Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

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PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 2 hours 21 min ago

metabolomics; +18 new citations

Tue, 13/11/2018 - 15:51
18 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 2018/11/13PubMed 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.

metabolomics; +18 new citations

Tue, 13/11/2018 - 12:51
18 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 2018/11/13PubMed 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.

Hepatic metabolomics reveals that liver injury increases PCB 126-induced oxidative stress and metabolic dysfunction.

Mon, 12/11/2018 - 12:32
Hepatic metabolomics reveals that liver injury increases PCB 126-induced oxidative stress and metabolic dysfunction. Chemosphere. 2018 Oct 30;217:140-149 Authors: Deng P, Barney J, Petriello MC, Morris AJ, Wahlang B, Hennig B Abstract The deleterious effects of PCB 126 are complex, and the role of the liver in modifying toxic insult is not well understood. We utilized metabolomics approaches to compare liver metabolites significantly affected by PCB 126 in control mice and a diet induced liver injury mouse model. In this 14-week study, mice were fed either an amino acid supplemented control diet (CD) or a methionine-choline deficient diet (MCD) which promoted nonalcoholic steatohepatitis (NASH) and were subsequently exposed to PCB 126. The liver metabolome was profiled by a global metabolomic analysis using LC-MS. There were clear differences between PCB 126 exposed and control mice in the hepatic metabolomic profiles (216 and 266 metabolites were altered in CD-fed and MCD-fed mice respectively after PCB 126 exposure). PCB 126 modulated glycerophospholipid metabolism, glutathione metabolism, and CoA biosynthesis pathways irrespective of diet; indicating that the disturbance in lipid metabolism and thiol metabolites are general markers of PCB 126 exposure irrespective of liver health. Additionally, metabolites associated with oxidative stress and mitochondrial dysfunction were greatly elevated in PCB 126 exposed mice with compromised livers (e.g., 4-hydroxy-nonenal glutathione, oxylipids, uric acid, and acylcarnitines). Moreover, PCB 126 exposure downregulated redox genes, and the effect was more pronounced in liver injury mice. In conclusion, this study demonstrates that PCB 126 could induce oxidative stress and metabolic dysfunction, and pre-existing liver injury can markedly modify PCB 126-induced metabolic changes. Using metabolic profiling, this study suggests mechanism of enhanced PCB 126 toxicity under liver injury settings. PMID: 30415113 [PubMed - as supplied by publisher]

Added value of plasma metabolomics to describe maternal effects in rat maternal and prenatal toxicity studies.

Mon, 12/11/2018 - 12:32
Added value of plasma metabolomics to describe maternal effects in rat maternal and prenatal toxicity studies. Toxicol Lett. 2018 Nov 08;: Authors: Keller J, Mellert W, Sperber S, Kamp H, Jiang X, Fabian E, Herold M, Walk T, Strauss V, van Ravenzwaay B Abstract For regulatory purposes prenatal developmental toxicity (OECD 414) studies are routinely performed in our laboratories. The suitability of metabolomics as technology to identify maternal toxicity in such studies was investigated. Plasma was sampled from pregnant, non-fasted rats on gestation day 20 before cesarean section. Metabolite profiling was performed by gas- and liquid-chromatography-tandem mass spectrometry techniques. The sensitivity of routinely examined maternal toxicity parameters (OECD No. 414) was compared to those of metabolome analysis. Evaluating 44 studies, the metabolome-derived NOEL was more sensitive in 45% of the cases in detecting maternal toxicity than the maternal NOAEL. Metabolome patterns indicative for liver effects and 4-hydroxyphenylpyruvate dioxygenase (HPPD) enzyme-inhibition were established in pregnant rats based on regulated metabolites using reference compounds. The HPPD inhibition and liver toxicity patterns in pregnant rats were reasonably comparable to the ones established in non-pregnant, fasted rats. Metabolomics is a useful tool for an improved and mechanism-based identification of maternal toxicity in maternal and prenatal toxicity studies. The data suggest that the current classical maternal toxicity parameters may underestimate the extent of effects of compounds on the dams. PMID: 30414988 [PubMed - as supplied by publisher]

Variations in Microbial Diversity and Metabolite Profiles of the Tropical Marine Sponge Xestospongia muta with Season and Depth.

