Dynamic Patterns of serum metabolites in fulminant hepatic failure pigs

Zhou, Pengcheng; Li, Jianzhou; Shao, Li; Lv, Guoliang; Zhao, Liang; Huang, Huaiyang; Zhang, Anye; Pan, Xiaoping; Liu, Wei; Xie, Qing; Chen, Deying; Guo, Yongzheng; Hao, Shaorui; Xu, Wei; Li, Lanjuan

doi:10.1007/s11306-011-0381-5

Cited by 8 publications

(7 citation statements)

References 26 publications

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“…Secondly, the efficiency and therapeutic mechanisms of FBBAL remain to be revealed. Considering that the liver is the main organ of metabolism and that hepatic failure always results in serious disturbance of endogenous metabolites 10 , it would be useful to study the performance and therapeutic mechanisms of an FBBAL with respect to metabolism. Nevertheless, most previous research has focused on a few metabolic parameters due to the limits of technology 11 and has thus revealed limited information.…”

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confidence: 99%

Efficacy of Fluidized Bed Bioartificial Liver in Treating Fulminant Hepatic Failure in Pigs: A Metabolomics Study

Zhou

Shao

Zhao

et al. 2016

Sci Rep

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Bioartificial livers may act as a promising therapy for fulminant hepatic failure (FHF) with better accessibility and less injury compared to orthotopic liver transplantation. This study aims to evaluate the efficacy and safety of a fluidized bed bioartificial liver (FBBAL) and to explore its therapeutic mechanisms based on metabolomics. FHF was induced by D-galactosamine. Eighteen hours later, pigs were treated with an FBBAL containing encapsulated primary porcine hepatocytes (B group), with a sham FBBAL (containing cell-free capsules, S group) or with only intensive care (C group) for 6 h. Serum samples were assayed using ultra-performance liquid chromatography-mass spectrometry. The difference in survival time (51.6 ± 7.9 h vs. 49.3 ± 6.6 h) and serum metabolome was negligible between the S and C groups, whereas FBBAL treatment significantly prolonged survival time (70.4 ± 11.5h, P < 0.01) and perturbed the serum metabolome, resulting in a marked decrease in phosphatidylcholines, lysophosphatidylcholines, sphingomyelinase, and fatty acids and an increase in conjugated bile acids. The FBBAL exhibits some liver functions and may exert its therapeutic effect by altering the serum metabolome of FHF pigs. Moreover, alginate–chitosan capsules have less influence on serum metabolites. Nevertheless, the alterations were not universally beneficial, revealing that much should be done to improve the FBBAL.

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confidence: 99%

Efficacy of Fluidized Bed Bioartificial Liver in Treating Fulminant Hepatic Failure in Pigs: A Metabolomics Study

Zhou

Shao

Zhao

et al. 2016

Sci Rep

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“…Our previous study revealed that gas chromatography/mass spectrometry (GC–MS)-based metabolomics can be used to discriminate between hepatic failure and healthy controls using various biomarkers and can be used to predict the severity of hepatic failure . In a drug-induced FHF pig model, using liquid chromatography/mass spectrometry (LC–MS)-based metabolomics, we have identified biomarkers that are significantly different from those obtained from GC–MS analysis, in addition to 4 dynamic patterns of serum metabolites present in FHF . These results confirm that metabolites undergo great fluctuations in FHF.…”

Section: Introductionmentioning

confidence: 55%

Return of the Metabolic Trajectory to the Original Area after Human Bone Marrow Mesenchymal Stem Cell Transplantation for the Treatment of Fulminant Hepatic Failure

