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1.
Specific sweat metabolite profile in ocular Behcet's disease.
Cui, X, Zhang, L, Su, G, Kijlstra, A, Yang, P
International immunopharmacology. 2021;:107812
Abstract
BACKGROUND Behcet's disease (BD) is an autoimmune disorder with the serious possibility of blindness, calling for further research on its pathogenesis. Our aim was to study the metabolite composition of sweat in BD and to identify possible biomarkers. METHODS Metabolomics analysis was performed on sweat samples from 20 BD patients and 18 normal controls by liquid chromatography tandem mass spectrometry. RESULTS A significantly different metabolic profile of sweat was observed when BD patients were compared with healthy controls. The result of the orthogonal partial least squared-discrimination analysis (OPLS-DA) showed that these two comparison groups could be separated with a relatively satisfactory fitting degree (R2Y = 0.995 and Q2 = 0.817 in positive ion mode; R2Y = 0.991 and Q2 = 0.721 in negative ion mode). Based on OPLS-DA, a panel of metabolites was selected as candidate biomarkers, including l-citrulline, l-pyroglutamic acid, urocanic acid, 2-oxoadipic acid, cholesterol 3-sulfate, and pentadecanoic acid. CONCLUSION This is the first report on the metabolite profile of sweat in BD. Our results demonstrated a significantly different metabolite composition of sweat in BD compared to that of healthy controls.
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2.
Effect of early time-restricted feeding on the metabolic profile of adults with excess weight: A systematic review with meta-analysis.
Pureza, IROM, Macena, ML, da Silva Junior, AE, Praxedes, DRS, Vasconcelos, LGL, Bueno, NB
Clinical nutrition (Edinburgh, Scotland). 2021;(4):1788-1799
Abstract
BACKGROUND & AIMS Time-restricted feeding (TRF) studies have been summarized in previous systematic reviews, but these were not specific for individuals with excess weight and studies involving early time-restricted feeding (eTRF). This meta-analysis aimed to evaluate the effect of eTRF on the metabolic profile of adults with excess weight. METHODS Data were extracted from MEDLINE, CENTRAL, LILACS, Web of Science, ClinicalTrials.gov, OpenGrey.eu, Greylit, and by manual search. Randomized controlled trials in which the participants were older than 18 years, with a body mass index greater than 25 kg/m2 and that were allocated in an intervention with eTRF were included. The studies should have assessed any of the following outcomes from the metabolic profile: resting metabolic rate, triacylglycerol, total cholesterol, HDL-cholesterol, and LDL-cholesterol, fasting blood glucose, insulin, HOMA-IR, C-reactive protein, Interleukin-6, cortisol, leptin, Ghrelin, Peptide YY and glucagon-like peptide, hemodynamic parameters, and appetite. The risk of bias was assessed using the Cochrane collaboration tool. Publication bias was examined with a funnel plot and Egger's test. GRADE was used to assess the overall quality of evidence. RESULTS Ten articles from nine randomized clinical trials, with 264 individuals, were included in qualitative analysis and eight articles with 184 individuals were included in the meta-analysis. There were significant effects on the fasting blood glucose (WMD: -2.75; 95% CI [-4.59; -0.90] mg/dL; p < 0.01; I2 = 88.7%; 7 studies) and HOMA-IR. (WMD: -0.50; 95% CI [-0.82; -0.19]; p < 0.01; I2 = 50.8%; 4 studies). The other outcomes were not significant. Three studies showed a high risk of bias. Seven outcomes were classified as very low quality and one as low quality. There was evidence of publication bias for fasting blood glucose. CONCLUSIONS Although the eTRF regimen seems to have a beneficial effect on the fasting blood glucose and HOMA-IR of individuals with excess weight, the results of this meta-analysis should be analyzed with caution due to the low-quality evidence.
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3.
Cellular Bioenergetic and Metabolic Changes in Patients with Autism Spectrum Disorder.
