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Sidorov EV, Smith K, Xu C, Route M, Sanghera DK. Corroborated evidence on change of metabolome after ischemic stroke due to large vessel occlusion. Metabolomics 2025; 21:41. [PMID: 40123037 DOI: 10.1007/s11306-025-02235-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 02/05/2025] [Indexed: 03/25/2025]
Abstract
INTRODUCTION Metabolomic studies which search for acute ischemic stroke (AIS) biomarkers commonly have contradictory findings. Robust methodology is required to understand true metabolome changes after AIS. METHODS To improve validity, we obtained corroborative evidence on change of serum metabolome after AIS by: (1) focusing on patients with large vessel occlusion (LVO), (2) combining cross-sectional and longitudinal study designs, and (3) performing analysis using different metabolome platforms: Nuclear Magnetic Resonance (NMR) and Liquid Chromatography-Mass Spectrometry (LC-MS). In the cross-sectional part we compared serum metabolome of 84 AIS patients and 82 controls using NMR at 48-72 h, while in the longitudinal part we prospectively analyzed serum metabolome using LC-MS on 15 AIS patients at < 24 h, 48-72 h, 5-7 days, 80-120 days. We hypothesized that serum metabolites elevated in cross-sectional part would show rising trajectory in longitudinal part, and vice versa. RESULTS We found that glycerol, phosphatidylethanolamine (PE), ceramide, phenylalanine and their derivatives had consistent increases, while other key metabolites including histidine, tyrosine, valine, glutamine, phosphatidylcholine (PC), sphingomyelin, fatty acids (FA) had consistent decreases after AIS. CONCLUSION We identified corroborated changes in metabolome after AIS across different technologies and study designs. These changes correspond to loss of nerve cell membrane integrity and activation of alternative metabolic pathways in the setting of blood brain barrier (BBB) disruption. If proven on a larger sample, our findings may improve prediction of mortality, and functional outcomes after AIS.
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Affiliation(s)
- Evgeny V Sidorov
- Department of Neurology, University of Oklahoma Health Sciences Center (OUHSC), 920 S.L.Young Blvd #2040, Oklahoma City, 73014, USA.
- Oklahoma Center for Neuroscience, OUHSC, Oklahoma City, USA.
| | - Kyle Smith
- Department of Neurology, University of Oklahoma Health Sciences Center (OUHSC), 920 S.L.Young Blvd #2040, Oklahoma City, 73014, USA
| | - Chao Xu
- Department of Biostatistics and Epidemiology, OUHSC, Oklahoma City, USA
| | - Madhusmita Route
- Oklahoma Center for Neuroscience, OUHSC, Oklahoma City, USA
- Department of Pediatrics, College of Medicine, OUHSC, 940 Stanton Y Blvd, BMSB 317D, Oklahoma City, 73014, USA
- Department of Pharmaceutical Sciences, OUHSC, Oklahoma City, USA
| | - Dharambir K Sanghera
- Oklahoma Center for Neuroscience, OUHSC, Oklahoma City, USA.
- Department of Pediatrics, College of Medicine, OUHSC, 940 Stanton Y Blvd, BMSB 317D, Oklahoma City, 73014, USA.
- Department of Pharmaceutical Sciences, OUHSC, Oklahoma City, USA.
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Wang M, Hu Q, Wang N, Jiang Y, Dong T, Cao S, Zhou A. Glutathione Attenuates Copper Levels and Alleviates Hepatic Injury in TX Mice. Biol Trace Elem Res 2024:10.1007/s12011-024-04384-1. [PMID: 39304592 DOI: 10.1007/s12011-024-04384-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 09/16/2024] [Indexed: 09/22/2024]
Abstract
Wilson's disease (WD) is an inherited disorder that is characterized by abnormal copper metabolism, and treatment of this condition in the clinic focuses on promoting copper ion excretion. Glutathione (GSH) is a tripeptide compound whose active group is a sulfhydryl group, which is involved in many important biochemical reactions. Thus, the antioxidant and integrative detoxification effects of GSH have attracted attention. Whether GSH promotes copper ion excretion and reduces oxidative stress to alleviate WD-related liver injury is the focus of this study. Here, we used toxic milk (TX) mice as a model to study WD, and we treated these mice with GSH. We observed that GSH was effective at promoting copper excretion by TX mice. In addition, GSH has been shown to be effective in attenuating liver injury, including improving the structure and morphology of stem tissue and reducing hepatocyte necrosis. The effects of GSH on hepatic oxidative stress were determined by measuring catalase, malondialdehyde and total superoxide dismutase. The results showed that GSH could increase hepatic antioxidant enzyme activities, reduce lipid peroxidation levels and attenuate liver injury. In conclusion, GSH may exert its hepatic benefits by promoting copper ion excretion and preventing oxidative stress.
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Affiliation(s)
- Mengzhen Wang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230038, China
- Key Laboratory of Xin'an Medicine of the Ministry of Education, Hefei, 230038, China
| | - Qiang Hu
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230038, China
- Key Laboratory of Xin'an Medicine of the Ministry of Education, Hefei, 230038, China
| | - Ni Wang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230038, China
- Key Laboratory of Xin'an Medicine of the Ministry of Education, Hefei, 230038, China
| | - Yuge Jiang
- Key Laboratory of Xin'an Medicine of the Ministry of Education, Hefei, 230038, China
| | - Ting Dong
- The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, 230031, China
| | - Shijian Cao
- The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, 230031, China.
| | - An Zhou
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230038, China.
- Key Laboratory of Xin'an Medicine of the Ministry of Education, Hefei, 230038, China.
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Raza W, Öhman A, Kanninen KM, Jalava P, Zeng XW, de Crom TOE, Ikram MA, Oudin A. Metabolic profiles associated with exposure to ambient particulate air pollution: findings from the Betula cohort. Front Public Health 2024; 12:1401006. [PMID: 39193206 PMCID: PMC11348805 DOI: 10.3389/fpubh.2024.1401006] [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: 03/14/2024] [Accepted: 07/01/2024] [Indexed: 08/29/2024] Open
Abstract
Introduction Air pollution is a significant contributor to morbidity and mortality globally and has been linked to an increased risk of dementia. Previous studies within the Betula cohort in Northern Sweden have demonstrated associations between air pollution and dementia, as well as distinctive metabolomic profiles in dementia patients compared to controls. This study aimed to investigate whether air pollution is associated with quantitative changes in metabolite levels within this cohort, and whether future dementia status would modify this association. Methods Both short-term and long-term exposure to air pollution were evaluated using high spatial resolution models and measured data. Air pollution from vehicle exhaust and woodsmoke were analyzed separately. Metabolomic profiling was conducted on 321 participants, including 58 serum samples from dementia patients and a control group matched for age, sex, and education level, using nuclear magnetic resonance spectroscopy. Results No statistically significant associations were found between any metabolites and any measures of short-term or long-term exposure to air pollution. However, there were trends potentially suggesting associations between both long-term and short-term exposure to air pollution with lactate and glucose metabolites. Notably, these associations were observed despite the lack of correlation between long-term and short-term air pollution exposure in this cohort. There were also tendencies for associations between air pollution from woodsmoke to be more pronounced in participants that would later develop dementia, suggesting a potential effect depending on urban/rural factors. Discussion While no significant associations were found, the trends observed in the data suggest potential links between air pollution exposure and changes in lactate and glucose metabolites. These findings provide some new insights into the link between air pollution and metabolic markers in a low-exposure setting. However, addressing existing limitations is crucial to improve the robustness and applicability of future research in this area. The pronounced associations in participants who later developed dementia may indicate an influence of urban/rural factors, warranting further investigation.
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Affiliation(s)
- Wasif Raza
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Anders Öhman
- Department of Medical and Translational Biology, Umeå University, Umeå, Sweden
| | - Katja M. Kanninen
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
| | - Pasi Jalava
- Department of Environmental and Biological Sciences, University of Eastern Finland, Kuopio, Finland
| | - Xiao-wen Zeng
- Department of Preventive Medicine, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | | | - M. Arfan Ikram
- Department of Laboratory Medicine, Lund University, Lund, Sweden
| | - Anna Oudin
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
- Department of Environmental and Biological Sciences, University of Eastern Finland, Kuopio, Finland
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Zhou J, Wang J, Li D, Zhang Z, Wang C, Zhang X, Xu X, Gao J. An inulin-type fructan CP-A from Codonopsis pilosula alleviates TNBS-induced ulcerative colitis based on serum-untargeted metabolomics. Am J Physiol Gastrointest Liver Physiol 2024; 326:G216-G227. [PMID: 38193197 DOI: 10.1152/ajpgi.00214.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 12/12/2023] [Accepted: 12/21/2023] [Indexed: 01/10/2024]
Abstract
Ulcerative colitis (UC) is an inflammatory disease with abdominal pain, diarrhea, and bloody stool as the main symptoms. Several studies have confirmed that polysaccharides are effective against UC. It is commonly accepted that the traditional benefits of Radix Codonopsis can be attributed to its polysaccharide contents, and inulin-type fructan CP-A is the main active monomer in the polysaccharide components. Herein, we established a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced UC rat model and lipopolysaccharide (LPS)-induced colonic epithelial cell model (NCM460) to investigate the effect of CP-A on UC. Untargeted metabolomics studies were conducted to identify differential metabolites using ultra-high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS) and enrich metabolic pathways in rat serum. The in vivo assays demonstrated that CP-A reduces colonic macroscopic injury, disease activity index (DAI), histopathological score, interleukin (IL)-8, and tumor necrosis factor-α (TNF-α) levels, as well as the expression of intercellular adhesion molecules. On the other hand, CP-A increases IL-10 and transforming growth factor-β (TGF-β) levels. The in vitro experiments indicated that CP-A treatment could reduce nitric oxide (NO) and IL-1β after LPS stimulation. The metabolomics results suggested that CP-A therapy for UC may be related to the mammalian target of rapamycin (mTOR) signaling pathway. The in vitro and in vivo validation of the pathway showed similar results, indicating that CP-A alleviates UC by preventing the activation of mTOR/p70S6K signaling pathway. These findings offer a fresh approach to treating UC and a theoretical foundation for the future advancement of CP-A.NEW & NOTEWORTHY We report that an inulin-type fructan from Codonopsis pilosula CP-A exhibits a therapeutic effect on experimental colitis. Its mechanism may be to alleviate intestinal inflammation by preventing the activation of mammalian target of rapamycin (mTOR)/p70S6K signaling pathway. These findings offer a fresh approach to treating ulcerative colitis (UC) and a theoretical foundation for the future advancement of CP-A.
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Affiliation(s)
- Jiangtao Zhou
- School of Pharmacy, Shanxi Medical University, Taiyuan, People's Republic of China
- Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, People's Republic of China
- Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan, People's Republic of China
| | - Jiajing Wang
- School of Pharmacy, Shanxi Medical University, Taiyuan, People's Republic of China
| | - Deyun Li
- School of Pharmacy, Shanxi Medical University, Taiyuan, People's Republic of China
| | - Zhijia Zhang
- Urology Surgery, Shanxi Provincial People's Hospital, Taiyuan, People's Republic of China
| | - Changjian Wang
- School of Pharmacy, Shanxi Medical University, Taiyuan, People's Republic of China
| | - Xuepeng Zhang
- School of Pharmacy, Shanxi Medical University, Taiyuan, People's Republic of China
| | - Xiexin Xu
- School of Pharmacy, Shanxi Medical University, Taiyuan, People's Republic of China
| | - Jianping Gao
- School of Pharmacy, Shanxi Medical University, Taiyuan, People's Republic of China
- Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, People's Republic of China
- Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan, People's Republic of China
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Ghini V, Meoni G, Vignoli A, Di Cesare F, Tenori L, Turano P, Luchinat C. Fingerprinting and profiling in metabolomics of biosamples. PROGRESS IN NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY 2023; 138-139:105-135. [PMID: 38065666 DOI: 10.1016/j.pnmrs.2023.10.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 10/13/2023] [Accepted: 10/15/2023] [Indexed: 12/18/2023]
Abstract
This review focuses on metabolomics from an NMR point of view. It attempts to cover the broad scope of metabolomics and describes the NMR experiments that are most suitable for each sample type. It is addressed not only to NMR specialists, but to all researchers who wish to approach metabolomics with a clear idea of what they wish to achieve but not necessarily with a deep knowledge of NMR. For this reason, some technical parts may seem a bit naïve to the experts. The review starts by describing standard metabolomics procedures, which imply the use of a dedicated 600 MHz instrument and of four properly standardized 1D experiments. Standardization is a must if one wants to directly compare NMR results obtained in different labs. A brief mention is also made of standardized pre-analytical procedures, which are even more essential. Attention is paid to the distinction between fingerprinting and profiling, and the advantages and disadvantages of fingerprinting are clarified. This aspect is often not fully appreciated. Then profiling, and the associated problems of signal assignment and quantitation, are discussed. We also describe less conventional approaches, such as the use of different magnetic fields, the use of signal enhancement techniques to increase sensitivity, and the potential of field-shuttling NMR. A few examples of biomedical applications are also given, again with the focus on NMR techniques that are most suitable to achieve each particular goal, including a description of the most common heteronuclear experiments. Finally, the growing applications of metabolomics to foodstuffs are described.
