Steroid hormones have diverse roles in pregnancy; some help stabilise pregnancy and influence the stability of pregnancy and the onset of labour. Changes and disorders in steroidogenesis may be involved in several pregnancy pathologies. To date, only a few studies have performed a very limited steroid analysis in multiple pregnancies. Our teams investigated multiple pregnancies regarding the biosynthesis, transport, and effects of steroids. We recruited two groups of patients: pregnant women with multiple pregnancies as the study group, and a control singleton pregnancies group. Blood samples were drawn from the participants and analysed. Information about the mother, foetus, delivery, and newborn was extracted from medical records. The data were then analysed. The gestational age of twin pregnancies during delivery ranged from 35 + 3 to 39 + 3 weeks, while it was 38 + 1 to 41 + 1 weeks for the controls. Our findings provide answers to questions regarding the steroidome in multiple pregnancies. Results demonstrate differences in the steroidome between singleton and twin pregnancies. These were based on the presence of two placentae and two foetal adrenal glands, both with separate enzymatic activity. Since every newborn was delivered by caesarean section, analysis was not negatively influenced by changes in the steroid metabolome associated with the spontaneous onset of labour.
- MeSH
- císařský řez MeSH
- kojenec MeSH
- lidé MeSH
- metabolom MeSH
- novorozenec MeSH
- retrospektivní studie MeSH
- steroidy MeSH
- těhotenství s dvojčaty * MeSH
- těhotenství MeSH
- výsledek těhotenství * MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND AIMS: Treatment with anti-tumour necrosis factor α antibodies [anti-TNF] changes the dysbiotic faecal bacteriome in Crohn's disease [CD]. However, it is not known whether these changes are due to decreasing mucosal inflammatory activity or whether similar bacteriome reactions might be observed in gut-healthy subjects. Therefore, we explored changes in the faecal bacteriome and metabolome upon anti-TNF administration [and therapeutic response] in children with CD and contrasted those to anti-TNF-treated children with juvenile idiopathic arthritis [JIA]. METHODS: Faecal samples collected longitudinally before and during anti-TNF therapy were analysed with regard to the bacteriome by massively parallel sequencing of the 16S rDNA [V4 region] and the faecal metabolome by 1H nuclear magnetic resonance imaging. The response to treatment by mucosal healing was assessed by the MINI index at 3 months after the treatment started. We also tested several representative gut bacterial strains for in vitro growth inhibition by infliximab. RESULTS: We analysed 530 stool samples from 121 children [CD 54, JIA 18, healthy 49]. Bacterial community composition changed on anti-TNF in CD: three members of the class Clostridia increased on anti-TNF, whereas the class Bacteroidia decreased. Among faecal metabolites, glucose and glycerol increased, whereas isoleucine and uracil decreased. Some of these changes differed by treatment response [mucosal healing] after anti-TNF. No significant changes in the bacteriome or metabolome were noted upon anti-TNF in JIA. Bacterial growth was not affected by infliximab in a disc diffusion test. CONCLUSIONS: Our findings suggest that gut mucosal healing is responsible for the bacteriome and metabolome changes observed in CD, rather than any general effect of anti-TNF.
- MeSH
- Bacteria MeSH
- Crohnova nemoc * patologie MeSH
- dítě MeSH
- infliximab farmakologie terapeutické užití MeSH
- inhibitory TNF farmakologie terapeutické užití MeSH
- lidé MeSH
- metabolom MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The metabolome is the biochemical basis of plant form and function, but we know little about its macroecological variation across the plant kingdom. Here, we used the plant functional trait concept to interpret leaf metabolome variation among 457 tropical and 339 temperate plant species. Distilling metabolite chemistry into five metabolic functional traits reveals that plants vary on two major axes of leaf metabolic specialization-a leaf chemical defense spectrum and an expression of leaf longevity. Axes are similar for tropical and temperate species, with many trait combinations being viable. However, metabolic traits vary orthogonally to life-history strategies described by widely used functional traits. The metabolome thus expands the functional trait concept by providing additional axes of metabolic specialization for examining plant form and function.
- MeSH
- dlouhověkost * MeSH
- fenotyp MeSH
- listy rostlin MeSH
- metabolom * MeSH
- Publikační typ
- časopisecké články MeSH
Our aim in this study was to characterize and investigate the secretome of Paenibacillus sp. S-12 by nanoLC-MS/MS tool-based analysis of trypsin digested culture supernatant proteins. Using a bioinformatics and combined approach of mass spectrometry, we identified 657 proteins in the secretome. Bioinformatic tools such as PREDLIPO, SecretomeP 2.0, SignalP 4.1, and PSORTb were used for the subcellular localization and categorization of secretome on basis of signal peptides. Among the identified proteins, more than 25% of the secretome proteins were associated with virulence proteins including flagellar, adherence, and immune modulators. Gene ontology analysis using Blast2GO tools categorized 60 proteins of the secretome into biological processes, cellular components, and molecular functions. KEGG pathway analysis identified the enzymes or proteins involved in various biosynthesis and degradation pathways. Functional analysis of secretomes reveals a large number of proteins involved in the uptake and exchange of nutrients, colonization, and chemotaxis. A good number of proteins were involved in survival and defense mechanism against oxidative stress, the production of toxins and antimicrobial compounds. The present study is the first report of the in-depth protein profiling of Paenibacillus bacterium. In summary, the current findings of Paenibacillus sp. S-12 secretome provide basic information to understand its survival and the possible pathogenic mechanism.