Sun, 11/11/2018 - 12:24
Related Articles Variations in Microbial Diversity and Metabolite Profiles of the Tropical Marine Sponge Xestospongia muta with Season and Depth. Microb Ecol. 2018 Nov 10;: Authors: Villegas-Plazas M, Wos-Oxley ML, Sanchez JA, Pieper DH, Thomas OP, Junca H Abstract Xestospongia muta is among the most emblematic sponge species inhabiting coral reefs of the Caribbean Sea. Besides being the largest sponge species growing in the Caribbean, it is also known to produce secondary metabolites. This study aimed to assess the effect of depth and season on the symbiotic bacterial dynamics and major metabolite profiles of specimens of X. muta thriving in a tropical marine biome (Portobelo Bay, Panamá), which allow us to determine whether variability patterns are similar to those reported for subtropical latitudes. The bacterial assemblages were characterized using Illumina deep-sequencing and metabolomic profiles using UHPLC-DAD-ELSD from five depths (ranging 9-28 m) across two seasons (spring and autumn). Diverse symbiotic communities, representing 24 phyla with a predominance of Proteobacteria and Chloroflexi, were found. Although several thousands of OTUs were determined, most of them belong to the rare biosphere and only 23 to a core community. There was a significant difference between the structure of the microbial communities in respect to season (autumn to spring), with a further significant difference between depths only in autumn. This was partially mirrored in the metabolome profile, where the overall metabolite composition did not differ between seasons, but a significant depth gradient was observed in autumn. At the phyla level, Cyanobacteria, Firmicutes, Actinobacteria, and Spirochaete showed a mild-moderate correlation with the metabolome profile. The metabolomic profiles were mainly characterized by known brominated polyunsaturated fatty acids. This work presents findings about the composition and dynamics of the microbial assemblages of X. muta expanding and confirming current knowledge about its remarkable diversity and geographic variability as observed in this tropical marine biome. PMID: 30413836 [PubMed - as supplied by publisher]

Biomarker Phenotype for Early Diagnosis and Triage of Sepsis to the Pediatric Intensive Care Unit.

Sun, 11/11/2018 - 12:24
Related Articles Biomarker Phenotype for Early Diagnosis and Triage of Sepsis to the Pediatric Intensive Care Unit. Sci Rep. 2018 Nov 09;8(1):16606 Authors: Mickiewicz B, Thompson GC, Blackwood J, Jenne CN, Winston BW, Vogel HJ, Joffe AR Abstract Early diagnosis and triage of sepsis improves outcomes. We aimed to identify biomarkers that may advance diagnosis and triage of pediatric sepsis. Serum and plasma samples were collected from young children (1-23 months old) with sepsis on presentation to the Pediatric Intensive Care Unit (PICU-sepsis, n = 46) or Pediatric Emergency Department (PED-sepsis, n = 58) and PED-non-sepsis patients (n = 19). Multivariate analysis was applied to distinguish between patient groups. Results were compared to our results for older children (2-17 years old). Common metabolites and protein-mediators were validated as potential biomarkers for a sepsis-triage model to differentiate PICU-sepsis from PED-sepsis in children age 1 month-17 years. Metabolomics in young children clearly separated the PICU-sepsis and PED-sepsis cohorts: sensitivity 0.71, specificity 0.93, and AUROC = 0.90 ± 0.03. Adding protein-mediators to the model did not improve performance. The seven metabolites common to the young and older children were used to create the sepsis-triage model. Validation of the sepsis-triage model resulted in sensitivity: 0.83 ± 0.02, specificity: 0.88 ± 0.05 and AUROC 0.93 ± 0.02. The metabolic-based biomarkers predicted which sepsis patients required care in a PICU versus those that could be safely cared for outside of a PICU. This has potential to inform appropriate triage of pediatric sepsis, particularly in EDs with less experience evaluating children. PMID: 30413795 [PubMed - in process]

The Salt-Stress Response of the Transgenic Plum Line J8-1 and Its Interaction with the Salicylic Acid Biosynthetic Pathway from Mandelonitrile.

