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29 results for “Serum Metabolomics”
Impact of Short-term Fructose-enriched Diet on Serum Metabolome by Normal- and Over-weighed Women.
ClinicalTrials.gov study NCT03444233. IPD Sharing: UNDECIDED. Countries: 0. Publications: 0.
Establishment and Validation of an Early Diagnostic Model for Bladder Cancer Based on Serum and Urine Metabolomics
ClinicalTrials.gov study NCT04966962. IPD Sharing: Not stated. Countries: 0. Publications: 0.
Inhaled Ozone (O3)-Induces Changes in Serum Metabolomic and Liver Transcriptomic Profiles in Rats
GEO Series GSE59329. Rattus norvegicus. 32 samples. Type: Expression profiling by array.
NMR based serum metabolomics analysis revealed similar serum metabolic alterations in Ischemic and Hemorrhagic Stroke patients
<p><strong>Background and Objective: </strong>Brain stroke (caused by interrupted blood supply to the brain) is one of the most common causes of disability and is the second highest cause of death in the world. Early diagnosis and treatment raises the chance of surviving a stroke, and can result in little or no disability. Treatment is based on the type of stroke and its primary cause; for ischaemic stroke (IS), medication or surgery or both can be recommended, whereas, for haemorrhagic stroke (HS, also known as intracerebral hemorrhage), surgery is recommended. However, there are scarcity of clinical markers which can differentiate IS from HS and further can provide information about severity of cerebral ischemia, endothelial injury, blood–brain barrier disruption, atherosclerosis, thrombus formation, inflammation, and oxidative stress. Metabolomics is a promising approach for identification of metabolic biomarkers and alterations associated with the diseased biology The present study is an effort to identify the diagnostic panel of serum metabolic profiles to differentiate between IS and HS patients and further could help predicting the severity of the cerebral ischemia. <strong>Methods:</strong> Blood serum samples were collected from suspected brain stroke patients at hospital admission within 6 hours after onset. The serum samples of patients clinically confirmed for IS and HS were only analysed using 800 MHz NMR spectroscopy. For comparative evaluation, the serum samples from 60 age and sex matched normal control (NC) subjects were also obtained for NMR analysis. The partial least square-discriminant analysis (PLS-DA) was performed to confirm the serum metabolic disparity between the study groups and metabolic features of discriminatory relevance were identified making composite use of mean decrease accuracy (MDA) score values estimated for metabolic features employing machine learning random forest (RF) classification analysis. The diagnostic potential of discriminatory metabolites were finally evaluated using receiver operating characteristic (ROC) curve analysis. <strong>Results</strong>: The serum metabolic profiles of total 107 brain stroke patients (48 IS and 60 HS) were measured and compared with those of 60 age and sex matched normal control (NC) subjects. Compared to NC, the serum levels of various amino acids (histidine, glutamine, threonine, alanine, glycine, dimethylglycine, pyruvate, etc.) were found to be decreased in both HS and IS patients, whereas those of creatine, mannitol, mannose, malonate and organic acids (such as acetate, 3-hydroxybutyrate and 3-hydroxy-isobutyrate) were found to be increased in the sera of brain stroke patients. However, the area under ROC (AUROC) curve values for majority of metabolic features found to be less than 0.8 for the discrimination between IS and HS suggesting that circulatory metabolic features lack sufficient sensitivity and specificity. <strong>Conclusions:</strong> The study provided primary evidence that various circulatory metabolites (including histidine, glutamine, and alanine) exhibited strong diagnostic potential for distinguishing brain stroke condition from NC subject, however, poor diagnostic accuracy in distinguishing IS from HS. Nevertheless, these metabolic changes can be used to assess the severity of brain stroke condition and monitoring patient response to treatment in emergency settings.</p>
