|
1
|
Saito N. Basic accuracy of a 1D NOESY with presaturation method using standard solutions of amino and maleic acids. Anal Bioanal Chem 2024; 416:5721-5731. [PMID: 39177791 DOI: 10.1007/s00216-024-05491-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Revised: 07/31/2024] [Accepted: 08/09/2024] [Indexed: 08/24/2024]
Abstract
1D NOESY with presaturation (NOESY-presat) is the most popular water suppression method. When D2O solutions of L-phenylalanine or L-valine were measured using NOESY, the absolute concentration biases increased with longer mixing and evolution times, reaching a maximum of 54% with respect to the preparation values. At mixing and evolution times of 0 ms and 0 µs, respectively, the absolute concentration biases were reduced to less than 3%. The remaining biases were caused by the off-resonance effect, which was prevented by setting the frequency offset to an intermediate value between the analyte and internal standard 3-(trimethylsilyl)-1-propanesulfonic acid-d6 (DSS-d6) signals. Nevertheless, NOESY-presat gave maximum absolute biases of 26% and 11% for glycine and maleic acid concentrations, respectively, in three H2O/D2O (90/10 vol%) solutions. The proposed NOESY-dual-presat method reduced the absolute biases to below 4%. However, water suppression was insufficient but was improved by setting the frequency offset to the same as the presaturation offset with the H2O signal, although the absolute biases rose to 5 to 13%. Quantitative analyses using NOESY-presat and NOESY-dual-presat require careful consideration of the off-resonance effect.
Collapse
Affiliation(s)
- Naoki Saito
- Center for Environmental Standards and Measurement, Health and Environmental Risk Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki, 305-8506, Japan.
| |
Collapse
|
|
2
|
Li W, Dong H, Niu K, Wang HY, Cheng W, Song H, Ying AK, Zhai X, Li K, Yu H, Guo DS, Wang Y. Analyzing urinary hippuric acid as a metabolic health biomarker through a supramolecular architecture. Talanta 2024; 278:126480. [PMID: 38972275 DOI: 10.1016/j.talanta.2024.126480] [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: 02/01/2024] [Revised: 06/10/2024] [Accepted: 06/25/2024] [Indexed: 07/09/2024]
Abstract
The prevalence of metabolic disorders has been found to increase concomitantly with alternations in habitual diet and lifestyle, indicating the importance of metabolic health monitoring for early warning of high-risk status and suggesting effective intervention strategies. Hippuric acid (HA), as one of the most abundant metabolites from the gut microbiota, holds potential as a regulator of metabolic health. Accordingly, it is imperative to establish an efficient, sensitive, and affordable method for large-scale population monitoring, revealing the association between HA level and metabolic disorders. Upon systematic screening of macrocycle•dye reporter pair, a supramolecular architecture (guanidinomethyl-modified calix[5]arene, GMC5A) was employed to sense urinary HA by employing fluorescein (Fl), whose complexation behavior was demonstrated by theoretical calculations, accomplishing quantification of HA in urine from 249 volunteers in the range of 0.10 mM and 10.93 mM. Excitedly, by restricted cubic spline, urinary HA concentration was found to have a significantly negative correlation with the risk of metabolic disorders when it exceeded 0.76 mM, suggesting the importance of dietary habits, especially the consumption of fruits, coffee, and tea, which was unveiled from a simple questionnaire survey. In this study, we accomplished a high throughput and sensitive detection of urinary HA based on supramolecular sensing with the GMC5A•Fl reporter pair, which sheds light on the rapid quantification of urinary HA as an indicator of metabolic health status and early intervention by balancing the daily diet.
Collapse
Affiliation(s)
- Wenhui Li
- National Key Laboratory of Chinese Medicine Modernization, State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Hua Dong
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300193, China
| | - Kejing Niu
- National Key Laboratory of Chinese Medicine Modernization, State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Huan-Yu Wang
- College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), Frontiers Science Center for New Organic Matter, Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin, 300071, China
| | - Wenqian Cheng
- National Key Laboratory of Chinese Medicine Modernization, State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Hualong Song
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300193, China
| | - An-Kang Ying
- College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), Frontiers Science Center for New Organic Matter, Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin, 300071, China
| | - Xiaobing Zhai
- Faculty of Applied Sciences, Macao Polytechnic University, Macau, China
| | - Kefeng Li
- Faculty of Applied Sciences, Macao Polytechnic University, Macau, China
| | - Huijuan Yu
- National Key Laboratory of Chinese Medicine Modernization, State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, China.
| | - Dong-Sheng Guo
- College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), Frontiers Science Center for New Organic Matter, Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin, 300071, China.
| | - Yuefei Wang
- National Key Laboratory of Chinese Medicine Modernization, State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, China.
| |
Collapse
|
|
3
|
Rodríguez-Muguruza S, Altuna-Coy A, Arreaza-Gil V, Mendieta-Homs M, Castro-Oreiro S, Poveda-Elices MJ, del Castillo-Piñol N, Fontova-Garrofé R, Chacón MR. A serum metabolic biomarker panel for early rheumatoid arthritis. Front Immunol 2023; 14:1253913. [PMID: 37720214 PMCID: PMC10502709 DOI: 10.3389/fimmu.2023.1253913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 08/14/2023] [Indexed: 09/19/2023] Open
Abstract
Objective There is an urgent need for novel biomarkers to improve the early diagnosis of rheumatoid arthritis (ERA). Current serum biomarkers used in the management of ERA, including rheumatoid factor and anti-cyclic citrullinated peptide (ACPA), show limited specificity and sensitivity. Here, we used metabolomics to uncover new serum biomarkers of ERA. Methods We applied an untargeted metabolomics approach including gas chromatography time-of-flight mass spectrometry in serum samples from an ERA cohort (n=32) and healthy controls (n=19). Metabolite set enrichment analysis was performed to explore potentially important biological pathways. Partial least squares discriminant analysis and variable importance in projection analysis were performed to construct an ERA biomarker panel. Results Significant differences in the content of 11/81 serum metabolites were identified in patients with ERA. Receiver operating characteristic (ROC) analysis showed that a panel of only three metabolites (glyceric acid, lactic acid, and 3-hydroxisovaleric acid) could correctly classify 96.7% of patients with ERA, with an area under the ROC curve of 0.963 and with 94.4% specificity and 93.5% sensitivity, outperforming ACPA-based diagnosis by 2.9% and, thus, improving the preclinical detection of ERA. Aminoacyl-tRNA biosynthesis and serine, glycine, and phenylalanine metabolism were the most significant dysregulated pathways in patients with ERA. Conclusion A metabolomics serum-based biomarker panel composed of glyceric acid, lactic acid, and 3-hydroxisovaleric acid offers potential for the early clinical diagnosis of RA.
Collapse
Affiliation(s)
- Samantha Rodríguez-Muguruza
- Disease Biomarkers and Molecular Mechanisms Group, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain
- Rheumatology Department, Joan XXIII University Hospital, Tarragona, Spain
| | - Antonio Altuna-Coy
- Disease Biomarkers and Molecular Mechanisms Group, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain
| | - Verónica Arreaza-Gil
- Disease Biomarkers and Molecular Mechanisms Group, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain
| | - Marina Mendieta-Homs
- Disease Biomarkers and Molecular Mechanisms Group, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain
| | | | | | | | - Ramon Fontova-Garrofé
- Disease Biomarkers and Molecular Mechanisms Group, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain
- Rheumatology Department, Joan XXIII University Hospital, Tarragona, Spain
| | - Matilde R. Chacón
- Disease Biomarkers and Molecular Mechanisms Group, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain
| |
Collapse
|
|
4
|
Chasapi SA, Karagkouni E, Kalavrizioti D, Vamvakas S, Zompra A, Takis PG, Goumenos DS, Spyroulias GA. NMR-Based Metabolomics in Differential Diagnosis of Chronic Kidney Disease (CKD) Subtypes. Metabolites 2022; 12:490. [PMID: 35736423 PMCID: PMC9230636 DOI: 10.3390/metabo12060490] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 05/23/2022] [Accepted: 05/25/2022] [Indexed: 02/01/2023] Open
Abstract
Chronic Kidney Disease (CKD) is considered as a major public health problem as it can lead to end-stage kidney failure, which requires replacement therapy. A prompt and accurate diagnosis, along with the appropriate treatment, can delay CKD's progression, significantly. Herein, we sought to determine whether CKD etiology can be reflected in urine metabolomics during its early stage. This is achieved through the analysis of the urine metabolic fingerprint from 108 CKD patients by means of Nuclear Magnetic Resonance (NMR) spectroscopy metabolomic analysis. We report the first NMR-metabolomics data regarding the three most common etiologies of CKD: Chronic Glomerulonephritis (IgA and Membranous Nephropathy), Diabetic Nephropathy (DN) and Hypertensive Nephrosclerosis (HN). Analysis aided a moderate glomerulonephritis clustering, providing characterization of the metabolic fluctuations between the CKD subtypes and control disease. The urine metabolome of IgA Nephropathy reveals a specific metabolism, reflecting its different etiology or origin and is useful for determining the origin of the disease. In contrast, urine metabolomes from DN and HN patients did not reveal any indicative metabolic pattern, which is consistent with their fused clinical phenotype. These findings may contribute to improving diagnostics and prognostic approaches for CKD, as well as improving our understanding of its pathology.
