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Singh P, Singh R, Pasricha C, Kumari P. Navigating liver health with metabolomics: A comprehensive review. Clin Chim Acta 2025; 566:120038. [PMID: 39536895 DOI: 10.1016/j.cca.2024.120038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Revised: 11/06/2024] [Accepted: 11/10/2024] [Indexed: 11/16/2024]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease worldwide, affecting one-fourth of the world's population. With more than half of the world's population, the Asia-Pacific region contributed 62.6 % of liver-related fatal incidents in 2015. Currently, liver imaging techniques such as computed tomography (CT), nuclear magnetic resonance (NMR) spectroscopy, and ultrasound are non-invasive imaging methods to diagnose the disease. A liver biopsy is the gold standard test for establishing the definite diagnosis of non-alcoholic steatohepatitis (NASH). However, there are still significant problems with sample variability and the procedure's invasiveness. Numerous studies have indicated various non-invasive biomarkers for both fibrosis and steatosis to counter the invasiveness of diagnostic procedures. Metabolomics could be a promising method for detecting early liver diseases, investigating pathophysiology, and developing drugs. Metabolomics, when utilized with other omics technologies, can result in a deeper understanding of biological systems. Metabolomics has emerged as a prominent research topic, offering extensive opportunities to investigate biomarkers for liver diseases that are both sensitive and specific. In this review, we have described the recent studies involving the use of a metabolomics approach in the diagnosis of liver diseases, which would be beneficial for the early detection and treatment of liver diseases.
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Affiliation(s)
- Preetpal Singh
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Ravinder Singh
- Chitkara College of Pharmacy, Chitkara University, Punjab, India.
| | - Chirag Pasricha
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Pratima Kumari
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
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Sun J, Chen Y, Wang T, Ali W, Ma Y, Yuan Y, Gu J, Bian J, Liu Z, Zou H. Baicalin and N-acetylcysteine regulate choline metabolism via TFAM to attenuate cadmium-induced liver fibrosis. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 125:155337. [PMID: 38241915 DOI: 10.1016/j.phymed.2024.155337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 10/14/2023] [Accepted: 01/05/2024] [Indexed: 01/21/2024]
Abstract
(Background): Cadmium is an environmental pollutant associated with several liver diseases. Baicalin and N-Acetylcysteine have antioxidant and hepatoprotective effects. (Purpose): However, it is unclear whether baicalin and N-Acetylcysteine can alleviate Cadmium -induced liver fibrosis by regulating metabolism, or whether they exert a synergistic effect. (Study design): We treated Cadmium-poisoned mice with baicalin, N-Acetylcysteine, or baicalin+ N-Acetylcysteine. We studied the effects of baicalin and N-Acetylcysteine on Cadmium-induced liver fibers and their specific mechanisms. (Methods): We used C57BL/6 J mice, and AML12, and HSC-6T cells to establish in vitro assays and in vivo models. (Results): Metabolomics was used to detect the effect of baicalin and N-Acetylcysteine on liver metabolism, which showed that compared with the control group, the Cadmium group had increased fatty acid and amino acid levels, with significantly reduced choline and acetylcholine contents. Baicalin and N-Acetylcysteine alleviated these Cadmium-induced metabolic changes. We further showed that choline alleviated Cadmium -induced liver inflammation and fibrosis. In addition, cadmium significantly promoted extracellular leakage of lactic acid, while choline alleviated the cadmium -induced destruction of the cell membrane structure and lactic acid leakage. Western blotting showed that cadmium significantly reduced mitochondrial transcription factor A (TFAM) and Choline Kinase α(CHKα2) levels, and baicalin and N-Acetylcysteine reversed this effect. Overexpression of Tfam in mouse liver and AML12 cells increased the expression of CHKα2 and the choline content, alleviating and cadmium-induced lactic acid leakage, liver inflammation, and fibrosis. (Conclusion): Overall, baicalin and N-Acetylcysteine alleviated cadmium-induced liver damage, inflammation, and fibrosis to a greater extent than either drug alone. TFAM represents a target for baicalin and N-Acetylcysteine, and alleviated cadmium-induced liver inflammation and fibrosis by regulating hepatic choline metabolism.
