Association between Brain and Plasma Glutamine Levels in Healthy Young Subjects Investigated by MRS and LC/MS.
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ABSTRACT:
SUBMITTER: Takado Y
PROVIDER: S-EPMC6682979 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-BSST860 | biostudies-other
Project description:BackgroundSex and gender have a large impact in human health and disease prediction. According to genomic/genetics, men differ from women by a limited number of genes in Y chromosome, while the phenotypes of the 2 sexes differ markedly.MethodsIn this study, serum samples from six healthy Bahraini men and women were analyzed by liquid chromatography-mass spectrometry (LC-MS/MS). Bioinformatics databases and tools were used for protein/peptide (PPs) identification and gene localization. The PPs that differed significantly (p < 0.05, ANOVA) in abundance with a fold change (FC) of ≥1.5 were identified.ResultsRevealed 20 PPs, 11 were upregulated in women with very high FC (up to 8 folds), and 9 were upregulated in men but with much lower FC. The PPs are encoded by genes located in autosomal chromosomes, indicative of sex-biased gene expression. The only PP related to sex, the sex hormone-binding globulin, was upregulated in women. The remaining PPs were involved in immunity, lipid metabolism, gene expression, connective tissue, and others, with some overlap in function.ConclusionsThe upregulated PPs in men or women are mostly reflecting the functon or risk/protection provided by the PPs to the specific sex, e.g., Apo-B100 of LDLC. Finally, the basis of sex-biased gene expression and sex phenotypic differences needs further investigation.
| S-EPMC10024626 | biostudies-literature
Project description:We present the first validated metabolic network model for analysis of flux through key pathways of tumor intermediary metabolism, including glycolysis, the oxidative and non-oxidative arms of the pentose pyrophosphate shunt, the TCA cycle as well as its anaplerotic pathways, pyruvate-malate shuttling, glutaminolysis, and fatty acid biosynthesis and oxidation. The model that is called Bonded Cumomer Analysis for application to (13)C magnetic resonance spectroscopy ((13)C MRS) data and Fragmented Cumomer Analysis for mass spectrometric data is a refined and efficient form of isotopomer analysis that can readily be expanded to incorporate glycogen, phospholipid, and other pathways thereby encompassing all the key pathways of tumor intermediary metabolism. Validation was achieved by demonstrating agreement of experimental measurements of the metabolic rates of oxygen consumption, glucose consumption, lactate production, and glutamate pool size with independent measurements of these parameters in cultured human DB-1 melanoma cells. These cumomer models have been applied to studies of DB-1 melanoma and DLCL2 human diffuse large B-cell lymphoma cells in culture and as xenografts in nude mice at 9.4 T. The latter studies demonstrate the potential translation of these methods to in situ studies of human tumor metabolism by MRS with stable (13)C isotopically labeled substrates on instruments operating at high magnetic fields (≥7 T). The melanoma studies indicate that this tumor line obtains 51% of its ATP by mitochondrial metabolism and 49% by glycolytic metabolism under both euglycemic (5 mM glucose) and hyperglycemic conditions (26 mM glucose). While a high level of glutamine uptake is detected corresponding to ~50% of TCA cycle flux under hyperglycemic conditions, and ~100% of TCA cycle flux under euglycemic conditions, glutaminolysis flux and its contributions to ATP synthesis were very small. Studies of human lymphoma cells demonstrated that inhibition of mammalian target of rapamycin (mTOR) signaling produced changes in flux through the glycolytic, pentose shunt, and TCA cycle pathways that were evident within 8 h of treatment and increased at 24 and 48 h. Lactate was demonstrated to be a suitable biomarker of mTOR inhibition that could readily be monitored by (1)H MRS and perhaps also by FDG-PET and hyperpolarized (13)C MRS methods.
| S-EPMC4908130 | biostudies-literature
Project description:Melatonin (MEL) and its chemical precursor N-acetylserotonin (NAS) are believed to be potential biomarkers for sleep-related disorders. Measurement of these compounds, however, has proven to be difficult due to their low circulating levels, especially that of NAS. Few methods offer the sensitivity, specificity and dynamic range needed to monitor MEL and its precursors and metabolites in small blood samples, such as those obtained from pediatric patients. In support of our ongoing study to determine the safety, tolerability and PK dosing strategies for MEL in treating insomnia in children with autism spectrum disorder, two highly sensitive LC-MS/MS assays were developed for the quantitation of MEL and precursor NAS at pg/mL levels in small volumes of human plasma. A validated electrospray ionization (ESI) method was used to quantitate high levels of MEL in PK studies, and a validated nanospray (nESI) method was developed for quantitation of MEL and NAS at endogenous levels. In both assays, plasma samples were processed by centrifugal membrane dialysis after addition of stable isotopic internal standards, and the components were separated by either conventional LC using a Waters SymmetryShield RP18 column (2.1?×?100 ?mm, 3.5?µm) or on a polyimide-coated, fused-silica capillary self-packed with 17?cm AquaC18 (3?µm, 125?Å). Quantitation was done using the SRM transitions m/z 233???174 and m/z 219???160 for MEL and NAS, respectively. The analytical response ratio versus concentration curves were linear for MEL (nanoflow LC: 11.7-1165? pg/mL, LC: 1165-116,500 ?pg/mL) and for NAS (nanoflow LC: 11.0-1095 ?pg/mL).