In nematodes that invade the gastro-intestinal tract of the ruminant, the process of larval exsheathment marks the transition from the free-living to the parasitic stages of these parasites. To investigate the secretome associated with larval exsheathment, a closed in vitro system that effectively reproduces the two basic components of an anaerobic rumen environment (CO2 and 39 °C) was developed to trigger exsheathment in one of the most pathogenic and model gastrointestinal parasitic nematodes, Haemonchus contortus (barber's pole worm). This study reports the use of multimodal untargeted metabolomics and lipidomics methodologies to identify the metabolic signatures and compounds secreted during in vitro larval exsheathment in the H. contortus infective third-stage larva (iL3). A combination of statistical and chemoinformatic analyses using three analytical platforms revealed a panel of metabolites detected post exsheathment and associated with amino acids, purines, as well as select organic compounds. The major lipid classes identified by the non-targeted lipidomics method applied were lysophosphatidylglycerols, diglycerides, fatty acyls, glycerophospholipids, and a triglyceride. The identified metabolites may serve as metabolic signatures to improve tractability of parasitic nematodes for characterizing small molecule host-parasite interactions related to pathogenesis, vaccine and drug design, as well as the discovery of metabolic biomarkers.
- MeSH
- Haemonchus * MeSH
- hlístice * MeSH
- larva MeSH
- přežvýkavci MeSH
- sekretom MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Considerable variation exists in platelet reactivity to stimulation among healthy individuals. Various metabolites and metabolic pathways influence platelet reactivity, but a comprehensive overview of these associations is missing. The gut microbiome has a strong influence on the plasma metabolome. Here, we investigated the association of platelet reactivity with results of untargeted plasma metabolomics and gut microbiome profiling. METHODS: We used data from a cohort of 534 healthy adult Dutch volunteers (the 500 Functional Genomics study). Platelet activation and reactivity were measured by the expression of the alpha-granule protein P-selectin and the binding of fibrinogen to the activated integrin αIIbβ3, both in unstimulated blood and after ex vivo stimulation with platelet agonists. Plasma metabolome was measured using an untargeted metabolic profiling approach by quadrupole time-of-flight mass spectrometry. Gut microbiome data were measured by shotgun metagenomic sequencing from stool samples. RESULTS: Untargeted metabolomics yielded 1,979 metabolites, of which 422 were identified to play a role in a human metabolic pathway. Overall, 92/422 (21.8%) metabolites were significantly associated with at least one readout of platelet reactivity. The majority of associations involved lipids, especially members of eicosanoids, including prostaglandins and leukotrienes. Dietary-derived polyphenols were also found to inhibit platelet reactivity. Validation of metabolic pathways with functional microbial profiles revealed two overlapping metabolic pathways ("alanine, aspartate, and glutamate metabolism" and "arginine biosynthesis") that were associated with platelet reactivity. CONCLUSION: This comprehensive overview is an resource for understanding the regulation of platelet reactivity by the plasma metabolome and the possible contribution of the gut microbiota.
- MeSH
- dospělí MeSH
- krevní plazma MeSH
- lidé MeSH
- metabolom MeSH
- metabolomika metody MeSH
- střevní mikroflóra * MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Proton MR spectra of the brain, especially those measured at short and intermediate echo times, contain signals from mobile macromolecules (MM). A description of the main MM is provided in this consensus paper. These broad peaks of MM underlie the narrower peaks of metabolites and often complicate their quantification but they also may have potential importance as biomarkers in specific diseases. Thus, separation of broad MM signals from low molecular weight metabolites enables accurate determination of metabolite concentrations and is of primary interest in many studies. Other studies attempt to understand the origin of the MM spectrum, to decompose it into individual spectral regions or peaks and to use the components of the MM spectrum as markers of various physiological or pathological conditions in biomedical research or clinical practice. The aim of this consensus paper is to provide an overview and some recommendations on how to handle the MM signals in different types of studies together with a list of open issues in the field, which are all summarized at the end of the paper.
