PubMed

Related Articles Metagenomic insights into resistant starch degradation by human gut microbiota. Appl Environ Microbiol. 2018 Sep 28;: Authors: Vital M, Howe A, Bergeron N, Krauss RM, Jansson JK, Tiedje JM Abstract Several studies monitoring alterations of the community structure upon resistant starch (RS) interventions are available, although comprehensive function-based analyses are lacking. Recently, a multiomics approach based on 16S rRNA gene-sequencing, metaproteomics and metabolomics on fecal samples from individuals subjected to high and low doses of type-2 RS (RS2; 48 g and 3 g/2500 kcal, respectively, daily for 2 weeks) in a cross-over intervention experiment was performed. In the present study, we did pathway-based metagenomic analyses on samples from a subset of individuals (n=12) from that study to get additional, detailed insights into the functional structure at high resolution during RS2 intervention. A mechanistic framework based on obtained results is proposed where primary degradation was governed by Firmicutes, with Ruminococcus bromii as a major taxon involved, providing fermentation substrates and increased acetate concentrations for growth of various major butyrate-producers exhibiting the enzyme butyryl-CoA:acetate CoA-transferase. H2-scavenging sulfite reducers and acetogens concurrently increased. Individual responses of gut microbiota were noted where seven of the 12 participants displayed all features of the outlined pattern, whereas four individuals showed mixed behavior and one subject was unresponsive. Intervention order did not affect the outcome emphasizing a constant substrate supply for maintaining specific functional communities.Significance Manipulating gut microbiota is increasingly recognized as a promising approach to reduce various non-communicable diseases such as obesity and type-2-diabetes. Specific dietary supplements including resistant starches (RS) are often in focus, yet comprehensive insights into functional responses of microbiota are largely lacking. Furthermore, unresponsiveness in certain individuals is only poorly understood. Our data indicate that distinct parts of microbiota work jointly to degrade RS and successively form health-promoting fermentation end products. It highlights the need to consider both primary degraders and specific, more downstream acting bacterial groups in order to achieve desired intervention outcomes. The gained insights will assist the design of personalized treatment strategies based on individual's microbiota. PMID: 30266729 [PubMed - as supplied by publisher]

Related Articles Clinical and metabolic characterization of obese subjects without non-alcoholic fatty liver: a targeted metabolomics approach. Diabetes Metab. 2018 Sep 25;: Authors: Feldman A, Eder SK, Felder TK, Paulweber B, Zandanell S, Stechemesser L, Schranz M, Strebinger G, Huber-Schönauer U, Niederseer D, Patsch W, Weghuber D, Tevini J, Datz C, Aigner E Abstract INTRODUCTION: -: As a small proportion of obese individuals do not develop metabolic complications and non-alcoholic fatty liver disease (NAFLD), this study aimed to provide a comprehensive clinical, metabolic and genetic description of obese subjects with healthy livers. METHODS: -: A total of 183 subjects were stratified, according to BMI, presence of metabolic syndrome, biochemical liver tests and hepatic steatosis on ultrasound, into: (i) lean controls (n = 69); (ii) obese healthy (n = 50); and (iii) obese NAFLD (n = 62) groups. Detailed clinical, genetic and metabolic evaluations were then performed. RESULTS: -: Obese healthy subjects did not differ in glucose parameters from lean controls, and had a lower rate of minor TM6SF2 gene variants compared with obese NAFLD (2/49 vs 11/60, respectively; P =  0.035) and lean controls (13/64; P =  0.035), but significantly higher leptin concentrations than lean controls (P <  0.001); they also higher adiponectin concentrations (P <  0.001), and lower TNF-α and IL-6 concentrations (P =  0.01 and P <  0.001, respectively), than obese NAFLD subjects. Also, metabolomic studies identified ether- and ester-containing phospholipids [PC ae C44:6, PC ae C42:5, PC aa C40:4; P <  0.001, corrected by the false discovery rate (FDR) method] and found that the amino-acids lysine, glycine and isoleucine (FDR < 0.001) differed between the two obese groups, but not between lean controls and obese healthy subjects. CONCLUSION: -: Obese people with healthy livers are characterized by intact glucose homoeostasis, lower proinflammatory cytokine levels, and higher adiponectin and leptin concentrations compared with obese people with NAFLD. In addition, the major allele of TM6SF2, a set of phosphatidylcholines and several amino acids are associated with healthy livers in obesity. PMID: 30266576 [PubMed - as supplied by publisher]