Collapse
Affiliation(s)
- Styliani A. Chasapi
- Department of Pharmacy, University of Patras, 26504 Patras, Greece; (S.A.C.); (E.K.); (A.Z.)
| | - Evdokia Karagkouni
- Department of Pharmacy, University of Patras, 26504 Patras, Greece; (S.A.C.); (E.K.); (A.Z.)
| | - Dimitra Kalavrizioti
- Department of Nephrology and Renal Transplantation, University Hospital of Patras, 26504 Patras, Greece; (D.K.); (S.V.)
| | - Sotirios Vamvakas
- Department of Nephrology and Renal Transplantation, University Hospital of Patras, 26504 Patras, Greece; (D.K.); (S.V.)
| | - Aikaterini Zompra
- Department of Pharmacy, University of Patras, 26504 Patras, Greece; (S.A.C.); (E.K.); (A.Z.)
| | - Panteleimon G. Takis
- Section of Bioanalytical Chemistry, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, South Kensington Campus, London SW7 2AZ, UK;
- National Phenome Centre, Department of Metabolism, Digestion and Reproduction, Imperial College London, Hammersmith Campus, IRDB Building, London W120NN, UK
| | - Dimitrios S. Goumenos
- Department of Nephrology and Renal Transplantation, University Hospital of Patras, 26504 Patras, Greece; (D.K.); (S.V.)
| | - Georgios A. Spyroulias
- Department of Pharmacy, University of Patras, 26504 Patras, Greece; (S.A.C.); (E.K.); (A.Z.)
| |
Collapse
|
|
5
|
Vignoli A, Fornaro A, Tenori L, Castelli G, Cecconi E, Olivotto I, Marchionni N, Alterini B, Luchinat C. Metabolomics Fingerprint Predicts Risk of Death in Dilated Cardiomyopathy and Heart Failure. Front Cardiovasc Med 2022; 9:851905. [PMID: 35463749 PMCID: PMC9021397 DOI: 10.3389/fcvm.2022.851905] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 03/01/2022] [Indexed: 11/17/2022] Open
Abstract
Background Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Metabolomics may help refine risk assessment and potentially guide HF management, but dedicated studies are few. This study aims at stratifying the long-term risk of death in a cohort of patients affected by HF due to dilated cardiomyopathy (DCM) using serum metabolomics via nuclear magnetic resonance (NMR) spectroscopy. Methods A cohort of 106 patients with HF due to DCM, diagnosed and monitored between 1982 and 2011, were consecutively enrolled between 2010 and 2012, and a serum sample was collected from each participant. Each patient underwent half-yearly clinical assessments, and survival status at the last follow-up visit in 2019 was recorded. The NMR serum metabolomic profiles were retrospectively analyzed to evaluate the patient's risk of death. Overall, 26 patients died during the 8-years of the study. Results The metabolomic fingerprint at enrollment was powerful in discriminating patients who died (HR 5.71, p = 0.00002), even when adjusted for potential covariates. The outcome prediction of metabolomics surpassed that of N-terminal pro b-type natriuretic peptide (NT-proBNP) (HR 2.97, p = 0.005). Metabolomic fingerprinting was able to sub-stratify the risk of death in patients with both preserved/mid-range and reduced ejection fraction [hazard ratio (HR) 3.46, p = 0.03; HR 6.01, p = 0.004, respectively]. Metabolomics and left ventricular ejection fraction (LVEF), combined in a score, proved to be synergistic in predicting survival (HR 8.09, p = 0.0000004). Conclusions Metabolomic analysis via NMR enables fast and reproducible characterization of the serum metabolic fingerprint associated with poor prognosis in the HF setting. Our data suggest the importance of integrating several risk parameters to early identify HF patients at high-risk of poor outcomes.
Collapse
Affiliation(s)
- Alessia Vignoli
- Department of Chemistry “Ugo Schiff”, Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy
- Interuniversity Consortium for Magnetic Resonance of Metalloproteins, Sesto Fiorentino, Italy
| | | | - Leonardo Tenori
- Department of Chemistry “Ugo Schiff”, Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy
- Interuniversity Consortium for Magnetic Resonance of Metalloproteins, Sesto Fiorentino, Italy
| | | | - Elisabetta Cecconi
- Division of Cardiovascular and Perioperative Medicine, Careggi University Hospital, Florence, Italy
| | - Iacopo Olivotto
- Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy
| | - Niccolò Marchionni
- Division of General Cardiology, Department of Experimental and Clinical Medicine, Careggi University Hospital, University of Florence, Florence, Italy
| | - Brunetto Alterini
- Division of Cardiovascular and Perioperative Medicine, Careggi University Hospital, Florence, Italy
- *Correspondence: Brunetto Alterini
| | - Claudio Luchinat
- Department of Chemistry “Ugo Schiff”, Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy
- Interuniversity Consortium for Magnetic Resonance of Metalloproteins, Sesto Fiorentino, Italy
- Claudio Luchinat
| |
Collapse
|
|
6
|
De Simone G, Balducci C, Forloni G, Pastorelli R, Brunelli L. Hippuric acid: Could became a barometer for frailty and geriatric syndromes? Ageing Res Rev 2021; 72:101466. [PMID: 34560280 DOI: 10.1016/j.arr.2021.101466] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 09/07/2021] [Accepted: 09/17/2021] [Indexed: 12/11/2022]
Abstract
Aging is a natural biological event that has some downsides such as increased frailty, decline in cognitive and physical functions leading to chronical diseases, and lower quality of life. There is therefore a pressing need of reliable biomarkers to identify populations at risk of developing age-associated syndromes in order to improve their quality of life, promote healthy ageing and a more appropriate clinical management, when needed. Here we discuss the importance of hippuric acid, an endogenous co-metabolite, as a possible hallmark of human aging and age-related diseases, summarizing the scientific literature over the last years. Hippuric acid, the glycine conjugate of benzoic acid, derives from the catabolism by means of intestinal microflora of dietary polyphenols found in plant-based foods (e.g. fruits, vegetables, tea and coffee). In healthy conditions hippuric acid levels in blood and/or urine rise significantly during aging while its excretion drops in conditions related with aging, including cognitive impairments, rheumatic diseases, sarcopenia and hypomobility. This literature highlights the utility of hippuric acid in urine and plasma as a plausible hallmark of frailty, related to low fruit and vegetable intake and changes in gut microflora.
Collapse
Affiliation(s)
- Giulia De Simone
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - Claudia Balducci
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | | | | | - Laura Brunelli
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
| |
Collapse
|
|
7
|
Effects of a Diet Based on Foods from Symbiotic Agriculture on the Gut Microbiota of Subjects at Risk for Metabolic Syndrome. Nutrients 2021; 13:nu13062081. [PMID: 34204572 PMCID: PMC8235411 DOI: 10.3390/nu13062081] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 06/14/2021] [Indexed: 12/20/2022] Open
Abstract
Diet is a major driver of gut microbiota variation and plays a role in metabolic disorders, including metabolic syndrome (MS). Mycorrhized foods from symbiotic agriculture (SA) exhibit improved nutritional properties, but potential benefits have never been investigated in humans. We conducted a pilot interventional study on 60 adults with ≥ 1 risk factors for MS, of whom 33 consumed SA-derived fresh foods and 27 received probiotics over 30 days, with a 15-day follow-up. Stool, urine and blood were collected over time to explore changes in gut microbiota, metabolome, and biochemical, inflammatory and immunologic parameters; previous dietary habits were investigated through a validated food-frequency questionnaire. The baseline microbiota showed alterations typical of metabolic disorders, mainly an increase in Coriobacteriaceae and a decrease in health-associated taxa, which were partly reversed after the SA-based diet. Improvements were observed in metabolome, MS presence (two out of six subjects no longer had MS) or components. Changes were more pronounced with less healthy baseline diets. Probiotics had a marginal, not entirely favorable, effect, although one out of three subjects no longer suffered from MS. These findings suggest that improved dietary patterns can modulate the host microbiota and metabolome, counteracting the risk of developing MS.