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Affiliation(s)
- Jian Sun
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, PR China
| | - Yan Chen
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, PR China
| | - Tao Wang
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, PR China
| | - Waseem Ali
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, PR China
| | - Yonggang Ma
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China
| | - Yan Yuan
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China
| | - Jianhong Gu
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China
| | - Jianchun Bian
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China
| | - Zongping Liu
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China
| | - Hui Zou
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
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Tuerxun K, He J, Ibrahim I, Yusupu Z, Yasheng A, Xu Q, Tang R, Aikebaier A, Wu Y, Tuerdi M, Nijiati M, Zou X, Xu T. Bioartificial livers: a review of their design and manufacture. Biofabrication 2022; 14. [PMID: 35545058 DOI: 10.1088/1758-5090/ac6e86] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 05/11/2022] [Indexed: 11/11/2022]
Abstract
Acute liver failure (ALF) is a rapidly progressive disease with high morbidity and mortality rates. Liver transplantation and artificial liver support systems, such as artificial livers (ALs) and bioartificial livers (BALs), are the two major therapies for ALF. Compared to ALs, BALs are composed of functional hepatocytes that provide essential liver functions, including detoxification, metabolite synthesis, and biotransformation. Furthermore, BALs can potentially provide effective support as a form of bridging therapy to liver transplantation or spontaneous recovery for patients with ALF. In this review, we systematically discussed the currently available state-of-the-art designs and manufacturing processes for BAL support systems. Specifically, we classified the cell sources and bioreactors that are applied in BALs, highlighted the advanced technologies of hepatocyte culturing and bioreactor fabrication, and discussed the current challenges and future trends in developing next generation BALs for large scale clinical applications.
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Affiliation(s)
- Kahaer Tuerxun
- Department of hepatobiliary and pancreatic surgery, First People's Hospital of Kashi, 120th, Yingbin Road, Kashi, Xinjiang, 844000, CHINA
| | - Jianyu He
- Department of Mechanical Engineering, Tsinghua University, 30 Shuangqing Road, Haidian District, Beijing, Beijing, 100084, CHINA
| | - Irxat Ibrahim
- Department of hepatobiliary and pancreatic surgery, First People's Hospital of Kashi, 120th, Yingbin Road, Kashi, Xinjiang, China, Kashi, Xinjiang, 844000, CHINA
| | - Zainuer Yusupu
- Department of Ultrasound, First People's Hospital of Kashi, 120th, Yingbin Road, Kashi, Xinjiang, China, Kashi, Xinjiang, 844000, CHINA
| | - Abudoukeyimu Yasheng
- Department of hepatobiliary and pancreatic surgery, First People's Hospital of Kashi, 120th, Yingbin Road, Kashi, Xinjiang, 844000, CHINA
| | - Qilin Xu
- Department of hepatobiliary and pancreatic surgery, First People's Hospital of Kashi, 120th, Yingbin Road, Kashi, Xinjiang, 844000, CHINA
| | - Ronghua Tang
- Department of hepatobiliary and pancreatic surgery, First People's Hospital of Kashi, 120th, Yingbin Road, Kashi, Xinjiang, 844000, CHINA
| | - Aizemaiti Aikebaier
- Department of hepatobiliary and pancreatic surgery, First People's Hospital of Kashi, 120th, Yingbin Road, Kashi, Xinjiang, 844000, CHINA
| | - Yuanquan Wu
- Department of hepatobiliary and pancreatic surgery, First People's Hospital of Kashi, 120th, Yingbin Road, Kashi, Xinjiang, China, Kashi, Xinjiang, 844000, CHINA
| | - Maimaitituerxun Tuerdi
- Department of hepatobiliary and pancreatic surgery, First People's Hospital of Kashi, 120th, Yingbin Road, Kashi, Xinjiang, China, Kashi, Xinjiang, 844000, CHINA
| | - Mayidili Nijiati
- Medical imaging center, First People's Hospital of Kashi, 120th, Yingbin Road, Kashi, Xinjiang, China, Kashi, Xinjiang, 844000, CHINA
| | - Xiaoguang Zou
- Hospital Organ, First People's Hospital of Kashi, 120th, Yingbin Road, Kashi, Xinjiang, 844000, CHINA
| | - Tao Xu
- Tsinghua University, 30 Shuangqing Road, Haidian District, Beijing, 100084, CHINA
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Zhou PC, Sun LQ, Shao L, Yi LZ, Li N, Fan XG. Establishment of a pattern recognition metabolomics model for the diagnosis of hepatocellular carcinoma. World J Gastroenterol 2020; 26:4607-4623. [PMID: 32884220 PMCID: PMC7445864 DOI: 10.3748/wjg.v26.i31.4607] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Revised: 05/27/2020] [Accepted: 07/21/2020] [Indexed: 02/06/2023] Open
Abstract
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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Affiliation(s)
- Peng-Cheng Zhou
- Hunan Key Laboratory of Viral Hepatitis and Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- Department of Infectious Diseases and Infection Control Center, The third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Infection Control Center, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Lun-Quan Sun
- Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Li Shao