- MeSH
- dospělí MeSH
- konsensus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipidy chemie MeSH
- magnetická rezonanční tomografie MeSH
- makromolekulární látky metabolismus MeSH
- metabolom MeSH
- mladý dospělý MeSH
- mozek diagnostické zobrazování MeSH
- počítačové zpracování signálu MeSH
- protonová magnetická rezonanční spektroskopie * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- teoretické modely MeSH
- znalecký posudek * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Glucose tolerance represents a complex phenotype in which many tissues play important roles and interact to regulate metabolic homeostasis. Here, we perform an analysis of 13C6-glucose tissue distribution, which maps the metabolome and lipidome across 12 metabolically relevant mouse organs and plasma, with integrated 13C6-glucose-derived carbon tracing during oral glucose tolerance test (OGTT). We measure time profiles of water-soluble metabolites and lipids and integrate the global metabolite response into metabolic pathways. During the OGTT, glucose use is turned on with specific kinetics at the organ level, but fasting substrates like β-hydroxybutyrate are switched off in all organs simultaneously. Timeline profiling of 13C-labeled fatty acids and triacylglycerols across tissues suggests that brown adipose tissue may contribute to the circulating fatty acid pool at maximal plasma glucose levels. The GTTAtlas interactive web application serves as a unique resource for the exploration of whole-body glucose metabolism and time profiles of tissue and plasma metabolites during the OGTT.
- MeSH
- biologické markery krev MeSH
- časové faktory MeSH
- chromatografie kapalinová MeSH
- energetický metabolismus * MeSH
- glukózový toleranční test * MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
- krevní glukóza metabolismus MeSH
- lipidomika MeSH
- lipidy krev MeSH
- metabolom * MeSH
- metabolomika * MeSH
- myši inbrední C57BL MeSH
- tandemová hmotnostní spektrometrie MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
3-Quinuclidinyl benzilate (BZ) ranks among incapacitating military warfare agents. It acts as a competitive inhibitor on muscarinic receptors leading to non-lethal mental impairment. The present study aimed to investigate toxicokinetics of BZ in rats. Moreover, BZ can be exploited to produce a pharmacological model of Alzheimer's disease; thus, this paper focuses mainly on the BZ distribution to the brain. Wistar rats were administered i.p. with BZ (2 and 10 mg/kg). The BZ concentration was determined using LC-MS/MS in plasma, urine, bile, brain, kidney and liver. The sample preparation was based on a solid phase extraction (liquids) or protein precipitation (organ homogenates). The plasma concentration peaked at 3 min (204.5 ± 55.4 and 2185.5 ± 465.4 ng/ml). The maximal concentration in the brain was reached several minutes later. Plasma elimination half-life was 67.9 ± 3.4 in the 2 mg/kg group and 96.6 ± 27.9 in the 10 mg/kg group. BZ concentrations remained steady in the brain, with slow elimination (t1/2 506.9 ± 359.5 min). Agent BZ is excreted mainly via the urine. Steady BZ concentration in the brain could explain the previously published duration of the significant impairment in passive avoidance tasks in rats after an injection of BZ.
- MeSH
- antagonisté muskarinových receptorů krev metabolismus toxicita moč MeSH
- chinuklidinylbenzilát krev metabolismus toxicita moč MeSH
- krysa rodu rattus MeSH
- metabolom MeSH
- moč MeSH
- mozek metabolismus MeSH
- potkani Wistar MeSH
- toxikokinetika MeSH
- žluč metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Mitochondria play an essential role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Previously, we found that succinate-activated respiration was the most affected mitochondrial parameter in mice with mild NAFLD. In this study, we focused on the role of succinate dehydrogenase (SDH) in NAFLD pathogenesis. To induce the progression of NAFLD to nonalcoholic steatohepatitis (NASH), C57BL/6J mice were fed a Western-style diet (WD) or control diet for 30 weeks. NAFLD severity was evaluated histologically and the expression of selected proteins and genes was assessed. Mitochondrial respiration was measured by high-resolution respirometry. Liver redox status was assessed using glutathione, malondialdehyde, and mitochondrial production of reactive oxygen species (ROS). Metabolomic analysis was performed by GC/MS. WD consumption for 30 weeks led to reduced succinate-activated respiration. We also observed decreased SDH activity, decreased expression of the SDH activator sirtuin 3, decreased gene expression of SDH subunits, and increased levels of hepatic succinate, an important signaling molecule. Succinate receptor 1 (SUCNR1) gene and protein expression were reduced in the livers of WD-fed mice. We did not observe signs of oxidative damage compared to the control group. The changes observed in WD-fed mice appear to be adaptive to prevent mitochondrial respiratory chain overload and massive ROS production.
- MeSH
- apoptóza MeSH
- biologické markery MeSH
- buněčné dýchání MeSH
- fibróza MeSH
- jaterní mitochondrie metabolismus MeSH
- kyselina jantarová metabolismus MeSH
- metabolom MeSH
- metabolomika metody MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- náchylnost k nemoci MeSH
- nealkoholová steatóza jater etiologie metabolismus patologie MeSH
- oxidace-redukce * MeSH
- oxidační stres * MeSH
- sukcinátdehydrogenasa metabolismus MeSH
- západní dieta * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
