Molecular classification and clinical diagnosis of acute-on-chronic liver failure patients by serum metabolomics

Meng, Yijun; Zhou, Chao; Tian, Dong; Jia, Hongmei; Li, Zhiqing; Chen, Yang; Ba, Yi; Wu, Huikun; Zou, Zhong‐Mei

doi:10.1016/j.jpba.2021.114004

Cited by 7 publications

(3 citation statements)

References 25 publications

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“…Because of its convenient and non-invasive characteristics, serum metabonomics is increasingly used in the diagnosis of diseases and the establishment of prognostic models. For example, in NAFLD ( Lewinska et al, 2021 ), liver failure ( Yu et al, 2021 ), PBC ( Bell et al, 2015 ), and other diseases, through the metabonomics analysis of the serum of normal and diseased people, we can well-distinguish between normal and diseased people. Metabonomics is also often combined with gut microbiome analysis to establish multi-group diagnostic models ( Gao et al, 2019 ; Gong et al, 2020 ; Lu et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Nanosecond pulse effectively ablated hepatocellular carcinoma with alterations in the gut microbiome and serum metabolites

Zou

Sun

Chen³

et al. 2023

Front. Pharmacol.

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Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death in the world. Nanosecond pulsed electric fields (nsPEFs) have emerged as a new treatment for cancer. This study aims to identify the effectiveness of nsPEFs in the treatment of HCC and analyze the alterations in the gut microbiome and serum metabonomics after ablation.Methods: C57BL/6 mice were randomly divided into three groups: healthy control mice (n = 10), HCC mice (n = 10), and nsPEF-treated HCC mice (n = 23). Hep1-6 cell lines were used to establish the HCC model in situ. Histopathological staining was performed on tumor tissues. The gut microbiome was analyzed by 16S rRNA sequencing. Serum metabolites were analyzed by liquid chromatography–mass spectrometry (LC-MS) metabolomic analysis. Spearman’s correlation analysis was carried out to analyze the correlation between the gut microbiome and serum metabonomics.Results: The fluorescence image showed that nsPEFs were significantly effective. Histopathological staining identified nuclear pyknosis and cell necrosis in the nsPEF group. The expression of CD34, PCNA, and VEGF decreased significantly in the nsPEF group. Compared with normal mice, the gut microbiome diversity of HCC mice was increased. Eight genera including Alistipes and Muribaculaceae were enriched in the HCC group. Inversely, these genera decreased in the nsPEF group. LC-MS analysis confirmed that there were significant differences in serum metabolism among the three groups. Correlation analysis showed crucial relationships between the gut microbiome and serum metabolites that are involved in nsPEF ablation of HCC.Conclusion: As a new minimally invasive treatment for tumor ablation, nsPEFs have an excellent ablation effect. The alterations in the gut microbiome and serum metabolites may participate in the prognosis of HCC ablation.

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Section: Discussionmentioning

confidence: 99%

Nanosecond pulse effectively ablated hepatocellular carcinoma with alterations in the gut microbiome and serum metabolites

Zou

Sun

Chen³

et al. 2023

Front. Pharmacol.

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“…Diseases often impair the normal metabolism of the body, and disordered metabolic conditions can be effectively measured by metabolomics studies, aiding in the diagnosis and treatment of diseases ( Yu et al, 2021 ). Therefore, in the current study, we propose to use the untargeted and targeted metabolomics method to systematically explore the therapeutic mechanism of HLJDD and its fractions in the treatment of AD, which will allow us to specifically understand how the signaling has been altered during the treatment, and how changes in signaling can attenuate metabolic disorders in the body.…”

Section: Discussionmentioning

confidence: 99%

Study on the Molecular Basis of Huanglian Jiedu Decoction Against Atopic Dermatitis Integrating Chemistry, Biochemistry, and Metabolomics Strategies

Jing

Chen

et al. 2021

Front. Pharmacol.