- Institute of Translational Medicine, The Affiliated Hospital, Hangzhou Normal University, Hangzhou 311121, Zhejiang Province, China
| | - Lun-Zhao Yi
- Yunnan Food Safety Research Institute, Kunming University of Science and Technology, Kunming 650500, Yunnan Province, China
| | - Ning Li
- Hunan Key Laboratory of Viral Hepatitis and Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- Department of Blood Transfusion, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Xue-Gong Fan
- Hunan Key Laboratory of Viral Hepatitis and Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
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Chamuleau RAFM, Hoekstra R. End-stage liver failure: filling the treatment gap at the intensive care unit. J Artif Organs 2019; 23:113-123. [PMID: 31535298 PMCID: PMC7228976 DOI: 10.1007/s10047-019-01133-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Accepted: 09/09/2019] [Indexed: 12/14/2022]
Abstract
End-stage liver failure is a condition of collapsing liver function with mortality rates up to 80. Liver transplantation is the only lifesaving therapy. There is an unmet need for therapy to extend the waiting time for liver transplantation or regeneration of the native liver. Here we review the state-of-the-art of non-cell based and cell-based artificial liver support systems, cell transplantation and plasma exchange, with the first therapy relying on detoxification, while the others aim to correct also other failing liver functions and/or modulate the immune response. Meta-analyses on the effect of non-cell based systems show contradictory outcomes for different types of albumin purification devices. For bioartificial livers proof of concept has been shown in animals with liver failure. However, large clinical trials with two different systems did not show a survival benefit. Two clinical trials with plasma exchange and one with transplantation of mesenchymal stem cells showed positive outcomes on survival. Detoxification therapies lack adequacy for most patients. Correction of additional liver functions, and also modulation of the immune system hold promise for future therapy of liver failure.
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Affiliation(s)
- Robert A F M Chamuleau
- Amsterdam UMC, University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, AG&M, Academic Medical Center, Meibergdreef 69-71, S1-176, 1105 BK, Amsterdam, The Netherlands.
| | - Ruurdtje Hoekstra
- Amsterdam UMC, University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, AG&M, Academic Medical Center, Meibergdreef 69-71, S1-176, 1105 BK, Amsterdam, The Netherlands
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He YT, Qi YN, Zhang BQ, Li JB, Bao J. Bioartificial liver support systems for acute liver failure: A systematic review and meta-analysis of the clinical and preclinical literature. World J Gastroenterol 2019; 25:3634-3648. [PMID: 31367162 PMCID: PMC6658398 DOI: 10.3748/wjg.v25.i27.3634] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Revised: 05/03/2019] [Accepted: 05/31/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Acute liver failure (ALF) has a high mortality varying from 80% to 85% with rapid progress in multi-organ system failure. Bioartificial liver (BAL) support systems have the potential to provide temporary support to bridge patients with ALF to liver transplantation or spontaneous recovery. In the past decades, several BAL support systems have been conducted in clinical trials. More recently, concerns have been raised on the renovation of high-quality cell sources and configuration of BAL support systems to provide more benefits to ALF models in preclinical experiments. AIM To investigate the characteristics of studies about BAL support systems for ALF, and to evaluate their effects on mortality. METHODS Eligible clinical trials and preclinical experiments on large animals were identified on Cochrane Library, PubMed, and EMbase up to March 6, 2019. Two reviewers independently extracted the necessary information, including key BAL indicators, survival and indicating outcomes, and adverse events during treatment. Descriptive analysis was used to identify the characteristics of the included studies, and a meta-analysis including only randomized controlled trial (RCT) studies was done to calculate the overall effect of BAL on mortality among humans and large animals, respectively. RESULTS Of the 30 selected studies, 18 were clinical trials and 12 were preclinical experiments. The meta-analysis result suggested that BAL might reduce mortality in ALF in large animals, probably due to the recent improvement of BAL, including the type, cell source, cell mass, and bioreactor, but seemed ineffective for humans [BAL vs control: relative risk (95% confidence interval), 0.27 (0.12-0.62) for animals and 0.72 (0.48-1.08) for humans]. Liver and renal functions, hematologic and coagulative parameters, encephalopathy index, and neurological indicators seemed to improve after BAL, with neither meaningful adverse events nor porcine endogenous retrovirus infection. CONCLUSION BAL may reduce the mortality of ALF by bridging the gap between preclinical experiments and clinical trials. Clinical trials using improved BAL must be designed scientifically and conducted in the future to provide evidence for transformation.