Sun, 11/11/2018 - 12:24
Related Articles The Salt-Stress Response of the Transgenic Plum Line J8-1 and Its Interaction with the Salicylic Acid Biosynthetic Pathway from Mandelonitrile. Int J Mol Sci. 2018 Nov 08;19(11): Authors: Bernal-Vicente A, Cantabella D, Petri C, Hernández JA, Diaz-Vivancos P Abstract Salinity is considered as one of the most important abiotic challenges that affect crop productivity. Plant hormones, including salicylic acid (SA), are key factors in the defence signalling output triggered during plant responses against environmental stresses. We have previously reported in peach a new SA biosynthetic pathway from mandelonitrile (MD), the molecule at the hub of the cyanogenic glucoside turnover in Prunus sp. In this work, we have studied whether this new SA biosynthetic pathway is also present in plum and the possible role this pathway plays in plant plasticity under salinity, focusing on the transgenic plum line J8-1, which displays stress tolerance via an enhanced antioxidant capacity. The SA biosynthesis from MD in non-transgenic and J8-1 micropropagated plum shoots was studied by metabolomics. Then the response of J8-1 to salt stress in presence of MD or Phe (MD precursor) was assayed by measuring: chlorophyll content and fluorescence parameters, stress related hormones, levels of non-enzymatic antioxidants, the expression of two genes coding redox-related proteins, and the content of soluble nutrients. The results from in vitro assays suggest that the SA synthesis from the MD pathway demonstrated in peach is not clearly present in plum, at least under the tested conditions. Nevertheless, in J8-1 NaCl-stressed seedlings, an increase in SA was recorded as a result of the MD treatment, suggesting that MD could be involved in the SA biosynthesis under NaCl stress conditions in plum plants. We have also shown that the plum line J8-1 was tolerant to NaCl under greenhouse conditions, and this response was quite similar in MD-treated plants. Nevertheless, the MD treatment produced an increase in SA, jasmonic acid (JA) and reduced ascorbate (ASC) contents, as well as in the coefficient of non-photochemical quenching (qN) and the gene expression of Non-Expressor of Pathogenesis-Related 1 (NPR1) and thioredoxin H (TrxH) under salinity conditions. This response suggested a crosstalk between different signalling pathways (NPR1/Trx and SA/JA) leading to salinity tolerance in the transgenic plum line J8-1. PMID: 30413110 [PubMed - in process]

metabolomics; +16 new citations

Sat, 10/11/2018 - 15:16
16 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 2018/11/10PubMed 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.

metabolomics; +16 new citations

Sat, 10/11/2018 - 12:16
16 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 2018/11/10PubMed 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.

metabolomics; +27 new citations

Fri, 09/11/2018 - 14:49
27 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 2018/11/09PubMed 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.

Characterisation of the Toxoplasma gondii tyrosine transporter and its phosphorylation by the calcium-dependent protein kinase 3.

Thu, 08/11/2018 - 14:34
Related Articles Characterisation of the Toxoplasma gondii tyrosine transporter and its phosphorylation by the calcium-dependent protein kinase 3. Mol Microbiol. 2018 Nov 06;: Authors: Wallbank BA, Dominicus CS, Broncel M, Legrave N, MacRae JI, Staines HM, Treeck M Abstract Toxoplasma gondii parasites rapidly exit their host cell when exposed to calcium ionophores. Calcium-dependent protein kinase 3 (TgCDPK3) was previously identified as a key mediator in this process, as TgCDPK3 knockout (∆cdpk3) parasites fail to egress in a timely manner. Phosphoproteomic analysis comparing WT with ∆cdpk3 parasites revealed changes in the TgCDPK3-dependent phosphoproteome that included proteins important for regulating motility, but also metabolic enzymes, indicating that TgCDPK3 controls processes beyond egress. Here we have investigated a predicted direct target of TgCDPK3, ApiAT5-3, a putative transporter of the major facilitator superfamily, and show that it is rapidly phosphorylated at serine 56 after induction of calcium signalling. Conditional knockout of apiAT5-3 results in transcriptional up-regulation of most ribosomal subunits, but no alternative transporters, and subsequent parasite death. Mutating the S56 to a non-phosphorylatable alanine leads to a fitness cost, suggesting that phosphorylation of this residue is beneficial, albeit not essential, for tyrosine import. Using a combination of metabolomics and heterologous expression, we confirmed a primary role in tyrosine import for ApiAT5-3. However, no significant differences in tyrosine import could be detected in phosphorylation site mutants showing that if tyrosine transport is affected by S56 phosphorylation, its regulatory role is subtle. This article is protected by copyright. All rights reserved. PMID: 30402958 [PubMed - as supplied by publisher]

Predictive Role of Urinary Metabolic Profile for Abnormal MRI Score in Preterm Neonates.

