PubMed

Related Articles How could metabolomics change pediatric health? Ital J Pediatr. 2020 Mar 27;46(1):37 Authors: Bardanzellu F, Fanos V Abstract In the last years, 'omics' technologies, and especially metabolomics, emerged as expanding scientific disciplines and promising technologies in the characterization of several pathophysiological processes.In detail, metabolomics, able to detect in a dynamic way the whole set of molecules of low molecular weight in cells, tissues, organs, and biological fluids, can provide a detailed phenotypic portray, representing a metabolic "snapshot."Thanks to its numerous strength points, metabolomics could become a fundamental tool in human health, allowing the exact evaluation of individual metabolic responses to pathophysiological stimuli including drugs, environmental changes, lifestyle, a great number of diseases and other epigenetics factors.Moreover, if current metabolomics data will be confirmed on larger samples, such technology could become useful in the early diagnosis of diseases, maybe even before the clinical onset, allowing a clinical monitoring of disease progression and helping in performing the best therapeutic approach, potentially predicting the therapy response and avoiding overtreatments. Moreover, the application of metabolomics in nutrition could provide significant information on the best nutrition regimen, optimal infantile growth and even in the characterization and improvement of commercial products' composition.These are only some of the fields in which metabolomics was applied, in the perspective of a precision-based, personalized care of human health.In this review, we discuss the available literature on such topic and provide some evidence regarding clinical application of metabolomics in heart diseases, auditory disturbance, nephrouropathies, adult and pediatric cancer, obstetrics, perinatal conditions like asphyxia, neonatal nutrition, neonatal sepsis and even some neuropsychiatric disorders, including autism.Our research group has been interested in metabolomics since several years, performing a wide spectrum of experimental and clinical studies, including the first metabolomics analysis of human breast milk. In the future, it is reasonable to predict that the current knowledge could be applied in daily clinical practice, and that sensible metabolomics biomarkers could be easily detected through cheap and accurate sticks, evaluating biofluids at the patient's bed, improving diagnosis, management and prognosis of sick patients and allowing a personalized medicine. A dream? May be I am a dreamer, but I am not the only one. PMID: 32216818 [PubMed - as supplied by publisher]

Related Articles Rapid Prostate Cancer Non-invasive Biomarker Screening Using Segmented Flow Mass Spectrometry-based Untargeted Metabolomics. J Proteome Res. 2020 Mar 27;: Authors: Pinto FG, Mahmud I, Harmon TA, Rubio VY, Garrett TJ Abstract Spectrometric methods with rapid biomarker detection capacity through untargeted metabolomics are becoming essential in the clinical cancer research. Liquid chromatography-mass spectrometry (LC-MS) is a rapidly developing metabolomic-based biomarker technique due its high sensitivity, reproducibility, and separation efficiency. However, its transla-tion to clinical diagnostics is often limited due to long data acquisition times (~20 min/sample) and laborious sample extraction procedures when employed for large-scale metabolomics studies. Here, we developed a segmented flow approach coupled with high-resolution mass spectrometry (SF-HRMS) for untargeted metabolomics which has the capability to acquire data in less than 1.5 min/sample with robustness and reproducibility relative to LC-HRMS. The SF-HRMS results demonstrate the capability for screening metabolite-based urinary biomarkers associated with prostate cancer (PCa). The study shows that SF-HRMS-based global metabolomics has the potential to evolve into a rapid biomarker screening tool for clinical research. PMID: 32216312 [PubMed - as supplied by publisher]

25 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/03/28PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

25 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/03/28PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