Serum based clinical metabolomics analysis by NMR revealed abnormalities in mannose and myo-inositol metabolism in Scleroderma
<p><strong>Background and hypothesis</strong></p> <p>Systemic sclerosis (SSc) is a chronic autoimmune disorder characterized by fibrosis of the skin and internal organs, as well as vascular damage. Recent research has suggested that abnormal metabolism of certain sugars, such as mannose and myo-inositol, may contribute to the development and progression of SSc. Clinical studies have found that SSc patients have increased mannose and decreased myoinositol levels in their blood plasma/serum samples compared to those of healthy controls, suggesting that abnormal mannose and myoinositol metabolism may contribute to SSc pathogenesis. However, further research on patient cohorts of different ethnicity is imperative to validate these findings and understanding the mechanisms underlying these metabolic abnormalities and to develop new therapies that target these pathways. The present hypothesis-free NMR based clinical metabolomics study is an effort in this direction to compare the circulatory levels of mannose, myo-inositol and other endogenous metabolites in the sera of scleroderma patients and control subjects so that to validate the proposed abnormalities in mannose and myo-inositol metabolic pathways and association between them. The selected metabolic features and the metabolic ratio i.e. myo-inositol to mannose ratio (MMR) were further evaluated for their clinical potential in diagnostic and prognostic screening. <strong>Methods: </strong>The serum sample from 83 SSc patients meeting ACR 1980 criteria for Systemic Sclerosis, and 43 age and sex matched normal controls, were analyzed using one dimensional (1D) <sup>1</sup>H NMR spectroscopy coupled with multivariate statistical analysis such as Partial Least Square-Discriminate Analysis (PLS-DA). The NMR spectra were analysed using NMR suite of commercial software CHENOMX (www.chenomx.com/) and the metabolic concentrations were measured with respect to endogenous metabolite formate (as an internal calibration standard and concentration was set to 30 µM). For evaluating serum metabolic disparity between the study groups, the machine learning model was generated using random forest (RF) classification method and the Mean decrease accuracy (MDA) scores were used to identify the distinctive metabolic abnormalities in SSc. Univariate receiver operator characteristic (ROC) curve analysis was used to evaluate the diagnostic potential of the selected metabolic features. <strong>Results: </strong>There was clear distinction between SSc and healthy controls on the PLS-DA score plots and aberrant metabolic changes were evident in the sera of SSc patients. The sera of SSc patients were characterized by decreased serum levels of alanine, valine, <strong>myoinositol</strong>, creatinine, pyruvate, and lactate; whereas the serum levels of, acetate, 3-hydroxybutyrate and <strong>mannose</strong> were found to be significantly elevated. The majority of these metabolic alterations found to be well consistence with those reported previously in other clinical metabolomics studies [1,2]. Further, the circulatory MMR levels were estimated as [Myo-inositol/ Mannose] and compared between the study groups. Like myo-inositol, the MMR levels were also found to be significantly decreased in SSc patients. <strong>Conclusion: </strong>The altered levels of myo-inositol and other endogenous metabolites in the sera of SSc patients suggested abnormalities in myo-inositol metabolism in SSc patients and future studies are warranted to underscore its role in the pathobiology of scleroderma.</p> <p><strong>References:</strong></p> <p><strong>[1] </strong>Federica Murgia, Silvia Svegliati, Simone Poddighe, Milena Lussu, Aldo Manzin, Tatiana Spadoni, Colomba Fischetti, Armando Gabrielli, and Luigi Atzori. "Metabolomic profile of systemic sclerosis patients." Scientific Reports 8, no. 1 (2018): 7626.</p> <p><strong>[2].</strong> Thomas Bögl, Franz Mlynek, Markus Himmelsbach, Norbert Sepp, Wolfgang Buchberger, and Marija Geroldinger-Simić. "Plasma metabolomic profiling reveals four possibly disrupted mechanisms in systemic sclerosis." Biomedicines 10, no. 3 (2022): 607.</p>