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Affiliation(s)
- Veronica Ghini
- Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy; Department of Chemistry "Ugo Schiff", University of Florence, Sesto Fiorentino, Italy
| | - Gaia Meoni
- Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy; Department of Chemistry "Ugo Schiff", University of Florence, Sesto Fiorentino, Italy
| | - Alessia Vignoli
- Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy; Department of Chemistry "Ugo Schiff", University of Florence, Sesto Fiorentino, Italy
| | - Francesca Di Cesare
- Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy; Department of Chemistry "Ugo Schiff", University of Florence, Sesto Fiorentino, Italy
| | - Leonardo Tenori
- Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy; Department of Chemistry "Ugo Schiff", University of Florence, Sesto Fiorentino, Italy; Consorzio Interuniversitario Risonanze Magnetiche Metallo Proteine (CIRMMP), Sesto Fiorentino, Italy
| | - Paola Turano
- Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy; Department of Chemistry "Ugo Schiff", University of Florence, Sesto Fiorentino, Italy; Consorzio Interuniversitario Risonanze Magnetiche Metallo Proteine (CIRMMP), Sesto Fiorentino, Italy.
| | - Claudio Luchinat
- Consorzio Interuniversitario Risonanze Magnetiche Metallo Proteine (CIRMMP), Sesto Fiorentino, Italy; Giotto Biotech S.r.l., Sesto Fiorentino, Italy.
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Jaggard MKJ, Boulangé CL, Graça G, Akhbari P, Vaghela U, Bhattacharya R, Williams HRT, Lindon JC, Gupte CM. The effect of liquid-liquid extraction on metabolite detection and analysis using NMR spectroscopy in human synovial fluid. J Pharm Biomed Anal 2023; 226:115254. [PMID: 36701879 DOI: 10.1016/j.jpba.2023.115254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 01/09/2023] [Accepted: 01/13/2023] [Indexed: 01/15/2023]
Abstract
The evaluation of joint disease using synovial fluid is an emerging field of metabolic profiling. The analysis is challenged by multiple macromolecules which can obscure the small molecule chemistry. The use of protein precipitation and extraction has been evaluated previously, but not in synovial fluid. We systematically review the published NMR spectroscopy methods of synovial fluid analysis and investigated the efficacy of three different protein precipitation techniques: methanol, acetonitrile and trichloroacetic acid. The trichloroacetic wash removed the most protein. However, metabolite recoveries were universally very poor. Acetonitrile liquid/liquid extraction gave metabolite gains from four unknown compounds with spectral peaks at δ = 1.91 ppm, 3.64 ppm, 3.95 ppm & 4.05 ppm. The metabolite recoveries for acetonitrile were between 1.5 and 7 times higher than the methanol method, across all classes of metabolite. The methanol method was more effective in removing protein as reported by the free GAG undefined peak (44 % vs 125 %). However, qualitative evaluation showed that acetonitrile and methanol provided good restoration of the spectra to baseline. The methanol extraction has issues of a gelatinous substrate in the samples. All metabolite recoveries had a CV of > 15 %. A recommendation of acetonitrile liquid/liquid extraction was made for human synovial fluid (HSF) analysis. This is due to consistency, effective protein precipitation, recovery of metabolites and additional compounds not previously visible.
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Affiliation(s)
- Matthew K J Jaggard
- Department of Orthopaedics & Trauma, Imperial College Healthcare NHS Trust, Mary's Hospital, Praed Street, Paddington, London W2 1NY, UK; Department of Surgery and Cancer, Imperial College London, South Kensington, London SW7 2AZ, UK.
| | - Claire L Boulangé
- Department of Metabolism, Digestion and Reproduction, Imperial College London, South Kensington, London SW7 2AZ, UK; Department of Surgery and Cancer, Imperial College London, South Kensington, London SW7 2AZ, UK
| | - Gonçalo Graça
- Department of Metabolism, Digestion and Reproduction, Imperial College London, South Kensington, London SW7 2AZ, UK
| | - Pouya Akhbari
- Department of Orthopaedics & Trauma, Imperial College Healthcare NHS Trust, Mary's Hospital, Praed Street, Paddington, London W2 1NY, UK; Department of Surgery and Cancer, Imperial College London, South Kensington, London SW7 2AZ, UK
| | - Uddhav Vaghela
- School of Medicine, Imperial College London, South Kensington, London SW7 2AZ, UK
| | - Rajarshi Bhattacharya
- Department of Orthopaedics & Trauma, Imperial College Healthcare NHS Trust, Mary's Hospital, Praed Street, Paddington, London W2 1NY, UK
| | - Horace R T Williams
- Department of Metabolism, Digestion and Reproduction, Imperial College London, South Kensington, London SW7 2AZ, UK; Department of Gastroenterology, Imperial College NHS Trust, Mary's Hospital, Praed Street, Paddington, London W2 1NY, UK
| | - John C Lindon
- Department of Surgery and Cancer, Imperial College London, South Kensington, London SW7 2AZ, UK
| | - Chinmay M Gupte
- Department of Orthopaedics & Trauma, Imperial College Healthcare NHS Trust, Mary's Hospital, Praed Street, Paddington, London W2 1NY, UK; Department of Surgery and Cancer, Imperial College London, South Kensington, London SW7 2AZ, UK
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Tian Y, Li G, Du X, Zeng T, Chen L, Xu W, Gu T, Tao Z, Lu L. Integration of LC-MS-Based and GC-MS-Based Metabolic Profiling to Reveal the Effects of Domestication and Boiling on the Composition of Duck Egg Yolks. Metabolites 2023; 13:metabo13010135. [PMID: 36677059 PMCID: PMC9866831 DOI: 10.3390/metabo13010135] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 12/27/2022] [Accepted: 01/05/2023] [Indexed: 01/18/2023] Open
Abstract
Egg yolks contain abundant lipids, proteins, and minerals that provide not only essential nutrients for embryonic development but also cheap sources of nutrients for consumers worldwide. Previous composition analyses of egg yolks primarily focused on nutrients such as lipids and minerals. However, few studies have reported the effects of domestication and heating on yolk composition and characteristics. The objective of this study was to investigate the impact of domestication and boiling on the metabolite contents of egg yolks via untargeted metabolomics using GC-MS and LC-MS. In this study, eggs were collected from Fenghua teals, captive mallards, and Shaoxing ducks. Twelve duck eggs (half raw and half cooked) were randomly selected from each variety, and the egg yolks were separated for metabolic profiling. The analysis identified 1205 compounds in the egg yolks. Domestication generated more differential metabolites than boiling, which indicated that the changes in the metabolome of duck egg yolk caused by domestication were greater than those caused by boiling. In a comparative analysis of domestic and mallard ducks, 48 overlapping differential metabolites were discovered. Among them, nine metabolites were upregulated in domesticated ducks, including monoolein, emodin, daidzein, genistein, and glycitein, which may be involved in lipid metabolism; some of them may also act as phytoestrogens (flavonoids). Another 39 metabolites, including imethylethanolamine, harmalan, mannitol, nornicotine, linoleic acid, diphenylamine, proline betaine, alloxanthin, and resolvin d1, were downregulated by domestication and were linked to immunity, anti-inflammatory, antibacterial, and antioxidant properties. Furthermore, four overlapping differential metabolites that included amino acids and dipeptides were discovered in paired comparisons of the raw and boiled samples. Our findings provided new insights into the molecular response of duck domestication and supported the use of metabolomics to examine the impact of boiling on the composition of egg yolks.
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Affiliation(s)
- Yong Tian
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Animal Science & Veterinary, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
- Key Laboratory of Livestock and Poultry Resources (Poultry) Evaluation and Utilization, Ministry of Agriculture and Rural Affairs of China, Hangzhou 310021, China
| | - Guoqin Li
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Animal Science & Veterinary, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
- Key Laboratory of Livestock and Poultry Resources (Poultry) Evaluation and Utilization, Ministry of Agriculture and Rural Affairs of China, Hangzhou 310021, China
| | - Xizhong Du
- Institute of Animal Husbandry and Veterinary Medicine, Jinhua Academy of Agricultural Sciences, Jinhua 321017, China
| | - Tao Zeng
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Animal Science & Veterinary, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
- Key Laboratory of Livestock and Poultry Resources (Poultry) Evaluation and Utilization, Ministry of Agriculture and Rural Affairs of China, Hangzhou 310021, China
| | - Li Chen
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Animal Science & Veterinary, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
- Key Laboratory of Livestock and Poultry Resources (Poultry) Evaluation and Utilization, Ministry of Agriculture and Rural Affairs of China, Hangzhou 310021, China
| | - Wenwu Xu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Animal Science & Veterinary, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
- Key Laboratory of Livestock and Poultry Resources (Poultry) Evaluation and Utilization, Ministry of Agriculture and Rural Affairs of China, Hangzhou 310021, China
| | - Tiantian Gu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Animal Science & Veterinary, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
- Key Laboratory of Livestock and Poultry Resources (Poultry) Evaluation and Utilization, Ministry of Agriculture and Rural Affairs of China, Hangzhou 310021, China
| | - Zhengrong Tao
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Animal Science & Veterinary, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
| | - Lizhi Lu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Animal Science & Veterinary, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
- Key Laboratory of Livestock and Poultry Resources (Poultry) Evaluation and Utilization, Ministry of Agriculture and Rural Affairs of China, Hangzhou 310021, China
- Correspondence: ; Tel.: +86-571-8640-6682
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Liu T, Qin M, Xiong X, Lai X, Gao Y. Multi-omics approaches for deciphering the complexity of traditional Chinese medicine syndromes in stroke: A systematic review. Front Pharmacol 2022; 13:980650. [PMID: 36147315 PMCID: PMC9489218 DOI: 10.3389/fphar.2022.980650] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 08/08/2022] [Indexed: 12/03/2022] Open
Abstract
Background: Deciphering the biological basis of traditional Chinese medicine (TCM) syndromes in complex diseases is challenging. Rapid advances in multi-omics approaches provide new opportunities to unveil the biological basis of TCM syndromes. We intend to summarize the latest significant progress and highlight the crucial value of applying multi-omics approaches to reveal TCM syndromes of stroke in a new horizon. Methods: We systematically searched PubMed, EMBASE, Web of Science Core Collection (WOSCC), Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), Wanfang database and China Biology Medicine Database (SinoMed) for relevant studies from their inception to 31 March 2022, and conducted a comprehensive systematic review (PROSPERO registration number: CRD42021285922). Results: A total of 43 relevant studies were included in the final systematic review, genomics, transcriptomics, proteomics, and metabolomics were all involved. Some gene polymorphisms, differential lncRNAs, mRNAs, miRNAs, proteins, and metabolites may be associated with TCM syndromes of stroke. In addition, some studies conducted a preliminary exploration on the different diseases with the same TCM syndrome. The results showed that thioredoxin-dependent peroxidase reductase may be the specific marker protein of Liver-yang transforming into wind syndrome, and the network formed by mir-146b-5p, -199a-5p, and 23 targeted mRNAs may be the biomarker of Blood-stasis syndrome. Conclusion: Multi-omics technologies have served as powerful tools to investigate the complexity of TCM syndromes and may hold the promise of promoting the modernization of TCM as well as personalized medicine of TCM in stroke.
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Affiliation(s)
- Tingting Liu
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Mingzhen Qin
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Xuejiao Xiong
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Xinxing Lai
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Ying Gao
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Chinese Medicine Key Research Room of Brain Disorders Syndrome and Treatment of the National Administration of Traditional Chinese Medicine, Beijing, China
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Zhang K, Pan X, Zheng J, Liu Y, Sun L. The metabolic analysis in human aortic tissues of aortic dissection. J Clin Lab Anal 2022; 36:e24623. [PMID: 35881684 PMCID: PMC9459286 DOI: 10.1002/jcla.24623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 07/10/2022] [Accepted: 07/12/2022] [Indexed: 12/04/2022] Open
Abstract
Background The metabolic profile of human aortic tissues is of great importance. Among the analytical platforms utilized in metabolomics, LC‐MS provides broad metabolome coverage. The non‐targeted metabolomics can comprehensively detect the entire metabolome of an organism and find the metabolic characteristics that have significant changes in the experimental group and the control group and elucidate the metabolic pathway concerning the recognized metabolites. Employing non‐targeted metabolomics is helpful to develop biomarkers for disease diagnosis and disease pathology research; for instance, Aortic aneurysm (AA) and Aortic dissection (AD). Aim This study sought to describe the non‐targeted analysis of 18 aortic tissue samples, comparing between AA and AD. Material & Methods Our experimental flow included dividing the samples into (AA, nine samples) and (AD, nine samples), SCIEX quadrupole timeofflight tandem mass spectrometer (TripleTOF) 6600+ mass spectrometer data refinement, MetDNA database analysis, and pathway analysis. We performed an initial validation by setting quality control parameters to evaluate the stability of the analysis system during the computer operation. We then used the repeatability of the control samples to examine the stability of the instrument during the entire analysis process to ensure the reliability of the results. Results Our study found 138 novel metabolites involved in galactose metabolism. Discussion 138 novel metabolites found in this study will be further studied in the future. Conclusion Our study found 138 novel metabolites between AA and AD, which will provide viable clinical data for future studies aimed to implement galactose markers in aortic tissue analysis.