23 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/03/27PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Related Articles Variations in microbiota composition of laboratory mice influence Citrobacter rodentium infection via variable short-chain fatty acid production. PLoS Pathog. 2020 Mar 24;16(3):e1008448 Authors: Osbelt L, Thiemann S, Smit N, Lesker TR, Schröter M, Gálvez EJC, Schmidt-Hohagen K, Pils MC, Mühlen S, Dersch P, Hiller K, Schlüter D, Neumann-Schaal M, Strowig T Abstract The composition of the intestinal microbiota influences the outcome of enteric infections in human and mice. However, the role of specific members and their metabolites contributing to disease severity is largely unknown. Using isogenic mouse lines harboring distinct microbiota communities, we observed highly variable disease kinetics of enteric Citrobacter rodentium colonization after infection. Transfer of communities from susceptible and resistant mice into germ-free mice verified that the varying susceptibilities are determined by microbiota composition. The strongest differences in colonization were observed in the cecum and could be maintained in vitro by coculturing cecal bacteria with C. rodentium. Cohousing of animals as well as the transfer of cultivable bacteria from resistant to susceptible mice led to variable outcomes in the recipient mice. Microbiome analysis revealed that a higher abundance of butyrate-producing bacteria was associated with the resistant phenotype. Quantification of short-chain fatty acid (SCFA) levels before and after infection revealed increased concentrations of acetate, butyrate and propionate in mice with delayed colonization. Addition of physiological concentrations of butyrate, but not of acetate and/or propionate strongly impaired growth of C. rodentium in vitro. In vivo supplementation of susceptible, antibiotic-treated and germ-free mice with butyrate led to the same level of protection, notably only when cecal butyrate concentration reached a concentration higher than 50 nmol/mg indicating a critical threshold for protection. In the recent years, commensal-derived primary and secondary bacterial metabolites emerged as potent modulators of hosts susceptibility to infection. Our results provide evidence that variations in SCFA production in mice fed fibre-rich chow-based diets modulate susceptibility to colonization with Enterobacteriaceae not only in antibiotic-disturbed ecosystems but even in undisturbed microbial communities. These findings emphasise the need for microbiota normalization across laboratory mouse lines for infection experiments with the model-pathogen C. rodentium independent of investigations of diet and antibiotic usage. PMID: 32208465 [PubMed - as supplied by publisher]

Related Articles Bacterially produced metabolites protect C. elegans neurons from degeneration. PLoS Biol. 2020 Mar;18(3):e3000638 Authors: Urrutia A, García-Angulo VA, Fuentes A, Caneo M, Legüe M, Urquiza S, Delgado SE, Ugalde J, Burdisso P, Calixto A Abstract Caenorhabditis elegans and its cognate bacterial diet comprise a reliable, widespread model to study diet and microbiota effects on host physiology. Nonetheless, how diet influences the rate at which neurons die remains largely unknown. A number of models have been used in C. elegans as surrogates for neurodegeneration. One of these is a C. elegans strain expressing a neurotoxic allele of the mechanosensory abnormality protein 4 (MEC-4d) degenerin/epithelial Na+ (DEG/ENaC) channel, which causes the progressive degeneration of the touch receptor neurons (TRNs). Using this model, our study evaluated the effect of various dietary bacteria on neurodegeneration dynamics. Although degeneration of TRNs was steady and completed at adulthood in the strain routinely used for C. elegans maintenance (Escherichia coli OP50), it was significantly reduced in environmental and other laboratory bacterial strains. Strikingly, neuroprotection reached more than 40% in the E. coli HT115 strain. HT115 protection was long lasting well into old age of animals and was not restricted to the TRNs. Small amounts of HT115 on OP50 bacteria as well as UV-killed HT115 were still sufficient to produce neuroprotection. Early growth of worms in HT115 protected neurons from degeneration during later growth in OP50. HT115 diet promoted the nuclear translocation of DAF-16 (ortholog of the FOXO family of transcription factors), a phenomenon previously reported to underlie neuroprotection caused by down-regulation of the insulin receptor in this system. Moreover, a daf-16 loss-of-function mutation abolishes HT115-driven neuroprotection. Comparative genomics, transcriptomics, and metabolomics approaches pinpointed the neurotransmitter γ-aminobutyric acid (GABA) and lactate as metabolites differentially produced between E. coli HT115 and OP50. HT115 mutant lacking glutamate decarboxylase enzyme genes (gad), which catalyze the conversion of GABA from glutamate, lost the ability to produce GABA and also to stop neurodegeneration. Moreover, in situ GABA supplementation or heterologous expression of glutamate decarboxylase in E. coli OP50 conferred neuroprotective activity to this strain. Specific C. elegans GABA transporters and receptors were required for full HT115-mediated neuroprotection. Additionally, lactate supplementation also increased anterior ventral microtubule (AVM) neuron survival in OP50. Together, these results demonstrate that bacterially produced GABA and other metabolites exert an effect of neuroprotection in the host, highlighting the role of neuroactive compounds of the diet in nervous system homeostasis. PMID: 32208418 [PubMed - in process]