Related Articles Plasma metabolomics pilot study suggests age and sex-based differences in the metabolic response to traumatic injury. Injury. 2018 Sep 17;: Authors: Lusczek ER, Myers C, Popovsky K, Mulier K, Beilman G, Sawyer R Abstract INTRODUCTION: Age and sex affect outcomes from trauma. Older patients tend to be under-triaged, consume more healthcare resources, and experience worse outcomes relative to younger patients. Sex has also been associated with different outcomes, with women experiencing better outcomes than men. While baseline metabolism differs with both age and sex, no study has examined how these differences affect the response to trauma. We used high-throughput metabolomics to assess metabolic differences associated with blunt trauma according to age and sex. METHODS: Metabolic profiles were constructed using nuclear magnetic resonance spectroscopy for trauma patients age 21-40 years (n = 20, 55% male) and >65 years (n = 22, 41% male) from plasma samples obtained on Day 1 and Day 3 of each patient's hospital stay. These were compared to profiles constructed from plasma obtained from healthy controls of the same age (21-40: n = 23, 61% male; 65+: n = 26, 50% male). Differences in metabolic profiles were assessed with partial least squares discriminant analysis. RESULTS: Trauma elicits an overwhelming global stress response that includes more subtle differences in metabolism related to age and gender. Significant differences due to normal aging were also identified. Many of the metabolites measured were present in similar levels in healthy controls age 65+ as they were in trauma patients of all ages. Sex-based differences in metabolism were observed in younger trauma patients on Day 3 but not in older patients. CONCLUSIONS: Differences in energy metabolism and oxidative stress were implicated in the response to trauma in all patients. Older trauma patients may enter the trauma state with pre-existing oxidative stress and energy deficits that complicate recovery. Sex-based differences in recovery from trauma support the large body of work demonstrating the role of sex in recovery from trauma. PMID: 30266291 [PubMed - as supplied by publisher]

Related Articles Integration of Omics Approaches toward Understanding Whitefly Transmission of Viruses. Adv Virus Res. 2018;102:199-223 Authors: Wintermantel WM Abstract Viruses transmitted by whiteflies are predominantly classified as having either persistent circulative or semipersistent transmission, and the majority of studies have addressed transmission of viruses in the genera Begomovirus (family Geminiviridae) and Crinivirus (family Closteroviridae), respectively. Early studies on vector transmission primarily addressed individual aspects of transmission; however, with the breadth of new technology now available, an increasingly greater number of studies involve coordinated research that is beginning to assemble a more complete picture of how whiteflies and viruses have coevolved to facilitate transmission. In particular the integration of gene expression and metabolomic studies into broader research topics is providing knowledge of changes within the whitefly vector in response to the presence of viruses that would have been impossible to identify previously. Examples include comparative studies on the response of Bemisia tabaci to begomovirus and crinivirus infection of common host plants, evolution of whitefly endosymbiont relationships, and opportunities to evaluate responses to specific transmission-related events. Integration of metabolomics, as well as the application of electrical penetration graphing, can lead to an ability to monitor the changes that occur in vector insects associated with specific aspects of virus transmission. Through gaining more complete knowledge of the mechanisms behind whitefly transmission of viruses new control strategies will undoubtedly emerge for control of whiteflies and the viruses they transmit. PMID: 30266174 [PubMed - in process]

