PubMed

Related Articles MS2 and LC libraries for untargeted metabolomics: Enhancing method development and identification confidence. J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Apr 04;1145:122105 Authors: Folberth J, Begemann K, Jöhren O, Schwaninger M, Othman A Abstract As part of the "omics" technologies in the life sciences, metabolomics is becoming increasingly important. In untargeted metabolomics, unambiguous metabolite identification and the inevitable coverage bias that comes with the selection of analytical conditions present major challenges. Reliable compound annotation is essential for translating metabolomics data into meaningful biological information. Here, we developed a fast and transferable method for generating in-house MS2 libraries to improve metabolite identification. Using the new method we established an in-house MS2 library that includes over 4,000 fragmentation spectra of 506 standard compounds for 6 different normalized collision energies (NCEs). Additionally, we generated a comprehensive liquid chromatography (LC) library by testing 57 different LC-MS conditions for 294 compounds. We used the library information to develop an untargeted metabolomics screen with maximum coverage of the metabolome that was successfully tested in a study of 360 human serum samples. The current work demonstrates a workflow for LC-MS/MS-based metabolomics, with enhanced metabolite identification confidence and the possibility to select suitable analysis conditions according to the specific research interest. PMID: 32305706 [PubMed - as supplied by publisher]

Related Articles Sex-dependent changes in the skin mucus metabolome of discus fish (Symphysodon haraldi) during biparental care. J Proteomics. 2020 Apr 16;:103784 Authors: Wen B, Zhou JQ, Gao JZ, Chen HR, Shen YQ, Chen ZZ Abstract Discus fish Symphysodon spp. employs an unusual parental care where fry feed on parental skin mucus after hatching. Here, we investigated the mucus metabolites of parental and non-parental discus by using non-targeted metabolomics. Statistical analysis of the skin mucus metabolome revealed sex-dependent changes of mucus between parental and non-parental discus, as well as sex-specific differences between parental fish. Differential metabolites reflected that mucus of both parents was rich in prostaglandin A1, but only male contained more oligosaccharides (gentiobiose and D-melezitose) and nucleotides (guanine and cytosine), and only female detected more thymine. Moreover, differential metabolites revealed the metabolic status of parental discus, including the inhibition of biosynthesis of amino acids, e.g., L-phenylalanine (parents), L-aspartic acid (female) and taurine (male) and the activation of metabolism of these amino acids; the increase of metabolism of fatty acids such as α-Linolenic acid (female), arachidonic acid (female) and linoleic acid (male); the perturbation of metabolism of carbohydrate and energy including starch and sucrose metabolism (parents), ascorbate and aldarate metabolism (parents), amino sugar and nucleotide sugar metabolism (female), pentose and glucuronate interconversions (male) and glyoxylate and dicarboxylate metabolism (male). These results might suggest sex-specific metabolic changes in the skin mucus of discus fish during parental care. SIGNIFICANCE: We detected the low-molecular-weight compounds present in the parental mucus of discus fish evolving for offspring and revealed the possible metabolic changes associated with parental care. These results are helpful to gain further insights on the functional and regulatory aspects of skin mucus of discus during parental care. PMID: 32305595 [PubMed - as supplied by publisher]

Related Articles Exploiting the natural variation in tomato to define pathway structure and metabolic regulation of fruit polyphenolics in the lycopersicum complex. Mol Plant. 2020 Apr 16;: Authors: Tohge T, Scossa F, Wendenburg R, Frasse P, Balbo I, Watanabe M, Alseekh S, Jadhav SS, Delfin JC, Lohse M, Giavalisco P, Usadel B, Zhang Y, Luo J, Bouzayen M, Fernie AR Abstract Whilst the structures of plant primary metabolic pathways are generally well defined and highly conserved across species, those defining specialized metabolism are less well characterized and more highly variable across species. Here, we investigate polyphenolic metabolism in the lycopersicum complex by characterizing the underlying biosynthetic and decorative reactions which comprise the metabolic network of polyphenols across eight different species of tomato. For this purpose, GC- and LC-MS based metabolomics were carried out, in concert with the evaluation of cross-hybridized-microarray for MapMan based-transcriptomic analysis, and publically available RNA sequencing data for annotation of biosynthetic genes respectively, in different tissues of Solanum lycopersicum and wild tomato species. The combined data was used to compile species-specific metabolic networks of polyphenolic metabolism allowing the proposal of an entire pan-species biosynthetic framework as well as to annotate functions of decoration enzymes involved in the creation of metabolic diversity of the flavonoid pathway. The combined results are discussed both in the context of current understanding of tomato flavonol biosynthesis as well as a global view of metabolic shift during fruit ripening. Our results are providing an example as to how large-scale biology approaches can be used for the definition and refinement of large pathways of specialized metabolism. PMID: 32305499 [PubMed - as supplied by publisher]