Related Articles Triclocarban-induced responses of endogenous and xenobiotic metabolism in human hepatic cells: Toxicity assessment based on nontargeted metabolomics approach. J Hazard Mater. 2020 Mar 05;392:122475 Authors: Zhang H, Lu Y, Liang Y, Jiang L, Cai Z Abstract Humans are frequently exposed to the antimicrobial triclocarban (TCC) due to its widespread use in consumer and personal care products. However, there is a paucity of research on potential hepatotoxic risks of TCC exposure. In this study, nontargeted metabolomics approach was applied to simultaneously investigate TCC-induced perturbation of endogenous metabolites and generation of xenobiotic metabolites in human hepatic cells. In normal hepatocytes, TCC exposure induced cellular redox imbalance as evidenced by the decrease of glutathione metabolism and overproduction of reactive oxygen species (ROS), resulting in DNA damage and lipid peroxidation. Defective oxidative phosphorylation and increased purine metabolism were two potential sources of elevated ROS. However, in cancerous hepatocytes, TCC exposure enhanced glutathione metabolism, glycolysis, and glutaminolysis, which contributed to the cellular homeostasis of redox and energy status, as well as the progression of liver cancer. As a xenobiotic, metabolic activation of TCC through phase I hydroxylation was observed. The hepatic cytotoxicity follows the order of 6-OH-TCC > 2'-OH-TCC > 3'-OH-TCC > DHC, with EC50 values of 2.42, 3.38, 7.38, and 24.8 μM, respectively, in 48 h-treated normal cells. This study improves current understanding of TCC-triggered hepatotoxicity, and provides novel perspectives for evaluating the interaction of environmental pollutants with biological systems. PMID: 32208312 [PubMed - as supplied by publisher]

Related Articles Integrated analysis of physiological, transcriptomic and metabolomic responses and tolerance mechanism of nitrite exposure in Litopenaeus vannamei. Sci Total Environ. 2020 Apr 01;711:134416 Authors: Xiao J, Liu QY, Du JH, Zhu WL, Li QY, Chen XL, Chen XH, Liu H, Zhou XY, Zhao YZ, Wang HL Abstract Nitrite accumulation in aquatic environments is a potential risk factor that disrupts multiple physiological functions in aquatic animals. In this study, the physiology, transcriptome and metabolome of the control group (LV-C), nitrite-tolerance group (LV-NT) and nitrite-sensitive group (LV-NS) were investigated to identify the stress responses and mechanisms underlying the nitrite tolerance of Litopenaeus vannamei. After LV-NT and LV-NS were subjected to nitrite stress, the hemocyanin contents were significantly decreased, and hepatopancreas showed severe histological damage compared with LV-C. Likewise, the antioxidant enzymes were also significantly changed after nitrite exposure. The transcriptome data revealed differentially expressed genes associated with immune system, cytoskeleton remodeling and apoptosis in LV-NT and LV-NS. The combination of transcriptomic and metabolomic analysis revealed nitrite exposure disturbed metabolism processes in L. vannamei, including amino acid metabolism, nucleotide metabolism and lipid metabolism. The multiple comparative analysis implicated that higher nitrite tolerance of LV-NT than LV-NS may be attributed to enhanced hypoxia inducible factor-1α expression to regulate energy supply and gaseous exchange. Moreover, LV-NT showed higher antioxidative ability, detoxification gene expression and enhanced fatty acids contents after nitrite exposure in relative to LV-NS. Collectively, all these results will greatly provide new insights into the molecular mechanisms underlying the stress responses and tolerance of nitrite exposure in L. vannamei. PMID: 32000302 [PubMed - indexed for MEDLINE]