| S-EPMC3319463 | biostudies-literature
Project description:To support a phase III randomized trial of the multi-targeted tyrosine kinase inhibitor cabozantinib in neuroendocrine tumors, we developed a high-performance liquid chromatography mass spectrometry method to quantitate cabozantinib in 50 μL of human plasma. After acetonitrile protein precipitation, chromatographic separation was achieved with a Phenomenex synergy polar reverse phase (4 μm, 2 × 50 mm) column and a gradient of 0.1% formic acid in acetonitrile and 0.1% formic acid in water over a 5-min run time. Detection was performed on a Quattromicro quadrupole mass spectrometer with electrospray, positive-mode ionization. The assay was linear over the concentration range 50-5000 ng/mL and proved to be accurate (103.4-105.4%) and precise (<5.0%CV). Hemolysis (10% RBC) and use of heparin as anticoagulant did not impact quantitation. Recovery from plasma varied between 103.0-107.7% and matrix effect was -47.5 to -41.3%. Plasma freeze-thaw stability (97.7-104.9%), stability for 3 months at -80°C (103.4-111.4%), and stability for 4 h at room temperature (100.1-104.9%) were all acceptable. Incurred sample reanalysis of (N = 64) passed: 100% samples within 20% difference, -0.7% median difference and 1.1% median absolute difference. External validation showed a bias of less than 1.1%. This assay will help further define the clinical pharmacokinetics of cabozantinib.
| S-EPMC8946687 | biostudies-literature
Project description:BackgroundMetabolomics has the potential to be a powerful and sensitive approach for investigating the low molecular weight metabolite profiles present in maternal fluids and their role in pregnancy.FindingsIn this Data Note, LC-MS metabolome, lipidome and carnitine profiling data were collected from 180 healthy pregnant women, representing six time points spanning all three trimesters, and providing sufficient coverage to model the progression of normal pregnancy.ConclusionsAs a relatively large scale, real-world dataset with robust numbers of quality control samples, the data are expected to prove useful for algorithm optimization and development, with the potential to augment studies into abnormal pregnancy. All data and ISA-TAB format enriched metadata are available for download in the MetaboLights and GigaScience databases.
| S-EPMC4391677 | biostudies-literature
Project description:We have developed a simple and accurate HPLC method for measurement of fecal bile acids using phenacyl derivatives of unconjugated bile acids, and applied it to the measurement of fecal bile acids in cirrhotic patients. The HPLC method has the following steps: 1) lyophilization of the stool sample; 2) reconstitution in buffer and enzymatic deconjugation using cholylglycine hydrolase/sulfatase; 3) incubation with 0.1 N NaOH in 50% isopropanol at 60°C to hydrolyze esterified bile acids; 4) extraction of bile acids from particulate material using 0.1 N NaOH; 5) isolation of deconjugated bile acids by solid phase extraction; 6) formation of phenacyl esters by derivatization using phenacyl bromide; and 7) HPLC separation measuring eluted peaks at 254 nm. The method was validated by showing that results obtained by HPLC agreed with those obtained by LC-MS/MS and GC-MS. We then applied the method to measuring total fecal bile acid (concentration) and bile acid profile in samples from 38 patients with cirrhosis (17 early, 21 advanced) and 10 healthy subjects. Bile acid concentrations were significantly lower in patients with advanced cirrhosis, suggesting impaired bile acid synthesis.