Thu, 08/11/2018 - 14:34
Related Articles Predictive Role of Urinary Metabolic Profile for Abnormal MRI Score in Preterm Neonates. Dis Markers. 2018;2018:4938194 Authors: Tataranno ML, Perrone S, Longini M, Coviello C, Tassini M, Vivi A, Calderisi M, deVries LS, Groenendaal F, Buonocore G, Benders MJNL Abstract Background and Objective: Early identification of neonates at risk for brain injury is important to start appropriate intervention. Urinary metabolomics is a source of potential, noninvasive biomarkers of brain disease. We studied the urinary metabolic profile at 2 and 10 days in preterm neonates with normal/mild and moderate/severe MRI abnormalities at term equivalent age. Methods: Urine samples were collected at two and 10 days after birth in 30 extremely preterm infants and analyzed using proton magnetic resonance spectroscopy. A 3 T MRI was performed at term equivalent age, and images were scored for white matter (WM), cortical grey matter (cGM), deep GM, and cerebellar abnormalities. Infants were divided in two groups: normal/mild and moderately/severely abnormal MRI scores. Results: No significant clustering was seen between normal/mild and moderate/severe MRI scores for all regions at both time points. The ROC curves distinguished neonates at 2 and 10 days who later developed a markedly less mature cGM score from the others (2 d: area under the curve (AUC) = 0.72, specificity (SP) = 65%, sensitivity (SE) = 75% and 10 d: AUC = 0.80, SP = 78%, SE = 80%) and a moderately to severely abnormal WM score (2 d: AUC = 0.71, specificity (SP) = 80%, sensitivity (SE) = 72% and 10 d: AUC = 0.69, SP = 64%, SE = 89%). Conclusions: Early urinary spectra of preterm infants were able to discriminate metabolic profiles in patients with moderately/severely abnormal cGM and WM scores at term equivalent age. Urine spectra are promising for early identification of neonates at risk of brain damage and allow understanding of the pathogenesis of altered brain development. PMID: 30402168 [PubMed - in process]

Drought-induced susceptibility for Cenangium ferruginosum leads to progression of Cenangium-dieback disease in Pinus koraiensis.

Thu, 08/11/2018 - 14:34
Related Articles Drought-induced susceptibility for Cenangium ferruginosum leads to progression of Cenangium-dieback disease in Pinus koraiensis. Sci Rep. 2018 Nov 06;8(1):16368 Authors: Ryu M, Mishra RC, Jeon J, Lee SK, Bae H Abstract Recently, the occurrence of "Cenangium-dieback" has been frequent and devastating. Cenangium-dieback is caused by an endophytic fungus Cenangium ferruginosum in stressed pine trees. Progression of the disease in terms of molecular interaction between host and pathogen is not well studied and there is a need to develop preventive strategies. Thus, we simulated disease conditions and studied the associated transcriptomics, metabolomics, and hormonal changes. Pinus koraiensis seedlings inoculated with C. ferruginosum were analyzed both under drought and well-watered conditions. Transcriptomic analysis suggested decreased expression of defense-related genes in C. ferruginosum-infected seedlings experiencing water-deficit. Further, metabolomic analysis indicated a decrease in the key antimicrobial terpenoids, flavonoids, and phenolic acids. Hormonal analysis revealed a drought-induced accumulation of abscisic acid and a corresponding decline in the defense-associated jasmonic acid levels. Pathogen-associated changes were also studied by treating C. ferruginosum with metabolic extracts from pine seedlings (with and without drought) and polyethylene glycol to simulate the effects of direct drought. From RNA sequencing and metabolomic analysis it was determined that drought did not directly induce pathogenicity of C. ferruginosum. Collectively, we propose that drought weakens pine immunity, which facilitates increased C. ferruginosum growth and results in conversion of the endophyte into the phytopathogen causing dieback. PMID: 30401938 [PubMed - in process]

Untargeted metabolomics reveals transformation pathways and metabolic response of the earthworm Perionyx excavatus after exposure to triphenyl phosphate.