Related Articles Lipidomics perturbations in the brain of adult zebrafish (Danio rerio) after exposure to chiral ibuprofen. Sci Total Environ. 2020 Apr 15;713:136565 Authors: Zhang W, Song Y, Chai T, Liao G, Zhang L, Jia Q, Qian Y, Qiu J Abstract The stereoselective effects of chiral ibuprofen (IBU) were studied using lipidomics by exposing adult zebrafish (Danio rerio) to an environmental concentration of 5 μg/L for 28 days. After treatment with rac-/R-(-)-/S-(+)-IBU, the brain tissue of the zebrafish was harvested to analyze for lipid metabolites by using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Results showed that the six classes of lipids, namely, glycerophospholipids, sterol lipids, prenol lipids, fatty acyls, glycerolipids, and sphingolipids, including 46 biomarkers, were affected after exposure. The different influences on metabolites were observed in the rac-/R-(-)-/S-(+)-IBU-treated samples. The rac-IBU treatment remarkably affected nine lipids. The R-(-)-IBU and S-(+)-IBU treatments had remarkably effects on six and four lipids, respectively. According to the HMDB database and KEGG pathways, nine important lipids were successfully matched to the involved biochemical pathways, such as glycerophospholipid metabolism, arachidonic acid metabolism, and linoleic acid metabolism. Therefore, IBU can cause disorders in the metabolism of the brain lipids of adult zebrafish and affect the composition of biological membranes, inflammatory responses, and cardiovascular and cerebrovascular diseases. The significant difference in the effects of R-(-)-IBU and S-(+)-IBU on lipidomics indicated that chiral IBU has stereoselective toxicity to aquatic organisms. Our study provided new insights into the environmental toxicology and highlighted the hazard of pharmaceutical and personal care product pollution in aquatic environments. PMID: 31954244 [PubMed - indexed for MEDLINE]

Characterising a healthy adult with a rare HAO1 knockout to support a therapeutic strategy for primary hyperoxaluria. Elife. 2020 Mar 24;9: Authors: McGregor TL, Hunt KA, Yee E, Mason D, Nioi P, Ticau S, Pelosi M, Loken PR, Finer S, Lawlor DA, Fauman EB, Huang QQ, Griffiths CJ, MacArthur DG, Trembath RC, Oglesbee D, Lieske JC, Erbe DV, Wright J, van Heel DA Abstract By sequencing autozygous human populations we identified a healthy adult woman with lifelong complete knockout of HAO1 (expected ~1 in 30 million outbred people). HAO1 (glycolate oxidase) silencing is the mechanism of lumasiran, an investigational RNA interference therapeutic for primary hyperoxaluria type 1. Her plasma glycolate levels were 12 times, and urinary glycolate 6 times, the upper limit of normal observed in healthy reference individuals (n=67). Plasma metabolomics and lipidomics (1871 biochemicals) revealed 18 markedly elevated biochemicals (>5sd outliers versus n=25 controls) suggesting additional HAO1 effects. Comparison with lumasiran preclinical and clinical trial data suggested she has <2% residual glycolate oxidase activity. Cell line p.Leu333SerfsTer4 expression showed markedly reduced HAO1 protein levels and cellular protein mis-localisation. In this woman, lifelong HAO1 knockout is safe and without clinical phenotype, de-risking a therapeutic approach and informing therapeutic mechanisms. Unlocking evidence from the diversity of human genetic variation can facilitate drug development. PMID: 32207686 [PubMed - as supplied by publisher]

NormAE: Deep Adversarial Learning Model to Remove Batch Effects in Liquid Chromatography Mass Spectrometry-Based Metabolomics Data. Anal Chem. 2020 Mar 24;: Authors: Rong Z, Tan Q, Cao L, Zhang L, Deng K, Huang Y, Zhu ZJ, Li Z, Li K Abstract Untargeted metabolomics based on liquid chromatography-mass spectrometry is affected by nonlinear batch effects, which cover up biological effects, result in nonreproducibility, and are difficult to be calibrate. In this study, we propose a novel deep learning model, called Normalization Autoencoder (NormAE), which is based on nonlinear autoencoders (AEs) and adversarial learning. An additional classifier and ranker are trained to provide adversarial regularization during the training of the AE model, latent representations are extracted by the encoder, and then the decoder reconstructs the data without batch effects. The NormAE method was tested on two real metabolomics data sets. After calibration by NormAE, the quality control samples (QCs) for both data sets gathered most closely in a PCA score plot (average distances decreased from 56.550 and 52.476 to 7.383 and 14.075, respectively) and obtained the highest average correlation coefficients (from 0.873 and 0.907 to 0.997 for both). Additionally, NormAE significantly improved biomarker discovery (median number of differential peaks increased from 322 and 466 to 1140 and 1622, respectively). NormAE was compared with four commonly used batch effect removal methods. The results demonstrated that using NormAE produces the best calibration results. PMID: 32207605 [PubMed - as supplied by publisher]