Gevezova, M, Minchev, D, Pacheva, I, Sbirkov, Y, Yordanova, R, Timova, E, Kotetarov, V, Ivanov, I, Sarafian, V
Current topics in medicinal chemistry. 2021;(11):985-994
Abstract
BACKGROUND Although Autism Spectrum Disorder (ASD) is considered a heterogeneous neurological disease in childhood, a growing body of evidence associates it with mitochondrial dysfunction explaining the observed comorbidities. INTRODUCTION The aim of this study is to identify variations in cellular bioenergetics and metabolism dependent on mitochondrial function in ASD patients and healthy controls using Peripheral Blood Mononuclear Cells (PBMCs). We hypothesized that PBMCs may reveal the cellular pathology and provide evidence of bioenergetic and metabolic changes accompanying the disease. METHODS PBMC from children with ASD and a control group of the same age and gender were isolated. All patients underwent an in-depth clinical evaluation. A well-characterized cohort of Bulgarian children is selected. Bioenergetic and metabolic studies of isolated PBMCs are performed with a Seahorse XFp analyzer. RESULTS Our data show that PBMCs from patients with ASD have increased respiratory reserve capacity (by 27.5%), increased maximal respiration (by 67%) and altered adaptive response to oxidative stress induced by DMNQ. In addition, we demonstrate а strong dependence on fatty acids and impaired ability to reprogram cell metabolism. The listed characteristics are not observed in the control group. These results can contribute to a better understanding of the underlying causes of ASD, which is crucial for selecting a successful treatment. CONCLUSION The current study, for the first time, provides a functional analysis of cell bioenergetics and metabolic changes in a group of Bulgarian patients with ASD. It reveals physiological abnormalities that do not allow mitochondria to adapt and meet the increased energetic requirements of the cell. The link between mitochondria and ASD is not yet fully understood, but this may lead to the discovery of new approaches for nutrition and therapy.
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4.
Urinary metabolomic profiling reveals difference between two traditional Chinese medicine subtypes of coronary heart disease.
Guo, N, Chen, Y, Yang, X, Yan, H, Fan, B, Quan, J, Wang, M, Yang, H
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 2021;:122808
Abstract
The World Health Organization has shown that coronary heart disease (CHD) is a more common cause of death than cancer. In traditional Chinese medicine (TCM), CHD is classified as a form of thoracic obstruction that can be divided in different subtypes including Qi stagnation with blood stasis (QS) and Qi deficiency with blood stasis (QD). Different treatment strategies are used based on this subtyping. Owing to the lack of scientific markers in the diagnosis of these subtypes, subjective judgments made by clinicians have limited the objective manner for utility of TCM in the treatment of CHD. Untargeted (UHPLC-QTOF-MS) and targeted (UHPLC-MS/MS) metabolomics approaches were employed to search significantly different metabolites related to the QS or QD subtypes of CHD with angina pectoris in this study. A total of 42 metabolites were obtained in the untargeted metabolomics analysis and 34 amino acids were detected in the targeted metabolomics analysis. In total, 16 metabolites were found significantly different among different groups. The results showed distinct metabolic profiles of urine samples not only between CHD patients and healthy controls, but also between the two subtypes of CHD. Pathway analysis of the significantly varied metabolites revealed that there were subtype-related differences in the activity of pathways. Therefore, urinary metabolomics can reveal the pathological changes of CHD in different subtypes, make the diagnosis of CHD in different subtypes in an objective manner and comprehensive and contribute to personalized treatment by providing scientific evidence.
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5.
Untargeted metabolomics reveals plasma metabolites predictive of ectopic fat in pancreas and liver as assessed by magnetic resonance imaging: the TOFI_Asia study.
Wu, ZE, Fraser, K, Kruger, MC, Sequeira, IR, Yip, W, Lu, LW, Plank, LD, Murphy, R, Cooper, GJS, Martin, JC, et al
International journal of obesity (2005). 2021;(8):1844-1854
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Abstract
BACKGROUND Excess visceral obesity and ectopic organ fat is associated with increased risk of cardiometabolic disease. However, circulating markers for early detection of ectopic fat, particularly pancreas and liver, are lacking. METHODS Lipid storage in pancreas, liver, abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from 68 healthy or pre-diabetic Caucasian and Chinese women enroled in the TOFI_Asia study was assessed by magnetic resonance imaging/spectroscopy (MRI/S). Plasma metabolites were measured with untargeted liquid chromatography-mass spectroscopy (LC-MS). Multivariate partial least squares (PLS) regression identified metabolites predictive of VAT/SAT and ectopic fat; univariate linear regression adjusting for potential covariates identified individual metabolites associated with VAT/SAT and ectopic fat; linear regression adjusted for ethnicity identified clinical and anthropometric correlates for each fat depot. RESULTS PLS identified 56, 64 and 31 metabolites which jointly predicted pancreatic fat (R2Y = 0.81, Q2 = 0.69), liver fat (RY2 = 0.8, Q2 = 0.66) and VAT/SAT ((R2Y = 0.7, Q2 = 0.62)) respectively. Among the PLS-identified metabolites, none of them remained significantly associated with pancreatic fat after adjusting for all covariates. Dihydrosphingomyelin (dhSM(d36:0)), 3 phosphatidylethanolamines, 5 diacylglycerols (DG) and 40 triacylglycerols (TG) were associated with liver fat independent of covariates. Three DGs and 12 TGs were associated with VAT/SAT independent of covariates. Notably, comparison with clinical correlates showed better predictivity of ectopic fat by these PLS-identified plasma metabolite markers. CONCLUSIONS Untargeted metabolomics identified candidate markers of visceral and ectopic fat that improved fat level prediction over clinical markers. Several plasma metabolites were associated with level of liver fat and VAT/SAT ratio independent of age, total and visceral adiposity, whereas pancreatic fat deposition was only associated with increased sulfolithocholic acid independent of adiposity-related parameters, but not age.