Related Articles Targeted and untargeted metabolomics applied to occupational exposure to hyperbaric atmosphere. Toxicol Lett. 2020 Apr 16;: Authors: Tranfo G, Marchetti E, Pigini D, Miccheli A, Spagnoli M, Sciubba F, Conta G, Tomassini A, Fattorini L Abstract Occupational exposure to hyperbaric atmosphere occurs in workers who carry out their activity in environments where breathing air pressure is at least 10% higher than pressure at sea level, and operations can be divided in Dry or Wet activities. The increased air pressure implies the formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), consumption of antioxidants and reduction of antioxidant enzyme activity, causing lipid peroxidation, DNA and RNA damage. The present study was aimed to establish the relation between hyperbaric exposure and metabolic changes due to ROS unbalance, by means of the determination of urinary biomarkers of oxidatively generated damage to DNA and RNA during a controlled diving session. The investigated biomarkers were 8-oxo-7,8-dihydroguanine (8-oxoGua), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo). The experimental session involved six experienced divers subjected to 3 atmospheres absolute for 30 minutes in two different experiments, in both dry and wet conditions. Urine samples were collected at t = 0 (before exposure) and 30 (end of exposure),90, 240, 480 and 720 minutes. The concentration of 8-oxoGua, 8-oxoGuo, and 8-oxodGuo was determined by isotopic dilution high performance liquid chromatography (HPLC-MS/MS). In all subjects there is an increase of the urinary excretion of 8oxo-Guo and 8oxo-dGuo, in both conditions, after 1.5 - 4 hours from the start of the experiment, and that the values tend to return to the baseline after 12 hours. Besides that, also the nucleic magnetic resonance (NMR)-based untargeted metabolomics was employed for the same objective on the same samples, confirming a different metabolic response in the subjects exposed to dry or wet conditions. In particular, the observed hypoxanthine urinary level increases during the underwater hyperbaric exposure, in agreement with the trend observed for 8-oxoGuo and 8-oxodGuo levels. Present results confirmed the relationship between exposure and oxidative stress and depicted a clear temporal trend of the investigated biomarkers. Due to the possible negative consequences of oxidative stress on workers, present research shows a new line in term of risk prevention. PMID: 32305374 [PubMed - as supplied by publisher]

Related Articles Influence of regionality and maturation time on the chemical fingerprint of whisky. Food Chem. 2020 Apr 03;323:126748 Authors: Roullier-Gall C, Signoret J, Coelho C, Hemmler D, Kajdan M, Lucio M, Schäfer B, Gougeon RD, Schmitt-Kopplin P Abstract Understanding the chemical composition of whisky and the impact of each step in the manufacturing process provides a basis for responding to the challenges of producing high quality spirits. In this study, the objective was to discriminate whiskies according to their geographical origin and authenticate the maturation time in cask based on the non-volatile profiles. The combination of FT-ICR-MS and chemometrics allowed the distinction of whiskies from four geographical origins in Scotland (Highlands, Lowlands, Speyside and Islay). Statistical modeling was also used to discriminate whiskies according to the maturation time in cask and reveal chemical markers associated with the ageing regardless of the origin or the production process. Interestingly, the flow of transfer of compounds from wood barrels to distillates is not constant and homogeneous over the maturation time. The largest transfer of compounds from the barrel to the whisky was observed around twelve years of maturation. PMID: 32304953 [PubMed - as supplied by publisher]