Fungal and plant metabolites in industrially-processed fruit juices in Nigeria. Food Addit Contam Part B Surveill. 2020 Mar 24;:1-7 Authors: Ayeni KI, Sulyok M, Krska R, Ezekiel CN Abstract There is scarce data on the mycotoxin profile in retailed fruit juices in Nigeria. Thirty-five industrially-processed fruit juice samples randomly purchased from retailers in Ogun state, Nigeria, were analysed for the presence of > 650 toxic fungal and plant metabolites using a liquid chromatography tandem mass spectrometric method. Only 18 metabolites, including 3-nitropropionic acid, alternariol methylether and emodin, but excluding citrinin, fumonisin B2, ochratoxin A and patulin, were detected in trace levels in at least one juice sample. Amygdalin, a plant cyanogen, was quantified (2.05-359 µg/L) in 40% of the samples. Although the levels of mycotoxins and toxic plant metabolites found in the juice may be relatively low, daily consumption of juices containing such low levels may contribute to dietary exposures to these natural chemical contaminants in consumers. Fruit juice processors should be encouraged to adhere strictly to good manufacturing practices in order to keep mycotoxins away from the final products. PMID: 32207373 [PubMed - as supplied by publisher]

Related Articles A population-based resource for intergenerational metabolomics analyses in pregnant women and their children: the Generation R Study. Metabolomics. 2020 Mar 23;16(4):43 Authors: Voerman E, Jaddoe VWV, Uhl O, Shokry E, Horak J, Felix JF, Koletzko B, Gaillard R Abstract INTRODUCTION: Adverse exposures in early life may predispose children to cardio-metabolic disease in later life. Metabolomics may serve as a valuable tool to disentangle the metabolic adaptations and mechanisms that potentially underlie these associations. OBJECTIVES: To describe the acquisition, processing and structure of the metabolomics data available in a population-based prospective cohort from early pregnancy onwards and to examine the relationships between metabolite profiles of pregnant women and their children at birth and in childhood. METHODS: In a subset of 994 mothers-child pairs from a prospective population-based cohort study among pregnant women and their children from Rotterdam, the Netherlands, we used LC-MS/MS to determine concentrations of amino acids, non-esterified fatty acids, phospholipids and carnitines in blood serum collected in early pregnancy, at birth (cord blood), and at child's age 10 years. RESULTS: Concentrations of diacyl-phosphatidylcholines, acyl-alkyl-phosphatidylcholines, alkyl-lysophosphatidylcholines and sphingomyelines were the highest in early pregnancy, concentrations of amino acids and non-esterified fatty acids were the highest at birth and concentrations of alkyl-lysophosphatidylcholines, free carnitine and acyl-carnitines were the highest at age 10 years. Correlations of individual metabolites between pregnant women and their children at birth and at the age of 10 years were low (range between r = - 0.10 and r = 0.35). CONCLUSION: Our results suggest that unique metabolic profiles are present among pregnant women, newborns and school aged children, with limited intergenerational correlations between metabolite profiles. These data will form a valuable resource to address the early metabolic origins of cardio-metabolic disease. PMID: 32206914 [PubMed - in process]

Related Articles Pheochromocytoma/paraganglioma: recent updates in genetics, biochemistry, immunohistochemistry, metabolomics, imaging and therapeutic options. Gland Surg. 2020 Feb;9(1):105-123 Authors: Antonio K, Valdez MMN, Mercado-Asis L, Taïeb D, Pacak K Abstract Pheochromocytomas and paragangliomas (PPGLs), rare chromaffin/neural crest cell tumors, are commonly benign in their clinical presentation. However, there are a number of cases presenting as metastatic and their diagnosis and management becomes a dilemma because of their rarity. PPGLs are constantly evolving entities in the field of endocrinology brought about by endless research and discoveries, especially in genetics. Throughout the years, our knowledge and perception of these tumors and their genetic background has greatly expanded and changed, and each new discovery leads to advancement in the diagnosis, treatment and follow-up of PPGLs. In this review, we discuss the recent updates in the genetics, biochemistry, immunohistochemistry, metabolomics, imaging and treatment options of PPGLs. PMID: 32206603 [PubMed]