Related Articles Effects of red blood cell (RBC) transfusion on sickle cell disease recipient plasma and RBC metabolism. Transfusion. 2018 Sep 28;: Authors: Culp-Hill R, Srinivasan J, Gehrke S, Kamyszek R, Ansari A, Shah N, Welsby I, D'Alessandro A Abstract BACKGROUND: Exchange transfusion is a mainstay in the treatment of sickle cell anemia. Transfusion recipients with sickle cell disease (SCD) can be transfused over 10 units per therapy, an intervention that replaces circulating sickle red blood cells (RBCs) with donor RBCs. Storage of RBCs makes the intervention logistically feasible. The average storage duration for units transfused at the Duke University Medical Center is approximately 2 weeks, a time window that should anticipate the accumulation of irreversible storage lesion to the RBCs. However, no metabolomics study has been performed to date to investigate the impact of exchange transfusion on recipients' plasma and RBC phenotypes. STUDY DESIGN AND METHODS: Plasma and RBCs were collected from patients with sickle cell anemia before transfusion and within 5 hours after exchange transfusion with up to 11 units, prior to metabolomics analyses. RESULTS: Exchange transfusion significantly decreased plasma levels of markers of systemic hypoxemia like lactate, succinate, sphingosine 1-phosphate, and 2-hydroxyglutarate. These metabolites accumulated in transfused RBCs, suggesting that RBCs may act as scavenger/reservoirs. Transfused RBCs displayed higher glycolysis, total adenylate pools, and 2,3-diphosphoglycerate, consistent with increased capacity to deliver oxygen. Plasma levels of acyl-carnitines and amino acids decreased, while fatty acids and potentially harmful phthalates increased upon exchange transfusion. CONCLUSION: Metabolic phenotypes confirm the benefits of the transfusion therapy in transfusion recipients with SCD and the reversibility of some of the metabolic storage lesion upon transfusion in vivo in 2-week-old RBCs. However, results also suggest that potentially harmful plasticizers are transfused. PMID: 30265764 [PubMed - as supplied by publisher]

Related Articles GC-MS based metabolomics study of fermented stipe of Sparassis crispa. Food Sci Biotechnol. 2018 Aug;27(4):1111-1118 Authors: Seo SH, Park SE, Kim EJ, Son HS Abstract GC-MS coupled with multivariate statistical analysis was performed to understand metabolites difference between pileus and stipe of Sparassis crispa (cauliflower mushroom). Metabolic changes of S. crispa after fermentation by different microorganisms were also investigated. PCA score plot showed a clear separation between pileus and stipe of S. crispa regardless of fermentation. However, OPLS-DA score plot showed clear separation among fermented S. crispa samples according to microbial strain used, indicating that both pileus and stipe fermented with the same strain showed similar pattern of metabolites. Fructose, lactic acid, citric acid, malic acid, and phosphoric acid were metabolites that contributed to the discrimination of fermented S. crispa samples. Results of this study provide novel insights into intrinsic characteristics of stipe of S. crispa which is cheaper than pileus as ingredient for alternative functional food. PMID: 30263841 [PubMed]

Related Articles Compositional analyses of diverse phytochemicals and polar metabolites from different-colored potato (Solanum tubersum L.) tubers. Food Sci Biotechnol. 2017;26(5):1379-1389 Authors: Lee W, Yeo Y, Oh S, Cho KS, Park YE, Park SK, Lee SM, Cho HS, Park SY Abstract Lipophilic bioactive compounds and hydrophilic primary metabolites from potato (solanum tubersum L.) tubers with different-colored flesh (white-, yellow-, red-, and purple) were characterized. The carotenoid content was relatively higher in red-colored potatoes, in which lutein was most plentiful. Among the other lipophilic compounds analyzed, including policosanols, tocopherols, and phytosterols, octacosanol was measured in the largest amount, followed by β-sitosterol, irrespective of color variations. Forty-three hydrophilics consisting of amino acids, organic acids, sugars, and sugar alcohols and 18 lipophilics were subjected to data-mining processes. The results of multivariate statistical analyses clearly distincted the different varieties and separated red-fleshed potatoes from other color-fleshed potatoes according to abundance of amino acids, sugars, and carotenoids. This study confirmed the metabolic association-related biochemical pathway between metabolite characteristic and color differences in potato tubers. These results can facilitate understanding the metabolic differences among diverse colored potatoes and provide fruitful information for genetic engineering of potato cultivars. PMID: 30263673 [PubMed]