Elevated circulatory proline to glutamine ratio (PQR) in Patients with endometriosis revealed by targeted NMR based serum metabolomics
<p>Endometriosis (EM) is a chronic pain condition affecting women in reproductive age and involves the growth of uterine lining (endometrium) outside of the uterus. EM is often associated with altered inflammatory and immune processes and shares some cancer-like characteristics such as activated glutaminolysis. However, preclinical studies suggest mitochondrial dysfunction and decreased energy production in uterine endometriosis tissue. As proline catabolism in mitochondria serve as an important source of energy production and previous transcriptomics studies have demonstrated that there is reduced activity of proline oxidase (POX, a mitochondrial inner-membrane flavoenzyme involved in the catabolic degradation of the proline) due to overexpression of microRNA (known as MiR-23b). Based on this, we hypothesized and demonstrated that circulatory proline to glutamine ratio (PQR) are elevated in the EM patients and may serve as an indicative biomarker to improve the clinical diagnosis of EM. </p>
Metabolic disparity between Cord serum and amniotic fluid revealed by 1H NMR based metabolomics approach
<p>During pregnancy, a developing fetus (within amniotic sac and connected to the placenta through umbilical cord) is surrounded by a viscous yellowish amniotic fluid. After delivery, umbilical cord blood is collected as it contains stem cells which can be used as intervention of major hematopoietic or genetic disorders. The amniotic fluid is also used to diagnose the genetic disorders in developing fetus which may also have impact on the metabolic profiles of amniotic fluid. The present study has been designed to identify and quantify the concentration profiles of metabolites present in the cord blood and amniotic fluid. For this, 21 samples of cord blood serum and amniotic fluid were collected in pair and metabolic profiles were measured using 1D 1H CPMG NMR spectroscopy and compared using multivariate statistical analysis tools. The analytical variations have been minimized using formate as an internal reference and its concentration was set to 0.01 mM (nearly close to the detection limit of the 800 MHz NMR spectrometer).</p>
Dataset related to article "A 'Multiomic' Approach of Saliva Metabolomics, Microbiota, and Serum Biomarkers to Assess the Need of Hospitalization in COVID-19"
<p>*These authors contributed equally to the work<sup> #</sup>Corresponding author</p> <p>This record contains raw data related to article “A ‘Multiomic’ Approach of Saliva Metabolomics, Microbiota, and Serum Biomarkers to Assess the Need of Hospitalization in COVID-19"</p> <p>Abstract:</p> <p>The SARS-CoV-2 pandemic has overwhelmed the treatment capacity of the healthcare systems during the highest viral diffusion rate. Patients reaching the emergency department had to be either hospitalized or discharged. Still, the decision was taken based on the individual assessment of the actual clinical condition, without specific biomarkers to predict future improvement or deterioration. Often discharged patients returned to the hospital for aggravation of their condition. Here we have developed a new combined approach of omics to identify factors that could distinguish COVID-19 inpatients from outpatients. We tested the metabolome in the saliva and identified nine metabolites that separated the inpatient from the outpatient population, but not completely. When combined with serum biomarkers, just two salivary metabolites (myo-inositol and 2-pyrollidine acetic acid) and one serum protein, Chitinase 3-like-1(CHI3L1) were sufficient to separate the two groups completely. These metabolites positively or negatively correlated with four modulated microbiota taxa. This is a proof-of-concept that a combined omic analysis can be used to stratify patients.</p>