Related Articles Cultivar, site or harvest date: the gordian knot of wine terroir. Metabolomics. 2020 Apr 17;16(5):52 Authors: Schmidtke LM, Antalick G, Šuklje K, Blackman JW, Boccard J, Deloire A Abstract INTRODUCTION: The complex interactions of vine cultivars, and localised regional climate associated with specific vineyard sites are important attributes to the concept of terroir and significant contributors to grape maturity and wine sensory profiles. An improved understanding of the influence of each factor and their interactions is a challenging conundrum, and will enable more efficient production targeting specific wine styles. OBJECTIVES: To characterise the metabolic flux of grape berries and resulting wines to characterise the relative impact of site specific climate, cultivar, and grape maturity based upon berry sugar accumulation models that consistently target specific wine styles. METHODS: A spatial and temporal study of grape and wine composition was undertaken for two important cultivars in two distinct regions of New South Wales. Measures of composition and wine sensory ratings were simultaneously analysed using a multiblock algorithm taking advantage of the ANOVA framework to identify important contributions to wine style arising from grape maturity, vineyard site and cultivar. RESULTS: A consistent flux of grape and wine constituents is evident for wine made from sequentially harvested grapes from the same vineyard with increasing levels of grape maturity. Contributions of region and vineyard site to wine style could also be elucidated. Differences in metabolite flux in grapes and resulting wines between cultivars growing in similar conditions are evident. CONCLUSIONS: The combination of a metabolomics and multiblock data decomposition approach may be successfully used to profile and elucidate the contribution of abiotic factors to grape and wine composition and provide improved understanding of the terroir concept. PMID: 32303865 [PubMed - as supplied by publisher]

Related Articles Dual mass spectrometry as a tool to improve annotation and quantification in targeted plasma lipidomics. Metabolomics. 2020 Apr 17;16(5):53 Authors: Gao L, Cazenave-Gassiot A, Burla B, Wenk MR, Torta F Abstract INTRODUCTION: High quality data, based on reliable quantification and clear identification of the reported lipid species, are required for the clinical translation of human plasma lipidomic studies. OBJECTIVE: Lipid quantification can be efficiently performed on triple quadrupole (QqQ) mass spectrometers in targeted multiple reaction monitoring (MRM) mode. However, a series of issues can be encountered when aiming at unambiguous identification and accurate quantification, including (i) resolving peaks of polyunsaturated species, (ii) discriminating between plasmanyl-, plasmenyl- and odd chain species and (iii) resolving the isotopic overlap between co-eluting lipid species. METHODS: As a practical tool to improve the quality of targeted lipidomics studies, we applied a Dual MS platform by simultaneously coupling a reversed-phase liquid chromatography separation to a QqQ and a quadrupole-time of flight (Q-ToF) mass spectrometers. In one single experiment, this platform allows to correctly identify, by high-resolution MS and MS/MS, the peaks that are quantified by MRM. RESULTS: As proof of concept, we applied the platform on glycerophosphocholines (GPCs) and sphingomyelins (SMs), which are highly abundant in human plasma and play crucial roles in various physiological functions. Our results demonstrated that Dual MS could provide a higher level of confidence in the identification and quantification of GPCs and SMs in human plasma. The same approach can also be applied to improve the study of other lipid classes and expanded for the identification of novel lipid molecular species. CONCLUSIONS: This methodology might have a great potential to achieve a better specificity in the quantification of lipids by targeted lipidomics in high-throughput studies. PMID: 32303853 [PubMed - as supplied by publisher]

Related Articles Physical activity reduces anxiety and regulates brain fatty acid synthesis. Mol Brain. 2020 Apr 17;13(1):62 Authors: Liśkiewicz A, Przybyła M, Wojakowska A, Marczak Ł, Bogus K, Nowacka-Chmielewska M, Liśkiewicz D, Małecki A, Barski J, Lewin-Kowalik J, Toborek M Abstract Physical activity impacts brain functions, but the direct mechanisms of this effect are not fully recognized or understood. Among multidimensional changes induced by physical activity, brain fatty acids (FA) appear to play an important role; however, the knowledge in this area is particularly scarce. Here we performed global metabolomics profiling of the hippocampus and the frontal cortex (FC) in a model of voluntary running in mice. Examined brain structures responded differentially to physical activity. Specifically, the markers of the tricarboxylic acid (TCA) cycle were downregulated in the FC, whereas glycolysis was enhanced in the hippocampus. Physical activity stimulated production of myristic, palmitic and stearic FA; i.e., the primary end products of de novo lipogenesis in the brain, which was accompanied by increased expression of hippocampal fatty acid synthase (FASN), suggesting stimulation of lipid synthesis. The changes in the brain fatty acid profile were associated with reduced anxiety level in the running mice. Overall, the study examines exercise-related metabolic changes in the brain and links them to behavioral outcomes. PMID: 32303271 [PubMed - as supplied by publisher]