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Affiliation(s)
- Kefeng Zhang
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.,Beijing Aortic Disease Center, Beijing, China
| | - Xudong Pan
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.,Beijing Aortic Disease Center, Beijing, China
| | - Jun Zheng
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.,Beijing Aortic Disease Center, Beijing, China
| | - Yongmin Liu
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.,Beijing Aortic Disease Center, Beijing, China
| | - Lizhong Sun
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.,Beijing Aortic Disease Center, Beijing, China
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10
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Abstract
BACKGROUND Marine ecosystems are hosts to a vast array of organisms, being among the most richly biodiverse locations on the planet. The study of these ecosystems is very important, as they are not only a significant source of food for the world but also have, in recent years, become a prolific source of compounds with therapeutic potential. Studies of aspects of marine life have involved diverse fields of marine science, and the use of metabolomics as an experimental approach has increased in recent years. As part of the "omics" technologies, metabolomics has been used to deepen the understanding of interactions between marine organisms and their environment at a metabolic level and to discover new metabolites produced by these organisms. AIM OF REVIEW This review provides an overview of the use of metabolomics in the study of marine organisms. It also explores the use of metabolomics tools common to other fields such as plants and human metabolomics that could potentially contribute to marine organism studies. It deals with the entire process of a metabolomic study, from sample collection considerations, metabolite extraction, analytical techniques, and data analysis. It also includes an overview of recent applications of metabolomics in fields such as marine ecology and drug discovery and future perspectives of its use in the study of marine organisms. KEY SCIENTIFIC CONCEPTS OF REVIEW The review covers all the steps involved in metabolomic studies of marine organisms including, collection, extraction methods, analytical tools, statistical analysis, and dereplication. It aims to provide insight into all aspects that a newcomer to the field should consider when undertaking marine metabolomics.
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Affiliation(s)
- Lina M Bayona
- Natural Products Laboratory, Institute of Biology, Leiden University, 2333 BE, Leiden, The Netherlands
| | - Nicole J de Voogd
- Naturalis Biodiversity Center, Marine Biodiversity, 2333 CR, Leiden, The Netherlands
- Institute of Environmental Sciences, Leiden University, 2333 CC, Leiden, The Netherlands
| | - Young Hae Choi
- Natural Products Laboratory, Institute of Biology, Leiden University, 2333 BE, Leiden, The Netherlands.
- College of Pharmacy, Kyung Hee University, 130-701, Seoul, Republic of Korea.
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11
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Sari B, Isik M, Eylem CC, Kilic C, Okesola BO, Karakaya E, Emregul E, Nemutlu E, Derkus B. Omics Technologies for High-Throughput-Screening of Cell-Biomaterial Interactions. Mol Omics 2022; 18:591-615. [DOI: 10.1039/d2mo00060a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Recent research effort in biomaterial development has largely focused on engineering bio-instructive materials to stimulate specific cell signaling. Assessing the biological performance of these materials using time-consuming and trial-and-error traditional...
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12
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Xu D, Zheng X, Li C, Wu J, Sun L, Qin X, Fan X. Insights into the response mechanism of Litopenaeus vannamei exposed to cold stress during live transport combining untargeted metabolomics and biochemical assays. J Therm Biol 2022; 104:103200. [DOI: 10.1016/j.jtherbio.2022.103200] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Revised: 01/17/2022] [Accepted: 01/21/2022] [Indexed: 01/22/2023]
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13
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Huang W, Zhang Z, Niu L, Hu X, Teka T, Han L, Pan G, Wang Q. Rapid discovery of potentially vasodilative compounds from Uncaria by UHPLC/Q-Orbitrap-MS based metabolomics and correlation analysis. J Pharm Biomed Anal 2021; 206:114384. [PMID: 34607203 DOI: 10.1016/j.jpba.2021.114384] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 08/30/2021] [Accepted: 09/15/2021] [Indexed: 01/08/2023]
Abstract
The genus Uncaria belongs to the family of Rubiaceae, which contains approximately 34 species. It has been widely used as a traditional Chinese medicine (TCM) in China to treat hypertension, fevers, headaches, gastrointestinal illness, epilepsy, wounds, and ulcers. Uncaria rhynchophylla. (Miq.) Miq. ex Hvail.(URM) and Uncaria hirsuta Havil.(UHH) are mainly used as remedies for hypertension, which both belong to the resource of "Gou-teng" in the Chinese Pharmacopoeia. However, the authentic antihypertensive components of Uncaria still have not been fully elucidated until now. In this work, we firstly explored and compared the vasorelaxation effect of URM and UHH on the isolated rat mesenteric artery ring. Then, the variations of metabolite profiles between URM and UHH samples were investigated by UHPLC/Q-Orbitrap-MS, and 16 different metabolites have been found through multivariate statistical analysis. Further, the potential vasodilative compounds which include corynoxeine, isocorynoxeine, isorhynchophylline, rhynchophylline, hirsuteine and hirsutine were screened through the correlation analysis between metabolites and anti-hypertension activities. And the relaxation effects of the six compounds on the mesenteric artery have verified. The results indicated that metabolomics combined with correlation analysis could be effective strategies to rapid explore the active compounds from TCM.
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Affiliation(s)
- Wenwen Huang
- Tianjin State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai, Tianjin 301617, China
| | - Zhonglian Zhang
- Yunnan Key Laboratory of Southern Medicine Utilization, Yunnan Branch of Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Jinghong 666100, China
| | - Lu Niu
- Tianjin State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai, Tianjin 301617, China
| | - Xiaohan Hu
- Tianjin State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai, Tianjin 301617, China
| | - Tekleab Teka
- Tianjin State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai, Tianjin 301617, China
| | - Lifeng Han
- Tianjin State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai, Tianjin 301617, China
| | - Guixiang Pan
- Second Affiliated hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China.
| | - Qilong Wang
- Tianjin State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai, Tianjin 301617, China.
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14
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Kikuchi J, Yamada S. The exposome paradigm to predict environmental health in terms of systemic homeostasis and resource balance based on NMR data science. RSC Adv 2021; 11:30426-30447. [PMID: 35480260 PMCID: PMC9041152 DOI: 10.1039/d1ra03008f] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Accepted: 08/31/2021] [Indexed: 12/22/2022] Open
Abstract
The environment, from microbial ecosystems to recycled resources, fluctuates dynamically due to many physical, chemical and biological factors, the profile of which reflects changes in overall state, such as environmental illness caused by a collapse of homeostasis. To evaluate and predict environmental health in terms of systemic homeostasis and resource balance, a comprehensive understanding of these factors requires an approach based on the "exposome paradigm", namely the totality of exposure to all substances. Furthermore, in considering sustainable development to meet global population growth, it is important to gain an understanding of both the circulation of biological resources and waste recycling in human society. From this perspective, natural environment, agriculture, aquaculture, wastewater treatment in industry, biomass degradation and biodegradable materials design are at the forefront of current research. In this respect, nuclear magnetic resonance (NMR) offers tremendous advantages in the analysis of samples of molecular complexity, such as crude bio-extracts, intact cells and tissues, fibres, foods, feeds, fertilizers and environmental samples. Here we outline examples to promote an understanding of recent applications of solution-state, solid-state, time-domain NMR and magnetic resonance imaging (MRI) to the complex evaluation of organisms, materials and the environment. We also describe useful databases and informatics tools, as well as machine learning techniques for NMR analysis, demonstrating that NMR data science can be used to evaluate the exposome in both the natural environment and human society towards a sustainable future.
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Affiliation(s)
- Jun Kikuchi
- Environmental Metabolic Analysis Research Team, RIKEN Center for Sustainable Resource Science 1-7-22 Suehiro-cho, Tsurumi-ku Yokohama 230-0045 Japan
- Graduate School of Bioagricultural Sciences, Nagoya University Furo-cho, Chikusa-ku Nagoya 464-8601 Japan
- Graduate School of Medical Life Science, Yokohama City University 1-7-29 Suehiro-cho, Tsurumi-ku Yokohama 230-0045 Japan
| | - Shunji Yamada
- Environmental Metabolic Analysis Research Team, RIKEN Center for Sustainable Resource Science 1-7-22 Suehiro-cho, Tsurumi-ku Yokohama 230-0045 Japan
- Prediction Science Laboratory, RIKEN Cluster for Pioneering Research 7-1-26 Minatojima-minami-machi, Chuo-ku Kobe 650-0047 Japan
- Data Assimilation Research Team, RIKEN Center for Computational Science 7-1-26 Minatojima-minami-machi, Chuo-ku Kobe 650-0047 Japan
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15
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Su F, Wang H, Wang Y, Ye L, Zhu P, Gu J, Su W. NMR-based Metabolomic Techniques Identify the Anticancer Effects of Three Polyphyllins in HepG2 Cells. CURR PHARM ANAL 2021. [DOI: 10.2174/1573412917666210823090145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:
Rhizoma Paridis (RP) is a traditional Chinese herb used for the treatment of
tumors, detoxification and hemostasia. Studies show the main components of RP are Polyphyllin I
(PPI), polyphyllin VI (PPVI), and polyphyllin VII (PPVII). However, the pharmaco-mechanisms of
these compounds are not clear.
Objective:
By used 1
H nuclear magnetic resonance (1
H-NMR) based metabolomics approach to identify the Anticancer effects of PPI, PPVI and PPVII in HepG2 cells.
Methods 1
H nuclear magnetic resonance (1
H-NMR) based metabolomics approach was applied to investigate the toxicological effect of PPI, PPVI, PPVII on HepG2 cells. Multivariate statistical analysis
was employed to examine the metabolic changes and abnormal metabolic pathways, including Principal
Component Analysis (PCA), Partial Least Squares Discriminant Analysis (PLS-DA), and orthogonal
PLS-DA (OPLS-DA).
Results:
The results showed that the effects of metabolic phenotypes were affected separately by PPI,
PPVI, and PPVII. The metabolic phenotypes were also changed over time. The characteristic metabolites were varied by affecting different polyphylins, which were identified by the reconstructed OPLSDA loading plots. According to the characteristic metabolites, the mainly disturbed metabolic pathways
were found, such as alanine, aspartate and glutamate metabolism, pyruvate metabolism, glycine, serine,
and threonine metabolism.
Conclusion:
The current work could allow us to understand the therapeutic effect of RP in metabolism. It also indicated that RP would be a promising candidate for liver cancer treatment.
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Affiliation(s)
- Feng Su
- College of Pharmaceutical Science, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou 310000, China
| | - Haibo Wang
- Zhejiang Hongyuan Pharmaceutical Co., Ltd., Linhai 317000, China
| | - Yifan Wang
- College of Pharmaceutical Science, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou 310000, China
| | - Lv Ye
- Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou 310000, China
| | - Peixi Zhu
- Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou 310000, China
| | - Jinping Gu
- College of Pharmaceutical Science, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou 310000, China
| | - Weike Su
- College of Pharmaceutical Science, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou 310000, China
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16
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Wang Y, Chen T, Gan Z, Li H, Li Y, Zhang Y, Zhao X. Metabolomic analysis of untargeted bovine uterine secretions in dairy cows with endometritis using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. Res Vet Sci 2021; 139:51-58. [PMID: 34252702 DOI: 10.1016/j.rvsc.2021.07.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 06/26/2021] [Accepted: 07/01/2021] [Indexed: 10/20/2022]
Abstract
Endometritis is among the most common bovine uterine diseases; as a cause of infertility, it affects the progress of the cattle industry. In this study, we used a novel technique based on ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry for comparative metabolomics of uterine secretions in healthy cows and cows with endometritis, classified based on clinical symptoms. Univariate and multivariate statistical analyses revealed significant differences between the two groups (n = 12). Compared with healthy uterine secretion samples, in the clinical endometritis samples, coumaric acid, benzoic acid, and equol were downregulated. However, l-phenylalanine, glutamine, succinic acid, linoleate, arachidonic acid, and other metabolites were upregulated, revealing variations between healthy cows and cows with endometritis (p < 0.05). This metabolomic approach may provide an in-depth understanding of endometritis pathobiology, along with a theoretical framework for the diagnosis and treatment of this bovine disease.
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Affiliation(s)
- Yuanyuan Wang
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China
| | - Tingting Chen
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China
| | - Ze Gan
- College of Life Science and Technology, Gansu Agricultural University, Lanzhou 730070, China
| | - Haijiang Li
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China
| | - Yina Li
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China
| | - Yong Zhang
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China; College of Life Science and Technology, Gansu Agricultural University, Lanzhou 730070, China
| | - Xingxu Zhao
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China; College of Life Science and Technology, Gansu Agricultural University, Lanzhou 730070, China.
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17
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Research Progress of Urine Biomarkers in the Diagnosis, Treatment, and Prognosis of Bladder Cancer. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021. [PMID: 33959906 DOI: 10.1007/978-3-030-63908-2_5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/13/2024]
Abstract
Bladder cancer (BC) is one of the most common tumor with high incidence. Relative to other cancers, BC has a high rate of recurrence, which results in increased mortality. As a result, early diagnosis and life-long monitoring are clinically significant for improving the long-term survival rate of BC patients. At present, the main methods of BC detection are cystoscopy and biopsy; however, these procedures can be invasive and expensive. This can lead to patient refusal and reluctance for monitoring. There are several BC biomarkers that have been approved by the FDA, but their sensitivity, specificity, and diagnostic accuracy are not ideal. More research is needed to identify suitable biomarkers that can be used for early detection, evaluation, and observation. There has been heavy research in the proteomics and genomics of BC and many potential biomarkers have been found. Although the advent of metabonomics came late, with the recent development of advanced analytical technology and bioinformatics, metabonomics has become a widely used diagnostic tool in clinical and biomedical research. It should be emphasized that despite progress in new biomarkers for BC diagnosis, there remains challenges and limitations in metabonomics research that affects its translation into clinical practice. In this chapter, the latest literature on BC biomarkers was reviewed.
