PubMed

Phosphatidylcholine PC ae C44:6 in cerebrospinal fluid is a sensitive biomarker for bacterial meningitis. J Transl Med. 2020 Jan 07;18(1):9 Authors: de Araujo LS, Pessler K, Sühs KW, Novoselova N, Klawonn F, Kuhn M, Kaever V, Müller-Vahl K, Trebst C, Skripuletz T, Stangel M, Pessler F Abstract BACKGROUND: The timely diagnosis of bacterial meningitis is of utmost importance due to the need to institute antibiotic treatment as early as possible. Moreover, the differentiation from other causes of meningitis/encephalitis is critical because of differences in management such as the need for antiviral or immunosuppressive treatments. Considering our previously reported association between free membrane phospholipids in cerebrospinal fluid (CSF) and CNS involvement in neuroinfections we evaluated phosphatidylcholine PC ae C44:6, an integral constituent of cell membranes, as diagnostic biomarker for bacterial meningitis. METHODS: We used tandem mass spectrometry to measure concentrations of PC ae C44:6 in cell-free CSF samples (n = 221) from patients with acute bacterial meningitis, neuroborreliosis, viral meningitis/encephalitis (herpes simplex virus, varicella zoster virus, enteroviruses), autoimmune neuroinflammation (anti-NMDA-receptor autoimmune encephalitis, multiple sclerosis), facial nerve and segmental herpes zoster (shingles), and noninflammatory CNS disorders (Bell's palsy, Tourette syndrome, normal pressure hydrocephalus). RESULTS: PC ae C44:6 concentrations were significantly higher in bacterial meningitis than in all other diagnostic groups, and were higher in patients with a classic bacterial meningitis pathogen (e.g. Streptococcus pneumoniae, Neisseria meningitidis, Staphylococcus aureus) than in those with less virulent or opportunistic pathogens as causative agents (P = 0.026). PC ae C44:6 concentrations were only moderately associated with CSF cell count (Spearman's ρ = 0.45; P = 0.009), indicating that they do not merely reflect neuroinflammation. In receiver operating characteristic curve analysis, PC ae C44:6 equaled CSF cell count in the ability to distinguish bacterial meningitis from viral meningitis/encephalitis and autoimmune CNS disorders (AUC 0.93 both), but had higher sensitivity (91% vs. 41%) and negative predictive value (98% vs. 89%). A diagnostic algorithm comprising cell count, lactate and PC ae C44:6 had a sensitivity of 97% (specificity 87%) and negative predictive value of 99% (positive predictive value 61%) and correctly diagnosed three of four bacterial meningitis samples that were misclassified by cell count and lactate due to low values not suggestive of bacterial meningitis. CONCLUSIONS: Increased CSF PC ae C44:6 concentrations in bacterial meningitis likely reflect ongoing CNS cell membrane stress or damage and have potential as additional, sensitive biomarker to diagnose bacterial meningitis in patients with less pronounced neuroinflammation. PMID: 31910875 [PubMed - in process]