Collapse
|
|
8
|
Di Donato S, Vignoli A, Biagioni C, Malorni L, Mori E, Tenori L, Calamai V, Parnofiello A, Di Pierro G, Migliaccio I, Cantafio S, Baraghini M, Mottino G, Becheri D, Del Monte F, Miceli E, McCartney A, Di Leo A, Luchinat C, Biganzoli L. A Serum Metabolomics Classifier Derived from Elderly Patients with Metastatic Colorectal Cancer Predicts Relapse in the Adjuvant Setting. Cancers (Basel) 2021; 13:cancers13112762. [PMID: 34199435 PMCID: PMC8199587 DOI: 10.3390/cancers13112762] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 05/14/2021] [Accepted: 05/29/2021] [Indexed: 12/26/2022] Open
Abstract
Simple Summary Around 30–40% of patients with early stage colorectal cancer (eCRC) experience relapse after surgery. Current recommendations for adjuvant therapy are based on suboptimal risk-stratification tools. In elderly patients, risk of relapse assessment is particularly important to ultimately avoid unnecessary chemotherapy-related toxicity in this frailer population. Serum metabolomics via NMR spectroscopy may improve risk stratification by identifying patients with residual micrometastases after surgery and thus at higher risk of relapse. We evaluated the serum metabolomic fingerprints of 94 elderly patients with eCRC (65 relapse free and 29 relapsed), and of 75 elderly patients with metastatic disease. Metabolomics efficiently discriminated patients with relapse-free eCRC from those with metastatic disease, correctly predicting relapse in 69% of relapsed eCRC patients. The metabolomic score was strongly and independently associated with prognosis. Our data suggest metabolomics as a valid addition to standard tools to refine risk stratification for eCRC and warrant further investigation. Abstract Adjuvant treatment for patients with early stage colorectal cancer (eCRC) is currently based on suboptimal risk stratification, especially for elderly patients. Metabolomics may improve the identification of patients with residual micrometastases after surgery. In this retrospective study, we hypothesized that metabolomic fingerprinting could improve risk stratification in patients with eCRC. Serum samples obtained after surgery from 94 elderly patients with eCRC (65 relapse free and 29 relapsed, after 5-years median follow up), and from 75 elderly patients with metastatic colorectal cancer (mCRC) obtained before a new line of chemotherapy, were retrospectively analyzed via proton nuclear magnetic resonance spectroscopy. The prognostic role of metabolomics in patients with eCRC was assessed using Kaplan–Meier curves. PCA-CA-kNN could discriminate the metabolomic fingerprint of patients with relapse-free eCRC and mCRC (70.0% accuracy using NOESY spectra). This model was used to classify the samples of patients with relapsed eCRC: 69% of eCRC patients with relapse were predicted as metastatic. The metabolomic classification was strongly associated with prognosis (p-value 0.0005, HR 3.64), independently of tumor stage. In conclusion, metabolomics could be an innovative tool to refine risk stratification in elderly patients with eCRC. Based on these results, a prospective trial aimed at improving risk stratification by metabolomic fingerprinting (LIBIMET) is ongoing.
Collapse
Affiliation(s)
- Samantha Di Donato
- Department of Medical Oncology, New Hospital of Prato S. Stefano, 59100 Prato, Italy; (L.M.); (E.M.); (V.C.); (A.P.); (G.D.P.); (F.D.M.); (E.M.); (A.M.); (A.D.L.); (L.B.)
- Correspondence: ; Tel.: +39-057-480-2520
| | - Alessia Vignoli
- Magnetic Resonance Center, University of Florence, 50019 Sesto Fiorentino, Italy; (A.V.); (L.T.); (C.L.)
- Department of Chemistry “Ugo Schiff”, University of Florence, 50019 Sesto Fiorentino, Italy
| | - Chiara Biagioni
- Bioinformatics Unit, Medical Oncology Department, New Hospital of Prato S. Stefano, 59100 Prato, Italy;
| | - Luca Malorni
- Department of Medical Oncology, New Hospital of Prato S. Stefano, 59100 Prato, Italy; (L.M.); (E.M.); (V.C.); (A.P.); (G.D.P.); (F.D.M.); (E.M.); (A.M.); (A.D.L.); (L.B.)
- “Sandro Pitigliani” Translational Research Unit, New Hospital of Prato, Stefano, 59100 Prato, Italy;
| | - Elena Mori
- Department of Medical Oncology, New Hospital of Prato S. Stefano, 59100 Prato, Italy; (L.M.); (E.M.); (V.C.); (A.P.); (G.D.P.); (F.D.M.); (E.M.); (A.M.); (A.D.L.); (L.B.)
| | - Leonardo Tenori
- Magnetic Resonance Center, University of Florence, 50019 Sesto Fiorentino, Italy; (A.V.); (L.T.); (C.L.)
- Department of Chemistry “Ugo Schiff”, University of Florence, 50019 Sesto Fiorentino, Italy
| | - Vanessa Calamai
- Department of Medical Oncology, New Hospital of Prato S. Stefano, 59100 Prato, Italy; (L.M.); (E.M.); (V.C.); (A.P.); (G.D.P.); (F.D.M.); (E.M.); (A.M.); (A.D.L.); (L.B.)
| | - Annamaria Parnofiello
- Department of Medical Oncology, New Hospital of Prato S. Stefano, 59100 Prato, Italy; (L.M.); (E.M.); (V.C.); (A.P.); (G.D.P.); (F.D.M.); (E.M.); (A.M.); (A.D.L.); (L.B.)
- Department of Medicine (DAME), University of Udine, 33100 Udine, Italy
| | - Giulia Di Pierro
- Department of Medical Oncology, New Hospital of Prato S. Stefano, 59100 Prato, Italy; (L.M.); (E.M.); (V.C.); (A.P.); (G.D.P.); (F.D.M.); (E.M.); (A.M.); (A.D.L.); (L.B.)
| | - Ilenia Migliaccio
- “Sandro Pitigliani” Translational Research Unit, New Hospital of Prato, Stefano, 59100 Prato, Italy;
| | - Stefano Cantafio
- Department of Surgery, New Hospital of Prato S. Stefano, 59100 Prato, Italy; (S.C.); (M.B.)
| | - Maddalena Baraghini
- Department of Surgery, New Hospital of Prato S. Stefano, 59100 Prato, Italy; (S.C.); (M.B.)
| | - Giuseppe Mottino
- Department of Geriatrics, New Hospital of Prato S. Stefano, 59100 Prato, Italy; (G.M.); (D.B.)
| | - Dimitri Becheri
- Department of Geriatrics, New Hospital of Prato S. Stefano, 59100 Prato, Italy; (G.M.); (D.B.)
| | - Francesca Del Monte
- Department of Medical Oncology, New Hospital of Prato S. Stefano, 59100 Prato, Italy; (L.M.); (E.M.); (V.C.); (A.P.); (G.D.P.); (F.D.M.); (E.M.); (A.M.); (A.D.L.); (L.B.)
| | - Elisangela Miceli
- Department of Medical Oncology, New Hospital of Prato S. Stefano, 59100 Prato, Italy; (L.M.); (E.M.); (V.C.); (A.P.); (G.D.P.); (F.D.M.); (E.M.); (A.M.); (A.D.L.); (L.B.)
| | - Amelia McCartney
- Department of Medical Oncology, New Hospital of Prato S. Stefano, 59100 Prato, Italy; (L.M.); (E.M.); (V.C.); (A.P.); (G.D.P.); (F.D.M.); (E.M.); (A.M.); (A.D.L.); (L.B.)
- School of Clinical Sciences, Monash University, 3168 Clayton, Australia
| | - Angelo Di Leo
- Department of Medical Oncology, New Hospital of Prato S. Stefano, 59100 Prato, Italy; (L.M.); (E.M.); (V.C.); (A.P.); (G.D.P.); (F.D.M.); (E.M.); (A.M.); (A.D.L.); (L.B.)
| | - Claudio Luchinat
- Magnetic Resonance Center, University of Florence, 50019 Sesto Fiorentino, Italy; (A.V.); (L.T.); (C.L.)