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18
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Lee SH, Lee G, Seo JE, Hasan M, Kwon OS, Jung BH. Employing metabolomic approaches to determine the influence of age on experimental autoimmune encephalomyelitis (EAE). Mol Immunol 2021; 135:84-94. [PMID: 33873097 DOI: 10.1016/j.molimm.2021.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 03/12/2021] [Accepted: 04/07/2021] [Indexed: 10/21/2022]
Abstract
The immune system plays a critical role not only in homeostasis of the body but also in pathogenesis. Autoimmunity and dysregulation of the immune balance are closely related to age. To examine the influence of age on autoimmunity, the pathophysiological features of experimental autoimmune encephalomyelitis (EAE) induced at different ages were elucidated on the basis of plasma-level metabolic changes. In the present study, female 6 week-old (6 W) and 15 month-old (15 M) C57BL/6 mice were immunized for EAE induction. The plasma and tissue samples were collected to determine the phenotypic characteristics. The activity of NADPH oxidase in plasma and the IL-6 concentrations in the brain and spinal cord were higher in both EAE groups compared to those in the control groups as well as in the 15 M EAE (15 M-E) group compared to those in the 6 W EAE (6 W-E) group. The metabolomic profiles related to characteristics of EAE were characterized by the biosynthesis of unsaturated fatty acids and the metabolism of tryptophan, tyrosine and sphingolipid. The reduced availability of unsaturated fatty acids and perturbations in tryptophan metabolism were high risk factors for EAE development regardless of age. The changes in tyrosine metabolism and sphingolipid metabolites were more dramatic in the 15 M-E group. From these findings, it can be concluded that changes in unsaturated fatty acid and tryptophan metabolism contributed to the development of EAE, whereas changes in sphingolipid and tyrosine metabolism, which corresponded to age, were additional risk factors that influenced the incidence and severity of EAE.
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Affiliation(s)
- Soo Hyun Lee
- Department of Medical Records and Health Information Management, College of Nursing and Health, Kongju National University, 56 Kongjudaehakro, Kongju, Chungnam, 314-701, Republic of Korea
| | - Gakyung Lee
- Molecular Recognition Research Center, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea; Division of Bio-Medical Science & Technology, KIST-School, Korea University of Science and Technology (UST), Seoul, 02792, Republic of Korea
| | - Ji-Eun Seo
- Doping Control Center, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
| | - Mahbub Hasan
- Doping Control Center, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea; Department of Biochemistry and Molecular Biology, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, 8100, Bangladesh
| | - Oh-Seung Kwon
- Division of Bio-Medical Science & Technology, KIST-School, Korea University of Science and Technology (UST), Seoul, 02792, Republic of Korea; Doping Control Center, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
| | - Byung Hwa Jung
- Molecular Recognition Research Center, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea; Division of Bio-Medical Science & Technology, KIST-School, Korea University of Science and Technology (UST), Seoul, 02792, Republic of Korea.
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Jendoubi T. Approaches to Integrating Metabolomics and Multi-Omics Data: A Primer. Metabolites 2021; 11:184. [PMID: 33801081 PMCID: PMC8003953 DOI: 10.3390/metabo11030184] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Revised: 03/17/2021] [Accepted: 03/18/2021] [Indexed: 12/14/2022] Open
Abstract
Metabolomics deals with multiple and complex chemical reactions within living organisms and how these are influenced by external or internal perturbations. It lies at the heart of omics profiling technologies not only as the underlying biochemical layer that reflects information expressed by the genome, the transcriptome and the proteome, but also as the closest layer to the phenome. The combination of metabolomics data with the information available from genomics, transcriptomics, and proteomics offers unprecedented possibilities to enhance current understanding of biological functions, elucidate their underlying mechanisms and uncover hidden associations between omics variables. As a result, a vast array of computational tools have been developed to assist with integrative analysis of metabolomics data with different omics. Here, we review and propose five criteria-hypothesis, data types, strategies, study design and study focus- to classify statistical multi-omics data integration approaches into state-of-the-art classes under which all existing statistical methods fall. The purpose of this review is to look at various aspects that lead the choice of the statistical integrative analysis pipeline in terms of the different classes. We will draw particular attention to metabolomics and genomics data to assist those new to this field in the choice of the integrative analysis pipeline.
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Affiliation(s)
- Takoua Jendoubi
- Department of Statistical Science, University College London, London WC1E 6BT, UK
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Lima AR, Pinto J, Amaro F, Bastos MDL, Carvalho M, Guedes de Pinho P. Advances and Perspectives in Prostate Cancer Biomarker Discovery in the Last 5 Years through Tissue and Urine Metabolomics. Metabolites 2021; 11:181. [PMID: 33808897 PMCID: PMC8003702 DOI: 10.3390/metabo11030181] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 03/10/2021] [Accepted: 03/17/2021] [Indexed: 02/07/2023] Open
Abstract
Prostate cancer (PCa) is the second most diagnosed cancer in men worldwide. For its screening, serum prostate specific antigen (PSA) test has been largely performed over the past decade, despite its lack of accuracy and inability to distinguish indolent from aggressive disease. Metabolomics has been widely applied in cancer biomarker discovery due to the well-known metabolic reprogramming characteristic of cancer cells. Most of the metabolomic studies have reported alterations in urine of PCa patients due its noninvasive collection, but the analysis of prostate tissue metabolome is an ideal approach to disclose specific modifications in PCa development. This review aims to summarize and discuss the most recent findings from tissue and urine metabolomic studies applied to PCa biomarker discovery. Eighteen metabolites were found consistently altered in PCa tissue among different studies, including alanine, arginine, uracil, glutamate, fumarate, and citrate. Urine metabolomic studies also showed consistency in the dysregulation of 15 metabolites and, interestingly, alterations in the levels of valine, taurine, leucine and citrate were found in common between urine and tissue studies. These findings unveil that the impact of PCa development in human metabolome may offer a promising strategy to find novel biomarkers for PCa diagnosis.
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Affiliation(s)
- Ana Rita Lima
- UCIBIO/REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; (J.P.); (F.A.); (M.d.L.B.)
| | - Joana Pinto
- UCIBIO/REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; (J.P.); (F.A.); (M.d.L.B.)
| | - Filipa Amaro
- UCIBIO/REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; (J.P.); (F.A.); (M.d.L.B.)
| | - Maria de Lourdes Bastos
- UCIBIO/REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; (J.P.); (F.A.); (M.d.L.B.)
| | - Márcia Carvalho
- UCIBIO/REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; (J.P.); (F.A.); (M.d.L.B.)
- UFP Energy, Environment and Health Research Unit (FP-ENAS), University Fernando Pessoa, Praça Nove de Abril, 349, 4249-004 Porto, Portugal
- Faculty of Health Sciences, University Fernando Pessoa, Rua Carlos da Maia, 296, 4200-150 Porto, Portugal
| | - Paula Guedes de Pinho
- UCIBIO/REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; (J.P.); (F.A.); (M.d.L.B.)
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21
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Hou DM, Jia T, Li Q, Wang ZK, Zhu WL. Metabonomics of white adipose tissue and brown adipose tissue in Tupaia belangeri during cold acclimation. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY D-GENOMICS & PROTEOMICS 2021; 38:100823. [PMID: 33721582 DOI: 10.1016/j.cbd.2021.100823] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 02/26/2021] [Accepted: 03/01/2021] [Indexed: 01/07/2023]
Abstract
In the present study, liquid chromatography-mass spectrometer (LC-MS) was used to perform untargeted metabolomics analysis of white adipose tissue (WAT) and brown adipose tissue (BAT) in Tupaia belangeri during cold acclimation. Differences in biochemical composition between WAT and BAT were compared. Clarifying how the two adipose tissues respond to the lower temperature in terms of metabolomics, which elucidate the metabolic process and energy homeostasis regulation mechanism in T. belangeri. The results showed that there were 34, 59 and 20 differential metabolites in the WAT, BAT and WAT compared with BAT, respectively. WAT and BAT had significant differences in various metabolic pathways such as sugar metabolism, amino acid metabolism, lipid metabolism, and nucleotide metabolism, which were closely related to the different biological roles of the two tissues. Increasing the concentrations of intermediate products of tricarboxylic acid (TCA) cycle, pyruvic acid, and phosphoenolpyruvic acid (PEP) in WAT and increasing the metabolites in TCA cycle, glyoxylate and dicarboxylate metabolism pathways in BAT, likely to increase the thermogenic capacity in T. belangeri in response to cold stress. There were more differential metabolic pathways in BAT during cold acclimation than that of in WAT. Moreover, compared to WAT, BAT responds to cold stress by adjusting the concentration of nucleotide metabolites.
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Affiliation(s)
- Dong-Min Hou
- Key Laboratory of Ecological Adaptive Evolution and Conservation on Animals-Plants in Southwest Mountain Ecosystem of Yunnan Province Higher Institutes College, School of Life Science, Yunnan Normal University, Kunming 650500, Yunnan, China; Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China
| | - Ting Jia
- Yunnan University of Bussiness Management, Kunming 650106, Yunnan, China
| | - Qi Li
- Key Laboratory of Ecological Adaptive Evolution and Conservation on Animals-Plants in Southwest Mountain Ecosystem of Yunnan Province Higher Institutes College, School of Life Science, Yunnan Normal University, Kunming 650500, Yunnan, China
| | - Zheng-Kun Wang
- Key Laboratory of Ecological Adaptive Evolution and Conservation on Animals-Plants in Southwest Mountain Ecosystem of Yunnan Province Higher Institutes College, School of Life Science, Yunnan Normal University, Kunming 650500, Yunnan, China
| | - Wan-Long Zhu
- Key Laboratory of Ecological Adaptive Evolution and Conservation on Animals-Plants in Southwest Mountain Ecosystem of Yunnan Province Higher Institutes College, School of Life Science, Yunnan Normal University, Kunming 650500, Yunnan, China.
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The influence of sample collection, handling and low temperature storage upon NMR metabolic profiling analysis in human synovial fluid. J Pharm Biomed Anal 2021; 197:113942. [PMID: 33607503 DOI: 10.1016/j.jpba.2021.113942] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 01/25/2021] [Accepted: 01/29/2021] [Indexed: 12/12/2022]
Abstract
The impact of metabolism upon the altered pathology of joint disease is rapidly becoming recognized as an important area of study. Synovial joint fluid is an attractive and representative biofluid of joint disease. A systemic review revealed little evidence of the metabolic stability of synovial joint fluid collection, handling or storage, despite recent reports characterizing the metabolic phenotype in joint disease. We aim to report the changes in small molecule detection within human synovial fluid (HSF) using nuclear magnetic resonance (NMR) spectroscopy at varying storage temperatures, durations and conditions. HSF was harvested by arthrocentesis from patients with isolated monoarthropathy or undergoing joint replacement (n = 30). Short-term storage (0-12 h, 4°C & 18°C) and the effect of repeated freeze-thaw cycles (-80°C to 18°C) was assessed. Long-term storage was evaluated by early (-80°C, <21days) and late analysis (-80°C, 10-12 months). 1D NMR spectroscopy experiments, NOESYGPPR1D and CPMG identified metabolites and semi-quantification was performed. Samples demonstrated broad stability to freeze-thaw cycling and refrigeration of <4 h. Short-term room temperature or refrigerated storage showed significant variation in 2-ketoisovalerate, valine, dimethylamine, succinate, 2-hydroxybutyrate, and acetaminophen glucuronide. Lipid and macromolecule detection was variable. Long-term storage demonstrated significant changes in: acetate, acetoacetate, creatine, N,N-dimethylglycine, dimethylsulfone, 3-hydroxybutyrate and succinate. Changeable metabolites during short-term storage appeared to be energy-synthesis intermediates. Most metabolites were stable for the first four hours at room temperature or refrigeration, with notable exceptions. We therefore recommend that HSF samples should be kept refrigerated for no more than 4 hours prior to freezing at -80°C. Furthermore, storage of HSF samples for 10-12 months before analysis can affect the detection of selected metabolites.
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Chen L, Jiang E, Guan Y, Xu P, Shen Q, Liu Z, Zhu W, Chen L, Liu H, Dong H. Safety of high-dose Puerariae Lobatae Radix in adolescent rats based on metabolomics. Food Sci Nutr 2021; 9:794-810. [PMID: 33598164 PMCID: PMC7866568 DOI: 10.1002/fsn3.2044] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Revised: 11/14/2020] [Accepted: 11/18/2020] [Indexed: 12/18/2022] Open
Abstract
Puerariae Lobatae Radix (PLR) is the dried root of the leguminous plant Pueraria lobata and is a common component of health products and medicines. Although it is considered safe, some studies have reported that PLR has hepatotoxicity and estrogen-like effects. In this study, the safety of high doses of PLR water extract administered to adolescent SD rats for 30 days was evaluated by biochemical, histopathological, and metabolomic analyses. Overall, there were no significant differences between the low-dose and blank control groups in parameter values, including organ wet weight, organ coefficient, routine blood indicators, serum biochemical indexes of liver and renal function, levels of estradiol and testosterone, histopathological parameters, and primary differential metabolite profiles. Compared with the blank control group, the high-dose group may have a certain effect on the liver. These effects might be mediated by abnormal phenylalanine, tyrosine, and tryptophan biosynthesis or phenylalanine metabolism. However, histopathological analyses did not show differences in the liver, kidney, breast, uterus, ovary, testis, and epididymis between the control group and the group treated with a high dose of PLR water extract. PLR water extract did not significantly promote the precocity of male and female sexual organs. Overall, PLR water extract is relatively safe for adolescent SD rats.