Related Articles EirA is a novel protein essential for intracellular replication of Coxiella burnetii. Infect Immun. 2020 Mar 23;: Authors: Kuba M, Neha N, Newton P, Lee YW, Bennett-Wood V, Hachani A, De Souza DP, Nijagal B, Dayalan S, Tull D, McConville MJ, Sansom FM, Newton HJ Abstract The zoonotic bacterial pathogen Coxiella burnetii is the causative agent of Q fever, a febrile illness which can cause a serious chronic infection. C. burnetii is a unique intracellular bacterium which replicates within host lysosome-derived vacuoles. The ability of C. burnetii to replicate within this normally hostile compartment is dependent on the activity of the Dot/Icm type 4B secretion system. In a previous study, a transposon mutagenesis screen suggested that disruption of the gene encoding the novel protein CBU2072 rendered C. burnetii incapable of intracellular replication. This protein, subsequently named EirA (Essential for intracellular replication A), is indispensable for intracellular replication and virulence, as demonstrated by infection of human cell lines, and in vivo infection of Galleria mellonella The putative N-terminal signal peptide is essential for protein function but is not required for localization of EirA to the bacterial inner membrane compartment and axenic culture supernatant. In the absence of EirA, C. burnetii remains viable but non-replicative within the host phagolysosome, as co-infection with C. burnetii expressing native EirA rescues the replicative defect in the mutant strain. In addition, while the bacterial ultrastructure appears intact, there is an altered metabolic profile shift in the absence of EirA, suggesting that EirA may impact overall metabolism. Most strikingly, in the absence of EirA, Dot/Icm effector translocation was inhibited even when EirA deficient C. burnetii replicated in WT supported Coxiella-containing vacuoles. EirA may therefore have a novel role in control of Dot/Icm activity and may therefore represent an important new therapeutic target. PMID: 32205404 [PubMed - as supplied by publisher]

Related Articles Obesity and NRF2-mediated cytoprotection: Where is the missing link? Pharmacol Res. 2020 Mar 20;:104760 Authors: Vasileva LV, Savova MS, Amirova KM, Dinkova-Kostova AT, Georgiev MI Abstract The expanding dimensions of the global health crisis of overweight population has defined the term "globesity". Among the most common pathological conditions connected with excessive adiposity are hyperglycemia, insulin resistance, dyslipidemia and hypertension which result in chronic non-communicable diseases (NCD) such as metabolic syndrome (MetS), type 2 diabetes (T2D), and nonalchoholic steatohepatitis (NASH). The contribution of inflammatory-immune reactions in obesity and its related co-morbidities is unequivocal. Increased levels of free fatty acids (FFA), reactive oxygen species (ROS) and reactive nitrogen species (RNS) overloads the homeostatic system resulting in pro-inflammatory adipokines secretion, immune-activation and chronic inflammation in obesity. The cellular mechanisms of defense against oxidative stress are orchestrated by the transcription factor nuclear factor erythroid 2 p45-related factor 2 (NRF2). Excessive oxidative stress in the cell activates NRF2 which upregulates genes encoding major cytoprotective enzymes such as NAD(P)H:quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO1), and glutathione S-transferases (GST). The present review aims to clarify the interconnections between chronic inflammation, oxidative overload and NRF2-mediated cytoprotection as potential therapeutic approach in obesity. PMID: 32205234 [PubMed - as supplied by publisher]

Related Articles Comparison of nonfasting and fasting lipoprotein subfractions and size in 15,397 apparently healthy individuals: An analysis from the VITamin D and OmegA-3 TriaL. J Clin Lipidol. 2020 Feb 21;: Authors: Farukhi ZM, Demler OV, Caulfield MP, Kulkarni K, Wohlgemuth J, Cobble M, Luttmann-Gibson H, Li C, Nelson JR, Cook NR, Buring JE, Krauss RM, Manson JE, Mora S Abstract BACKGROUND: Elevated postprandial triglycerides reflect a proatherogenic milieu, but underlying mechanisms are unclear. OBJECTIVE: We examined differences between fasting and nonfasting profiles of directly measured lipoprotein size and subfractions to assess if postprandial triglycerides reflected increases in very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and remnants, or small dense lipid depleted LDL (sdLDL) particles. METHODS: We conducted a cross-sectional analysis of 15,397 participants (10,135 fasting; 5262 nonfasting [<8 hours since last meal]) from the VITamin D and OmegA-3 TriaL. Baseline cholesterol subfractions were measured by the vertical auto profile method and particle subfractions by ion mobility. We performed multivariable linear regression adjusting for cardiovascular and lipoprotein-modifying risk factors. RESULTS: Mean age (SD) was 68.0 years (±7.0), with 50.9% women. Adjusted mean triglyceride concentrations were higher nonfasting by 17.8 ± 1.3%, with higher nonfasting levels of directly measured VLDL cholesterol (by 3.5 ± 0.6%) and total VLDL particles (by 2.0 ± 0.7%), specifically large VLDL (by 12.3 ± 1.3%) and medium VLDL particles (by 5.3 ± 0.8%), all P < .001. By contrast, lower concentrations of low density lipoprotein (LDL) and IDL cholesterol and particles were noted for nonfasting participants. sdLDL cholesterol levels and particle concentrations showed no statistically significant difference by fasting status (-1.3 ± 2.1% and 0.07 ± 0.6%, respectively, P > .05). CONCLUSIONS: Directly measured particle and cholesterol concentrations of VLDL, not sdLDL, were higher nonfasting and may partly contribute to the proatherogenicity of postprandial hypertriglyceridemia. These differences, although statistically significant, were small and may not fully explain the increased risk of postprandial hypertriglyceridemia. PMID: 32205068 [PubMed - as supplied by publisher]