- Department of Chemistry “Ugo Schiff”, University of Florence, 50019 Sesto Fiorentino, Italy
- Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (C.I.R.M.M.P.), 50019 Sesto Fiorentino, Italy
| | - Laura Biganzoli
- Department of Medical Oncology, New Hospital of Prato S. Stefano, 59100 Prato, Italy; (L.M.); (E.M.); (V.C.); (A.P.); (G.D.P.); (F.D.M.); (E.M.); (A.M.); (A.D.L.); (L.B.)
| |
Collapse
|
|
9
|
Vignoli A, Risi E, McCartney A, Migliaccio I, Moretti E, Malorni L, Luchinat C, Biganzoli L, Tenori L. Precision Oncology via NMR-Based Metabolomics: A Review on Breast Cancer. Int J Mol Sci 2021; 22:ijms22094687. [PMID: 33925233 PMCID: PMC8124948 DOI: 10.3390/ijms22094687] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 04/23/2021] [Accepted: 04/27/2021] [Indexed: 12/22/2022] Open
Abstract
Precision oncology is an emerging approach in cancer care. It aims at selecting the optimal therapy for the right patient by considering each patient’s unique disease and individual health status. In the last years, it has become evident that breast cancer is an extremely heterogeneous disease, and therefore, patients need to be appropriately stratified to maximize survival and quality of life. Gene-expression tools have already positively assisted clinical decision making by estimating the risk of recurrence and the potential benefit from adjuvant chemotherapy. However, these approaches need refinement to further reduce the proportion of patients potentially exposed to unnecessary chemotherapy. Nuclear magnetic resonance (NMR) metabolomics has demonstrated to be an optimal approach for cancer research and has provided significant results in BC, in particular for prognostic and stratification purposes. In this review, we give an update on the status of NMR-based metabolomic studies for the biochemical characterization and stratification of breast cancer patients using different biospecimens (breast tissue, blood serum/plasma, and urine).
Collapse
Affiliation(s)
- Alessia Vignoli
- Magnetic Resonance Center (CERM), University of Florence, 50019 Sesto Fiorentino, Italy; (A.V.); (L.T.)
- Department of Chemistry “Ugo Schiff”, University of Florence, 50019 Sesto Fiorentino, Italy
| | - Emanuela Risi
- Department of Medical Oncology, New Hospital of Prato S. Stefano, 59100 Prato, Italy; (E.R.); (A.M.); (I.M.); (E.M.); (L.M.); (L.B.)
| | - Amelia McCartney
- Department of Medical Oncology, New Hospital of Prato S. Stefano, 59100 Prato, Italy; (E.R.); (A.M.); (I.M.); (E.M.); (L.M.); (L.B.)
- School of Clinical Sciences, Monash University, Melbourne 3800, Australia
| | - Ilenia Migliaccio
- Department of Medical Oncology, New Hospital of Prato S. Stefano, 59100 Prato, Italy; (E.R.); (A.M.); (I.M.); (E.M.); (L.M.); (L.B.)
| | - Erica Moretti
- Department of Medical Oncology, New Hospital of Prato S. Stefano, 59100 Prato, Italy; (E.R.); (A.M.); (I.M.); (E.M.); (L.M.); (L.B.)
| | - Luca Malorni
- Department of Medical Oncology, New Hospital of Prato S. Stefano, 59100 Prato, Italy; (E.R.); (A.M.); (I.M.); (E.M.); (L.M.); (L.B.)
| | - Claudio Luchinat
- Magnetic Resonance Center (CERM), University of Florence, 50019 Sesto Fiorentino, Italy; (A.V.); (L.T.)
- Department of Chemistry “Ugo Schiff”, University of Florence, 50019 Sesto Fiorentino, Italy
- Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (C.I.R.M.M.P.), 50019 Sesto Fiorentino, Italy
- Correspondence: ; Tel.: +39-055-457-4296
| | - Laura Biganzoli
- Department of Medical Oncology, New Hospital of Prato S. Stefano, 59100 Prato, Italy; (E.R.); (A.M.); (I.M.); (E.M.); (L.M.); (L.B.)
| | - Leonardo Tenori
- Magnetic Resonance Center (CERM), University of Florence, 50019 Sesto Fiorentino, Italy; (A.V.); (L.T.)
- Department of Chemistry “Ugo Schiff”, University of Florence, 50019 Sesto Fiorentino, Italy
- Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (C.I.R.M.M.P.), 50019 Sesto Fiorentino, Italy
| |
Collapse
|
|
10
|
Jutley GS, Sahota K, Sahbudin I, Filer A, Arayssi T, Young SP, Raza K. Relationship Between Inflammation and Metabolism in Patients With Newly Presenting Rheumatoid Arthritis. Front Immunol 2021; 12:676105. [PMID: 34650548 PMCID: PMC8507469 DOI: 10.3389/fimmu.2021.676105] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 08/04/2021] [Indexed: 12/29/2022] Open
Abstract
Background Systemic inflammation in rheumatoid arthritis (RA) is associated with metabolic changes. We used nuclear magnetic resonance (NMR) spectroscopy-based metabolomics to assess the relationship between an objective measure of systemic inflammation [C-reactive protein (CRP)] and both the serum and urinary metabolome in patients with newly presenting RA. Methods Serum (n=126) and urine (n=83) samples were collected at initial presentation from disease modifying anti-rheumatic drug naïve RA patients for metabolomic profile assessment using 1-dimensional 1H-NMR spectroscopy. Metabolomics data were analysed using partial least square regression (PLS-R) and orthogonal projections to latent structure discriminant analysis (OPLS-DA) with cross validation. Results Using PLS-R analysis, a relationship between the level of inflammation, as assessed by CRP, and the serum (p=0.001) and urinary (p<0.001) metabolome was detectable. Likewise, following categorisation of CRP into tertiles, patients in the lowest CRP tertile and the highest CRP tertile were statistically discriminated using OPLS-DA analysis of both serum (p=0.033) and urinary (p<0.001) metabolome. The most highly weighted metabolites for these models included glucose, amino acids, lactate, and citrate. These findings suggest increased glycolysis, perturbation in the citrate cycle, oxidative stress, protein catabolism and increased urea cycle activity are key characteristics of newly presenting RA patients with elevated CRP. Conclusions This study consolidates our understanding of a previously identified relationship between serum metabolite profile and inflammation and provides novel evidence that there is a relationship between urinary metabolite profile and inflammation as measured by CRP. Identification of these metabolic perturbations provides insights into the pathogenesis of RA and may help in the identification of therapeutic targets.
Collapse
Affiliation(s)
- Gurpreet Singh Jutley
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and Institute for Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
| | - Kalvin Sahota
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and Institute for Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
| | - Ilfita Sahbudin
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and Institute for Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
| | - Andrew Filer
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and Institute for Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom.,Research Into Inflammatory Arthritis Centre, Versus Arthritis, University of Birmingham, Birmingham, United Kingdom
| | | | - Stephen P Young
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and Institute for Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
| | - Karim Raza
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and Institute for Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom.,Research Into Inflammatory Arthritis Centre, Versus Arthritis, University of Birmingham, Birmingham, United Kingdom.,Department of Rheumatology, Sandwell and West Birmingham NHS Trust, Birmingham, United Kingdom
| |
Collapse
|
|
11
|
Yang F, Li Q, Xiang J, Zhang H, Sun H, Ruan G, Tang Y. NMR-based plasma metabolomics of adult B-cell acute lymphoblastic leukemia. Mol Omics 2020; 17:153-159. [PMID: 33295915 DOI: 10.1039/d0mo00067a] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Acute lymphoblastic leukemia (ALL) is one of the common malignant tumors. Compared with childhood ALL, the treatment effect of adult B-cell ALL is less effective and remains a big challenge. In order to explore the pathogenesis of adult B-cell ALL and find new diagnostic biomarkers to develop sensitive diagnostic tools, we investigated the plasma metabolites of adult B-cell ALL by using 1H NMR (nuclear magnetic resonance) metabolomics. Relative to healthy controls, adult B-cell ALL patients showed abnormal metabolism, including glycolysis, gluconeogenesis, amino acid metabolism, fatty acid metabolism and choline phospholipid metabolism. What's more important, we also found that the optimal combination of choline, tyrosine and unsaturated lipids has the potential to diagnose and prognose adult B-cell ALL in the clinic.