Thu, 08/11/2018 - 14:34
Related Articles Untargeted metabolomics reveals transformation pathways and metabolic response of the earthworm Perionyx excavatus after exposure to triphenyl phosphate. Sci Rep. 2018 Nov 06;8(1):16440 Authors: Wang L, Huang X, Laserna AKC, Li SFY Abstract Triphenyl phosphate (TPHP) is one of the most highly utilized organophosphorus flame retardants, and has been frequently detected in various environmental matrices, including soil. So far, limited information is known regarding the potential toxicity of TPHP to the earthworm-soil ecosystem. We investigated the metabolism of TPHP and the perturbation of the endogenous metabolome in the earthworm, Perionyx excavatus, using gas chromatography mass spectrometry (GC-MS) and liquid chromatography quadrupole time-of-flight (LC-QTOF)-based untargeted metabolomics approach after acute exposure to TPHP for one and two days through a filter paper contact test, as well as after chronic exposure for 28 days in a soil microcosm experiment. TPHP showed low bioaccumulation potential in the earthworm-soil ecosystem at concentrations of 10 mg/kg and 50 mg/kg. Identified phase I metabolites include diphenyl phosphate, mono-hydroxylated and di-hydroxylated TPHP. Two groups of phase II metabolites, thiol conjugates (including mercaptolactic acid, cysteine, cysteinylglycine, and mercaptoethanol conjugates) and glucoside conjugates (including glucoside, glucoside-phosphate, and C14H19O10P conjugates), were putatively identified. Only acute TPHP exposure caused significant perturbations of the endogenous metabolome in earthworms, featuring fluctuations in amino acids, glucose, inosine and phospholipids. These results reveal novel phase II metabolism and toxicity of TPHP in P. excavatus. PMID: 30401822 [PubMed - in process]

Gut Microbial and Metabolic Responses to Salmonella enterica Serovar Typhimurium and Candida albicans.

Thu, 08/11/2018 - 14:34
Related Articles Gut Microbial and Metabolic Responses to Salmonella enterica Serovar Typhimurium and Candida albicans. MBio. 2018 Nov 06;9(6): Authors: Bratburd JR, Keller C, Vivas E, Gemperline E, Li L, Rey FE, Currie CR Abstract The gut microbiota confers resistance to pathogens of the intestinal ecosystem, yet the dynamics of pathogen-microbiome interactions and the metabolites involved in this process remain largely unknown. Here, we use gnotobiotic mice infected with the virulent pathogen Salmonella enterica serovar Typhimurium or the opportunistic pathogen Candida albicans in combination with metagenomics and discovery metabolomics to identify changes in the community and metabolome during infection. To isolate the role of the microbiota in response to pathogens, we compared mice monocolonized with the pathogen, uninfected mice "humanized" with a synthetic human microbiome, or infected humanized mice. In Salmonella-infected mice, by 3 days into infection, microbiome community structure and function changed substantially, with a rise in Enterobacteriaceae strains and a reduction in biosynthetic gene cluster potential. In contrast, Candida-infected mice had few microbiome changes. The LC-MS metabolomic fingerprint of the cecum differed between mice monocolonized with either pathogen and humanized infected mice. Specifically, we identified an increase in glutathione disulfide, glutathione cysteine disulfide, inosine 5'-monophosphate, and hydroxybutyrylcarnitine in mice infected with Salmonella in contrast to uninfected mice and mice monocolonized with Salmonella These metabolites potentially play a role in pathogen-induced oxidative stress. These results provide insight into how the microbiota community members interact with each other and with pathogens on a metabolic level.IMPORTANCE The gut microbiota is increasingly recognized for playing a critical role in human health and disease, especially in conferring resistance to both virulent pathogens such as Salmonella, which infects 1.2 million people in the United States every year (E. Scallan, R. M. Hoekstra, F. J. Angulo, R. V. Tauxe, et al., Emerg Infect Dis 17:7-15, 2011, https://doi.org/10.3201/eid1701.P11101), and opportunistic pathogens like Candida, which causes an estimated 46,000 cases of invasive candidiasis each year in the United States (Centers for Disease Control and Prevention, Antibiotic Resistance Threats in the United States, 2013, 2013). Using a gnotobiotic mouse model, we investigate potential changes in gut microbial community structure and function during infection using metagenomics and metabolomics. We observe that changes in the community and in biosynthetic gene cluster potential occur within 3 days for the virulent Salmonella enterica serovar Typhimurium, but there are minimal changes with a poorly colonizing Candida albicans In addition, the metabolome shifts depending on infection status, including changes in glutathione metabolites in response to Salmonella infection, potentially in response to host oxidative stress. PMID: 30401779 [PubMed - in process]

Revealing of the microRNA involved regulatory gene networks on terpenoid biosynthesis in Camellia sinensis in different growing time points.