Related Articles The C18:3n6/C22:4n6 ratio is a good lipid marker of chronic kidney disease (CKD) progression. Lipids Health Dis. 2020 Apr 17;19(1):77 Authors: Szczuko M, Kaczkan M, Małgorzewicz S, Rutkowski P, Dębska-Ślizień A, Stachowska E Abstract BACKGROUND: Chronic kidney disease (CKD) is a major challenge for public health due to increased risk of cardiovascular diseases (CVD) and premature death. The aim of this study was to determine the clinical picture of FA and the course of the pathophysiological mechanisms of CKD. METHODS: The study involved 149 patients with CKD and a control group including 43 people. Fatty acid profiles were investigated using gas chromatography. A total of 30 fatty acids and their derivatives were identified and quantified. The omega3, omega6, SFA, MUFA, and PUFA fatty acid contents were calculated. The correlation matrix was obtained for parameters relating to patients with CKD vs. FA, taking patients' sex into consideration. The index C18:3n6/C22:4n6 was calculated according to the length of the treatment. Statistica 12.0 software (Tulsa, Oklahoma, USA) was used for the statistical analyses. RESULTS: The results showed decreased levels of total PUFA and increased concentrations of MUFA, including the activation of the palmitic and oleic acid pathway. An increase in the levels of n-6 9C22: 4n6 family fatty acids in all the patients and a reduction in the n-3 family (EPA, DHA) were observed. C18:3n6 was negatively correlated and C22:4n6 was positively correlated with the duration of the treatment. The index C18:3n6/C22:4n6 was defined as a new marker in the progression of the disease. Moreover, the index C18:3n6/ C22:4n6 was drastically decreased in later period. Nervonic acid was higher in the CKD group. In the group of men with CKD, there was a negative correlation between the excretion of K+, anthropometric measurements, and the levels of EPA and DHA. CONCLUSIONS: The course of inflammation in CKD occurs through the decrease in PUFA and the synthesis of MUFA. The dominating cascade of changes is the elongation of GLA-C18:3n6 into DGLA-C20:3n6 and AA-C20:4n6. As CKD progresses, along with worsening anthropometrical parameters and increased secretion of potassium, the activity of Ʌ6-desaturase decreases, reducing the synthesis of EPA and DHA. The synthesis of AdA-C22:4n6 increases and the ratio C18:3n6/C22:4n6 drastically decreases after 5 years. This parameter can be used to diagnose disease progression. PMID: 32303226 [PubMed - as supplied by publisher]

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 2020/04/18PubMed 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 2020/04/17PubMed 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 2020/04/16PubMed 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.

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 2020/04/15PubMed 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.

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 2020/04/14PubMed 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.

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 2020/04/14PubMed 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.

Association of acyl carnitines and mortality in out-of-hospital-cardiac-arrest patients: Results of a prospective observational study. J Crit Care. 2020 Mar 26;58:20-26 Authors: Widmer M, Thommen EB, Becker C, Beck K, Vincent AM, Perrig S, Keller A, Bernasconi L, Neyer P, Marsch S, Pargger H, Sutter R, Tisljar K, Hunziker S Abstract PURPOSE: Out-of-hospital cardiac arrest (OHCA) is a leading cause of mortality, yet the prediction of its outcome remains challenging. Serum Acyl Carnitines (ACs), a biomarker of beta-oxidation, have been associated with cardiovascular events. We evaluated the association of different AC species with mortality and neurological outcome in a cohort of OHCA patients. MATERIAL AND METHODS: We consecutively included OHCA patients in this prospective observational study upon admission to the intensive care unit. We studied the association of thirty-nine different ACs measured at admission and 30-day mortality (primary endpoint), as well as neurological outcome at hospital discharge (secondary endpoint) using the Cerebral Performance Category scale. Multivariate models were adjusted for age, gender, comorbidities and shock markers. RESULTS: Of 281 included patients, 137 (48.8%) died within 30 days and of the 144 survivors (51.2%), 15 (10.4%) had poor neurological outcome. While several ACs were associated with mortality, AC C2 had the highest prognostic value for mortality (fully-adjusted odds ratio 4.85 (95%CI 1.8 to 13.06, p < .01), area under curve (AUC) 0.65) and neurological outcome (fully-adjusted odds ratio 3.96 (95%CI 1.47 to 10.66, p < .01), AUC 0.63). CONCLUSIONS: ACs are interesting surrogate biomarkers that are associated with mortality and poor neurological outcome in patients after OHCA and may help to improve the understanding of pathophysiological mechanisms and risk stratification. PMID: 32279017 [PubMed - as supplied by publisher]