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Affiliation(s)
- Limei Chen
- Jiangxi University of Traditional Chinese MedicineNanchangChina
| | - E. Jiang
- Jiangxi University of Traditional Chinese MedicineNanchangChina
| | - Yongmei Guan
- Jiangxi University of Traditional Chinese MedicineNanchangChina
| | - Pan Xu
- Jiangxi University of Traditional Chinese MedicineNanchangChina
| | - Qian Shen
- Jiangxi University of Traditional Chinese MedicineNanchangChina
| | - Zhiyong Liu
- Jiangxi University of Traditional Chinese MedicineNanchangChina
| | - Weifeng Zhu
- Jiangxi University of Traditional Chinese MedicineNanchangChina
| | - Lihua Chen
- Jiangxi University of Traditional Chinese MedicineNanchangChina
| | - Hongning Liu
- Jiangxi University of Traditional Chinese MedicineNanchangChina
| | - Huanhuan Dong
- Jiangxi University of Traditional Chinese MedicineNanchangChina
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24
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Kumar P, Kumar V. Role of NMR Metabolomics and MR Imaging in Colon Cancer. COLON CANCER DIAGNOSIS AND THERAPY 2021:43-66. [DOI: 10.1007/978-3-030-63369-1_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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25
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Akhbari P, Jaggard MK, Boulangé CL, Vaghela U, Graça G, Bhattacharya R, Lindon JC, Williams HRT, Gupte CM. Differences between infected and noninfected synovial fluid. Bone Joint Res 2021; 10:85-95. [PMID: 33502243 PMCID: PMC7845460 DOI: 10.1302/2046-3758.101.bjr-2020-0285.r1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
AIMS The diagnosis of joint infections is an inexact science using combinations of blood inflammatory markers and microscopy, culture, and sensitivity of synovial fluid (SF). There is potential for small molecule metabolites in infected SF to act as infection markers that could improve accuracy and speed of detection. The objective of this study was to use nuclear magnetic resonance (NMR) spectroscopy to identify small molecule differences between infected and noninfected human SF. METHODS In all, 16 SF samples (eight infected native and prosthetic joints plus eight noninfected joints requiring arthroplasty for end-stage osteoarthritis) were collected from patients. NMR spectroscopy was used to analyze the metabolites present in each sample. Principal component analysis and univariate statistical analysis were undertaken to investigate metabolic differences between the two groups. RESULTS A total of 16 metabolites were found in significantly different concentrations between the groups. Three were in higher relative concentrations (lipids, cholesterol, and N-acetylated molecules) and 13 in lower relative concentrations in the infected group (citrate, glycine, glycosaminoglycans, creatinine, histidine, lysine, formate, glucose, proline, valine, dimethylsulfone, mannose, and glutamine). CONCLUSION Metabolites found in significantly greater concentrations in the infected cohort are markers of inflammation and infection. They play a role in lipid metabolism and the inflammatory response. Those found in significantly reduced concentrations were involved in carbohydrate metabolism, nucleoside metabolism, the glutamate metabolic pathway, increased oxidative stress in the diseased state, and reduced articular cartilage breakdown. This is the first study to demonstrate differences in the metabolic profile of infected and noninfected human SF, using a noninfected matched cohort, and may represent putative biomarkers that form the basis of new diagnostic tests for infected SF. Cite this article: Bone Joint Res 2021;10(1):85-95.
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Affiliation(s)
- Pouya Akhbari
- Department of Trauma and Orthopaedics, Imperial College Healthcare NHS Trust, London, UK
| | - Matthew K Jaggard
- Department of Trauma and Orthopaedics, Imperial College Healthcare NHS Trust, London, UK
| | - Claire L Boulangé
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Uddhav Vaghela
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Gonçalo Graça
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Rajarshi Bhattacharya
- Department of Trauma and Orthopaedics, Imperial College Healthcare NHS Trust, London, UK
| | - John C Lindon
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | | | - Chinmay M Gupte
- Department of Trauma and Orthopaedics, Imperial College Healthcare NHS Trust, London, UK.,Department of Surgery and Cancer, Imperial College London, London, UK
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26
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Zeki ÖC, Eylem CC, Reçber T, Kır S, Nemutlu E. Integration of GC–MS and LC–MS for untargeted metabolomics profiling. J Pharm Biomed Anal 2020; 190:113509. [DOI: 10.1016/j.jpba.2020.113509] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 07/24/2020] [Accepted: 07/25/2020] [Indexed: 12/12/2022]
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27
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Panner Selvam MK, Finelli R, Agarwal A, Henkel R. Proteomics and metabolomics - Current and future perspectives in clinical andrology. Andrologia 2020; 53:e13711. [PMID: 32598566 DOI: 10.1111/and.13711] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 05/17/2020] [Accepted: 05/19/2020] [Indexed: 12/12/2022] Open
Abstract
Proteomics and metabolomics are emerging as promising tools to investigate the molecular mechanisms associated with male infertility. Proteins and metabolites play a pivotal role in regulating the molecular pathways associated with physiological functions of spermatozoa. Semen analysis, physical examination and laboratory work up cannot identify the etiology of infertility in 30%-40% of cases, which are classified as idiopathic. Therefore, the application of proteomics and metabolomics in the field of andrology will aid to overcome the limitations of the standard semen analysis. Understanding the molecular pathways associated with male infertility will help in planning ad hoc treatments, contributing to the clinical management of infertile patients. In this review, proteomics and metabolomics studies on spermatozoa and seminal plasma are discussed with a focus on molecular biomarkers associated with male infertility-related conditions.
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Affiliation(s)
| | - Renata Finelli
- American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Ashok Agarwal
- American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Ralf Henkel
- American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA.,Department of Medical Bioscience, University of the Western Cape, Bellville, South Africa
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Akhbari P, Karamchandani U, Jaggard MKJ, Graça G, Bhattacharya R, Lindon JC, Williams HRT, Gupte CM. Can joint fluid metabolic profiling (or "metabonomics") reveal biomarkers for osteoarthritis and inflammatory joint disease?: A systematic review. Bone Joint Res 2020; 9:108-119. [PMID: 32435463 PMCID: PMC7229296 DOI: 10.1302/2046-3758.93.bjr-2019-0167.r1] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Aims Metabolic profiling is a top-down method of analysis looking at metabolites, which are the intermediate or end products of various cellular pathways. Our primary objective was to perform a systematic review of the published literature to identify metabolites in human synovial fluid (HSF), which have been categorized by metabolic profiling techniques. A secondary objective was to identify any metabolites that may represent potential biomarkers of orthopaedic disease processes. Methods A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines using the MEDLINE, Embase, PubMed, and Cochrane databases. Studies included were case series, case control series, and cohort studies looking specifically at HSF. Results The primary analysis, which pooled the results from 17 published studies and four meeting abstracts, identified over 200 metabolites. Seven of these studies (six published studies, one meeting abstract) had asymptomatic control groups and collectively suggested 26 putative biomarkers in osteoarthritis, inflammatory arthropathies, and trauma. These can broadly be categorized into amino acids plus related metabolites, fatty acids, ketones, and sugars. Conclusion The role of metabolic profiling in orthopaedics is fast evolving with many metabolites already identified in a variety of pathologies. However, these results need to be interpreted with caution due to the presence of multiple confounding factors in many of the studies. Future research should include largescale epidemiological metabolic profiling studies incorporating various confounding factors with appropriate statistical analysis to account for multiple testing of the data. Cite this article:Bone Joint Res. 2020;9(3):108–119.
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Affiliation(s)
- Pouya Akhbari
- Department of Orthopaedics & Trauma, Imperial College Healthcare NHS Trust, London, UK
| | | | - Matthew K J Jaggard
- Department of Orthopaedics & Trauma, Imperial College Healthcare NHS Trust, London, UK
| | - Goncalo Graça
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Rajarshi Bhattacharya
- Department of Orthopaedics & Trauma, Imperial College Healthcare NHS Trust, London, UK
| | - John C Lindon
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Horace R T Williams
- Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Chinmay M Gupte
- Department of Surgery and Cancer, Imperial College London, and Department of Orthopaedics & Trauma, Imperial College Healthcare NHS Trust, London, UK
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29
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Xiao M, Qian K, Wang Y, Bao F. GC-MS metabolomics reveals metabolic differences of the farmed Mandarin fish Siniperca chuatsi in recirculating ponds aquaculture system and pond. Sci Rep 2020; 10:6090. [PMID: 32269294 PMCID: PMC7142152 DOI: 10.1038/s41598-020-63252-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Accepted: 03/26/2020] [Indexed: 01/16/2023] Open
Abstract
Siniperca chuatsi is currently one of the most important economic farmed freshwater fish in China. The aim of this study was to evaluate the metabolic profile of recirculating ponds aquaculture system (RAS)-farmed S. chuatsi. Gas Chromatography-Mass Spectrophotometry (GC-MS) metabolomic platform was used to comprehensively analyze the effects of recirculating ponds aquaculture system (RAS) on the Mandarin fish S. chuatsi metabolism. Database searching and statistical analysis revealed that there were altogether 335 metabolites quantified (similarity > 0) and 205 metabolites were identified by mass spectrum matching with a spectral similarity > 700. Among the 335 metabolites quantified, 33 metabolites were significantly different (VIP > 1 and p < 0.05) between RAS and pond groups. In these thirty-three metabolites, taurine, 1-Hexadecanol, Shikimic Acid, Alloxanoic Acid and Acetaminophen were higher in the pond group, while 28 metabolites were increased notably in the RAS group. The biosynthesis of unsaturated fatty acids, lysosome, tryptophan metabolism were recommended as the KEGG pathway maps for S. chuatsi farmed in RAS. RAS can provide comprehensive benefits to the effects of Siniperca chuatsi metabolism, which suggest RAS is an efficient, economic, and environmentally friendly farming system compared to pond system.
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Affiliation(s)
- Mingsong Xiao
- College of Life and Health Science, Anhui Science and Technology University, Fengyang, 233100, China.
| | - Kelin Qian
- Chuzhou Nanqiao District Yangtze River Aquaculture Breeding Ground, Chuzhou, 239000, China
| | - Yuliang Wang
- College of Life and Health Science, Anhui Science and Technology University, Fengyang, 233100, China
| | - Fangyin Bao
- College of Life and Health Science, Anhui Science and Technology University, Fengyang, 233100, China
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Sidorov E, Bejar C, Xu C, Ray B, Reddivari L, Chainakul J, Vanamala JKP, Sanghera DK. Potential Metabolite Biomarkers for Acute Versus Chronic Stage of Ischemic Stroke: A Pilot Study. J Stroke Cerebrovasc Dis 2020; 29:104618. [PMID: 31973907 DOI: 10.1016/j.jstrokecerebrovasdis.2019.104618] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 12/05/2019] [Accepted: 12/19/2019] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Metabolome profiling is used to identify biomarkers for acute ischemic stroke (AIS). Previous studies compared metabolite profiles in AIS and healthy controls, which did not account for factors that affect metabolome (genetics, medications). This pilot project evaluates the change in metabolite concentrations between the acute and chronic stage of stroke in the same cohort in order to minimize other factors impact. METHODS We performed global metabolome profile on serum of 20 and urine of 12 stroke patients in acute (72 hours) and chronic (3-5.2 months) stage and compared relative peak values using Wilcoxon and orthogonal partial least squares discriminant analysis methods. Chronic stage metabolite concentrations were considered baseline. We performed analysis to identify significantly overrepresented pathways using MetaboAnalyst. RESULTS Three serum metabolites asparagine (P = .045), tyrosine (P = .015), and xylose (P = .003) had significantly higher concentrations in acute stage. Seven out of top 10 serum metabolites ranked by Wilcoxon test P value were related to amino acid (AA) metabolism. Two urine metabolites glycine (P = .03) and acetylcarnitine (P = .05) had significantly different concentrations in the acute stage. Five of the top 10 urine metabolites related to AA metabolism. We identified 6 significant pathways after false discovery rate correction that were upregulated in the acute stage: (1) Aminoacyl-tRNA synthesis, (2) nitrogen, (3) alanine, aspartate, and glutamate, (4) branched-chain AA, (5) arginine and proline, and (6) phenylalanine metabolism. CONCLUSION Longitudinal study design confirms that AA metabolism heavily involved in the pathophysiology of acute brain ischemia. Prospective longitudinal studies with a higher number of participants are needed to establish useful stroke biomarkers.
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Affiliation(s)
- Evgeny Sidorov
- Department of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
| | - Cynthia Bejar
- Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
| | - Chao Xu
- Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
| | - Bappaditya Ray
- Department of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
| | - Lavanya Reddivari
- Department of Food Science, Purdue University, West Lafayete, Indiana
| | - Juliane Chainakul
- Department of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
| | - Jairam K P Vanamala
- Department of Food Science/Center for Molecular Immunology and Infectious Diseases, Penn State University, University Park, Pennsylvania
| | - Dharambir K Sanghera
- Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
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Akhbari P, Jaggard MK, Boulangé CL, Vaghela U, Graça G, Bhattacharya R, Lindon JC, Williams HRT, Gupte CM. Differences in the composition of hip and knee synovial fluid in osteoarthritis: a nuclear magnetic resonance (NMR) spectroscopy study of metabolic profiles. Osteoarthritis Cartilage 2019; 27:1768-1777. [PMID: 31491490 DOI: 10.1016/j.joca.2019.07.017] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Revised: 06/04/2019] [Accepted: 07/03/2019] [Indexed: 02/02/2023]
Abstract
OBJECTIVE The hip and knee joints differ biomechanically in terms of contact stresses, fluid lubrication and wear patterns. These differences may be reflected in the synovial fluid (SF) composition of the two joints, but the nature of these differences remains unknown. The objective was to identify differences in osteoarthritic hip and knee SF metabolites using metabolic profiling with Nuclear Magnetic Resonance (NMR) spectroscopy. DESIGN Twenty-four SF samples (12 hip, 12 knee) were collected from patients with end-stage osteoarthritis (ESOA) undergoing hip/knee arthroplasty. Samples were matched for age, gender, ethnicity and had similar medical comorbidities. NMR spectroscopy was used to analyse the metabolites present in each sample. Principal Component Analysis and Orthogonal Partial Least Squares Discriminant Analysis were undertaken to investigate metabolic differences between the groups. Metabolites were identified using 2D NMR spectra, statistical spectroscopy and by comparison to entries in published databases. RESULTS There were significant differences in the metabolic profile between the groups. Four metabolites were found in significantly greater quantities in the knee group compared to the hip group (N-acetylated molecules, glycosaminoglycans, citrate and glutamine). CONCLUSIONS This is the first study to indicate differences in the metabolic profile of hip and knee SF in ESOA. The identified metabolites can broadly be grouped into those involved in collagen degradation, the tricarboxylic acid cycle and oxidative metabolism in diseased joints. These findings may represent a combination of intra and extra-articular factors.