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Affiliation(s)
- Yu-Ting He
- Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Ya-Na Qi
- Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Bing-Qi Zhang
- Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jian-Bo Li
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Ji Bao
- Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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Wen C, Lin F, Huang B, Zhang Z, Wang X, Ma J, Lin G, Chen H, Hu L. Metabolomics Analysis in Acute Paraquat Poisoning Patients Based on UPLC-Q-TOF-MS and Machine Learning Approach. Chem Res Toxicol 2019; 32:629-637. [PMID: 30807114 DOI: 10.1021/acs.chemrestox.8b00328] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Most paraquat (PQ) poisoned patients died from acute multiple organ failure (MOF) such as lung, kidney, and heart. However, the exact mechanism of intoxication is still unclear. In order to find out the initial toxic mechanism of PQ poisoning, a blood metabolomics study based on ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and efficient machine learning approach was performed on 23 PQ poisoned patients and 29 healthy subjects. The initial PQ plasma concentrations of PQ poisoned patients were >1000 ng/mL, and the blood samples were collected at before first hemoperfusion (HP), after first HP, and after last HP. The results showed that PQ poisoned patients all differed from healthy subjects, whatever they were before or after first HP or after last HP. The efficient machine learning approaches selected key metabolites from three UPLC/Q-TOF-MS data sets which had the highest classification performance in terms of classification accuracy, Matthews Correlation Coefficients, sensitivity, and specificity, respectively. The mass identification revealed that the most important metabolite was adenosine, which sustained in low level, regardless of whether PQ poisoned patients received HP treatment. In conclusion, decreased adenosine was the most important metabolite in PQ poisoned patients. The metabolic disturbance caused by PQ poisoning cannot be improved by HP treatment even the PQ was cleared from the blood.
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Affiliation(s)
- Congcong Wen
- Laboratory Animal Center of Wenzhou Medical University , Wenzhou 325035 , China
| | | | - Binge Huang
- Laboratory Animal Center of Wenzhou Medical University , Wenzhou 325035 , China
| | - Zhiguang Zhang
- Laboratory Animal Center of Wenzhou Medical University , Wenzhou 325035 , China
| | - Xianqin Wang
- Laboratory Animal Center of Wenzhou Medical University , Wenzhou 325035 , China
| | - Jianshe Ma
- Laboratory Animal Center of Wenzhou Medical University , Wenzhou 325035 , China
| | | | - Huiling Chen
- College of Physics and Electronic Information Engineering , Wenzhou University , Wenzhou 325035 , China
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Zhou P, Zhou N, Shao L, Li J, Liu S, Meng X, Duan J, Xiong X, Huang X, Chen Y, Fan X, Zheng Y, Ma S, Li C, Wu A. Diagnosis of Clostridium difficile infection using an UPLC-MS based metabolomics method. Metabolomics 2018; 14:102. [PMID: 30830376 DOI: 10.1007/s11306-018-1397-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2017] [Accepted: 07/10/2018] [Indexed: 02/06/2023]
Abstract
INTRODUCTION The fecal metabolome of Clostridium difficile (CD) infection is far from being understood, particularly its non-volatile organic compounds. The drawbacks of current tests used to diagnose CD infection hinder their application. OBJECTIVE The aims of this study were to find new characteristic fecal metabolites of CD infection and develop a metabolomics model for the diagnosis of CD infection. METHODS Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) was used to characterize the fecal metabolome of CD positive and negative diarrhea and healthy control stool samples. RESULTS Diarrhea and healthy control samples showed distinct clusters in the principal components analysis score plot, and CD positive group and CD negative group demonstrated clearer separation in a partial least squares discriminate analysis model. The relative abundance of sphingosine, chenodeoxycholic acid, phenylalanine, lysophosphatidylcholine (C16:0), and propylene glycol stearate was higher, and the relative abundance of fatty amide, glycochenodeoxycholic acid, tyrosine, linoleyl carnitine, and sphingomyelin was lower in CD positive diarrhea groups, than in the CD negative group. A linear discriminant analysis model based on capsiamide, dihydrosphingosine, and glycochenodeoxycholic acid was further constructed to identify CD infection in diarrhea. The leave-one-out cross-validation accuracy and area under receiver operating characteristic curve for the training set/external validation set were 90.00/78.57%, and 0.900/0.7917 respectively. CONCLUSIONS Compared with other hospital-onset diarrhea, CD diarrhea has distinct fecal metabolome characteristics. Our UPLC-MS metabolomics model might be useful tool for diagnosing CD diarrhea.