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Atopic dermatitis (AD) is a common chronic relapsing skin inflammation, which severely affect the quality of life of patients. Inhibiting itching and enhancing immunity to mitigate scratching are key elements in the fight against AD. Huanglian Jiedu decoction (HLJDD) has multiple pharmacological effects in the treatment of AD. However, the effective ingredients and underlying molecular mechanisms have not yet been fully explored. Thus, this study integrates chemistry, biochemistry, and metabolomics strategies to evaluate the active substance basis of HLJDD against AD. First, HLJDD was split to five fractions (CPF, 40AEF, 90AEF, PEF and WEF) and 72 chemical components were identified. NSD (Non-similarity degree) among the different fractions showed significant chemical differences (>81%). Interleukin IL-13, IL-17A, IL-3, IL-31, IL-33, IL4, IL-5, TSLP, IgE, and histamine in the serum, and IL-4Rα, JAK1, and HRH4 levels in skin, participating in inhibiting itching and regulating immunity signaling, were found to be restored to varying degrees in AD treating with HLJDD and its fractions, especially 40AEF and CPF. Untargeted metabolomics analysis demonstrated that forty metabolites were differential metabolites in plasma between the HLJDD-treated group and the AD group, involving in histidine metabolism, arginine biosynthesis, pyrimidine metabolism, and so on. Further, targeted metabolomics analysis revealed that eleven differential metabolites, associating with physiological and biochemical indices, were significant improved in the HLJDD and its fractions groups. In conclusion, HLJDD exhibited anti-AD effects by inhibiting itching and enhancing immunity, which in turn regulating the levels of relative metabolites, and CPF and 40AEF were considered the most important components of HLJDD.

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“…As a result, profound metabolic alterations in glycometabolism, lipid metabolism, and amino acid metabolism have been found in ACLF, and the metabolic disorders further contribute to organ dysfunction/failure (7). Both the metabolomics and transcriptomics analyses reveal the immune-metabolism disorders in the peripheral blood of ACLF, and the metabolite ngerprint and the key differentially expressed genes have been identi ed (8)(9)(10)(11)(12). Through regulating the key metabolic pathway and genes, it may interrupt the vicious circle during the progression of ACLF and improve the prognosis.…”

mentioning

confidence: 99%

Intrahepatic Macrophage Reprogramming Associated with Lipid Metabolism in Hepatitis B Virus-Related Acute-on-Chronic Liver Failure

Peng,

Li,

Liu

et al. 2023

Preprint

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Background Acute-on-chronic liver failure (ACLF) is a severe syndrome with high short-term mortality, but the pathophysiology still remains largely unknown. Immune dysregulation and metabolic disorders contribute to the progression of ACLF, but the crosstalk between immunity and metabolism during ACLF is less understood. This study aims to depict the immune microenvironment in the liver during ACLF, and explore the role of lipid metabolic disorder on immunity.Methods Single-cell RNA-sequencing (scRNA-seq) was performed using the liver non-parenchymal cells (NPCs) and peripheral blood mononuclear cells (PBMCs) from healthy controls, cirrhosis patients and ACLF patients. A series of inflammation-related cytokines and chemokines were detected using liver and plasma samples. The lipid metabolomics targeted free fatty acids (FFAs) in the liver was also detected.Results The scRNA-seq analysis of liver NPCs showed a significant increase of monocytes/macrophages (Mono/Mac) infiltration in ACLF livers, whereas the resident Kupffer cells (KCs) were exhausted. A characterized TREM2+ Mono/Mac subpopulation was identified in ACLF, and showed immunosuppressive function. Combined with the scRNA-seq data from PBMCs, the pseudotime analysis revealed that the TREM2+ Mono/Mac were differentiated from the peripheral monocytes and correlated with lipid metabolism-related genes including APOE, APOC1, FABP5 and TREM2. The targeted lipid metabolomics proved the accumulation of unsaturated FFAs associated with α-linolenic acid (α-LA) and α-LA metabolism and beta oxidation of very long chain fatty acids in the ACLF livers, indicating that unsaturated FFAs might promote the differentiation of TREM2+ Mono/Mac during ACLF.Conclusions The reprogramming of macrophages was found in the liver during ACLF. The immunosuppressive TREM2+ macrophages were enriched in the ACLF liver and contributed to the immunosuppressive hepatic microenvironment. The accumulation of unsaturated FFAs in the ACLF liver promoted the reprogramming of the macrophages. It might be a potential target to improve the immune deficiency of ACLF patients through regulating lipid metabolism.

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Molecular classification and clinical diagnosis of acute-on-chronic liver failure patients by serum metabolomics

Cited by 7 publications

References 25 publications

Nanosecond pulse effectively ablated hepatocellular carcinoma with alterations in the gut microbiome and serum metabolites

Nanosecond pulse effectively ablated hepatocellular carcinoma with alterations in the gut microbiome and serum metabolites

Study on the Molecular Basis of Huanglian Jiedu Decoction Against Atopic Dermatitis Integrating Chemistry, Biochemistry, and Metabolomics Strategies

Intrahepatic Macrophage Reprogramming Associated with Lipid Metabolism in Hepatitis B Virus-Related Acute-on-Chronic Liver Failure

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