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6.
Metabolomics: small molecules that matter more.
Muthubharathi, BC, Gowripriya, T, Balamurugan, K
Molecular omics. 2021;(2):210-229
Abstract
Metabolomics, an analytical study with high-throughput profiling, helps to understand interactions within a biological system. Small molecules, called metabolites or metabolomes with the size of <1500 Da, depict the status of a biological system in a different manner. Currently, we are in need to globally analyze the metabolome and the pathways involved in healthy, as well as diseased conditions, for possible therapeutic applications. Metabolome analysis has revealed high-abundance molecules during different conditions such as diet, environmental stress, microbiota, and disease and treatment states. As a result, it is hard to understand the complete and stable network of metabolites of a biological system. This review helps readers know the available techniques to study metabolomics in addition to other major omics such as genomics, transcriptomics, and proteomics. This review also discusses the metabolomics in various pathological conditions and the importance of metabolomics in therapeutic applications.
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Determination of the Absolute Configuration of Bioactive Indole-Containing Pyrazino[2,1-b]quinazoline-3,6-diones and Study of Their In Vitro Metabolic Profile.
Long, S, Furlani, IL, Oliveira, JM, Resende, DISP, Silva, AMS, Gales, L, Pereira, JA, Kijjoa, A, Cass, QB, Oliveira, RV, et al
Molecules (Basel, Switzerland). 2021;(16)
Abstract
In recent decades, fungi-derived naturally occurring quinazolines have emerged as potential drug candidates. Nevertheless, most studies are conducted for bioactivity assays, and little is known about their absorption, distribution, metabolism, and elimination (ADME) properties. To perform metabolic studies, the synthesis of the naturally occurring quinazolinone, fiscalin B (1), and its chloro derivative, 4-((1H-indol-3-yl)methyl)-8,10-dichloro-1-isobutyl-1,2-dihydro-6H-pyrazino[2,1-b]quinazoline-3,6(4H)-dione (2), disclosed as an antibacterial agent, was performed in a gram scale using a microwave-assisted polycondensation reaction with 22% and 17% yields, respectively. The structure of the non-natural (+)-fiscalin B was established, for the first time, by X-ray crystallography as (1R,4S)-1, and the absolute configuration of the naturally occurring fiscalin B (-)-1 was confirmed by comparison of its calculated and experimental electronic circular dichroism (ECD) spectra as (1S,4R)-1. in vitro metabolic studies were monitored for this class of natural products for the first time by ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry (HRMS). The metabolic characteristics of 1 and 2 in human liver microsomes indicated hydration and hydroxylation mass changes introduced to the parent drugs.
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Metabolic imaging of human cumulus cells reveals associations among metabolic profiles of cumulus cells, patient clinical factors, and oocyte maturity.