Urine metabolomics signatures in reversible cerebral vasoconstriction syndrome. Cephalalgia. 2020 Jan 07;:333102419897621 Authors: Hsu WH, Wang SJ, Chao YM, Chen CJ, Wang YF, Fuh JL, Chen SP, Lin YL Abstract BACKGROUND: The pathophysiology of reversible cerebral vasoconstriction syndrome is unclear. An unbiased systems-based approach might help to illustrate the metabolite profiling and underlying pathophysiology. METHODS: Urine samples were collected from reversible cerebral vasoconstriction syndrome patients and matched controls recruited in Taipei Veterans General Hospital. 1H-Nuclear magnetic resonance was used to initially explore the metabolic profile, and liquid chromatography tandem mass spectrometry was then used to identify metabolic alterations in reversible cerebral vasoconstriction syndrome. Untargeted metabolite screening was randomly performed on 10 reversible cerebral vasoconstriction syndrome patients and 10 control subjects in the discovery phase. The selected untargeted metabolites were further validated on 47 reversible cerebral vasoconstriction syndrome patients during their ictal stage (with 40 of them having remission samples) and 47 controls in the replication phase. RESULTS AND CONCLUSION: Six metabolites-hippurate, citrate, 1,3,7-trimethyluric acid, ascorbic acid, D-glucurono-6,3-lactone, and D-threo-isocitric acid-with t-test derived p-value < 0.05 and VIP score >1, were identified as potential urine signatures that can well distinguish reversible cerebral vasoconstriction syndrome subjects at ictal stage from controls. Among them, citrate, hippurate, ascorbic acid, and D-glucurono-6,3-lactone were significantly lower, and 1,3,7-trimethyluric acid and D-threo-isocitric acid were higher in reversible cerebral vasoconstriction syndrome patients. Of these, four selected metabolites, citrate, D-glucurono-6,3-lactone, ascorbic acid, and 1,3,7-trimethyluric acid, returned to normal levels in remission. These metabolites are related to pathways associated with free radical scavenging, with the hub molecules being associated with endothelial dysfunction or sympathetic overactivity. Whether these metabolites and their implicated networks play a role in the pathogenesis of reversible cerebral vasoconstriction syndrome remains to be confirmed. PMID: 31910660 [PubMed - as supplied by publisher]

Related Articles Proteome Analysis Using Gel-LC-MS/MS. Curr Protoc Protein Sci. 2019 06;96(1):e93 Authors: Goldman AR, Beer LA, Tang HY, Hembach P, Zayas-Bazan D, Speicher DW Abstract This article describes processing of protein samples using 1D SDS gels prior to protease digestion for proteomics workflows that subsequently utilize reversed-phase nanocapillary ultra-high-pressure liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS). The resulting LC-MS/MS data are used to identify peptides and thereby infer proteins present in samples ranging from simple mixtures to very complex proteomes. Bottom-up proteome studies usually involve quantitative comparisons across several or many samples. For either situation, 1D SDS gels represent a simple, widely available technique that can be used to either fractionate complex proteomes or rapidly clean up low microgram samples with minimal losses. After gel separation and staining/destaining, appropriate gel slices are excised, and in-gel reduction, alkylation, and protease digestion are performed. Digests are then processed for LC-MS/MS analysis. Protocols are described for either sample fractionation with high-throughput processing of many samples or simple cleanup without fractionation. An optional strategy is to conduct in-solution reduction and alkylation prior to running gels, which is advantageous when a large number of samples will be separated into large numbers of fractions. Optimization of trypsin digestion parameters and comparison to in-solution protease digestion are also described. © 2019 by John Wiley & Sons, Inc. PMID: 31180188 [PubMed - indexed for MEDLINE]

29 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 2020/01/08PubMed 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.

24 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 2020/01/07PubMed 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.

24 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 2020/01/07PubMed 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.

High-throughput metabolomics reveals the perturbed metabolic pathways and biomarkers of Yang Huang syndrome as potential targets for evaluating the therapeutic effects and mechanism of geniposide. Front Med. 2020 Jan 03;: Authors: Fang H, Zhang A, Zhou X, Yu J, Song Q, Wang X Abstract High-throughput metabolomics can clarify the underlying molecular mechanism of diseases via the qualitative and quantitative analysis of metabolites. This study used the established Yang Huang syndrome (YHS) mouse model to evaluate the efficacy of geniposide (GEN). Urine metabolic data were quantified by ultraperformance liquid chromatography-tandem mass spectrometry. The non-target screening of the massive biological information dataset was performed, and a total of 33 metabolites, including tyramine glucuronide, aurine, and L-cysteine, were identified relating to YHS. These differential metabolites directly participated in the disturbance of phase I reaction and hydrophilic transformation of bilirubin. Interestingly, they were completely reversed by GEN. While, as the auxiliary technical means, we also focused on the molecular prediction and docking results in network pharmacological and integrated analysis part. We used integrated analysis to communicate the multiple results of metabolomics and network pharmacology. This study is the first to report that GEN indirectly regulates the metabolite "tyramine glucuronide" through its direct effect on the target heme oxygenase 1 in vivo. Meanwhile, heme oxygenase-1, a prediction of network pharmacology, was the confirmed metabolic enzyme of phase I reaction in hepatocytes. Our study indicated that the combination of high-throughput metabolomics and network pharmacology is a robust combination for deciphering the pathogenesis of the traditional Chinese medicine (TCM) syndrome. PMID: 31901116 [PubMed - as supplied by publisher]