| S-EPMC3995475 | biostudies-literature
Project description:Diet has a strong influence on many physiological processes, which in turn have important implications on a variety of pathological conditions. In this respect, microRNAs (miRNAs), a class of small non-coding RNAs playing a relevant epigenetic role in controlling gene expression, may represent mediators between the dietary intake and the healthy status. Despite great advances in the field of nutri-epigenomics, it remains unclear how miRNA expression is modulated by the diet and, specifically, the intake of specific nutrients. We investigated the whole circulating miRNome by small RNA-sequencing performed on plasma samples of 120 healthy volunteers with different dietary habits (vegans, vegetarians, and omnivores). Dietary intakes of specific nutrients were estimated for each subject from the information reported in the food-frequency questionnaire previously validated in the EPIC study. We focused hereby on the intake of 23 natural compounds (NCs) of the classes of lipids, micro-elements, and vitamins. We identified 78 significant correlations (rho > 0.300, p-value < 0.05) among the estimated daily intake of 13 NCs and the expression levels of 58 plasma miRNAs. Overall, vitamin D, sodium, and vitamin E correlated with the largest number of miRNAs. All the identified correlations were consistent among the three dietary groups and 22 of them were confirmed as significant (p-value < 0.05) by age-, gender-, and body-mass index-adjusted Generalized Linear regression Model analysis. miR-23a-3p expression levels were related with different NCs including a significant positive correlation with sodium (rho = 0.377) and significant negative correlations with lipid-related NCs and vitamin E. Conversely, the estimated intake of vitamin D was negatively correlated with the expression of the highest number of circulating miRNAs, particularly miR-1277-5p (rho = -0.393) and miR-144-3p (rho = -0.393). Functional analysis of the targets of sodium intake-correlated miRNAs highlighted terms related to cardiac development. A similar approach on targets of those miRNAs correlated with vitamin D intake showed an enrichment in genes involved in hormone metabolisms, while the response to chronic inflammation was among the top enriched processes involving targets of miRNAs negatively related with vitamin E intake. Our findings show that nutrients through the habitual diet influence circulating miRNA profiles and highlight that this aspect must be considered in the nutri-epigenomic research.
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Project description:Low-grade chronic inflammation (LGCI) is a common feature of non-communicable diseases. Cytokines play a crucial role in LGCI. This study aimed to assess how LGCI risk factors [e.g., age, body mass index (BMI), smoke, physical activity, and diet] may impact on specific cytokine levels in a healthy population. In total, 150 healthy volunteers were recruited and subjected to questionnaires about the last 7-day lifestyle, including smoking habit, physical activity, and food frequency. A panel of circulating cytokines, chemokines, and growth factors was analyzed by multiplex ELISA. BMI showed the heaviest impact on the correlation between LGCI-related risk factors and cytokines and was significantly associated with CRP levels. Aging was characterized by an increase in IL-1b, eotaxin, MCP-1, and MIP-1α. Smoking was related to higher levels of IL-1b and CCL5/RANTES, while physical activity was related to MIP-1α. Within the different eating habits, CRP levels were modulated by eggs, red meat, shelled fruits, and greens consumption; however, these associations were not confirmed in a multivariate model after adjusting for BMI. Nevertheless, red meat consumption was associated with an inflammatory pattern, characterized by an increase in IL-6 and IL-8. IL-8 levels were also increased with the frequent intake of sweets, while a higher intake of shelled fruits correlated with lower levels of IL-6. Moreover, IL-6 and IL-8 formed a cluster that also included IL-1b and TNF-α. In conclusion, age, BMI, smoke, physical activity, and dietary habits are associated with specific cytokines that may represent potential markers for LGCI.
| S-EPMC9270017 | biostudies-literature
Project description:Selection for disease resilience, which refers to the ability of an animal to maintain performance when exposed to disease, can reduce the impact of infectious diseases. However, direct selection for disease resilience is challenging because nucleus herds must maintain a high health status. A possible solution is indirect selection of indicators of disease resilience. To search for such indicators, we conducted phenotypic and genetic quantitative analyses of the abundances of 377 proteins in plasma samples from 912 young and visually healthy pigs and their relationships with performance and subsequent disease resilience after natural exposure to a polymicrobial disease challenge. Abundances of 100 proteins were significantly heritable (false discovery rate (FDR) <0.10). The abundance of some proteins was or tended to be genetically correlated (rg) with disease resilience, including complement system proteins (rg = -0.24, FDR = 0.001) and IgG heavy chain proteins (rg = -0.68, FDR = 0.22). Gene set enrichment analyses (FDR < 0.2) based on phenotypic and genetic associations of protein abundances with subsequent disease resilience revealed many pathways related to the immune system that were unfavorably associated with subsequent disease resilience, especially the innate immune system. It was not possible to determine whether the observed levels of these proteins reflected baseline levels in these young and visually healthy pigs or were the result of a response to environmental disturbances that the pigs were exposed to before sample collection. Nevertheless, results show that, under these conditions, the abundance of proteins in some immune-related pathways can be used as phenotypic and genetic predictors of disease resilience and have the potential for use in pig breeding and management.
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