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Affiliation(s)
- Pengcheng Zhou
- Infection Control Center, Xiangya Hospital, Central South University, Changsha, 410078, Hunan, People's Republic of China
| | - Ning Zhou
- Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People's Republic of China
| | - Li Shao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, People's Republic of China
| | - Jianzhou Li
- Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shanxi, People's Republic of China
| | - Sidi Liu
- Infection Control Center, Xiangya Hospital, Central South University, Changsha, 410078, Hunan, People's Republic of China
| | - Xiujuan Meng
- Infection Control Center, Xiangya Hospital, Central South University, Changsha, 410078, Hunan, People's Republic of China
| | - Juping Duan
- Infection Control Center, Xiangya Hospital, Central South University, Changsha, 410078, Hunan, People's Republic of China
| | - Xinrui Xiong
- Infection Control Center, Xiangya Hospital, Central South University, Changsha, 410078, Hunan, People's Republic of China
| | - Xun Huang
- Infection Control Center, Xiangya Hospital, Central South University, Changsha, 410078, Hunan, People's Republic of China
| | - Yuhua Chen
- Infection Control Center, Xiangya Hospital, Central South University, Changsha, 410078, Hunan, People's Republic of China
| | - Xuegong Fan
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China
| | - Yixiang Zheng
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China
| | - Shujuan Ma
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, 410078, Hunan, People's Republic of China
| | - Chunhui Li
- Infection Control Center, Xiangya Hospital, Central South University, Changsha, 410078, Hunan, People's Republic of China.
| | - Anhua Wu
- Infection Control Center, Xiangya Hospital, Central South University, Changsha, 410078, Hunan, People's Republic of China.
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Hu L, Hong G, Tang Y, Wang X, Wen C, Lin F, Lu Z. Early Metabolome Profiling and Prognostic Value in Paraquat-Poisoned Patients: Based on Ultraperformance Liquid Chromatography Coupled To Quadrupole Time-of-Flight Mass Spectrometry. Chem Res Toxicol 2017; 30:2151-2158. [PMID: 29099997 DOI: 10.1021/acs.chemrestox.7b00240] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Paraquat (PQ) has caused countless deaths throughout the world. There remains no effective treatment for PQ poisoning. Here we study the blood metabolome of PQ-poisoned patients using ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS). Patients were divided into groups according to blood PQ concentration. Healthy subjects served as controls. Metabolic features were statistically analyzed using multivariate pattern-recognition techniques to identify the most important metabolites. Selected metabolites were further compared with a series of clinical indexes to assess the prognostic value. PQ-poisoned patients showed substantial differences compared with healthy subjects. Based on variable of importance in the project (VIP) values and statistical analysis, 17 metabolites were selected and identified. These metabolites well-classified low PQ-poisoned patients, high PQ-poisoned patients, and healthy subjects, which was better than that of a complete blood count (CBC). Among the 17 metabolites, 20:3/18:1-PC (PC), LPA (0:0/16:0) (LPA), 19-oxo-deoxycorticosterone (19-oxo-DOC), and eicosapentaenoic acid (EPA) had prognostic value. In particular, EPA was the most sensitive one. Besides, the levels of EPA was correlated with LPA and 19-oxo-DOC. If EPA was excessively consumed, then prognosis was poor. In conclusion, the serum metabolome is substantially perturbed by PQ poisoning. EPA is the most important biomarker in early PQ poisoning.