Related Articles Overexpression of the histidine triad nucleotide-binding protein 2 protects cardiac function in the adult mice after acute myocardial infarction. Acta Physiol (Oxf). 2020 Jan 03;:e13439 Authors: Fan M, Chen Z, Huang Y, Xia Y, Chen A, Lu D, Wu Y, Zhang N, Zhang P, Li S, Chen J, Zhang Y, Aijun S, Yunzeng Z, Hu K, Juying Q, Ge J Abstract AIM: To explore the role of the histidine triad nucleotide-binding 2 (HINT2) protein in heart failure. METHODS: Neonatal mouse ventricle myocytes (NMVMs) and myocardial infarction-induced heart failure mice were used for in vitro or in vivo experiments. Adenovirus (ADV) and adeno-associated virus serum type 9 (AAV9) vectors were used to regulate HINT2 expression. The expression of HINT2 was determined by quantifying the mRNA and protein levels. Cell survival was analysed using the CCK-8 kit and TUNEL staining. Mitochondrial function was determined by the mitochondrial membrane potential and oxygen consumption rates. AAV9-HINT2 was injected 24 h post myocardial infarction following which transthoracic echocardiography and histological analyses were performed after 4 weeks. Positron emission tomography tomography-computed tomography (PET/CT) and targeted metabolomics analyses were used to explore the metabolic status in vivo. NAD levels were measured using a colorimetric kit. Computer-simulated rigid body molecular docking was performed using AUTODOCK4. Molecule binding kinetics assays were performed using biolayer interferometry. RESULTS: HINT2 was downregulated in NMVMs in hypoxia. ADV-HINT2-induced HINT2 overexpression improved NMVM survival after exposure to hypoxia. Mitochondrial function was preserved in the ADV-HINT2 group under hypoxic conditions. In vivo experiments showed that cardiac function and metabolic status was preserved by HINT2 overexpression. HINT2 overexpression restored mitochondrial NAD levels; this was dependent on nicotinamide mononucleotide(NMN）. Using computer-simulated molecular docking analysis and biolayer interferometry, we observed that HINT2 potentially binds and associates with NMN. CONCLUSION: HINT2 overexpression protects cardiac function in adult mice after myocardial infarction by maintaining mitochondrial NAD homeostasis. PMID: 31900976 [PubMed - as supplied by publisher]

Related Articles Normalized testosterone glucuronide (TG/AG) as a potential urinary biomarker for highly variable UGT2B17 in children 7 to 18 years. Clin Pharmacol Ther. 2020 Jan 03;: Authors: Zhang H, Basit A, Wolford C, Chen KF, Gaedigk A, Lin YS, Leeder JS, Prasad B Abstract UDP-glucuronosyltransferase 2B17 (UGT2B17) is a highly variable androgen- and drug-metabolizing enzyme. UGT2B17 exhibits a unique ontogeny profile characterized by a dramatic increase in hepatic protein expression from pre-pubertal age to adulthood. Age, sex, copy number variation (CNV), and single nucleotide polymorphisms only explain 26% of variability in protein expression, highlighting the need for a phenotypic biomarker for predicting inter-individual variability in glucuronidation of UGT2B17 substrates. Here we propose testosterone glucuronide (TG) normalized by androsterone glucuronide (TG/AG) as a urinary UGT2B17 biomarker, and examine the associations between urinary TG/AG and age, sex, and CNV. We performed targeted metabolomics of 12 androgen conjugates with LC-MS/MS in 63 pediatric subjects ages 7 to 18 years followed over 7 visits in 3 years. Consistent with the reported developmental trajectory of UGT2B17 protein expression, urinary TG/AG is significantly associated with age, sex, and CNV. In conclusion, TG/AG shows promise as a phenotypic urinary UGT2B17 biomarker. PMID: 31900930 [PubMed - as supplied by publisher]