Anthelmintic and metabolomic analyses of chicory (Cichorium intybus) identify an industrial by-product with potent in vitro antinematodal activity. Vet Parasitol. 2020 Mar 18;280:109088 Authors: Peña-Espinoza M, Valente AH, Bornancin L, Simonsen HT, Thamsborg SM, Williams AR, López-Muñoz R Abstract Chicory (Cichorium intybus) is a bioactive forage rich in sesquiterpene lactones (SLs) with reported in vitro and in vivo anthelmintic activity in livestock. However, the on-farm adoption of chicory as an anthelmintic crop is limited and may be facilitated by using standardised industrial chicory material. Chicory root pulp is a by-product obtained from industrial chicory roots after inulin extraction and can potentially retain SLs. However, SL content and associated anthelmintic activity of chicory root pulp have not been investigated. Here, we evaluated the anthelmintic activity of SL-enriched extracts from chicory root pulp and forage chicory, and used untargeted metabolomics and molecular networking to identify potential anthelmintic molecules. Six different sources of chicory material were used: fresh chicory root pulp (from industrial chicory roots C. intybus var. sativum; "Root Pulp"), fresh leaves from chicory cv. Spadona (sampled on four occasions) and fresh leaves from chicory cv. Choice. The resulting extracts were tested for anthelmintic activity against the free-living nematode Caenorhabditis elegans and the pig nematode Ascaris suum. The cytotoxicity of the chicory extracts was evaluated on mammalian (Vero) cells. In the C. elegans assays, the Root Pulp was the most potent extract and induced paralysis in >95% of worms exposed to >250  μg extract/mL (EC50 = 64.2 μg/mL). In the A. suum assays, the Root Pulp was also the most potent chicory extract to inhibit worm motility (EC50 = 87.6  μg/mL), followed closely by two of the Spadona leaf extracts (EC50 = 89.8  μg/mL and 112.2  μg/mL) The Root Pulp extract had the lowest cytotoxicity of all tested extracts towards mammalian cells, with a selectivity index of 5.37. Untargeted metabolomics revealed that chicory Root Pulp had a markedly different chemical profile in comparison with forage chicory extracts. Molecular networking confirmed several SLs and SL-derivatives mainly present in chicory root pulp, that may be responsible of its potent anti-parasitic activity. Bioactivity-based molecular networking of chicory root pulp and the most potent forage chicory extracts revealed a high predicted anthelmintic score for the guaianolide SL 11,13-dihydro-lactucopicrin. In conclusion, chicory root pulp showed potent and selective in vitro anthelmintic activity against C. elegans and A. suum, with low cytotoxicity in mammalian cells. The promising anthelmintic activity of chicory root pulp should be confirmed in vivo to further explore the potential of this agro-industrial by-product as a nutraceutical anthelmintic for livestock and as novel source of anti-parasitic compounds. PMID: 32278938 [PubMed - as supplied by publisher]