Collapse
Affiliation(s)
- Fengmin Yang
- National Laboratory for Molecular Sciences, Center for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry, Chinese Academy of Sciences, Beijing, P. R. China.
| | | | | | | | | | | | | |
Collapse
|
|
12
|
Vignoli A, Tenori L, Luchinat C, Saccenti E. Differential Network Analysis Reveals Molecular Determinants Associated with Blood Pressure and Heart Rate in Healthy Subjects. J Proteome Res 2020; 20:1040-1051. [PMID: 33274633 PMCID: PMC7786375 DOI: 10.1021/acs.jproteome.0c00882] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
![]()
There
is mounting evidence that subclinical
nonpathological high blood pressure and heart rate during youth and
adulthood steadily increase the risk of developing a cardiovascular
disease at a later stage. For this reason, it is important to understand
the mechanisms underlying the subclinical elevation of blood pressure
and heart rate in healthy, relatively young individuals. In the present
study, we present a network-based metabolomic study of blood plasma
metabolites and lipids measured using nuclear magnetic resonance spectroscopy
on 841 adult healthy blood donor volunteers, which were stratified
for subclinical low and high blood pressure (systolic and diastolic)
and heart rate. Our results indicate a rewiring of metabolic pathways
active in high and low groups, indicating that the subjects with subclinical
high blood pressure and heart rate could present latent cardiometabolic
dysregulations.
Collapse
Affiliation(s)
- Alessia Vignoli
- Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (CIRMMP), 50019 Sesto Fiorentino, Italy.,Magnetic Resonance Center (CERM), University of Florence, Via Luigi Sacconi 6, 50019 Sesto Fiorentino, Italy
| | - Leonardo Tenori
- Magnetic Resonance Center (CERM), University of Florence, Via Luigi Sacconi 6, 50019 Sesto Fiorentino, Italy.,Department of Chemistry "Ugo Schiff", University of Florence, 50019 Sesto Fiorentino, Italy
| | - Claudio Luchinat
- Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (CIRMMP), 50019 Sesto Fiorentino, Italy.,Magnetic Resonance Center (CERM), University of Florence, Via Luigi Sacconi 6, 50019 Sesto Fiorentino, Italy.,Department of Chemistry "Ugo Schiff", University of Florence, 50019 Sesto Fiorentino, Italy
| | - Edoardo Saccenti
- Laboratory of Systems and Synthetic Biology, Wageningen University & Research, 6708 WE Wageningen, The Netherlands
| |
Collapse
|
|
13
|
Nannini G, Meoni G, Amedei A, Tenori L. Metabolomics profile in gastrointestinal cancers: Update and future perspectives. World J Gastroenterol 2020; 26:2514-2532. [PMID: 32523308 PMCID: PMC7265149 DOI: 10.3748/wjg.v26.i20.2514] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 05/11/2020] [Accepted: 05/15/2020] [Indexed: 02/06/2023] Open
Abstract
Despite recent progress in diagnosis and therapy, gastrointestinal (GI) cancers remain one of the most important causes of death with a poor prognosis due to late diagnosis. Serum tumor markers and detection of occult blood in the stool are the current tests used in the clinic of GI cancers; however, these tests are not useful as diagnostic screening since they have low specificity and low sensitivity. Considering that one of the hallmarks of cancer is dysregulated metabolism and metabolomics is an optimal approach to illustrate the metabolic mechanisms that belong to living systems, is now clear that this -omics could open a new way to study cancer. In the last years, nuclear magnetic resonance (NMR) metabolomics has demonstrated to be an optimal approach for diseases' diagnosis nevertheless a few studies focus on the NMR capability to find new biomarkers for early diagnosis of GI cancers. For these reasons in this review, we will give an update on the status of NMR metabolomic studies for the diagnosis and development of GI cancers using biological fluids.
Collapse
Affiliation(s)
- Giulia Nannini
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Gaia Meoni
- Giotto Biotech Srl, and CERM (University of Florence), Florence 50019, Italy
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
- SOD of Interdisciplinary Internal Medicine, Azienda Ospedaliera Universitaria Careggi, Florence 50134, Italy
| | - Leonardo Tenori
- Consorzio Interuniversitario Risonanze Magnetiche di Metalloproteine, Florence 50019, Italy
| |
Collapse
|
|
14
|
Vignoli A, Paciotti S, Tenori L, Eusebi P, Biscetti L, Chiasserini D, Scheltens P, Turano P, Teunissen C, Luchinat C, Parnetti L. Fingerprinting Alzheimer's Disease by 1H Nuclear Magnetic Resonance Spectroscopy of Cerebrospinal Fluid. J Proteome Res 2020; 19:1696-1705. [PMID: 32118444 DOI: 10.1021/acs.jproteome.9b00850] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
In this study, we sought for a cerebrospinal fluid (CSF) metabolomic fingerprint in Alzheimer's disease (AD) patients characterized, according to the clinical picture and CSF AD core biomarkers (Aβ42, p-tau, and t-tau), both at pre-dementia (mild cognitive impairment due to AD, MCI-AD) and dementia stages (ADdem) and in a group of patients with a normal CSF biomarker profile (non-AD) using untargeted 1H nuclear magnetic resonance (NMR) spectroscopy-based metabolomics. This is a retrospective study based on two independent cohorts: a Dutch cohort, which comprises 20 ADdem, 20 MCI-AD, and 20 non-AD patients, and an Italian cohort, constituted by 14 ADdem and 12 non-AD patients. 1H NMR CSF spectra were analyzed using OPLS-DA. Metabolomic fingerprinting in the Dutch cohort provides a significant discrimination (86.1% accuracy) between ADdem and non-AD. MCI-AD patients show a good discrimination with respect to ADdem (70.0% accuracy) but only slight differences when compared with non-AD (59.6% accuracy). Acetate, valine, and 3-hydroxyisovalerate result to be altered in ADdem patients. Valine correlates with cognitive decline at follow-up (R = 0.53, P = 0.0011). The discrimination between ADdem and non-AD was confirmed in the Italian cohort. The CSF metabolomic fingerprinting shows a signature characteristic of ADdem patients with respect to MCI-AD and non-AD patients.
Collapse
Affiliation(s)
- Alessia Vignoli
- Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino 50019, Italy.,Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (C.I.R.M.M.P.), Sesto Fiorentino 50019, Italy
| | - Silvia Paciotti
- Laboratory of Clinical Neurochemistry, Department of Medicine, Section of Neurology, University of Perugia, Perugia 06123, Italy.,Department of Experimental Medicine, Section of Physiology and Biochemistry, University of Perugia, Perugia 06123, Italy
| | - Leonardo Tenori
- Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino 50019, Italy.,Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (C.I.R.M.M.P.), Sesto Fiorentino 50019, Italy
| | - Paolo Eusebi
- Laboratory of Clinical Neurochemistry, Department of Medicine, Section of Neurology, University of Perugia, Perugia 06123, Italy
| | - Leonardo Biscetti
- Laboratory of Clinical Neurochemistry, Department of Medicine, Section of Neurology, University of Perugia, Perugia 06123, Italy
| | - Davide Chiasserini
- Department of Experimental Medicine, Section of Physiology and Biochemistry, University of Perugia, Perugia 06123, Italy
| | - Philip Scheltens
- Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam 1081 HV, the Netherlands
| | - Paola Turano
- Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino 50019, Italy.,Department of Chemistry, University of Florence, Sesto Fiorentino 50019, Italy
| | - Charlotte Teunissen
- Department of Clinical Chemistry, Neurochemistry Lab and Biobank, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam 1081 HV, the Netherlands
| | - Claudio Luchinat
- Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino 50019, Italy.,Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (C.I.R.M.M.P.), Sesto Fiorentino 50019, Italy.,Department of Chemistry, University of Florence, Sesto Fiorentino 50019, Italy
| | - Lucilla Parnetti
- Laboratory of Clinical Neurochemistry, Department of Medicine, Section of Neurology, University of Perugia, Perugia 06123, Italy
| |
Collapse
|
|
15
|
Silva RA, Pereira TC, Souza AR, Ribeiro PR. 1H NMR-based metabolite profiling for biomarker identification. Clin Chim Acta 2020; 502:269-279. [PMID: 31778675 DOI: 10.1016/j.cca.2019.11.015] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 11/11/2019] [Accepted: 11/12/2019] [Indexed: 12/11/2022]
|
|
16
|
Vignoli A, Tenori L, Giusti B, Valente S, Carrabba N, Balzi D, Barchielli A, Marchionni N, Gensini GF, Marcucci R, Gori AM, Luchinat C, Saccenti E. Differential Network Analysis Reveals Metabolic Determinants Associated with Mortality in Acute Myocardial Infarction Patients and Suggests Potential Mechanisms Underlying Different Clinical Scores Used To Predict Death. J Proteome Res 2020; 19:949-961. [PMID: 31899863 PMCID: PMC7011173 DOI: 10.1021/acs.jproteome.9b00779] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
![]()
We
present here the differential analysis of metabolite–metabolite
association networks constructed from an array of 24 serum metabolites
identified and quantified via nuclear magnetic resonance spectroscopy
in a cohort of 825 patients of which 123 died within 2 years from
acute myocardial infarction (AMI). We investigated differences in
metabolite connectivity of patients who survived, at 2 years, the
AMI event, and we characterized metabolite–metabolite association
networks specific to high and low risks of death according to four
different risk parameters, namely, acute coronary syndrome classification,
Killip, Global Registry of Acute Coronary Events risk score, and metabolomics
NOESY RF risk score. We show significant differences in the connectivity
patterns of several low-molecular-weight molecules, implying variations
in the regulation of several metabolic pathways regarding branched-chain
amino acids, alanine, creatinine, mannose, ketone bodies, and energetic
metabolism. Our results demonstrate that the characterization of metabolite–metabolite
association networks is a promising and powerful tool to investigate
AMI patients according to their outcomes at a molecular level.
