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The effects of coenzyme Q10 supplementation on metabolic profiles and parameters of mental health in women with polycystic ovary syndrome.
Karamali, M, Gholizadeh, M
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2022;(1):45-49
Abstract
OBJECTIVE Evaluating the impact of coenzyme Q10 (CoQ10) supplementation on hormonal indices, mental health, and biomarkers of inflammatory responses and oxidative stress among female patients suffering from polycystic ovary syndrome (PCOS). METHODS The present double-blinded, placebo-controlled randomized clinical trial consisted of 55 PCOS women (aged 18-40 years old), who were randomized into groups receiving 100 mg/day of CoQ10 (28 cases) or placebo (27 cases) for 12 weeks. RESULTS The supplementation of CoQ10 decreased significantly the scores of Beck Depression Inventory (BDI) (p = .03) and Beck Anxiety Inventory (BAI) (p = .01) and high-sensitivity C-reactive protein (hs-CRP) level (p = .005) when comparing with the placebo group. Moreover, CoQ10 group exhibited a significant drop in total testosterone (p = .004), dehydroepiandrosterone sulfate (DHEAS) (p < .001), hirsutism (p = .002) and malondialdehyde (MDA) (p = .001) levels in the serum, and a significant rise in sex hormone-binding globulin (SHBG) (p < .001) and total antioxidant capacity (TAC) (p < .001) levels in the serum than the placebo group. CONCLUSIONS 12-week supplementation of CoQ10 to PCOS women showed beneficial impact on BDI, BAI, hs-CRP, total testosterone, DHEAS, hirsutism, SHBG, TAC and MDA levels.
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Effect of Dapagliflozin on Urine Metabolome in Patients with Type 2 Diabetes.
Bletsa, E, Filippas-Dekouan, S, Kostara, C, Dafopoulos, P, Dimou, A, Pappa, E, Chasapi, S, Spyroulias, G, Koutsovasilis, A, Bairaktari, E, et al
The Journal of clinical endocrinology and metabolism. 2021;(5):1269-1283
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Abstract
CONTEXT Inhibitors of sodium-glucose cotransporters-2 have cardio- and renoprotective properties. However, the underlying mechanisms remain indeterminate. OBJECTIVE To evaluate the effect of dapagliflozin on renal metabolism assessed by urine metabolome analysis in patients with type 2 diabetes. DESIGN Prospective cohort study. SETTING Outpatient diabetes clinic of a tertiary academic center. PATIENTS Eighty patients with hemoglobin A1c > 7% on metformin monotherapy were prospectively enrolled. INTERVENTION Fifty patients were treated with dapagliflozin for 3 months. To exclude that the changes observed in urine metabolome were merely the result of the improvement in glycemia, 30 patients treated with insulin degludec were used for comparison. MAIN OUTCOME MEASURE Changes in urine metabolic profile before and after the administration of dapagliflozin and insulin degludec were assessed by proton-nuclear magnetic resonance spectroscopy. RESULTS In multivariate analysis urine metabolome was significantly altered by dapagliflozin (R2X = 0.819, R2Y = 0.627, Q2Y = 0.362, and coefficient of variation analysis of variance, P < 0.001) but not insulin. After dapagliflozin, the urine concentrations of ketone bodies, lactate, branched chain amino acids (P < 0.001), betaine, myo-inositol (P < 0001), and N-methylhydantoin (P < 0.005) were significantly increased. Additionally, the urine levels of alanine, creatine, sarcosine, and citrate were also increased (P < 0001, P <0.0001, and P <0.0005, respectively) whereas anserine decreased (P < 0005). CONCLUSIONS Dapagliflozin significantly affects urine metabolome in patients with type 2 diabetes in a glucose lowering-independent way. Most of the observed changes can be considered beneficial and may contribute to the renoprotective properties of dapagliflozin.
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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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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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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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ZnO nanoparticle-based seed priming modulates early growth and enhances physio-biochemical and metabolic profiles of fragrant rice against cadmium toxicity.