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Affiliation(s)
- Lufeng Hu
- Department of Pharmacy, The First Affliated Hospital of Wenzhou Medical University , Wenzhou 325000, China
| | - Guangliang Hong
- Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou 325000, China
| | - Yahui Tang
- Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou 325000, China
| | - Xianqin Wang
- Analytical and Testing Center of Wenzhou Medical University , Wenzhou 325035, China
| | - Congcong Wen
- Analytical and Testing Center of Wenzhou Medical University , Wenzhou 325035, China
| | - Feiyan Lin
- Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou 325000, China
| | - Zhongqiu Lu
- Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou 325000, China
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10
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Feng L, Cai L, He GL, Weng J, Li Y, Pan MX, Jiang ZS, Peng Q, Gao Y. Novel D-galactosamine-induced cynomolgus monkey model of acute liver failure. World J Gastroenterol 2017; 23:7572-7583. [PMID: 29204057 PMCID: PMC5698250 DOI: 10.3748/wjg.v23.i42.7572] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2017] [Revised: 09/17/2017] [Accepted: 10/17/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To establish a simplified, reproducible D-galactosamine-induced cynomolgus monkey model of acute liver failure having an appropriate treatment window.
METHODS Sixteen cynomolgus monkeys were randomly divided into four groups (A, B, C and D) after intracranial pressure (ICP) sensor implantation. D-galactosamine at 0.3, 0.25, 0.20 + 0.05 (24 h interval), and 0.20 g/kg body weight, respectively, was injected via the small saphenous vein. Vital signs, ICP, biochemical indices, and inflammatory factors were recorded at 0, 12, 24, 36, 48, 72, 96, and 120 h after D-galactosamine administration. Progression of clinical manifestations, survival times, and results of H&E staining, TUNEL, and Masson staining were recorded.
RESULTS Cynomolgus monkeys developed different degrees of debilitation, loss of appetite, and jaundice after D-galactosamine administration. Survival times of groups A, B, and C were 56 ± 8.7 h, 95 ± 5.5 h, and 99 ± 2.2 h, respectively, and in group D all monkeys survived the 144-h observation period except for one, which died at 136 h. Blood levels of ALT, AST, CK, LDH, TBiL, Cr, BUN, and ammonia, prothrombin time, ICP, endotoxin, and inflammatory markers [(tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6)] significantly increased compared with baseline values in different groups (P < 0.05). Pathological results showed obvious liver cell necrosis that was positively correlated with the dose of D-galactosamine.
CONCLUSION We successfully established a simplified, reproducible D-galactosamine-induced cynomolgus monkey model of acute liver failure, and the single or divided dosage of 0.25 g/kg is optimal for creating this model.
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Affiliation(s)
- Lei Feng
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
| | - Lei Cai
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
| | - Guo-Lin He
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
| | - Jun Weng
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
| | - Yang Li
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
| | - Ming-Xin Pan
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
| | - Ze-Sheng Jiang
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
| | - Qing Peng
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
| | - Yi Gao
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
- State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510282, Guangdong Province, China
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11
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Selden C, Bundy J, Erro E, Puschmann E, Miller M, Kahn D, Hodgson H, Fuller B, Gonzalez-Molina J, Le Lay A, Gibbons S, Chalmers S, Modi S, Thomas A, Kilbride P, Isaacs A, Ginsburg R, Ilsley H, Thomson D, Chinnery G, Mankahla N, Loo L, Spearman CW. A clinical-scale BioArtificial Liver, developed for GMP, improved clinical parameters of liver function in porcine liver failure. Sci Rep 2017; 7:14518. [PMID: 29109530 PMCID: PMC5674071 DOI: 10.1038/s41598-017-15021-4] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Accepted: 10/20/2017] [Indexed: 12/15/2022] Open
Abstract
Liver failure, whether arising directly from acute liver failure or from decompensated chronic liver disease is an increasing problem worldwide and results in many deaths. In the UK only 10% of individuals requiring a liver transplant receive one. Thus the need for alternative treatments is paramount. A BioArtificial Liver machine could temporarily replace the functions of the liver, buying time for the patient's liver to repair and regenerate. We have designed, implemented and tested a clinical-scale BioArtificial Liver machine containing a biomass derived from a hepatoblastoma cell-line cultured as three dimensional organoids, using a fluidised bed bioreactor, together with single-use bioprocessing equipment, with complete control of nutrient provision with feedback BioXpert recipe processes, and yielding good phenotypic liver functions. The methodology has been designed to meet specifications for GMP production, required for manufacture of advanced therapy medicinal products (ATMPs). In a porcine model of severe liver failure, damage was assured in all animals by surgical ischaemia in pigs with human sized livers (1.2-1.6 kg liver weights). The BioArtificial liver (UCLBAL) improved important prognostic clinical liver-related parameters, eg, a significant improvement in coagulation, reduction in vasopressor requirements, improvement in blood pH and in parameters of intracranial pressure (ICP) and oxygenation.