Venturas, M, Yang, X, Kumar, K, Wells, D, Racowsky, C, Needleman, DJ
Fertility and sterility. 2021;(6):1651-1662
Abstract
OBJECTIVE To determine whether fluorescence lifetime imaging microscopy (FLIM) detects differences in metabolic state among cumulus cell samples and whether their metabolic state is associated with patient age, body mass index (BMI), and antimüllerian hormone (AMH) level and maturity of the oocyte. DESIGN Prospective observational study. SETTING Academic laboratory. PATIENT(S): Cumulus cell (CC) clusters from cumulus-oocyte complexes were collected from patients undergoing assisted reproductive technology treatment after oocyte retrieval and vitrified. INTERVENTION(S): Cumulus cell metabolism was assessed using FLIM to measure autofluorescence of nicotinamide adenine (phosphate) dinucleotide and flavine adenine dinucleotide, endogenous coenzymes essential for cellular respiration and glycolysis. Patient age, BMI, and AMH level and the maturity of the corresponding oocytes were recorded. MAIN OUTCOME MEASURE(S): Quantitative information from FLIM was obtained regarding metabolite concentrations from fluorescence intensity and metabolite enzyme engagement from fluorescence lifetimes. Associations were investigated between each FLIM parameter and oocyte maturity and patient age, BMI, and AMH. Variance between CC clusters within and between patients was determined. RESULT(S): Of 619 CC clusters from 193 patients, 90 were associated with immature oocytes and 505 with metaphase II oocytes. FLIM enabled quantitative measurements of the metabolic state of CC clusters. These parameters were significantly correlated with patient age and AMH independently, but not with BMI. Cumulus cell nicotinamide adenine (phosphate) dinucleotide FLIM parameters and redox ratio were significantly associated with maturity of the enclosed oocyte. CONCLUSION(S): FLIM detects variations in the metabolic state of CCs, showing a greater variance among clusters from each patient than between patients. Fluorescence lifetime imaging microscopy can detect CC metabolic associations with patient age and AMH and variations between mature and immature oocytes, suggesting the potential utility of this technique to help identify superior oocytes.
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Crosstalk among intestinal barrier, gut microbiota and serum metabolome after a polyphenol-rich diet in older subjects with "leaky gut": The MaPLE trial.
Peron, G, Gargari, G, Meroño, T, Miñarro, A, Lozano, EV, Escuder, PC, González-Domínguez, R, Hidalgo-Liberona, N, Del Bo', C, Bernardi, S, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(10):5288-5297
Abstract
BACKGROUND &AIM: The MaPLE study was a randomized, controlled, crossover trial involving adults ≥60 y.o. (n = 51) living in a residential care facility during an 8-week polyphenol-rich (PR)-diet. Results from the MaPLE trial showed that the PR-diet reduced the intestinal permeability (IP) in older adults by inducing changes to gut microbiota (GM). The present work aimed at studying the changes in serum metabolome in the MaPLE trial, as a further necessary step to depict the complex crosstalk between dietary polyphenols, GM, and intestinal barrier. METHODS Serum metabolome was monitored using a semi-targeted UHPLC-MS/MS analysis. Metataxonomic analysis (16S rRNA gene profiling) of GM was performed on faecal samples. Clinical characteristics and serum levels of the IP marker zonulin were linked to GM and metabolomics data in a multi-omics network. RESULTS Compared to the control diet, the PR-diet increased serum metabolites related to polyphenols and methylxanthine intake. Theobromine and methylxanthines, derived from cocoa and/or green tea, were positively correlated with butyrate-producing bacteria (the order Clostridiales and the genera Roseburia, Butyricicoccus and Faecalibacterium) and inversely with zonulin. A direct correlation between polyphenol metabolites hydroxyphenylpropionic acid-sulfate, 2-methylpyrogallol-sulfate and catechol-sulfate with Butyricicoccus was also observed, while hydroxyphenylpropionic acid-sulfate and 2-methylpyrogallol-sulfate negatively correlated with Methanobrevibacter. The multi-omics network indicated that participant's age, baseline zonulin levels, and changes in Porphyromonadaceae abundance were the main factors driving the effects of a PR-diet on zonulin. CONCLUSION Overall, these results reveal the complex relationships among polyphenols consumption, intestinal permeability, and GM composition in older adults, and they may be important when setting personalized dietary interventions for older adults. TRIAL REGISTRATION NUMBER ISRCTN10214981.
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10.
Metabolite reanalysis revealed potential biomarkers for COVID-19: a potential link with immune response.
Chen, X, Gu, M, Li, T, Sun, Y
Future microbiology. 2021;:577-588
Abstract
Aim: To understand the pathological progress of COVID-19 and to explore the potential biomarkers. Background: The COVID-19 pandemic is ongoing. There is metabolomics research about COVID-19 indicating the rich information of metabolomics is worthy of further data mining. Methods: We applied bioinformatics technology to reanalyze the published metabolomics data of COVID-19. Results: Benzoate, β-alanine and 4-chlorobenzoic acid were first reported to be used as potential biomarkers to distinguish COVID-19 patients from healthy individuals; taurochenodeoxycholic acid 3-sulfate, glucuronate and N,N,N-trimethyl-alanylproline betaine TMAP are the top classifiers in the receiver operating characteristic curve of COVID-severe and COVID-nonsevere patients. Conclusion: These unique metabolites suggest an underlying immunoregulatory treatment strategy for COVID-19.