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Affiliation(s)
- P Akhbari
- Department of Orthopaedics & Trauma, Imperial College Healthcare NHS Trust, London, United Kingdom.
| | - M K Jaggard
- Department of Orthopaedics & Trauma, Imperial College Healthcare NHS Trust, London, United Kingdom.
| | - C L Boulangé
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom.
| | - U Vaghela
- School of Medicine, Imperial College London, London, United Kingdom.
| | - G Graça
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom.
| | - R Bhattacharya
- Department of Orthopaedics & Trauma, Imperial College Healthcare NHS Trust, London, United Kingdom.
| | - J C Lindon
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom.
| | - H R T Williams
- Department of Digestive Diseases, Imperial College Healthcare NHS Trust, London, United Kingdom.
| | - C M Gupte
- Department of Orthopaedics & Trauma, Imperial College Healthcare NHS Trust, London, United Kingdom.
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Ingallina C, Capitani D, Mannina L, Carradori S, Locatelli M, Di Sotto A, Di Giacomo S, Toniolo C, Pasqua G, Valletta A, Simonetti G, Parroni A, Beccaccioli M, Vinci G, Rapa M, Giusti AM, Fraschetti C, Filippi A, Maccelli A, Crestoni ME, Fornarini S, Sobolev AP. Phytochemical and biological characterization of Italian "sedano bianco di Sperlonga" Protected Geographical Indication celery ecotype: A multimethodological approach. Food Chem 2019; 309:125649. [PMID: 31718835 DOI: 10.1016/j.foodchem.2019.125649] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Revised: 09/24/2019] [Accepted: 10/03/2019] [Indexed: 12/15/2022]
Abstract
Celery is a widely used vegetable known for its peculiar sensorial and nutritional properties. Here, the white celery (Apium graveolens L.) "sedano bianco di Sperlonga" PGI ecotype was investigated to obtain the metabolic profile of its edible parts (blade leaves and petioles) also related to quality, freshness and biological properties. A multi-methodological approach, including NMR, MS, HPLC-PDA, GC-MS and spectrophotometric analyses, was proposed to analyse celery extracts. Sugars, polyalcohols, amino acids, organic acids, phenols, sterols, fatty acids, phthalides, chlorophylls, tannins and flavonoids were detected in different concentrations in blade leaf and petiole extracts, indicating celery parts as nutraceutical sources. The presence of some phenols in celery extracts was here reported for the first time. Low contents of biogenic amines and mycotoxins confirmed celery quality and freshness. Regarding the biological properties, ethanolic celery extracts inhibited the oxidative-mediated DNA damage induced by tert-butylhydroperoxide and scavenged DPPH and ABTS radicals.
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Affiliation(s)
- Cinzia Ingallina
- Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, P.le Aldo Moro 5, 00185 Rome, Italy.
| | - Donatella Capitani
- Istituto per i Sistemi Biologici, Laboratorio di Risonanza Magnetica "Annalaura Segre", CNR, 00015 Monterotondo (Rome), Italy.
| | - Luisa Mannina
- Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, P.le Aldo Moro 5, 00185 Rome, Italy; Istituto per i Sistemi Biologici, Laboratorio di Risonanza Magnetica "Annalaura Segre", CNR, 00015 Monterotondo (Rome), Italy.
| | - Simone Carradori
- Dipartimento di Farmacia, Università di Chieti-Pescara "G. d'Annunzio", Via dei Vestini 31, 66100 Chieti, Italy.
| | - Marcello Locatelli
- Dipartimento di Farmacia, Università di Chieti-Pescara "G. d'Annunzio", Via dei Vestini 31, 66100 Chieti, Italy.
| | - Antonella Di Sotto
- Dipartimento di Fisiologia e Farmacologia "V. Ersparmer", Sapienza Università di Roma, P.le Aldo Moro 5, 00185 Rome, Italy.
| | - Silvia Di Giacomo
- Dipartimento di Fisiologia e Farmacologia "V. Ersparmer", Sapienza Università di Roma, P.le Aldo Moro 5, 00185 Rome, Italy.
| | - Chiara Toniolo
- Dipartimento di Biologia Ambientale, Sapienza Università di Roma, P.le Aldo Moro 5, 00185 Rome, Italy.
| | - Gabriella Pasqua
- Dipartimento di Biologia Ambientale, Sapienza Università di Roma, P.le Aldo Moro 5, 00185 Rome, Italy.
| | - Alessio Valletta
- Dipartimento di Biologia Ambientale, Sapienza Università di Roma, P.le Aldo Moro 5, 00185 Rome, Italy.
| | - Giovanna Simonetti
- Dipartimento di Sanità Pubblica e Malattie Infettive, Sapienza Università di Roma, P.le Aldo Moro 5, 00185 Rome, Italy.
| | - Alessia Parroni
- Dipartimento di Biologia Ambientale, Sapienza Università di Roma, P.le Aldo Moro 5, 00185 Rome, Italy.
| | - Marzia Beccaccioli
- Dipartimento di Biologia Ambientale, Sapienza Università di Roma, P.le Aldo Moro 5, 00185 Rome, Italy.
| | - Giuliana Vinci
- Dipartimento di Management, Laboratorio di Merceologia, Sapienza Università di Roma, Via del Castro Laurenziano 9, 00161 Rome, Italy.
| | - Mattia Rapa
- Dipartimento di Management, Laboratorio di Merceologia, Sapienza Università di Roma, Via del Castro Laurenziano 9, 00161 Rome, Italy.
| | - Anna Maria Giusti
- Dipartimento di Medicina Sperimentale Sapienza, Università di Roma, P.le Aldo Moro 5, 00185 Rome, Italy.
| | - Caterina Fraschetti
- Istituto per i Sistemi Biologici, Laboratorio di Risonanza Magnetica "Annalaura Segre", CNR, 00015 Monterotondo (Rome), Italy.
| | - Antonello Filippi
- Istituto per i Sistemi Biologici, Laboratorio di Risonanza Magnetica "Annalaura Segre", CNR, 00015 Monterotondo (Rome), Italy.
| | - Alessandro Maccelli
- Istituto per i Sistemi Biologici, Laboratorio di Risonanza Magnetica "Annalaura Segre", CNR, 00015 Monterotondo (Rome), Italy.
| | - Maria Elisa Crestoni
- Istituto per i Sistemi Biologici, Laboratorio di Risonanza Magnetica "Annalaura Segre", CNR, 00015 Monterotondo (Rome), Italy.
| | - Simonetta Fornarini
- Istituto per i Sistemi Biologici, Laboratorio di Risonanza Magnetica "Annalaura Segre", CNR, 00015 Monterotondo (Rome), Italy.
| | - Anatoly P Sobolev
- Istituto per i Sistemi Biologici, Laboratorio di Risonanza Magnetica "Annalaura Segre", CNR, 00015 Monterotondo (Rome), Italy.
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Chapman J, Gangadoo S, Truong VK, Cozzolino D. Spectroscopic approaches for rapid beer and wine analysis. Curr Opin Food Sci 2019. [DOI: 10.1016/j.cofs.2019.09.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Feng Z, Hou J, Yu Y, Wu W, Deng Y, Wang X, Zhi H, Zhang L, Wu W, Guo DA. Dissecting the Metabolic Phenotype of the Antihypertensive Effects of Five Uncaria Species on Spontaneously Hypertensive Rats. Front Pharmacol 2019; 10:845. [PMID: 31417403 PMCID: PMC6682664 DOI: 10.3389/fphar.2019.00845] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Accepted: 07/02/2019] [Indexed: 11/13/2022] Open
Abstract
The sourcing of plants from multiple botanical origins is a common phenomenon in traditional Chinese medicines. Uncaria Stem with Hooks (UHs) are approved for using five botanical origins in the Chinese Pharmacopoeia (2015 Edition). All five UHs are commonly used for treating hypertension even though the plants have different chromatographic fingerprints based on our previous study. However, their hypotensive effects and metabolic phenotypes have not been fully studied. In the present study, spontaneously hypertensive rats (SHRs) were orally administered five aqueous extracts (4 g crude drug/kg) prepared from the different UHs over a 6-week period. Systolic blood pressure (SBP) was measured every week, and urine was collected after SBP measurement. Untargeted metabonomics was performed using ultra performance liquid chromatography (UPLC) coupled with an LTQ-Orbitrap mass spectrometer. Bidirectional orthogonal projection to latent structures discriminant analysis (O2PLS-DA), Student's t test, and correlation analysis were used for pattern recognition and the selection of significant metabolites. A similar and prolonged reduction in SBP was observed in each of the groups given the five different UHs, while the metabolic profiles were perturbed slightly compared with that of SHR. Further analysis has shown that only a few common, different components were observed within the five groups, which showed the similar antihypertensive effect in spite of the distinct metabolic pathways due to their different alkaloid composition. These results help in understanding the mechanisms of the phenomenon "different species, same effect" of UHs.
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Affiliation(s)
- Zijin Feng
- College of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, China
| | - Jinjun Hou
- Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Yang Yu
- Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Wenyong Wu
- Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Yanping Deng
- Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Xia Wang
- Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Haijuan Zhi
- Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Linlin Zhang
- Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Wanying Wu
- Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - De-An Guo
- College of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, China.,Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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Gafson AR, Savva C, Thorne T, David M, Gomez-Romero M, Lewis MR, Nicholas R, Heslegrave A, Zetterberg H, Matthews PM. Breaking the cycle: Reversal of flux in the tricarboxylic acid cycle by dimethyl fumarate. NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION 2019; 6:e562. [PMID: 31086805 PMCID: PMC6481230 DOI: 10.1212/nxi.0000000000000562] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Accepted: 02/27/2019] [Indexed: 12/17/2022]
Abstract
Objective To infer molecular effectors of therapeutic effects and adverse events for dimethyl fumarate (DMF) in patients with relapsing-remitting MS (RRMS) using untargeted plasma metabolomics. Methods Plasma from 27 patients with RRMS was collected at baseline and 6 weeks after initiating DMF. Patients were separated into discovery (n = 15) and validation cohorts (n = 12). Ten healthy controls were also recruited. Metabolomic profiling using ultra-high-performance liquid chromatography mass spectrometry (UPLC-MS) was performed on the discovery cohort and healthy controls at Metabolon Inc (Durham, NC). UPLC-MS was performed on the validation cohort at the National Phenome Centre (London, UK). Plasma neurofilament concentration (pNfL) was assayed using the Simoa platform (Quanterix, Lexington, MA). Time course and cross-sectional analyses were performed to identify pharmacodynamic changes in the metabolome secondary to DMF and relate these to adverse events. Results In the discovery cohort, tricarboxylic acid (TCA) cycle intermediates fumarate and succinate, and TCA cycle metabolites succinyl-carnitine and methyl succinyl-carnitine increased 6 weeks following treatment (q < 0.05). Methyl succinyl-carnitine increased in the validation cohort (q < 0.05). These changes were not observed in the control population. Increased succinyl-carnitine and methyl succinyl-carnitine were associated with adverse events from DMF (flushing and abdominal symptoms). pNfL concentration was higher in patients with RRMS than in controls and reduced over 15 months of treatment. Conclusion TCA cycle intermediates and metabolites are increased in patients with RRMS treated with DMF. The results suggest reversal of flux through the succinate dehydrogenase complex. The contribution of succinyl-carnitine ester agonism at hydroxycarboxylic acid receptor 2 to both therapeutic effects and adverse events requires investigation.