Related Articles Modeling methylation data as an additional genetic variance component. BMC Proc. 2018;12(Suppl 9):29 Authors: Almeida M, Peralta J, Garcia J, Diego V, Goring H, Williams-Blangero S, Blangero J Abstract High-throughput platforms allow the characterization of thousands of previously known methylation sites. These platforms have great potential for investigating the epigenetic effects that are partially responsible for gene expression control. Methylation sites provide a bridge for the investigation of real-time environmental contributions on genomic events by the alteration of methylation status of those sites. Using the data provided by GAW20's organization committee, we calculated the heritability estimates of each cytosine-phosphate-guanine (CpG) island before and after the use of fenofibrate, a lipid-control drug. Surprisingly, we detected substantially high heritability estimates before drug usage. This somewhat unexpected high sample correlation was corrected by the use of principal components and the distributions of heritability estimates before and after fenofibrate treatment, which made the distributions comparable. The methylation sites located near a gene were collected and a genetic relationship matrix estimated to represent the overall correlation between samples. We implemented a random-effect association test to screen genes whose methylation patterns partially explain the observable high-density lipoprotein (HDL) heritability. Our leading association was observed for the TMEM52 gene that encodes a transmembrane protein, and is largely expressed in the liver, had not been previously associated with HDL until this manuscript. Using a variance component decomposition framework with the linear mixed model allows the integration of data from different sources, such as methylation, gene expression, metabolomics, and proteomics. The decomposition of the genetic variance component decomposition provides a flexible analytical approach for the challenges of this new omics era. PMID: 30263043 [PubMed]

Related Articles Aphid infestation in the phyllosphere affects primary metabolic profiles in the arbuscular mycorrhizal hyphosphere. Sci Rep. 2018 Sep 27;8(1):14442 Authors: Cabral C, Wollenweber B, António C, Rodrigues AM, Ravnskov S Abstract While effects of (a)biotic stress events in the phyllosphere have been studied intensively, possible influences of stress on the arbuscular mycorrhizal hyphosphere has scarcely been investigated. We hypothesised that stress challenge in the phyllosphere could alter primary metabolite profiles of the hyphosphere - the mycelial network connecting plants. Donor plants, connected to receiver plants by mycelial networks, were aphid-challenged during 84 h. Primary metabolite profiles in the hyphosphere were investigated. Gene-expression of plant defence gene PR1 was measured in one of the receiver plants during the challenge. Hexose levels in the hyphosphere increased when donor plants were aphid-challenged. This change in metabolic profile was influenced by leaf sampling from receiver plant. PR1 expression increased in donor plants 48 h after challenge, and consequently 60 h after, in receiver plants. We conclude that aphid infestation of donor plants modified primary carbon metabolism in the hyphosphere. Plant defence response in receiver plants, occurred 12 h after detection of response in the aphid-challenged donor plants. While this work is the first to reveal primary metabolic profiles of the AM hyphosphere, more work is needed to elucidate the possible role of transient changes of hexose metabolism in stress response and signalling processes in the hyphosphere of connected plants. PMID: 30262837 [PubMed - in process]