Serum metabolic disparity between pulmonary Sarcoidosis (SAR) and Tuberculosis (TB) revealed by NMR based metabolomics study
<p>Tuberculosis (TB) -a pulmonary granulomatous disease- is the leading cause of death worldwide from a single infectious disease agent especially in developing countries such as India. Current diagnostic methodologies often lack specificity and sensitivity; therefore, there is an immense clinical interest to investigate alternative biomarker signatures for obtaining a conclusive and suggestive diagnosis of TB. Particular challenge arises for treating physicians while differentiating TB from sarcoidosis (SAR) which is an uncommon granulomatous disease and shares the similar clinical, radiological and pathological features with TB. Symptoms common in TB such as cough, fever, fatigue, and weight-loss are often manifested in sarcoidosis as well. As India accounts for more than 26% of global burden of TB cases and epidemiological data about sarcoidosis is unknown, most of the sarcoidosis patients end up receiving anti tubercular therapy (ATT) erroneously, leading to delayed proper treatment and considerable risk of drug induced toxicity, whereas lung damage continues to progress in this backdrop. Therefore, there is an urgent unmet need to identify non-invasive biomarker(s) for differentiating sarcoidosis from TB. Metabolomics analysis of serum holds great potential to provide distinctive patterns of metabolic profiles relevant to underlying disease processes and thus may aid in rapid clinical diagnosis and guiding appropriate treatment.</p> <p>Starting our efforts in this direction, the serum metabolic profiles of sarcoidosis and active TB patients were measured using 800 MHz NMR Spectroscopy and compared using the multivariate and univariate statistical analysis tools. The partial least square discriminatory analysis (PLS-DA) revealed significant serum metabolic disparity between SAR and TB with respect to normal control subjects [1-5]. Compared to SAR, the sera of TB patients were characterized by (a) elevated levels of lactate, acetate, 3-hydroxybutyrate (3HB), glutamate and succinate (b) decreased levels of glucose, citrate, pyruvate, glutamine, and various lipid and membrane metabolites (such as very-low/low density lipoproteins (VLDL/LDL), polyunsaturated fatty acids, etc.).</p> <p>The altered circulatory levels of glucose (decreased) and lactate (increased) were found well consistent with previous report [6] demonstrating that infection with Mycobacterium tuberculosis (MTb) induces the Warburg effect in mouse lungs. A very recent study reported increased production of glutamate from mitochondrial glutaminolysis and pleiotropic roles of glutamine metabolism in the metabolic reprogramming of MTb infected M1-like macrophages [7]. A previous study published in Science [8] reported the suppression of oxidative stress by 3HB. Another study published in scientific report demonstrated that of <em>Mycobacterium tuberculosis</em> (MTb) secretory protein ESAT-induces GLUT-1 mediated enhanced glucose uptake by macrophages and increased fatty acid biosynthesis (to drive foamy macrophage differentiation) which in turn results in release of 3HB in the extracellular environment [9]. Based on previously reported metabolic derangements in MTb infected systems and our results derived from NMR-based serum metabolomics, the following remarks have been drawn:</p> <ul> <li><strong>Active TB infection </strong>induces Warburg effect as inferred from the decreased serum levels of glucose and elevated levels of lactate</li> <li><strong>Active TB infection </strong>causes increased biosynthesis of fatty acids as inferred from the decreased serum levels of citrate