Collapse
Affiliation(s)
- Alessia Vignoli
- Magnetic Resonance Center (CERM) , University of Florence , Sesto Fiorentino 50019 , Italy.,Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (C.I.R.M.M.P.) , Sesto Fiorentino 50019 , Italy
| | - Leonardo Tenori
- Magnetic Resonance Center (CERM) , University of Florence , Sesto Fiorentino 50019 , Italy.,Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (C.I.R.M.M.P.) , Sesto Fiorentino 50019 , Italy.,Department of Experimental and Clinical Medicine , University of Florence , Florence 50134 Italy
| | - Betti Giusti
- Department of Experimental and Clinical Medicine , University of Florence , Florence 50134 Italy.,Atherothrombotic Diseases Center , Careggi Hospital , Florence 50134 , Italy.,Excellence Centre for Research, Transfer and High Education for the Development of DE NOVO Therapies (DENOTHE) , University of Florence , Florence 50134 , Italy
| | - Serafina Valente
- Department of Experimental and Clinical Medicine , University of Florence , Florence 50134 Italy.,Atherothrombotic Diseases Center , Careggi Hospital , Florence 50134 , Italy.,Excellence Centre for Research, Transfer and High Education for the Development of DE NOVO Therapies (DENOTHE) , University of Florence , Florence 50134 , Italy
| | - Nazario Carrabba
- Department of Cardiovascular and Thoracic Surgery , Careggi Hospital , Florence 50134 , Italy
| | - Daniela Balzi
- Unit of Epidemiology , ASL 10, Florence 50122 , Italy
| | | | - Niccolò Marchionni
- Department of Experimental and Clinical Medicine , University of Florence , Florence 50134 Italy
| | | | - Rossella Marcucci
- Department of Experimental and Clinical Medicine , University of Florence , Florence 50134 Italy.,Atherothrombotic Diseases Center , Careggi Hospital , Florence 50134 , Italy.,Excellence Centre for Research, Transfer and High Education for the Development of DE NOVO Therapies (DENOTHE) , University of Florence , Florence 50134 , Italy
| | - Anna Maria Gori
- Department of Experimental and Clinical Medicine , University of Florence , Florence 50134 Italy.,Atherothrombotic Diseases Center , Careggi Hospital , Florence 50134 , Italy.,Excellence Centre for Research, Transfer and High Education for the Development of DE NOVO Therapies (DENOTHE) , University of Florence , Florence 50134 , Italy
| | - Claudio Luchinat
- Magnetic Resonance Center (CERM) , University of Florence , Sesto Fiorentino 50019 , Italy.,Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (C.I.R.M.M.P.) , Sesto Fiorentino 50019 , Italy.,Department of Chemistry , University of Florence , Sesto Fiorentino 50019 , Italy
| | - Edoardo Saccenti
- Laboratory of Systems and Synthetic Biology , Wageningen University & Research , Wageningen 6708 WE , the Netherlands
| |
Collapse
|
|
17
|
Vignoli A, Santini G, Tenori L, Macis G, Mores N, Macagno F, Pagano F, Higenbottam T, Luchinat C, Montuschi P. NMR-Based Metabolomics for the Assessment of Inhaled Pharmacotherapy in Chronic Obstructive Pulmonary Disease Patients. J Proteome Res 2019; 19:64-74. [PMID: 31621329 DOI: 10.1021/acs.jproteome.9b00345] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The aim of this proof-of-concept, pilot study was the evaluation of the effects of steroid administration and suspension of an inhaled corticosteroid (ICS)-long-acting β2-agonist (LABA) extrafine fixed dose combination (FDC) on metabolomic fingerprints in subjects with chronic obstructive pulmonary disease (COPD). We hypothesized that a comprehensive metabolomics approach discriminates across inhaled pharmacotherapies and that their effects on metabolomic signatures depend on the biological fluids analyzed. We performed metabolomics via nuclear magnetic resonance (NMR) spectroscopy in exhaled breath condensate (EBC), sputum supernatants, serum, and urine. Fourteen patients suffering from COPD who were on regular inhaled fluticasone propionate/salmeterol therapy (visit 1) were consecutively treated with 2-week beclomethasone dipropionate/formoterol (visit 2), 4-week formoterol alone (visit 3), and 4-week beclomethasone/formoterol (visit 4). The comprehensive NMR-based metabolomics approach showed differences across all pharmacotherapies and that different biofluids provided orthogonal information. Serum formate was lower at visits 1 versus 3 (P = 0.03), EBC formate was higher at visit 1 versus 4 (P = 0.03), and urinary 1-methyl-nicotinamide was lower at 3 versus 4 visit (P = 0.002). NMR-based metabolomics of different biofluids distinguishes across inhaled pharmacotherapies, provides complementary information on the effects of an extrafine ICS/LABA FDC on metabolic fingerprints in COPD patients, and might be useful for elucidating the ICS mechanism of action.
Collapse
Affiliation(s)
- Alessia Vignoli
- Magnetic Resonance Center (CERM) , University of Florence , Via Luigi Sacconi 6 , Sesto Fiorentino , Italy 50019.,Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (CIRMMP) , Piazza San Marco 4 , Florence , Italy 50121
| | - Giuseppe Santini
- Department of Pharmacology, Faculty of Medicine, Catholic University of the Sacred Heart, Largo F. Vito, 1, Rome, Italy 00168,Pharmacology Unit, University Hospital Agostino Gemelli Foundation, IRCCS, Largo Agostino Gemelli, 8, Rome, Italy 00168
| | - Leonardo Tenori
- Magnetic Resonance Center (CERM) , University of Florence , Via Luigi Sacconi 6 , Sesto Fiorentino , Italy 50019.,Department of Experimental and Clinical Medicine , University of Florence , Largo Brambilla 3 , Florence , Italy 50100
| | - Giuseppe Macis
- Imaging Diagnostics,University Hospital Agostino Gemelli Foundation, IRCCS, Largo Agostino Gemelli, 8, Rome, Italy 00168
| | - Nadia Mores
- Department of Pharmacology, Faculty of Medicine, Catholic University of the Sacred Heart, Largo F. Vito, 1, Rome, Italy 00168,Pharmacology Unit, University Hospital Agostino Gemelli Foundation, IRCCS, Largo Agostino Gemelli, 8, Rome, Italy 00168
| | - Francesco Macagno
- Respiratory Medicine Unit,University Hospital Agostino Gemelli Foundation, IRCCS, Largo Agostino Gemelli, 8, Rome, Italy 00168
| | - Francesco Pagano
- Ageing Unit, University Hospital Agostino Gemelli Foundation, IRCCS, Largo Agostino Gemelli, 8, Rome, Italy 00168,Department of Internal Medicine and Geriatrics, Faculty of Medicine, Catholic University of the Sacred Heart, Largo F. Vito, 1, Rome, Italy 00168
| | - Tim Higenbottam
- Faculty of Pharmaceutical Medicine , Royal College of Physicians , London NW1 4LE , United Kingdom
| | - Claudio Luchinat
- Magnetic Resonance Center (CERM) , University of Florence , Via Luigi Sacconi 6 , Sesto Fiorentino , Italy 50019.,Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (CIRMMP) , Piazza San Marco 4 , Florence , Italy 50121.,Department of Chemistry "Ugo Schiff" , University of Florence , Via della Lastruccia 3 , Sesto Fiorentino , Italy 50019
| | - Paolo Montuschi
- Department of Pharmacology, Faculty of Medicine, Catholic University of the Sacred Heart, Largo F. Vito, 1, Rome, Italy 00168,Pharmacology Unit, University Hospital Agostino Gemelli Foundation, IRCCS, Largo Agostino Gemelli, 8, Rome, Italy 00168
| |
Collapse
|
|
18
|
|
|
19
|
Sobolev AP, Ciampa A, Ingallina C, Mannina L, Capitani D, Ernesti I, Maggi E, Businaro R, Del Ben M, Engel P, Giusti AM, Donini LM, Pinto A. Blueberry-Based Meals for Obese Patients with Metabolic Syndrome: A Multidisciplinary Metabolomic Pilot Study. Metabolites 2019; 9:metabo9070138. [PMID: 31295937 PMCID: PMC6680695 DOI: 10.3390/metabo9070138] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 07/05/2019] [Accepted: 07/07/2019] [Indexed: 12/23/2022] Open
Abstract
A pilot study was carried out on five obese/overweight patients suffering from metabolic syndrome, with the aim to evaluate postprandial effects of high fat/high glycemic load meals enriched by blueberries. Postprandial urine samples were analyzed by 1H-NMR spectroscopy after 2 and 4 h from ingestion to identify potential markers of blueberry intake. Significant decrease of methylamines, acetoacetate, acetone and succinate, known indicators of type 2 diabetes mellitus, were observed after the intake of meals enriched with blueberries. On the other hand, an accumulation of p-hydroxyphenyl-acetic acid and 3-(3’-hydroxyphenyl)-3-hydropropionic acid originating from gut microbial dehydrogenation of proanthocyanidins and procyanidins was detected. Real-time PCR-analysis of mRNAs obtained from mononuclear blood cells showed significant changes in cytokine gene expression levels after meals integrated with blueberries. In particular, the mRNAs expression of interleukin-6 (IL-6) and Transforming Growth Factor-β (TGF-β), pro and anti-inflammation cytokines, respectively, significantly decreased and increased after blueberry supplementation, indicating a positive impact of blueberry ingestion in the reduction of risk of inflammation. The combined analysis of the urine metabolome and clinical markers represents a promising approach in monitoring the metabolic impact of blueberries in persons with metabolic syndrome.