Related Articles Effects of the entomopathogenic fungus Metarhizium flavoviride on the fat body lipid composition of Zophobas morio larvae (Coleoptera: Tenebrionidae). Naturwissenschaften. 2020 Jan 03;107(1):7 Authors: Gołębiowski M, Urbanek A, Pietrzak A, Naczk AM, Bojke A, Tkaczuk C, Stepnowski P Abstract Insects employ different defense strategies against fungal infections and chemicals. We aimed to identify the lipid compositions of the fat body of Zophobas morio larvae before and after fungal infection with the entomopathogenic fungus Metarhizium flavoviride. We used gas chromatography-mass spectrometry to analyze lipid extracts of the fat body isolated of Z. morio 2, 5, and 7 days after fungal infection (treatment group) and compared it with the lipid extracts in a control group injected with physiological isotonic saline. In all the samples, fatty acids were the most abundant compound found in the fat body extracts, with hexadecanoic acid/C16:0 being the most abundant lipid. However, the types and concentrations of lipids changed after fungal infection, likely as an immune response. The most considerable changes occurred in the concentrations of long-chain fatty acids, i.e., hexadecanoic acid/C16:0, octadecenoic acid/C18:1, and octadecanoic acid/C18:0. Contents of methyl ester increased significantly after infection, but that of other esters, especially octanoic acid decyl ester/OADE, decreased on the 5th day after infection. To the best of our knowledge, this is the first detailed analysis of the changes in the lipid composition of the fat body of Z. morio larvae as a result of fungal infection. Our results suggest that entomopathogenic fungal infection affects the internal lipid composition of insects, potentially as a way of adjusting to such infection. These results can help understand infection processes and defense strategies of insects against fungal infection. Ultimately, they can contribute to the creation of more effective chemicals against pest insects. PMID: 31900598 [PubMed - in process]

Related Articles A variant near DHCR24 associates with microstructural properties of white matter and peripheral lipid metabolism in adolescents. Mol Psychiatry. 2020 Jan 03;: Authors: Sliz E, Shin J, Syme C, Patel Y, Parker N, Richer L, Gaudet D, Bennett S, Paus T, Pausova Z Abstract Visceral adiposity has been associated with altered microstructural properties of white matter in adolescents. Previous evidence suggests that circulating phospholipid PC(16:0/2:0) may mediate this association. To investigate the underlying biology, we performed a genome-wide association study (GWAS) of the shared variance of visceral fat, PC(16:0/2:0), and white matter microstructure in 872 adolescents from the Saguenay Youth Study. We further studied the metabolomic profile of the GWAS-lead variant in 931 adolescents. Visceral fat and white matter microstructure were assessed with magnetic resonance imaging. Circulating metabolites were quantified with serum lipidomics and metabolomics. We identified a genome-wide significant association near DHCR24 (Seladin-1) encoding a cholesterol-synthesizing enzyme (rs588709, p = 3.6 × 10-8); rs588709 was also associated nominally with each of the three traits (white matter microstructure: p = 2.1 × 10-6, PC(16:0/2:0): p = 0.005, visceral fat: p = 0.010). We found that the metabolic profile associated with rs588709 resembled that of a TM6SF2 variant impacting very low-density lipoprotein (VLDL) secretion and was only partially similar to that of a HMGCR variant. This suggests that the effect of rs588709 on VLDL lipids may arise due to altered phospholipid rather than cholesterol metabolism. The rs588709 was also nominally associated with circulating concentrations of omega-3 fatty acids in interaction with visceral fat and PC(16:0/2:0), and these fatty acid measures showed robust associations with white matter microstructure. Overall, the present study provides evidence that the DHCR24 locus may link peripheral metabolism to brain microstructure, an association with implications for cognitive impairment. PMID: 31900429 [PubMed - as supplied by publisher]