Related Articles Metabolomic Alterations in Thyrospheres and Adherent Parental Cells in Papillary Thyroid Carcinoma Cell Lines: A Pilot Study. Int J Mol Sci. 2018 Sep 27;19(10): Authors: Caria P, Tronci L, Dettori T, Murgia F, Santoru ML, Griffin JL, Vanni R, Atzori L Abstract Papillary thyroid carcinoma (PTC), is characterized by a heterogeneous group of cells, including cancer stem cells (CSCs), crucially involved in tumor initiation, progression and recurrence. CSCs appear to have a distinct metabolic phenotype, compared to non-stem cancer cells. How they adapt their metabolism to the cancer process is still unclear, and no data are yet available for PTC. We recently isolated thyrospheres, containing cancer stem-like cells, from B-CPAP and TPC-1 cell lines derived from PTC of the BRAF-like expression profile class, and stem-like cells from Nthy-ori3-1 normal thyreocyte-derived cell line. In the present study, gas chromatography/mass spectrometry metabolomic profiles of cancer thyrospheres were compared to cancer parental adherent cells and to non cancer thyrospheres profiles. A statistically significant decrease of glycolytic pathway metabolites and variations in Krebs cycle metabolites was found in thyrospheres versus parental cells. Moreover, cancer stem-like cells showed statistically significant differences in Krebs cycle intermediates, amino acids, cholesterol, and fatty acids content, compared to non-cancer stem-like cells. For the first time, data are reported on the metabolic profile of PTC cancer stem-like cells and confirm that changes in metabolic pathways can be explored as new biomarkers and targets for therapy in this tumor. PMID: 30262749 [PubMed - in process]

Related Articles Central nervous involvement is common in PGM1-CDG. Mol Genet Metab. 2018 Aug 21;: Authors: Radenkovic S, Witters P, Morava E Abstract PGM1, the enzyme responsible for the reversible inter-conversion of glucose-1-P and glucose-6-P, is also involved in glycosylation, leading to a wide range of clinical manifestations, such as congenital malformations, hypoglycemia, hormonal dysregulation, myopathy, hepatopathy, and cardiomyopathy. So far, PGM1 deficiency has not been associated with central nervous system involvement or intellectual disability. Seizures and neurologic involvement in PGM1-CDG were thought to be a consequence of hypoglycemia. We reviewed all reported PGM1 deficient patients for the presence of the central nervous system involvement, their treatment and disease history. We detected 17 patients out of the 41 reported PGM1-CDG cases with significant neurologic involvement. Several of these patients had no severe hypoglycemic episodes, or were adequately treated for hypoglycemia with no recurrent episodes of low blood sugars, while one patient had no reported hypoglycemic episodes. We suggest that neurological symptoms are frequent in PGM1-CDG and could present even in the absence of hypoglycemia. The central nervous system should be assessed early on during the diagnostic process to optimize outcome in patients with PGM1-CDG. PMID: 30262252 [PubMed - as supplied by publisher]

Related Articles Metabolomics profiling of xenobiotics in elite athletes: relevance to supplement consumption. J Int Soc Sports Nutr. 2018 Sep 27;15(1):48 Authors: Al-Khelaifi F, Diboun I, Donati F, Botrè F, Alsayrafi M, Georgakopoulos C, Yousri NA, Suhre K, Elrayess MA Abstract BACKGROUND: Supplements are widely used among elite athletes to maintain health and improve performance. Despite multiple studies investigating use of dietary supplements by athletes, a comprehensive profiling of serum supplement metabolites in elite athletes is still lacking. This study aims to analyze the presence of various xenobiotics in serum samples from elite athletes of different sports, focusing on metabolites that potentially originate from nutritional supplements. METHODS: Profiling of xenobiotics in serum samples from 478 elite athletes from different sports (football, athletics, cycling, rugby, swimming, boxing and rowing) was performed using non-targeted metabolomics-based mass spectroscopy combined with ultrahigh-performance liquid chromatography. Multivariate analysis was performed using orthogonal partial least squares discriminant analysis. Differences in metabolic levels among different sport groups were identified by univariate linear models. RESULTS: Out of the 102 detected xenobiotics, 21 were significantly different among sport groups including metabolites that potentially prolong exercise tolerance (caffeic acid), carry a nootropic effect (2-pyrrolidinone), exert a potent anti-oxidant effect (eugenol, ferulic acid 4 sulfate, thioproline, retinol), or originate from drugs for different types of injuries (ectoine, quinate). Using Gaussian graphical modelling, a metabolic network that links various sport group-associated xenobiotics was constructed to further understand their metabolic pathways. CONCLUSIONS: This pilot data provides evidence that athletes from different sports exhibit a distinct xenobiotic profile that may reflect their drug/supplement use, diet and exposure to various chemicals. Because of limitation in the study design, replication studies are warranted to confirm results in independent data sets, aiming ultimately for better assessment of dietary supplement use by athletes. PMID: 30261929 [PubMed - in process]