Thu, 08/11/2018 - 14:34
Related Articles Revealing of the microRNA involved regulatory gene networks on terpenoid biosynthesis in Camellia sinensis in different growing time points. J Agric Food Chem. 2018 Nov 06;: Authors: Zhao S, Wang X, Yan X, Guo L, Mi X, Xu Q, Zhu J, Wu A, Liu L, Wei C Abstract Tea, made from leaves of Camellia sinensis, has long been consumed worldwide for its unique taste and aroma. Terpenoids play important roles not only in tea beverage aroma formation, but also in the productivity and quality of tea plantation due to their significant contribution to light harvesting pigments and phytohormones. To date, however, the regulation of terpenoid synthase genes remains unclear. Herein, the analyses of metabolomics, sRNAs, degradome and transcriptomics were performed and integrated for identifying key regulatory miRNA-target circuits on terpenoid biosynthesis in leaf tissues over five different months in which the amount of terpenoids in tea leaves varies greatly. Four classes of miRNA-TF pairs which might play a central role in the regulation of terpenoid biosynthesis were also uncovered. Ultimately, a hypothetical model was proposed that mature miRNAs maintained by light regulator at both the transcriptional and posttranscriptional levels negatively regulate the targets to control terpenoid biosynthesis. PMID: 30400742 [PubMed - as supplied by publisher]

Endogenous Anti-Inflammatory Very-Long-Chain Dicarboxylic Acids: Potential Chemopreventive Lipids.

Thu, 08/11/2018 - 14:34
Related Articles Endogenous Anti-Inflammatory Very-Long-Chain Dicarboxylic Acids: Potential Chemopreventive Lipids. Metabolites. 2018 Nov 03;8(4): Authors: Wood PL Abstract In a paradigm shift, cancer research efforts are being dedicated to the discovery of chemopreventive agents. The goal of this approach is to delay or prevent the progression of augmented cell division to established cancer. Research has focused on dietary supplements, drugs, and endogenous lipids that possess anti-inflammatory properties. We undertook a lipidomics analysis of potential endogenous anti-inflammatory/anti-proliferative lipids in human plasma. We performed high-resolution mass spectrometric lipidomics analyses of plasma samples from controls and patients with colorectal, kidney, pancreatic, glioblastoma, and breast cancers. We present evidence that endogenous very-long-chain dicarboxylic acids (VLCDCA) are anti-inflammatory lipids that possess chemopreventative properties. In a family of VLCDCAs, we characterized VLCDCA 28:4, which is decreased in the plasma of patients with colorectal, kidney, and pancreatic cancers. The structure of this biomarker was validated by derivatization strategies, synthesis of the analytical standard, and tandem mass spectrometry. Our data suggest that VLCDCA 28:4 may be a useful blood biomarker for a number of cancers and that resupplying this lipid, via a prodrug for example, may offer a new anti-inflammatory therapeutic strategy for delaying or preventing the progression of cancer and other inflammatory diseases. PMID: 30400281 [PubMed]

The Dietary Total-Fat Content Affects the In Vivo Circulating C15:0 and C17:0 Fatty Acid Levels Independently.