Collapse
Affiliation(s)
- Anatoly Petrovich Sobolev
- Laboratorio di Risonanza Magnetica "Annalaura Segre", Istituto per i Sistemi Biologici, CNR, via Salaria km 29.300, I-00015 Monterotondo, Italy
| | - Alessandra Ciampa
- Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy
| | - Cinzia Ingallina
- Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy.
| | - Luisa Mannina
- Laboratorio di Risonanza Magnetica "Annalaura Segre", Istituto per i Sistemi Biologici, CNR, via Salaria km 29.300, I-00015 Monterotondo, Italy.
- Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy.
| | - Donatella Capitani
- Laboratorio di Risonanza Magnetica "Annalaura Segre", Istituto per i Sistemi Biologici, CNR, via Salaria km 29.300, I-00015 Monterotondo, Italy
| | - Ilaria Ernesti
- Sezione di Fisiopatologia Medica, Scienza dell'Alimentazione ed Endocrinologia - Dipartimento di Medicina Sperimentale, Sapienza Università di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy
| | - Elisa Maggi
- Dipartimento di Scienze e Biotecnologie medico-chirurgiche, Sapienza Università di Roma, Corso della Repubblica 79, 04100 Latina, Italy
| | - Rita Businaro
- Dipartimento di Scienze e Biotecnologie medico-chirurgiche, Sapienza Università di Roma, Corso della Repubblica 79, 04100 Latina, Italy
| | - Maria Del Ben
- Dipartimento di Medicina Interna e Specialità Mediche, Policlinico Umberto 1 Sapienza Università di Roma, viale del Policlinico 151, I-00185, Roma, Italy
| | - Petra Engel
- Consiglio per la Ricerca in Agricoltura e l'Analisi dell'Economia Agraria (CREA), Ufficio Rapporti Istituzionali e Relazioni Internazionali, Via Po 14, 00198 Roma, Italy
| | - Anna Maria Giusti
- Sezione di Fisiopatologia Medica, Scienza dell'Alimentazione ed Endocrinologia - Dipartimento di Medicina Sperimentale, Sapienza Università di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy
| | - Lorenzo M Donini
- Sezione di Fisiopatologia Medica, Scienza dell'Alimentazione ed Endocrinologia - Dipartimento di Medicina Sperimentale, Sapienza Università di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy
| | - Alessandro Pinto
- Sezione di Fisiopatologia Medica, Scienza dell'Alimentazione ed Endocrinologia - Dipartimento di Medicina Sperimentale, Sapienza Università di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy
| |
Collapse
|
|
20
|
Luo L, Kang J, He Q, Qi Y, Chen X, Wang S, Liang S. A NMR-Based Metabonomics Approach to Determine Protective Effect of a Combination of Multiple Components Derived from Naodesheng on Ischemic Stroke Rats. Molecules 2019; 24:molecules24091831. [PMID: 31086027 PMCID: PMC6539225 DOI: 10.3390/molecules24091831] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Revised: 04/24/2019] [Accepted: 05/10/2019] [Indexed: 12/27/2022] Open
Abstract
Naodesheng (NDS) is a widely used traditional Chinese medicine (TCM) prescription for the treatment of ischemic stroke. A combination of 10 components is derived from NDS. They are: Notoginsenoside R1, ginsenoside Rg1, ginsenoside b1, ginsenoside Rd, hydroxysafflor yellow A, senkyunolide I, puerarin, daidzein, vitexin, and ferulic acid. This study aimed to investigate the protective effect of the ten-component combination derived from NDS (TCNDS) on ischemic stroke rats with a middle cerebral artery occlusion (MCAO) model by integrating an NMR-based metabonomics approach with biochemical assessment. Our results showed that TCNDS could improve neurobehavioral function, decrease the cerebral infarct area, and ameliorate pathological features in MCAO model rats. In addition, TCNDS was found to decrease plasma lactate dehydrogenase (LDH) and malondialdehyde (MDA) production and increase plasma superoxide dismutase (SOD) production. Furthermore, 1H-NMR metabonomic analysis indicated that TCNDS could regulate the disturbed metabolites in the plasma, urine, and brain tissue of MCAO rats, and the possible mechanisms were involved oxidative stress, energy metabolism, lipid metabolism, amino acid metabolism, and inflammation. Correlation analysis were then performed to further confirm the metabolites involved in oxidative stress. Correlation analysis showed that six plasma metabolites had high correlations with plasma LDH, MDA, and SOD. This study provides evidence that an NMR-based metabonomics approach integrated with biochemical assessment can help to better understand the underlying mechanisms as well as the holistic effect of multiple compounds from TCM.
Collapse
Affiliation(s)
- Lan Luo
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
- Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administrationof TCM, Guangdong Pharmaceutical University, Guangzhou 510006, China.
- Engineering & Technology Research Center for Chinese Materia Medica Quality of the Universities of Guangdong Province, Guangdong Pharmaceutical University, Guangzhou 510006, China.
| | - Jiazhen Kang
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
- Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administrationof TCM, Guangdong Pharmaceutical University, Guangzhou 510006, China.
- Engineering & Technology Research Center for Chinese Materia Medica Quality of the Universities of Guangdong Province, Guangdong Pharmaceutical University, Guangzhou 510006, China.
| | - Qiong He
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
- Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administrationof TCM, Guangdong Pharmaceutical University, Guangzhou 510006, China.
- Engineering & Technology Research Center for Chinese Materia Medica Quality of the Universities of Guangdong Province, Guangdong Pharmaceutical University, Guangzhou 510006, China.
| | - Yue Qi
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
- Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administrationof TCM, Guangdong Pharmaceutical University, Guangzhou 510006, China.
- Engineering & Technology Research Center for Chinese Materia Medica Quality of the Universities of Guangdong Province, Guangdong Pharmaceutical University, Guangzhou 510006, China.
| | - Xingyu Chen
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
- Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administrationof TCM, Guangdong Pharmaceutical University, Guangzhou 510006, China.
- Engineering & Technology Research Center for Chinese Materia Medica Quality of the Universities of Guangdong Province, Guangdong Pharmaceutical University, Guangzhou 510006, China.
| | - Shumei Wang
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
- Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administrationof TCM, Guangdong Pharmaceutical University, Guangzhou 510006, China.
- Engineering & Technology Research Center for Chinese Materia Medica Quality of the Universities of Guangdong Province, Guangdong Pharmaceutical University, Guangzhou 510006, China.
| | - Shengwang Liang
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
- Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administrationof TCM, Guangdong Pharmaceutical University, Guangzhou 510006, China.
- Engineering & Technology Research Center for Chinese Materia Medica Quality of the Universities of Guangdong Province, Guangdong Pharmaceutical University, Guangzhou 510006, China.
| |
Collapse
|
|
21
|
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: 249] [Impact Index Per Article: 41.5] [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.