Related Articles Sequence analysis of cell-free DNA derived from cultured human bone osteosarcoma (143B) cells. Tumour Biol. 2018 Sep;40(9):1010428318801190 Authors: Bronkhorst AJ, Wentzel JF, Ungerer V, Peters DL, Aucamp J, de Villiers EP, Holdenrieder S, Pretorius PJ Abstract The true importance of cell-free DNA in human biology, together with the potential scale of its clinical utility, is tarnished by a lack of understanding of its composition and origin. In investigating the cell-free DNA present in the growth medium of cultured 143B cells, we previously demonstrated that the majority of cell-free DNA is neither a product of apoptosis nor necrosis. In the present study, we investigated the composition and origin of this cell-free DNA population using next-generation sequencing. We found that the cell-free DNA comprises mainly of repetitive DNA, including α-satellite DNA, mini satellites, and transposons that are currently active or exhibit the capacity to become reactivated. A significant portion of these cell-free DNA fragments originates from specific chromosomes, especially chromosomes 1 and 9. In healthy adult somatic cells, the centromeric and pericentromeric regions of these chromosomes are normally densely methylated. However, in many cancer types, these regions are preferentially hypomethylated. This can lead to double-stranded DNA breaks or it can directly impair the formation of proper kinetochore structures. This type of chromosomal instability is a precursor to the formation of nuclear anomalies, including lagging chromosomes and anaphase bridges. DNA fragments derived from these structures can recruit their own nuclear envelope and form secondary nuclear structures known as micronuclei, which can localize to the nuclear periphery and bud out from the membrane. We postulate that the majority of cell-free DNA present in the growth medium of cultured 143B cells originates from these micronuclei. PMID: 30261820 [PubMed - in process]

Related Articles Adaptation of a microbead assay for the easy evaluation of traditional anti-sickling medicines: application to DREPANOSTAT and FACA. Pharm Biol. 2018 Dec;56(1):385-392 Authors: Villaret J, Marti G, Dubois F, Reybier K, Gaudre N, Haddad M, Valentin A Abstract CONTEXT: Sickle cell disease is a common inherited blood disorder affecting millions of people worldwide. Due to lack of progress in drug discovery for a suitable treatment, sufferers often turn to traditional medicines that take advantage of the plant extracts activity used by traditional healers. OBJECTIVE: This study optimizes an anti-sickling screening test to identify preparations capable of reverting sickle cells back to the morphology of normal red blood cells. We focused on the miniaturization and practicability of the assay, so that it can be adapted to the laboratory conditions commonly found in less developed countries. MATERIALS AND METHODS: We tested two traditional anti-sickling herbal medicines, FACA® and DREPANOSTAT®, composed of Zanthoxylum zanthoxyloides (Lam.) Zepern. & Timler (Rutaceae) and Calotropis procera (Aiton) Dryand. (Apocynaceae) at screening concentrations of hydroethanol extracts from 0.2 to 1 mg/mL. Potential bioactive molecules present in the extracts were profiled using Ultra High Performance Liquid Chromatography coupled with High Resolution Mass Spectrometry (UHPLC-HRMS/MS) method, identified through HRMS, MS/MS spectra and in silico fragmentation tools. RESULTS: Hydroethanol extracts of FACA® and DREPANOSTAT® showed low anti-sickling activity, inhibiting less than 10% of the sickling process. The UHPLC-HRMS/MS profiles identified 28 compounds (18 in FACA® and 15 in DREPANOSTAT®, including common compounds) among which l-phenylalanine is already described as potential anti-sickling agent. When used as positive control, 7 mg/mL phenylalanine reduced the sickled RBC to 52%. DISCUSSION AND CONCLUSIONS: This assay has been optimized for the easy screening of plant extracts or extracted compounds from bioassay guided fractionation, valuable to laboratories from less developed countries. PMID: 30261794 [PubMed - in process]

17 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 2018/09/28PubMed 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.