Xin

Hao

et al. 2012

J. Proteome Res.

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Our recent study first demonstrated that human bone marrow mesenchymal stem cell (hBMSC) transplantation could prevent death from fulminant hepatic failure (FHF) in pigs. To further clarify the metabolic mechanism of hBMSC transplantation in FHF, the plasma collected from FHF pigs that received transplantation of hBMSCs was examined using metabolic analysis to identify the key molecular markers that regulate recovery. The results showed that obvious metabolic disturbance occurred during FHF, whereas the hBMSC transplantation group showed less severe liver injury. The metabolic trajectory returns to its original state at week 3 following the hBMSC transplantation. In total, the concentration of 26 metabolites, including conjugated bile acids, phosphatidylcholines, lysophosphatidylcholines, fatty acids, amino acid and sphingomyelin, are significantly different between the FHF group and the hBMSC transplantation group. Moreover, the time course of changes in the metabolites corresponded with that of the biochemical and histological analyses. Real-time PCR further confirmed that the gene expression of phospholipase A1, lecithin-cholesterol acyltransferase and lysophosphatidylcholine acyltransferase 1 decreased significantly, whereas that of phospholipase A2 remained stable, which explains the decrease of the phosphatidylcholines and lysophosphatidylcholines. These novel results have revealed a metabolic mechanism for the hBMSC transplantation in FHF, which could lead to the future development of treatment strategies for stem cell therapies.

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“…Hepatitis B virus (HBV) and HCV antigens and a biochemical panel including alanine aminotransferase, aspartate aminotransferase, glutamic-oxaloacetic transaminase, total bilirubin, direct bilirubin, total protein, and albumin were assayed in the clinical laboratory. Histopathological samples were prepared as described previously[ 13 ].…”

Section: Methodsmentioning

confidence: 99%

“…In previous studies, we established a pattern recognition metabolomics method based on sequential feature selection combined with linear discriminant analysis (LDA) to evaluate the severity of fulminant hepatic failure and for the differential diagnosis of Clostridium difficile infection[ 13 , 14 ]. In the current study, ultra-performance liquid chromatography-mass spectroscopy (UPLC-MS) was used to characterize the serum metabolomes of patients with HCC, patients with cirrhosis, and healthy controls.…”

Section: Introductionmentioning

confidence: 99%

Establishment of a pattern recognition metabolomics model for the diagnosis of hepatocellular carcinoma

Zhou

Sun

Shao

et al. 2020

WJG

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BACKGROUND Early diagnosis of hepatocellular carcinoma may help to ensure that patients have a chance for long-term survival; however, currently available biomarkers lack sensitivity and specificity. AIM To characterize the serum metabolome of hepatocellular carcinoma in order to develop a new metabolomics diagnostic model and identifying novel biomarkers for screening hepatocellular carcinoma based on the pattern recognition method. METHODS Ultra-performance liquid chromatography-mass spectroscopy was used to characterize the serum metabolome of hepatocellular carcinoma ( n = 30) and cirrhosis ( n = 29) patients, followed by sequential feature selection combined with linear discriminant analysis to process the multivariate data. RESULTS The concentrations of most metabolites, including proline, were lower in patients with hepatocellular carcinoma, whereas the hydroxypurine levels were higher in these patients. As ordinary analysis models failed to discriminate hepatocellular carcinoma from cirrhosis, pattern recognition analysis was used to establish a pattern recognition model that included hydroxypurine and proline. The leave-one-out cross-validation accuracy and area under the receiver operating characteristic curve analysis were 95.00% and 0.90 [95% Confidence Interval (CI): 0.81-0.99] for the training set, respectively, and 78.95% and 0.84 (95%CI: 0.67-1.00) for the validation set, respectively. In contrast, for α-fetoprotein, the accuracy and area under the receiver operating characteristic curve were 65.00% and 0.69 (95%CI: 0.52-0.86) for the training set, respectively, and 68.42% and 0.68 (95%CI: 0.41-0.94) for the validation set, respectively. The Z test revealed that the area under the curve of the linear discriminant analysis model was significantly higher than the area under the curve of α-fetoprotein ( P < 0.05) in both the training and validation sets. CONCLUSION Hydroxypurine and proline might be novel biomarkers for hepatocellular carcinoma, and this disease could be diagnosed by the metabolomics model based on pattern recognition.

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Dynamic Patterns of serum metabolites in fulminant hepatic failure pigs

Cited by 8 publications

References 26 publications

Efficacy of Fluidized Bed Bioartificial Liver in Treating Fulminant Hepatic Failure in Pigs: A Metabolomics Study

Efficacy of Fluidized Bed Bioartificial Liver in Treating Fulminant Hepatic Failure in Pigs: A Metabolomics Study

Return of the Metabolic Trajectory to the Original Area after Human Bone Marrow Mesenchymal Stem Cell Transplantation for the Treatment of Fulminant Hepatic Failure

Establishment of a pattern recognition metabolomics model for the diagnosis of hepatocellular carcinoma

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