with the highest mechanical modulus and strength significantly promote skull bone regeneration in rat and murine cranial defects. Mechanistically, using a transgenic mouse model, bulk RNA sequencing, and single-cell RNA sequencing, this work demonstrates that CGG-Cit hydrogels promote Gli1+ MSC migration via neutrophil-secreted oncostatin M. Results also indicate that citrate improves osteogenesis via enhanced histone H3K9 acetylation on osteogenic master genes. Taken together, the immune microenvironment- and MSC fate-regulated CGG-Cit hydrogels represent a highly efficient and facile approach toward skull bone tissue regeneration with great potential for bench-to-bedside translation.
研究领域:
生物材料
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再生医学
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干细胞生物学
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免疫学
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分子生物学
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骨组织工程
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产品关联
DOI
PubMed
高影响因子
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