34 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 2018/09/27PubMed 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.

34 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 2018/09/27PubMed 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.

19 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 2018/09/26PubMed 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.

Metabolic profiling of human plasma reveals the activation of 5-lipoxygenase in the acute attack of gouty arthritis. Rheumatology (Oxford). 2018 Sep 20;: Authors: Luo Y, Wang L, Peng A, Liu JY Abstract Objective: Monosodium urate-induced inflammation plays a vital role in acute gout (AG). Inflammation is a multi-stage process involved in the acute release of arachidonic acid and its metabolites. However, the function of the metabolism of arachidonic acid and other polyunsaturated fatty acids in AG is not well understood. This study aimed to investigate the modification of polyunsaturated fatty acid metabolism by AG. Methods: Plasma samples from patients with an AG attack (n = 26) and gender-matched healthy controls (n = 26) were analysed by metabolic profiling of polyunsaturated fatty acids. The findings were further validated with a second cohort (n = 20 each group). The associated mechanisms were investigated in whole blood cells from the second cohort and neutrophils in vitro. Results: Plasma metabolic profiling revealed a significant increase in leukotriene B4 (LTB4) for AG patients in both cohorts. The increase in plasma LTB4 was accounted for by the dynamic balance between the activation of 5-lipoxygenase and CYP4F3, the former mediating the biosynthesis of LTB4 and the latter mediating its metabolism. This was supported by significantly increased transcriptional levels of 5-lipoxygenase and CYP4F3 in whole blood cells from AG patients compared with those of controls, and the uric acid-caused dose-relevant and time-dependent activation of 5-lipoxygenase and CYP4F3 at the transcriptional and molecular levels in vitro. Conclusion: Increased LTB4 in AG patients is mainly due to activation of 5-lipoxygenase. 5-Lipoxygenase inhibition may be of therapeutic value clinically. PMID: 30247644 [PubMed - as supplied by publisher]

Integrative proteomics and metabolomics analysis reveals the toxicity of cationic liposomes to human normal hepatocyte cell line L02. Mol Omics. 2018 Sep 24;: Authors: Yu J, Chen J, Zhao H, Gao J, Li Y, Li Y, Xue J, Dahan A, Sun D, Zhang G, Zhang H Abstract Cationic liposomes (CLs) are vital nonviral vectors with a wide range of applications. Although the toxicity of CLs is far lower than that of viral vectors, increasing evidence suggests that there are limited clinical applications of CLs because of their potential toxicity. In the present study, the toxicity of CLs toward L02 cells was investigated and comprehensively analyzed based on proteomics and metabolomics data. Using quantitative iTRAQ-LC-MS/MS proteomics coupled with UHPLC-Q-TOF-MS based metabolomics, we determined that exposure to CLs generated 90 significantly altered proteins and 65 altered metabolites in cells. Metabolomic analysis also showed significant alterations in metabolic pathways, including small molecules involved in energy and lipid metabolism. Proteomics revealed that exposure to CLs significantly influenced multiple proteins, including those involved in the folding of proteins and metabolism. Furthermore, the proteins participated in oxidative stress, which also influenced lipid metabolism. Overall, our findings indicate that high-throughput metabolomics and proteomics can provide insight into the toxicological mechanisms of CLs using high-resolution mass spectrometry. To our knowledge, this is the first study combining proteomics and metabolomics to investigate the potential effects of CLs on any cells. Specifically, we integrated quantitative iTRAQ-based proteomics with UHPLC-Q-TOF-MS-based metabolomics datasets to comprehensively assess the potential mechanisms of CL toxicity towards L02 cells. PMID: 30247494 [PubMed - as supplied by publisher]