and increased levels of acetate and 3-Hydroxybutyrate (3-HB)</li> <li><strong>Active TB infection </strong>manipulates oxidative stress (OS) induced pathogen killing host-defense mechanism as inferred from decreased circulatory phenylalanine-to-tyrosine ratio (PTR) and 3HB (known to suppress OS)</li> <li><strong>Active TB infection </strong>induces augmented utilization of glutamine (an immunomodulatory nutrient) as inferred from the decreased serum levels of glutamine and increased serum levels of glutamate and succinate</li> <li><strong>Active TB infection </strong>induces dyslipidemia as inferred from the decreased NMR signals of very-low/low density lipoproteins (VLDL/LDL) and polyunsaturated fatty acids (PUFAs)</li> </ul> <p><strong>References:</strong></p> <ol> <li>Dinesh Kumar, Ritu Raj, Avinash Jain , Anupam Guleria, Umesh Kumar, Mohit K Rai, Harshit Singh, Saurabh Chaturvedi, Alok Nath, Durga P Misra and Vikas Agarwal, “Serum based metabolomics analysis revealed highly sensitive and specific panel of metabolic markers for differential diagnosis of Pulmonary Sarcoidosis and Tuberculosis” (Conference paper presented during IRACON-2018). F1000Research 2019, 8:304 (DOI: 10.7490/f1000research.1116481.1)</li> <li>Dinesh Kumar, Avinash Jain, Amit Kumar, Anupam Guleria, Ritu Raj, Harshit Singh, Mohit K Rai, Saurabh Chaturvedi, Alok Nath, Durga P Misra, and Vikas Agarwal, “Targeted nuclear magnetic resonance-based serum metabolomics analysis revealed significantly higher phenylalanine/tyrosine ratio in pulmonary sarcoidosis patients compared to tuberculosis patients”, (Conference Paper selected for Oral Presentation in IRACON 2018: OPC0034) Indian J Rheumatol (2018), vol 13 (Issue 6) Suppl S2:79-92 (DOI: 10.4103/0973-3698.247335)</li> <li>Avinash Jain, Amit Kumar, Harshit Singh, Mohit Kumar Rai, Saurabh Chaturvedi, Anupam Guleria, Alok Nath, Dinesh Kumar, Durga Prasanna Misra, and Vikas Agarwal, “Nuclear magnetic resonance (NMR) based Serum Metabolomics in Sarcoidosis and Tuberculosis – Search for a Biomarker”, (Received Best Oral Award) (Conference Paper selected for Oral Presentation in IRACON 2018: OPC0030) Indian J Rheumatol (2018), vol 13 (Issue 6) Suppl S2:79-92 (DOI: 10.4103/0973-3698.247335).</li> <li>Dinesh Kumar, Avinash Jain, Amit Kumar, Anupam Guleria, Alok Nath, Durga Prasanna Misra, Vikas Agarwal, “Diagnostic panel of biomarkers for the assessment of sarcoidosis and tuberculosis identified using NMR based serum metabolomics approach” (Poster Presented during BSRAC-2018) F1000Research (2018), 7:18 (doi: 10.7490/f1000research.1115194.1)</li> <li>Avinash Jain, Amit Kumar, Harshit Singh, Mohit K Rai, Saurabh Chaturvedi, Anupam Guleria, Alok Nath, Dinesh Kumar, Durga P Misra and Vikas Agarwal, “Nuclear magnetic resonance (NMR) based serum metabolomics in sarcoidosis and tuberculosis: search for a biomarker” (Poster Presentation during British Society for Rheumatology Annual Conference 2018 | BSRAC-2018) Rheumatology (April 2018), Vol 57, Issue suppl_3 (DOI: 10.1093/rheumatology/key075.338).</li> <li>Shi, L., Salamon, H., Eugenin, E.A., Pine, R., Cooper, A. and Gennaro, M.L., 2015. Infection with Mycobacterium tuberculosis induces the Warburg effect in mouse lungs. Scientific reports, 5(1), pp.1-13.</li> <li>Jiang, Qingkui, and Lanbo Shi. "Coordination of the uptake and metabolism of amino acids in Mycobacterium tuberculosis-infected macrophages." Frontiers in Immunology 12 (2021).</li> <li>Shimazu, T., Hirschey, M.D., Newman, J., He, W., Shirakawa, K., Le Moan, N., Grueter, C.A., Lim, H., Saunders, L.R., Stevens, R.D. and Newgard, C.B., 2013. Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. <em>Science</em>, <em>339</em>(6116), pp.211-214.</li> <li>Singh, V., Kaur, C., Chaudhary, V.K., Rao, K.V. and Chatterjee, S., 2015. M. tuberculosis secretory protein ESAT-6 induces metabolic flux perturbations to drive foamy macrophage differentiation. <em>Scientific reports</em>, <em>5</em>(1), pp.1-12.</li> </ol>
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