Thu, 08/11/2018 - 14:34
Related Articles The Dietary Total-Fat Content Affects the In Vivo Circulating C15:0 and C17:0 Fatty Acid Levels Independently. Nutrients. 2018 Nov 03;10(11): Authors: Jenkins B, Aoun M, Feillet-Coudray C, Coudray C, Ronis M, Koulman A Abstract Pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0) have been described as dietary biomarkers of dairy-fat consumption, with varying degrees of reliability between studies. It remains unclear how the total amount of dietary fat, representing one of the main confounding factors in these biomarker investigations, affects C15:0 and C17:0 circulating concentrations independent of their relative intake. Additionally, it is not clear how changes in the dietary total-fat affects other fatty acids in circulation. Through two dietary studies with different total-fat levels but maintaining identical fatty acid compositions, we were able to see how the dietary total-fat affects the fatty acids in circulation. We saw that there was a statistically significant, proportionate, and robust decrease in the endogenous C15:0 levels with an increase in dietary total-fat. However, there was no significant change in the circulating C17:0 concentrations as the total-fat increased. To conclude, the dietary total-fat content and fat-type have a very complex influence on the relative compositions of circulating fatty acids, which are independent of the actual dietary fatty acid composition. Knowing how to manipulate circulating C15:0 and C17:0 concentrations is far-reaching in nutritional/pathological research as they highlight a dietary route to attenuate the development of metabolic disease (both by reducing risk and improving prognosis). PMID: 30400275 [PubMed - in process]

Stable Isotope-Labeled Lipidomics to Unravel the Heterogeneous Development Lipotoxicity.

Thu, 08/11/2018 - 14:34
Related Articles Stable Isotope-Labeled Lipidomics to Unravel the Heterogeneous Development Lipotoxicity. Molecules. 2018 Nov 02;23(11): Authors: Shih LM, Tang HY, Lynn KS, Huang CY, Ho HY, Cheng ML Abstract Non-alcoholic fatty liver disease (NAFLD) as a global health problem has clinical manifestations ranging from simple non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), cirrhosis, and cancer. The role of different types of fatty acids in driving the early progression of NAFL to NASH is not understood. Lipid overload causing lipotoxicity and inflammation has been considered as an essential pathogenic factor. To correlate the lipid profiles with cellular lipotoxicity, we utilized palmitic acid (C16:0)- and especially unprecedented palmitoleic acid (C16:1)-induced lipid overload HepG2 cell models coupled with lipidomic technology involving labeling with stable isotopes. C16:0 induced inflammation and cell death, whereas C16:1 induced significant lipid droplet accumulation. Moreover, inhibition of de novo sphingolipid synthesis by myriocin (Myr) aggravated C16:0 induced lipoapoptosis. Lipid profiles are different in C16:0 and C16:1-treated cells. Stable isotope-labeled lipidomics elucidates the roles of specific fatty acids that affect lipid metabolism and cause lipotoxicity or lipid droplet formation. It indicates that not only saturation or monounsaturation of fatty acids plays a role in hepatic lipotoxicity but also Myr inhibition exasperates lipoapoptosis through ceramide in-direct pathway. Using the techniques presented in this study, we can potentially investigate the mechanism of lipid metabolism and the heterogeneous development of NAFLD. PMID: 30400243 [PubMed - in process]

Omics research project on prospective cohort studies from the Tohoku Medical Megabank Project.

Thu, 08/11/2018 - 14:34
Related Articles Omics research project on prospective cohort studies from the Tohoku Medical Megabank Project. Genes Cells. 2018 Jun;23(6):406-417 Authors: Koshiba S, Motoike I, Saigusa D, Inoue J, Shirota M, Katoh Y, Katsuoka F, Danjoh I, Hozawa A, Kuriyama S, Minegishi N, Nagasaki M, Takai-Igarashi T, Ogishima S, Fuse N, Kure S, Tamiya G, Tanabe O, Yasuda J, Kinoshita K, Yamamoto M Abstract Population-based prospective cohort studies are indispensable for modern medical research as they provide important knowledge on the influences of many kinds of genetic and environmental factors on the cause of disease. Although traditional cohort studies are mainly conducted using questionnaires and physical examinations, modern cohort studies incorporate omics and genomic approaches to obtain comprehensive physical information, including genetic information. Here, we report the design and midterm results of multi-omics analysis on population-based prospective cohort studies from the Tohoku Medical Megabank (TMM) Project. We have incorporated genomic and metabolomic studies in the TMM cohort study as both metabolome and genome analyses are suitable for high-throughput analysis of large-scale cohort samples. Moreover, an association study between the metabolome and genome show that metabolites are an important intermediate phenotype connecting genetic and lifestyle factors to physical and pathologic phenotypes. We apply our metabolome and genome analyses to large-scale cohort samples in the following studies. PMID: 29701317 [PubMed - indexed for MEDLINE]

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