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Affiliation(s)
- Arie R Gafson
- Division of Brain Sciences (T.T., R.N., P.M.M.), Department of Medicine, Imperial College, London; St Edmund Hall (C.S., P.M.M.), Oxford University, Oxford, UK; MRC-NIHR National Phenome Centre (M.D., M.G.-R., M.R.L.), Department of Surgery and Cancer, Imperial College; University College London Queen Square Institute of Neurology (A.H., H.Z.); UK Dementia Research Institute, University College London (A.H., H.Z.), London, UK; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy, the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; and UK Dementia Research Institute at Imperial College (P.M.M.), London
| | - Constantinos Savva
- Division of Brain Sciences (T.T., R.N., P.M.M.), Department of Medicine, Imperial College, London; St Edmund Hall (C.S., P.M.M.), Oxford University, Oxford, UK; MRC-NIHR National Phenome Centre (M.D., M.G.-R., M.R.L.), Department of Surgery and Cancer, Imperial College; University College London Queen Square Institute of Neurology (A.H., H.Z.); UK Dementia Research Institute, University College London (A.H., H.Z.), London, UK; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy, the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; and UK Dementia Research Institute at Imperial College (P.M.M.), London
| | - Tom Thorne
- Division of Brain Sciences (T.T., R.N., P.M.M.), Department of Medicine, Imperial College, London; St Edmund Hall (C.S., P.M.M.), Oxford University, Oxford, UK; MRC-NIHR National Phenome Centre (M.D., M.G.-R., M.R.L.), Department of Surgery and Cancer, Imperial College; University College London Queen Square Institute of Neurology (A.H., H.Z.); UK Dementia Research Institute, University College London (A.H., H.Z.), London, UK; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy, the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; and UK Dementia Research Institute at Imperial College (P.M.M.), London
| | - Mark David
- Division of Brain Sciences (T.T., R.N., P.M.M.), Department of Medicine, Imperial College, London; St Edmund Hall (C.S., P.M.M.), Oxford University, Oxford, UK; MRC-NIHR National Phenome Centre (M.D., M.G.-R., M.R.L.), Department of Surgery and Cancer, Imperial College; University College London Queen Square Institute of Neurology (A.H., H.Z.); UK Dementia Research Institute, University College London (A.H., H.Z.), London, UK; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy, the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; and UK Dementia Research Institute at Imperial College (P.M.M.), London
| | - Maria Gomez-Romero
- Division of Brain Sciences (T.T., R.N., P.M.M.), Department of Medicine, Imperial College, London; St Edmund Hall (C.S., P.M.M.), Oxford University, Oxford, UK; MRC-NIHR National Phenome Centre (M.D., M.G.-R., M.R.L.), Department of Surgery and Cancer, Imperial College; University College London Queen Square Institute of Neurology (A.H., H.Z.); UK Dementia Research Institute, University College London (A.H., H.Z.), London, UK; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy, the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; and UK Dementia Research Institute at Imperial College (P.M.M.), London
| | - Matthew R Lewis
- Division of Brain Sciences (T.T., R.N., P.M.M.), Department of Medicine, Imperial College, London; St Edmund Hall (C.S., P.M.M.), Oxford University, Oxford, UK; MRC-NIHR National Phenome Centre (M.D., M.G.-R., M.R.L.), Department of Surgery and Cancer, Imperial College; University College London Queen Square Institute of Neurology (A.H., H.Z.); UK Dementia Research Institute, University College London (A.H., H.Z.), London, UK; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy, the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; and UK Dementia Research Institute at Imperial College (P.M.M.), London
| | - Richard Nicholas
- Division of Brain Sciences (T.T., R.N., P.M.M.), Department of Medicine, Imperial College, London; St Edmund Hall (C.S., P.M.M.), Oxford University, Oxford, UK; MRC-NIHR National Phenome Centre (M.D., M.G.-R., M.R.L.), Department of Surgery and Cancer, Imperial College; University College London Queen Square Institute of Neurology (A.H., H.Z.); UK Dementia Research Institute, University College London (A.H., H.Z.), London, UK; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy, the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; and UK Dementia Research Institute at Imperial College (P.M.M.), London
| | - Amanda Heslegrave
- Division of Brain Sciences (T.T., R.N., P.M.M.), Department of Medicine, Imperial College, London; St Edmund Hall (C.S., P.M.M.), Oxford University, Oxford, UK; MRC-NIHR National Phenome Centre (M.D., M.G.-R., M.R.L.), Department of Surgery and Cancer, Imperial College; University College London Queen Square Institute of Neurology (A.H., H.Z.); UK Dementia Research Institute, University College London (A.H., H.Z.), London, UK; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy, the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; and UK Dementia Research Institute at Imperial College (P.M.M.), London
| | - Henrik Zetterberg
- Division of Brain Sciences (T.T., R.N., P.M.M.), Department of Medicine, Imperial College, London; St Edmund Hall (C.S., P.M.M.), Oxford University, Oxford, UK; MRC-NIHR National Phenome Centre (M.D., M.G.-R., M.R.L.), Department of Surgery and Cancer, Imperial College; University College London Queen Square Institute of Neurology (A.H., H.Z.); UK Dementia Research Institute, University College London (A.H., H.Z.), London, UK; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy, the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; and UK Dementia Research Institute at Imperial College (P.M.M.), London
| | - Paul M Matthews
- Division of Brain Sciences (T.T., R.N., P.M.M.), Department of Medicine, Imperial College, London; St Edmund Hall (C.S., P.M.M.), Oxford University, Oxford, UK; MRC-NIHR National Phenome Centre (M.D., M.G.-R., M.R.L.), Department of Surgery and Cancer, Imperial College; University College London Queen Square Institute of Neurology (A.H., H.Z.); UK Dementia Research Institute, University College London (A.H., H.Z.), London, UK; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy, the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; and UK Dementia Research Institute at Imperial College (P.M.M.), London
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Virzì G, Clementi A, Battaglia G, Ronco C. Multi-Omics Approach: New Potential Key Mechanisms Implicated in Cardiorenal Syndromes. Cardiorenal Med 2019; 9:201-211. [DOI: 10.1159/000497748] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Accepted: 01/31/2019] [Indexed: 11/19/2022] Open
Abstract
Cardiorenal syndromes (CRS) include a scenario of clinical interactions characterized by the heart and kidney dysfunction. The crosstalk between cardiac and renal systems is clearly evidenced but not completely understood. Multi-factorial mechanisms leading to CRS do not involve only hemodynamic parameters. In fact, in recent works on organ crosstalk endothelial injury, the alteration of normal immunologic balance, cell death, inflammatory cascades, cell adhesion molecules, cytokine and chemokine overexpression, neutrophil migration, leukocyte trafficking, caspase-mediated induction of apoptotic mechanisms and oxidative stress has been demonstrated to induce distant organ dysfunction. Furthermore, new alternative mechanisms using the multi-omics approach may be implicated in the pathogenesis of cardiorenal crosstalk. The study of “omics” modifications in the setting of cardiovascular and renal disease represents an emerging area of research. Over the last years, indeed, many studies have elucidated the exact mechanisms involved in gene expression and regulation, cellular communication and organ crosstalk. In this review, we analyze epigenetics, gene expression, small non-coding RNAs, extracellular vesicles, proteomics, and metabolomics in the setting of CRS.
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Yang LN, Pu JC, Liu LX, Wang GW, Zhou XY, Zhang YQ, Liu YY, Xie P. Integrated Metabolomics and Proteomics Analysis Revealed Second Messenger System Disturbance in Hippocampus of Chronic Social Defeat Stress Rat. Front Neurosci 2019; 13:247. [PMID: 30983951 PMCID: PMC6448023 DOI: 10.3389/fnins.2019.00247] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Accepted: 03/01/2019] [Indexed: 12/17/2022] Open
Abstract
Depression is a common and disabling mental disorder characterized by high disability and mortality, but its physiopathology remains unclear. In this study, we combined a non-targeted gas chromatography-mass spectrometry (GC-MS)-based metabolomic approach and isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis to elucidate metabolite and protein alterations in the hippocampus of rat after chronic social defeat stress (CSDS), an extensively used animal model of depression. Ingenuity pathway analysis (IPA) was conducted to integrate underlying relationships among differentially expressed metabolites and proteins. Twenty-five significantly different expressed metabolites and 234 differentially expressed proteins were identified between CSDS and control groups. IPA canonical pathways and network analyses revealed that intracellular second messenger/signal transduction cascades were most significantly altered in the hippocampus of CSDS rats, including cyclic adenosine monophosphate (cAMP), phosphoinositol, tyrosine kinase, and arachidonic acid systems. These results provide a better understanding of biological mechanisms underlying depression, and may help identify potential targets for novel antidepressants.
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Affiliation(s)
- Li-Ning Yang
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
| | - Jun-Cai Pu
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
| | - Lan-Xiang Liu
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
| | - Guo-Wei Wang
- School of Clinical Medicine, Ningxia Medical University, Yinchuan, China
| | - Xin-Yu Zhou
- Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yu-Qing Zhang
- Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yi-Yun Liu
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
| | - Peng Xie
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
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Park YH, Kong T, Roede JR, Jones DP, Lee K. A biplot correlation range for group-wise metabolite selection in mass spectrometry. BioData Min 2019; 12:4. [PMID: 30740145 PMCID: PMC6360680 DOI: 10.1186/s13040-019-0191-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Accepted: 01/10/2019] [Indexed: 02/08/2023] Open
Abstract
Background Analytic methods are available to acquire extensive metabolic information in a cost-effective manner for personalized medicine, yet disease risk and diagnosis mostly rely upon individual biomarkers based on statistical principles of false discovery rate and correlation. Due to functional redundancies and multiple layers of regulation in complex biologic systems, individual biomarkers, while useful, are inherently limited in disease characterization. Data reduction and discriminant analysis tools such as principal component analysis (PCA), partial least squares (PLS), or orthogonal PLS (O-PLS) provide approaches to separate the metabolic phenotypes, but do not offer a statistical basis for selection of group-wise metabolites as contributors to metabolic phenotypes. Methods We present a dimensionality-reduction based approach termed ‘biplot correlation range (BCR)’ that uses biplot correlation analysis with direct orthogonal signal correction and PLS to provide the group-wise selection of metabolic markers contributing to metabolic phenotypes. Results Using a simulated multiple-layer system that often arises in complex biologic systems, we show the feasibility and superiority of the proposed approach in comparison of existing approaches based on false discovery rate and correlation. To demonstrate the proposed method in a real-life dataset, we used LC-MS based metabolomics to determine spectrum of metabolites present in liver mitochondria from wild-type (WT) mice and thioredoxin-2 transgenic (TG) mice. We select discriminatory variables in terms of increased score in the direction of class identity using BCR. The results show that BCR provides means to identify metabolites contributing to class separation in a manner that a statistical method by false discovery rate or statistical total correlation spectroscopy can hardly find in complex data analysis for predictive health and personalized medicine. Electronic supplementary material The online version of this article (10.1186/s13040-019-0191-2) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Youngja H Park
- 1College of Pharmacy, Korea University, Sejong, 30019 South Korea
| | - Taewoon Kong
- 2Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, GA 30332 USA
| | - James R Roede
- 3Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Denver, CO 80045 USA
| | - Dean P Jones
- Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy and Critical Care Medicine, Atlanta, GA 30322 USA.,5Department of Medicine, Emory University, Atlanta, GA 30322 USA
| | - Kichun Lee
- 6Department of Industrial Engineering, Hanyang University, Seoul, 04763 South Korea
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Sidorov E, Sanghera DK, Vanamala JKP. Biomarker for Ischemic Stroke Using Metabolome: A Clinician Perspective. J Stroke 2019; 21:31-41. [PMID: 30732441 PMCID: PMC6372900 DOI: 10.5853/jos.2018.03454] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Accepted: 01/15/2019] [Indexed: 12/14/2022] Open
Abstract
Finding ischemic stroke biomarker is highly desirable because it can improve diagnosis even before a patient arrives to the hospital. Metabolome is one of new technologies that help to find biomarkers. Most metabolome-related ischemic stroke studies were done in Asia and had exploratory designs. Although failed to find specific biomarkers, they discovered several important metabolite-stroke associations which belong to three pathophysiological mechanisms: Excitotoxicity with activation of glutamate, resulting in the increase of glutamate derivatives proline and pyroglutamate; Oxidative stress with production of free radicals and perturbed concentrations of uric acid, matrix metalloproteinase-9, branch-chained amino acids, sphingolipids, homocysteine, asymmetric dimethylarginine, nitric oxide and folate cycle metabolites; and Stroke mediated inflammation, affecting phospholipid metabolism with perturbed levels of lysophosphatidylethanolamine and lysophosphatidylcholine. The discovered metabolite-stroke associations need further evaluation in prospective, high-quality studies with patients matched for age, risk factors, and medications.
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Affiliation(s)
- Evgeny Sidorov
- Department of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.,Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Dharambir K Sanghera
- Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.,Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.,Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.,Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Jairam K P Vanamala
- Department of Plant Science, Penn State University, University Park, PA, USA.,Department of Food Science/Center for Molecular Immunology and Infectious Diseases, Penn State University, University Park, PA, USA
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Vignoli A, Ghini V, Meoni G, Licari C, Takis PG, Tenori L, Turano P, Luchinat C. High-Throughput Metabolomics by 1D NMR. Angew Chem Int Ed Engl 2019; 58:968-994. [PMID: 29999221 PMCID: PMC6391965 DOI: 10.1002/anie.201804736] [Citation(s) in RCA: 230] [Impact Index Per Article: 38.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Indexed: 12/12/2022]
Abstract
Metabolomics deals with the whole ensemble of metabolites (the metabolome). As one of the -omic sciences, it relates to biology, physiology, pathology and medicine; but metabolites are chemical entities, small organic molecules or inorganic ions. Therefore, their proper identification and quantitation in complex biological matrices requires a solid chemical ground. With respect to for example, DNA, metabolites are much more prone to oxidation or enzymatic degradation: we can reconstruct large parts of a mammoth's genome from a small specimen, but we are unable to do the same with its metabolome, which was probably largely degraded a few hours after the animal's death. Thus, we need standard operating procedures, good chemical skills in sample preparation for storage and subsequent analysis, accurate analytical procedures, a broad knowledge of chemometrics and advanced statistical tools, and a good knowledge of at least one of the two metabolomic techniques, MS or NMR. All these skills are traditionally cultivated by chemists. Here we focus on metabolomics from the chemical standpoint and restrict ourselves to NMR. From the analytical point of view, NMR has pros and cons but does provide a peculiar holistic perspective that may speak for its future adoption as a population-wide health screening technique.