Related Articles Type 2 diabetes induced microbiome dysbiosis is associated with therapy resistance in pancreatic adenocarcinoma. Microb Cell Fact. 2020 Mar 24;19(1):75 Authors: Kesh K, Mendez R, Abdelrahman L, Banerjee S, Banerjee S Abstract Resistance to therapy is one of the major factors that contribute to dismal survival statistics in pancreatic cancer. While there are many tumor intrinsic and tumor microenvironment driven factors that contribute to therapy resistance, whether pre-existing metabolic diseases like type 2 diabetes (T2D) contribute to this has remained understudied. It is well accepted that hyperglycemia associated with type 2 diabetes changes the gut microbiome. Further, hyperglycemia also enriches for a "stem-like" population within the tumor. In the current study, we observed that in a T2D mouse model, the microbiome changed significantly as the hyperglycemia developed in these animals. Our results further showed that, tumors implanted in the T2D mice responded poorly to gemcitabine/paclitaxel (Gem/Pac) standard of care compared to those in the control group. A metabolomic reconstruction of the WGS of the gut microbiota further revealed that an enrichment of bacterial population involved in drug metabolism in the T2D group. Additionally, we also observed an increase in the CD133+ tumor cells population in the T2D model. These observations indicated that in an animal model for T2D, microbial dysbiosis is associated with increased resistance to chemotherapeutic compounds. PMID: 32204699 [PubMed - in process]

Related Articles Untargeted and Targeted Metabolomic Profiling of Australian Indigenous Fruits. Metabolites. 2020 Mar 19;10(3): Authors: Lim V, Gorji SG, Daygon VD, Fitzgerald M Abstract Selected Australian native fruits such as Davidson's plum, finger lime and native pepperberry have been reported to demonstrate potent antioxidant activity. However, comprehensive metabolite profiling of these fruits is limited, therefore the compounds responsible are unknown, and further, the compounds of nutritional value in these native fruits are yet to be described. In this study, untargeted and targeted metabolomics were conducted using the three fruits, together with assays to determine their antioxidant activities. The results demonstrate that targeted free and hydrolysed protein amino acids exhibited high amounts of essential amino acids. Similarly, important minerals like potassium were detected in the fruit samples. In antioxidant activity, Davidson's plum reported the highest activity in ferric reducing power (FRAP), finger lime in antioxidant capacity (ABTS), and native pepperberry in free radical scavenging (DPPH) and phosphomolybdenum assay. The compounds responsible for the antioxidant activity were tentatively identified using untargeted GC×GC-TOFMS and UHPLC-QqQ-TOF-MS/MS metabolomics. A clear discrimination into three clusters of fruits was observed using principal component analysis (PCA) and partial least squares (PLS) analysis. The correlation study identified a number of compounds that provide the antioxidant activities. GC×GC-TOFMS detected potent aroma compounds of limonene, furfural, and 1-R-α-pinene. Based on the untargeted and targeted metabolomics, and antioxidant assays, the nutritional potential of these Australian bush fruits is considerable and supports these indigenous fruits in the nutraceutical industry as well as functional ingredients for the food industry, with such outcomes benefiting Indigenous Australian communities. PMID: 32204361 [PubMed]