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Affiliation(s)
- Clare Selden
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom.
| | - James Bundy
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom
| | - Eloy Erro
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom
| | - Eva Puschmann
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom
| | - Malcolm Miller
- Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa
| | - Delawir Kahn
- Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa
| | - Humphrey Hodgson
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom
| | - Barry Fuller
- Dept. of Surgery, UCL Medical School, Royal Free Hospital, London, NW3 2QG, UK
| | - Jordi Gonzalez-Molina
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom
| | - Aurelie Le Lay
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom
| | - Stephanie Gibbons
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom
| | - Sherri Chalmers
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom
| | - Sunil Modi
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom
| | - Amy Thomas
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom
| | - Peter Kilbride
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom
| | - Agnes Isaacs
- Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa
| | - Richard Ginsburg
- Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa
| | - Helen Ilsley
- Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa
| | - David Thomson
- Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa
| | - Galya Chinnery
- Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa
| | - Ncedile Mankahla
- Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa
| | - Lizel Loo
- Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa
| | - C Wendy Spearman
- Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa
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12
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Paventi G, Pizzuto R, Passarella S. The occurrence of l-lactate dehydrogenase in the inner mitochondrial compartment of pig liver. Biochem Biophys Res Commun 2017; 489:255-261. [PMID: 28564593 DOI: 10.1016/j.bbrc.2017.05.154] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Accepted: 05/26/2017] [Indexed: 10/19/2022]
Abstract
Although pig represents a model species in biomedical research including studies dealing with liver patho-physiology, some aspects of liver metabolism need to be addressed. In particular, whether and how pig mitochondria can metabolize l-lactate remains to be established. We show here that pig liver mitochondria (PLM) possess their own l-lactate dehydrogenase (mL-LDH). This was shown both via immunological analysis and by assaying photometrically the L-LDH reaction in solubilised PLM. The mL-LDH reaction shows hyperbolic dependence on the substrate concentration, it is inhibited by oxamate and proves to differ from the cytosolic activity (cL-LDH), as revealed by the difference found in both pH profiles and temperature dependence of m- and cL-LDH. Titration experiments with digitonin show that mL-LDH is restricted in mitochondrial inner compartment. In agreement with the above findings, three genes in Sus scrofa genome encoded for L-LDH subunits which are predicted to have mitochondrial localization, as investigated by Target P 1.1 and PredSL analysis.
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Affiliation(s)
- Gianluca Paventi
- Department of Medicine and Health Sciences "Vincenzo Tiberio", University of Molise, via De Sanctis, 86100 Campobasso, Italy.
| | - Roberto Pizzuto
- Department of Medicine and Health Sciences "Vincenzo Tiberio", University of Molise, via De Sanctis, 86100 Campobasso, Italy
| | - Salvatore Passarella
- Department of Medicine and Health Sciences "Vincenzo Tiberio", University of Molise, via De Sanctis, 86100 Campobasso, Italy; School of Medicine and Surgery, University of Bari, Hospital Policlinico, Piazza Giulio Cesare, 11, 70124 Bari, Italy
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13
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Metabonomics Research Progress on Liver Diseases. Can J Gastroenterol Hepatol 2017; 2017:8467192. [PMID: 28321390 PMCID: PMC5339575 DOI: 10.1155/2017/8467192] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2016] [Revised: 12/18/2016] [Accepted: 02/09/2017] [Indexed: 12/12/2022] Open
Abstract
Metabolomics as the new omics technique develops after genomics, transcriptomics, and proteomics and has rapid development at present. Liver diseases are worldwide public health problems. In China, chronic hepatitis B and its secondary diseases are the common liver diseases. They can be diagnosed by the combination of history, virology, liver function, and medical imaging. However, some patients seldom have relevant physical examination, so the diagnosis may be delayed. Many other liver diseases, such as drug-induced liver injury (DILI), alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD), and autoimmune liver diseases, still do not have definite diagnostic markers; the diagnosis consists of history, medical imaging, and the relevant score. As a result, the clinical work becomes very complex. So it has broad prospects to explore the specific and sensitive biomarkers of liver diseases with metabolomics. In this paper, there are several summaries which are related to the current research progress and application of metabolomics on biomarkers of liver diseases.
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