Collapse
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
| |
Collapse
|
|
22
|
Vignoli A, Orlandini B, Tenori L, Biagini MR, Milani S, Renzi D, Luchinat C, Calabrò AS. Metabolic Signature of Primary Biliary Cholangitis and Its Comparison with Celiac Disease. J Proteome Res 2019; 18:1228-1236. [PMID: 30539636 DOI: 10.1021/acs.jproteome.8b00849] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by ongoing inflammatory destruction of the interlobular bile ducts, eventually leading to chronic cholestasis and biliary cirrhosis. This study primarily aims to define the metabolomic signature of PBC after comparison with healthy controls (HC). Second, it aims to evaluate the possible metabolic association between PBC and celiac disease (CD), an immune-mediated disorder frequently associated with PBC. Serum and urine samples from 20 PBC, 21 CD, and 19 sex-matched HC subjects were collected. 1H nuclear magnetic resonance (NMR) spectra for all samples were acquired, and multivariate statistics were used to evaluate the differences among the three groups and to provide information about the involved metabolites. The classification accuracies to discriminate PBC and HC groups were 78.9-84.6% for serum and 76.9% for urine. In comparison to HC, PBC patient sera were characterized by altered levels ( p value <0.05) of pyruvate, citrate, glutamate, glutamine, serine, tyrosine, phenylalanine, and lactate. PBC patient urine showed lower levels ( p value <0.05) of trigonelline and hippurate with respect to HC. Furthermore, the NMR metabolomic fingerprint was able to cluster PBC with respect to CD patients, and the classification accuracies in the discriminations between these groups were 81.9-91.7% for serum and 77.7% for urine. Our results show that PBC displays a unique metabolomic fingerprint, which led to speculation about an impaired energy metabolism, probably associated with an altered gut microbiota. PBC and CD showed two distinct metabolic fingerprints. These data could provide clues for the comprehension of the PBC pathogenetic mechanisms and the detection of novel therapeutic targets.
Collapse
Affiliation(s)
- Alessia Vignoli
- Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (C.I.R.M.M.P.) , Sesto Fiorentino , 50019 Italy
| | - Beatrice Orlandini
- Department of Experimental and Clinical Biomedical Sciences , University of Florence , Florence , 50139 Italy
| | - Leonardo Tenori
- Department of Experimental and Clinical Medicine , University of Florence , Florence , 50139 Italy.,Magnetic Resonance Center (CERM) , University of Florence , Sesto Fiorentino , 50019 Italy
| | - Maria Rosa Biagini
- Department of Experimental and Clinical Biomedical Sciences , University of Florence , Florence , 50139 Italy
| | - Stefano Milani
- Department of Experimental and Clinical Biomedical Sciences , University of Florence , Florence , 50139 Italy
| | - Daniela Renzi
- Department of Experimental and Clinical Biomedical Sciences , University of Florence , Florence , 50139 Italy.,Tuscany Referral Center for Adult Coeliac Disease , Florence , 50139 Italy
| | - Claudio Luchinat
- Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (C.I.R.M.M.P.) , Sesto Fiorentino , 50019 Italy.,Magnetic Resonance Center (CERM) , University of Florence , Sesto Fiorentino , 50019 Italy.,Department of Chemistry , University of Florence , Sesto Fiorentino , 50019 Italy
| | - Antonino Salvatore Calabrò
- Department of Experimental and Clinical Biomedical Sciences , University of Florence , Florence , 50139 Italy.,Tuscany Referral Center for Adult Coeliac Disease , Florence , 50139 Italy
| |
Collapse
|
|
23
|
Vignoli A, Tenori L, Giusti B, Takis PG, Valente S, Carrabba N, Balzi D, Barchielli A, Marchionni N, Gensini GF, Marcucci R, Luchinat C, Gori AM. NMR-based metabolomics identifies patients at high risk of death within two years after acute myocardial infarction in the AMI-Florence II cohort. BMC Med 2019; 17:3. [PMID: 30616610 PMCID: PMC6323789 DOI: 10.1186/s12916-018-1240-2] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Accepted: 12/14/2018] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Risk stratification and management of acute myocardial infarction patients continue to be challenging despite considerable efforts made in the last decades by many clinicians and researchers. The aim of this study was to investigate the metabolomic fingerprint of acute myocardial infarction using nuclear magnetic resonance spectroscopy on patient serum samples and to evaluate the possible role of metabolomics in the prognostic stratification of acute myocardial infarction patients. METHODS In total, 978 acute myocardial infarction patients were enrolled in this study; of these, 146 died and 832 survived during 2 years of follow-up after the acute myocardial infarction. Serum samples were analyzed via high-resolution 1H-nuclear magnetic resonance spectroscopy and the spectra were used to characterize the metabolic fingerprint of patients. Multivariate statistics were used to create a prognostic model for the prediction of death within 2 years after the cardiovascular event. RESULTS In the training set, metabolomics showed significant differential clustering of the two outcomes cohorts. A prognostic risk model predicted death with 76.9% sensitivity, 79.5% specificity, and 78.2% accuracy, and an area under the receiver operating characteristics curve of 0.859. These results were reproduced in the validation set, obtaining 72.6% sensitivity, 72.6% specificity, and 72.6% accuracy. Cox models were used to compare the known prognostic factors (for example, Global Registry of Acute Coronary Events score, age, sex, Killip class) with the metabolomic random forest risk score. In the univariate analysis, many prognostic factors were statistically associated with the outcomes; among them, the random forest score calculated from the nuclear magnetic resonance data showed a statistically relevant hazard ratio of 6.45 (p = 2.16×10-16). Moreover, in the multivariate regression only age, dyslipidemia, previous cerebrovascular disease, Killip class, and random forest score remained statistically significant, demonstrating their independence from the other variables. CONCLUSIONS For the first time, metabolomic profiling technologies were used to discriminate between patients with different outcomes after an acute myocardial infarction. These technologies seem to be a valid and accurate addition to standard stratification based on clinical and biohumoral parameters.
Collapse
Affiliation(s)
- Alessia Vignoli
- Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy.,Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine - C.I.R.M.M.P, Sesto Fiorentino, Italy
| | - Leonardo Tenori
- Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy.,Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Betti Giusti
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. .,Careggi Hospital, Florence, Italy.
| | | | | | | | | | | | - Niccolò Marchionni
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.,Careggi Hospital, Florence, Italy
| | | | - Rossella Marcucci
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.,Careggi Hospital, Florence, Italy
| | - Claudio Luchinat
- Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy.,Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine - C.I.R.M.M.P, Sesto Fiorentino, Italy.,Department of Chemistry, University of Florence, Sesto Fiorentino, Italy
| | - Anna Maria Gori
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.,Careggi Hospital, Florence, Italy
| |
Collapse
|
|
24
|
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
| |
Collapse
|
|
25
|
Metabolomics of Hydrazine-Induced Hepatotoxicity in Rats for Discovering Potential Biomarkers. DISEASE MARKERS 2018; 2018:8473161. [PMID: 29849827 PMCID: PMC5914126 DOI: 10.1155/2018/8473161] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Accepted: 11/20/2017] [Indexed: 01/05/2023]
Abstract
Metabolic pathway disturbances associated with drug-induced liver injury remain unsatisfactorily characterized. Diagnostic biomarkers for hepatotoxicity have been used to minimize drug-induced liver injury and to increase the clinical safety. A metabolomics strategy using rapid-resolution liquid chromatography/tandem mass spectrometry (RRLC-MS/MS) analyses and multivariate statistics was implemented to identify potential biomarkers for hydrazine-induced hepatotoxicity. The global serum and urine metabolomics of 30 hydrazine-treated rats at 24 or 48 h postdosing and 24 healthy rats were characterized by a metabolomics approach. Multivariate statistical data analyses and receiver operating characteristic (ROC) curves were performed to identify the most significantly altered metabolites. The 16 most significant potential biomarkers were identified to be closely related to hydrazine-induced liver injury. The combination of these biomarkers had an area under the curve (AUC) > 0.85, with 100% specificity and sensitivity, respectively. This high-quality classification group included amino acids and their derivatives, glutathione metabolites, vitamins, fatty acids, intermediates of pyrimidine metabolism, and lipids. Additionally, metabolomics pathway analyses confirmed that phenylalanine, tyrosine, and tryptophan biosynthesis as well as tyrosine metabolism had great interactions with hydrazine-induced liver injury in rats. These discriminating metabolites might be useful in understanding the pathogenesis mechanisms of liver injury and provide good prospects for drug-induced liver injury diagnosis clinically.
Collapse
|