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Affiliation(s)
- Alessia Vignoli
- C.I.R.M.M.P.Via Luigi Sacconi 650019 Sesto FiorentinoFlorenceItaly
| | - Veronica Ghini
- CERMUniversity of FlorenceVia Luigi Sacconi 650019 Sesto FiorentinoFlorenceItaly
| | - Gaia Meoni
- CERMUniversity of FlorenceVia Luigi Sacconi 650019 Sesto FiorentinoFlorenceItaly
| | - Cristina Licari
- CERMUniversity of FlorenceVia Luigi Sacconi 650019 Sesto FiorentinoFlorenceItaly
| | | | - Leonardo Tenori
- Department of Experimental and Clinical MedicineUniversity of FlorenceLargo Brambilla 3FlorenceItaly
| | - Paola Turano
- CERMUniversity of FlorenceVia Luigi Sacconi 650019 Sesto FiorentinoFlorenceItaly
- Department of Chemistry “Ugo Schiff”University of FlorenceVia della Lastruccia 3–1350019 Sesto FiorentinoFlorenceItaly
| | - Claudio Luchinat
- CERMUniversity of FlorenceVia Luigi Sacconi 650019 Sesto FiorentinoFlorenceItaly
- Department of Chemistry “Ugo Schiff”University of FlorenceVia della Lastruccia 3–1350019 Sesto FiorentinoFlorenceItaly
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Goshadrou F, Arefi Oskouie A, Eslami M, Nobakht Mothlagh Ghoochani BF. Effect of ghrelin on serum metabolites in Alzheimer's disease model rats; a metabolomics studies based on 1H-NMR technique. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2018; 21:1245-1254. [PMID: 30627368 PMCID: PMC6312673 DOI: 10.22038/ijbms.2018.30596.7373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Accepted: 06/21/2018] [Indexed: 11/06/2022]
Abstract
OBJECTIVES Alzheimer's disease (AD) is dysfunction of the central nervous system and as a neurodegenerative disease. The objective of this work is to investigate metabolic profiling in the serum of animal models of AD compared to healthy controls and then to peruse the role of ghrelin as a therapeutic approach for the AD. MATERIALS AND METHODS Nuclear magnetic resonance (NMR) technique was used for identification of metabolites that are differentially expressed in the serum of a rat model of the AD with or without ghrelin treatment. Using multivariate statistical analysis, models were built and indicated. RESULTS There were significant differences and high predictive power between AD and ghrelin-treated groups. The area under curve (AUC) of receiver operating characteristic (ROC) curve and Q2 were 0.870 and 0.759, respectively. A biomarker panel consisting of 14 metabolites was identified to discriminate the AD from the control group. Another panel of 12 serum metabolites was used to differentiate AD models from treated models. CONCLUSION Both panels had good agreements with clinical diagnosis. Analysis of the results displayed that ghrelin improved memory and cognitive abilities. Affected pathways by ghrelin included oxidative stress, and osteoporosis pathways and vascular risk factors.
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Affiliation(s)
- Fatemeh Goshadrou
- Faculty of Paramedical Sciences, Department of Basic Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Afsaneh Arefi Oskouie
- Faculty of Paramedical Sciences, Department of Basic Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Eslami
- Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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Vignoli A, Ghini V, Meoni G, Licari C, Takis PG, Tenori L, Turano P, Luchinat C. Hochdurchsatz‐Metabolomik mit 1D‐NMR. Angew Chem Int Ed Engl 2018. [DOI: 10.1002/ange.201804736] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Alessia Vignoli
- C.I.R.M.M.P. Via Luigi Sacconi 6 50019 Sesto Fiorentino Florence Italien
| | - Veronica Ghini
- CERMUniversity of Florence Via Luigi Sacconi 6 50019 Sesto Fiorentino Florence Italien
| | - Gaia Meoni
- CERMUniversity of Florence Via Luigi Sacconi 6 50019 Sesto Fiorentino Florence Italien
| | - Cristina Licari
- CERMUniversity of Florence Via Luigi Sacconi 6 50019 Sesto Fiorentino Florence Italien
| | | | - Leonardo Tenori
- Department of Experimental and Clinical MedicineUniversity of Florence Largo Brambilla 3 Florence Italien
| | - Paola Turano
- CERMUniversity of Florence Via Luigi Sacconi 6 50019 Sesto Fiorentino Florence Italien
- Department of Chemistry “Ugo Schiff”University of Florence Via della Lastruccia 3–13 50019 Sesto Fiorentino Florence Italien
| | - Claudio Luchinat
- CERMUniversity of Florence Via Luigi Sacconi 6 50019 Sesto Fiorentino Florence Italien
- Department of Chemistry “Ugo Schiff”University of Florence Via della Lastruccia 3–13 50019 Sesto Fiorentino Florence Italien
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Takis PG, Taddei A, Pini R, Grifoni S, Tarantini F, Bechi P, Luchinat C. Fingerprinting Acute Digestive Diseases by Untargeted NMR Based Metabolomics. Int J Mol Sci 2018; 19:ijms19113288. [PMID: 30360494 PMCID: PMC6274841 DOI: 10.3390/ijms19113288] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Revised: 10/18/2018] [Accepted: 10/19/2018] [Indexed: 12/18/2022] Open
Abstract
Precision medicine may significantly contribute to rapid disease diagnosis and targeted therapy, but relies on the availability of detailed, subject specific, clinical information. Proton nuclear magnetic resonance (1H–NMR) spectroscopy of body fluids can extract individual metabolic fingerprints. Herein, we studied 64 patients admitted to the Florence main hospital emergency room with severe abdominal pain. A blood sample was drawn from each patient at admission, and the corresponding sera underwent 1H–NMR metabolomics fingerprinting. Unsupervised Principal Component Analysis (PCA) analysis showed a significant discrimination between a group of patients with symptoms of upper abdominal pain and a second group consisting of patients with diffuse abdominal/intestinal pain. Prompted by this observation, supervised statistical analysis (Orthogonal Partial Least Squares–Discriminant Analysis (OPLS-DA)) showed a very good discrimination (>90%) between the two groups of symptoms. This is a surprising finding, given that neither of the two symptoms points directly to a specific disease among those studied here. Actually herein, upper abdominal pain may result from either symptomatic gallstones, cholecystitis, or pancreatitis, while diffuse abdominal/intestinal pain may result from either intestinal ischemia, strangulated obstruction, or mechanical obstruction. Although limited by the small number of samples from each of these six conditions, discrimination of these diseases was attempted. In the first symptom group, >70% discrimination accuracy was obtained among symptomatic gallstones, pancreatitis, and cholecystitis, while for the second symptom group >85% classification accuracy was obtained for intestinal ischemia, strangulated obstruction, and mechanical obstruction. No single metabolite stands up as a possible biomarker for any of these diseases, while the contribution of the whole 1H–NMR serum fingerprint seems to be a promising candidate, to be confirmed on larger cohorts, as a first-line discriminator for these diseases.
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Affiliation(s)
- Panteleimon G Takis
- Giotto Biotech, S.r.l, Via Madonna del Piano 6, 50019 Sesto Fiorentino, Italy.
| | - Antonio Taddei
- Department of Surgery and Translational Medicine, School of Medicine, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy.
| | - Riccardo Pini
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
| | - Stefano Grifoni
- Department of Emergency Medicine and Surgery, Careggi University Hospital, 50134 Florence, Italy.
| | - Francesca Tarantini
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
| | - Paolo Bechi
- Department of Surgery and Translational Medicine, School of Medicine, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy.
| | - Claudio Luchinat
- Giotto Biotech, S.r.l, Via Madonna del Piano 6, 50019 Sesto Fiorentino, Italy.
- Magnetic Resonance Center (CERM), University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy.
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Identification of metabolic phenotypes in childhood obesity by 1H NMR metabolomics of blood plasma. Future Sci OA 2018; 4:FSO310. [PMID: 30057787 PMCID: PMC6060399 DOI: 10.4155/fsoa-2017-0146] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Accepted: 04/05/2018] [Indexed: 12/18/2022] Open
Abstract
Aim: To identify the plasma metabolic profile associated with childhood obesity and its metabolic phenotypes. Materials & methods: The plasma metabolic profile of 65 obese and 37 normal-weight children was obtained using proton NMR spectroscopy. NMR spectra were rationally divided into 110 integration regions, which reflect relative metabolite concentrations, and were used as statistical variables. Results: Obese children show increased levels of lipids, N-acetyl glycoproteins, and lactate, and decreased levels of several amino acids, α-ketoglutarate, glucose, citrate, and cholinated phospholipids as compared with normal-weight children. Metabolically healthy children show lower levels of lipids and lactate, and higher levels of several amino acids and cholinated phospholipids, as compared with unhealthy children. Conclusion: This study reveals new valuable findings in the field of metabolomics and childhood obesity. Although validation should be performed, the proof of principle looks promising and justifies a deeper investigation of the diagnostic possibilities of proton NMR metabolomics in follow-up studies. Trial registration: NCT03014856. Registered January 9, 2017.
The plasma metabolic profile of childhood obesity and its metabolic phenotypes was identified using untargeted proton NMR spectroscopy combined with multivariate statistics. Obese children show increased plasma levels of lipids, N-acetyl glycoproteins and lactate, next to decreased levels of several amino acids, α-ketoglutarate, glucose, citrate and cholinated phospholipids as compared with normal-weight children. In addition, the metabolic profile of healthy and unhealthy obese children could be discriminated and although further validation should be performed, these findings might pave the way to a detailed diagnostic metabolic signature in children.
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Serum Metabolomics Study Based on LC-MS and Antihypertensive Effect of Uncaria on Spontaneously Hypertensive Rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:9281946. [PMID: 29849735 PMCID: PMC5904782 DOI: 10.1155/2018/9281946] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Revised: 10/15/2017] [Accepted: 11/26/2017] [Indexed: 12/15/2022]
Abstract
Our previous studies have shown that Uncaria has an important role in lowering blood pressure, but its intervention mechanism has not been clarified completely in the metabolic level. Therefore, in this study, a combination method of HPLC-TOF/MS-based metabolomics and multivariate statistical analyses was employed to explore the mechanism and evaluate the antihypertensive effect of Uncaria. Serum samples were analyzed and identified by HPLC-TOF/MS, while the acquired data was further processed by partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) to discover the perturbed metabolites. A clear cluster among the different groups was obtained, and 7 significantly changed potential biomarkers were screened out. These biomarkers were mainly associated with lipid metabolism (dihydroceramide, ceramide, PC, LysoPC, and TXA2) and vitamin and amino acids metabolism (nicotinamide riboside, 5-HTP). The result indicated that Uncaria could decrease the blood pressure effectively, partially by regulating the above biomarkers and metabolic pathways. Analyzing and verifying the specific biomarkers, further understanding of the therapeutic mechanism and antihypertensive effect of Uncaria was acquired. Metabolomics provided a new insight into estimate of the therapeutic effect and dissection of the potential mechanisms of traditional Chinese medicine (TCM) in treating hypertension.
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Schlippenbach TV, Oefner PJ, Gronwald W. Systematic Evaluation of Non-Uniform Sampling Parameters in the Targeted Analysis of Urine Metabolites by 1H, 1H 2D NMR Spectroscopy. Sci Rep 2018; 8:4249. [PMID: 29523811 PMCID: PMC5844889 DOI: 10.1038/s41598-018-22541-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Accepted: 02/23/2018] [Indexed: 11/15/2022] Open
Abstract
Non-uniform sampling (NUS) allows the accelerated acquisition of multidimensional NMR spectra. The aim of this contribution was the systematic evaluation of the impact of various quantitative NUS parameters on the accuracy and precision of 2D NMR measurements of urinary metabolites. Urine aliquots spiked with varying concentrations (15.6-500.0 µM) of tryptophan, tyrosine, glutamine, glutamic acid, lactic acid, and threonine, which can only be resolved fully by 2D NMR, were used to assess the influence of the sampling scheme, reconstruction algorithm, amount of omitted data points, and seed value on the quantitative performance of NUS in 1H,1H-TOCSY and 1H,1H-COSY45 NMR spectroscopy. Sinusoidal Poisson-gap sampling and a compressed sensing approach employing the iterative re-weighted least squares method for spectral reconstruction allowed a 50% reduction in measurement time while maintaining sufficient quantitative accuracy and precision for both types of homonuclear 2D NMR spectroscopy. Together with other advances in instrument design, such as state-of-the-art cryogenic probes, use of 2D NMR spectroscopy in large biomedical cohort studies seems feasible.
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Affiliation(s)
- Trixi von Schlippenbach
- Institute of Functional Genomics, University of Regensburg, Am BioPark 9, 93053, Regensburg, Germany
| | - Peter J Oefner
- Institute of Functional Genomics, University of Regensburg, Am BioPark 9, 93053, Regensburg, Germany
| | - Wolfram Gronwald
- Institute of Functional Genomics, University of Regensburg, Am BioPark 9, 93053, Regensburg, Germany.
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Dinges MM, Lytle C, Larive CK. 1H NMR-Based Identification of Intestinally Absorbed Metabolites by Ussing Chamber Analysis of the Rat Cecum. Anal Chem 2018; 90:4196-4202. [PMID: 29474787 DOI: 10.1021/acs.analchem.8b00393] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The large intestine (cecum and colon) is a complex biochemical factory of vital importance to human health. It plays a major role in digestion and absorption by salvaging nutrients from polysaccharides via fermentation initiated by the bacteria that comprise the gut microbiome. We hypothesize that the intestinal epithelium absorbs a limited number of luminal metabolites with bioactive potential while actively excluding those with toxic effects. To explore this concept, we combined 1H NMR detection with Ussing chamber measurements of absorptive transport by rat cecum. Numerous metabolites transported across the epithelium can be measured simultaneously by 1H NMR, a universal detector of organic compounds, alleviating the need for fluorescent or radiolabeled compounds. Our results demonstrate the utility of this approach to delineate the repertoire of fecal solutes that are selectively absorbed by the cecum and to determine their transport rates.
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Affiliation(s)
- Meredith M Dinges
- Department of Chemistry , University of California , Riverside , California 92521 , United States
| | - Christian Lytle
- School of Medicine , University of California , 900 University Avenue Riverside , California 92521 , United States
| | - Cynthia K Larive
- Department of Chemistry , University of California , Riverside , California 92521 , United States
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