Li, Y, Liang, L, Li, W, Ashraf, U, Ma, L, Tang, X, Pan, S, Tian, H, Mo, Z
Journal of nanobiotechnology. 2021;(1):75
Abstract
BACKGROUND Cadmium (Cd) is amongst the most toxic heavy metals that severely affects crop growth, whereas application of nanoparticles (NPs) to negate the toxic effects of heavy metals could be an effective management approach. In the present study, the seeds of two fragrant rice varieties i.e., Yuxiangyouzhan and Xiangyaxiangzhan under normal and Cd stress conditions i.e., 0 and 100 mg L- 1 applied with four levels of ZnO NPs i.e., 0, 25, 50, and 100 mg L- 1. RESULTS Seed priming with ZnO NPs had no significant effect on the seed germination (p > 0.05) however, it substantially improved the seedling growth and other related physiological attributes under the Cd stress. The mean fresh weight of the shoot, and whole seedling was increased by 16.92-27.88% and by 16.92-27.88% after ZnO NPs application. The root fresh weight, root-shoot length was also substantially improved under ZnO NPs treatment. Moreover, application of ZnO NPs induced modulations in physiological and biochemical attributes e.g., the superoxide dismutase (SOD) activity in root and shoot, the peroxidase (POD) activity and metallothionein contents in root were increased under low levels of ZnO NPs. The α-amylase and total amylase activity were improved by ZnO NPs application under Cd Stress. Besides, modulation in Zn concentration and ZnO NPs uptake in the seedling were detected. The metabolomic analysis indicated that various pathways such as alanine, aspartate and glutamate metabolism, phenylpropanoid biosynthesis, and taurine and hypotaurine metabolism were possibly important for rice response to ZnO NPs and Cd. CONCLUSION Overall, application of ZnO NPs substantially improved the early growth and related physio-biochemical attributes in rice. Our findings provide new insights regarding the effects of ZnO NPs on seed germination, and early growth of rice, and its potential applications in developing crop resilience against Cd contaminated soils.
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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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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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Genetic Studies of Metabolomics Change After a Liquid Meal Illuminate Novel Pathways for Glucose and Lipid Metabolism.
Li-Gao, R, Hughes, DA, van Klinken, JB, de Mutsert, R, Rosendaal, FR, Mook-Kanamori, DO, Timpson, NJ, Willems van Dijk, K
Diabetes. 2021;(12):2932-2946
Abstract
Humans spend the greater part of the day in a postprandial state. However, the genetic basis of postprandial blood measures is relatively uncharted territory. We examined the genetics of variation in concentrations of postprandial metabolites (t = 150 min) in response to a liquid mixed meal through genome-wide association studies (GWAS) performed in the Netherlands Epidemiology of Obesity (NEO) study (n = 5,705). The metabolite response GWAS identified an association between glucose change and rs10830963:G in the melatonin receptor 1B (β [SE] -0.23 [0.03], P = 2.15 × 10-19). In addition, the ANKRD55 locus led by rs458741:C showed strong associations with extremely large VLDL (XXLVLDL) particle response (XXLVLDL total cholesterol: β [SE] 0.17 [0.03], P = 5.76 × 10-10; XXLVLDL cholesterol ester: β [SE] 0.17 [0.03], P = 9.74 × 10-10), which also revealed strong associations with body composition and diabetes in the UK Biobank (P < 5 × 10-8). Furthermore, the associations between XXLVLDL response and insulinogenic index, HOMA-β, Matsuda insulin sensitivity index, and HbA1c in the NEO study implied the role of chylomicron synthesis in diabetes (with false discovery rate-corrected q <0.05). To conclude, genetic studies of metabolomics change after a liquid meal illuminate novel pathways for glucose and lipid metabolism. Further studies are warranted to corroborate biological pathways of the ANKRD55 locus underlying diabetes.
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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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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.