Related Articles Epigenetics meets proteomics in an epigenome-wide association study with circulating blood plasma protein traits. Nat Commun. 2020 Jan 03;11(1):15 Authors: Zaghlool SB, Kühnel B, Elhadad MA, Kader S, Halama A, Thareja G, Engelke R, Sarwath H, Al-Dous EK, Mohamoud YA, Meitinger T, Wilson R, Strauch K, Peters A, Mook-Kanamori DO, Graumann J, Malek JA, Gieger C, Waldenberger M, Suhre K Abstract DNA methylation and blood circulating proteins have been associated with many complex disorders, but the underlying disease-causing mechanisms often remain unclear. Here, we report an epigenome-wide association study of 1123 proteins from 944 participants of the KORA population study and replication in a multi-ethnic cohort of 344 individuals. We identify 98 CpG-protein associations (pQTMs) at a stringent Bonferroni level of significance. Overlapping associations with transcriptomics, metabolomics, and clinical endpoints suggest implication of processes related to chronic low-grade inflammation, including a network involving methylation of NLRC5, a regulator of the inflammasome, and associated pQTMs implicating key proteins of the immune system, such as CD48, CD163, CXCL10, CXCL11, LAG3, FCGR3B, and B2M. Our study links DNA methylation to disease endpoints via intermediate proteomics phenotypes and identifies correlative networks that may eventually be targeted in a personalized approach of chronic low-grade inflammation. PMID: 31900413 [PubMed - in process]

Related Articles Tissue-specific analysis of lipid species in Drosophila during overnutrition by UHPLC-MS/MS and MALDI-MSI. J Lipid Res. 2020 Jan 03;: Authors: Tuthill BF, Searcy LA, Yost RA, Musselman LP Abstract Diets high in calories can be used to model metabolic diseases including obesity and its associated comorbidities, in animals.  Drosophila melanogaster fed high-sugar diets exhibit complications of human obesity including hyperglycemia, hyperlipidemia, insulin resistance, cardiomyopathy, increased susceptibility to infection, and reduced longevity. We hypothesize that lipid storage in the high sugar-fed fly's fat body reaches a maximum capacity, resulting in the accumulation of toxic lipids in other tissues, or lipotoxicity.  We took two approaches to characterize tissue-specific lipotoxicity. Ultra-high-performance liquid chromatography- tandem mass spectrometry (UHPLC-MS/MS) and matrix-assisted laser desorption/ionization - mass spectrometry imaging (MALDI-MSI) enabled spatial and temporal localization of lipid species in the fat body, heart, and hemolymph. Substituent chain length was diet-dependent, with fewer odd-chain esterified fatty acids on high sugar diets in all sample types. By contrast, dietary effects on double-bond content differed among organs, consistent with a model where some substituent pools are shared, and others are spatially restricted. Both di- and tri-glycerides increased on high sugar diets in all sample types, similar to observations in obese humans. Interestingly, there were dramatic effects of sugar feeding on lipid ethers, which have not been previously associated with lipotoxicity. Taken together, we have identified candidate endocrine mechanisms and molecular targets that may be involved in metabolic disease and lipotoxicity. PMID: 31900315 [PubMed - as supplied by publisher]

22 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 2020/01/04PubMed 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.

22 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 2020/01/04PubMed 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 2020/01/03PubMed 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 2020/01/03PubMed 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.

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 2020/01/02PubMed 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.

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 2020/01/02PubMed 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 2020/01/01PubMed 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.