De novo discovery of metabolic heterogeneity with immunophenotype-guided imaging mass spectrometry. Mol Metab. 2020 Feb 14;36:100953 Authors: Prade VM, Kunzke T, Feuchtinger A, Rohm M, Luber B, Lordick F, Buck A, Walch A Abstract BACKGROUND: Imaging mass spectrometry enables in situ label-free detection of thousands of metabolites from intact tissue samples. However, automated steps for multi-omics analyses and interpretation of histological images have not yet been implemented in mass spectrometry data analysis workflows. The characterization of molecular properties within cellular and histological features is done via time-consuming, non-objective, and irreproducible definitions of regions of interest, which are often accompanied by a loss of spatial resolution due to mass spectra averaging. METHODS: We developed a new imaging pipeline called Spatial Correlation Image Analysis (SPACiAL), which is a computational multimodal workflow designed to combine molecular imaging data with multiplex immunohistochemistry (IHC). SPACiAL allows comprehensive and spatially resolved in situ correlation analyses on a cellular resolution. To demonstrate the method, matrix-assisted laser desorption-ionization (MALDI) Fourier-transform ion cyclotron resonance (FTICR) imaging mass spectrometry of metabolites and multiplex IHC staining were performed on the very same tissue section of mouse pancreatic islets and on human gastric cancer tissue specimens. The SPACiAL pipeline was used to perform an automatic, semantic-based, functional tissue annotation of histological and cellular features to identify metabolic profiles. Spatial correlation networks were generated to analyze metabolic heterogeneity associated with cellular features. RESULTS: To demonstrate the new method, the SPACiAL pipeline was used to identify metabolic signatures of alpha and beta cells within islets of Langerhans, which are cell types that are not distinguishable via morphology alone. The semantic-based, functional tissue annotation allows an unprecedented analysis of metabolic heterogeneity via the generation of spatial correlation networks. Additionally, we demonstrated intra- and intertumoral metabolic heterogeneity within HER2/neu-positive and -negative gastric tumor cells. CONCLUSIONS: We developed the SPACiAL workflow to provide IHC-guided in situ metabolomics on intact tissue sections. Diminishing the workload by automated recognition of histological and functional features, the pipeline allows comprehensive analyses of metabolic heterogeneity. The multimodality of immunohistochemical staining and extensive molecular information from imaging mass spectrometry has the advantage of increasing both the efficiency and precision for spatially resolved analyses of specific cell types. The SPACiAL method is a stepping stone for the objective analysis of high-throughput, multi-omics data from clinical research and practice that is required for diagnostics, biomarker discovery, or therapy response prediction. PMID: 32278304 [PubMed - as supplied by publisher]

Systems metabolomics: from metabolomic snapshots to design principles. Curr Opin Biotechnol. 2020 Apr 08;63:190-199 Authors: Damiani C, Gaglio D, Sacco E, Alberghina L, Vanoni M Abstract Metabolomics is a rapidly expanding technology that finds increasing application in a variety of fields, form metabolic disorders to cancer, from nutrition and wellness to design and optimization of cell factories. The integration of metabolic snapshots with metabolic fluxes, physiological readouts, metabolic models, and knowledge-informed Artificial Intelligence tools, is required to obtain a system-level understanding of metabolism. The emerging power of multi-omic approaches and the development of integrated experimental and computational tools, able to dissect metabolic features at cellular and subcellular resolution, provide unprecedented opportunities for understanding design principles of metabolic (dis)regulation and for the development of precision therapies in multifactorial diseases, such as cancer and neurodegenerative diseases. PMID: 32278263 [PubMed - as supplied by publisher]

Metabolic responses in Scophthalmus maximus kidney subjected to thermal stress. Fish Shellfish Immunol. 2020 Apr 08;: Authors: Yang S, Zhao T, Ma A, Huang Z, Liu Z, Cui W, Zhang J, Zhu C, Guo X, Yuan C Abstract Turbot (Scophthalmus maximus) is an economically important marine fish cultured in China. In this study, fish in the experimental group were exposed to four temperatures: 15, 20, 25 and 28 °C. Metabolomics analysis and quantitative real-time PCR were used to assess changes in metabolic profiling and gene expression associated with thermal stress. The results showed the levels of heat shock protein 70 (HSP70), heat shock protein 90 (HSP90), blood creatinine and cortisol in S. maximus were all significantly upregulated (P < 0.05), indicating a stress response at 25 °C or higher. Challenge with thermal stress significantly increased expression levels of succinate dehydrogenase (SDH), fructose-1, 6-bisphosphatase (FBPase), malate dehydrogenase (MDH), cytosolic phosphoenolpyruvate carboxykinase (cPEPCK), glucose-6-phosphatase (G6Pase) and aspartate aminotransferase (AST) (P < 0.05). However, there was no effect on the expression levels of lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and mitochondrial phosphoenolpyruvate carboxykinase (mPEPCK). Moreover, high temperature decreased levels of glycogenic amino acids, including histidine, threonine, glutamine, phenylalanine, arginine, serine, tyrosine, methionine and isoleucine. These findings suggest a significant correlation between gene expression and regulation of carbohydrate and amino acid metabolism in heat-stressed S. maximus kidney. In addition, the maintenance of aerobic metabolism and activation of gluconeogenesis appeared to be a critical metabolic strategy in combating heat stress in turbot kidney. PMID: 32278112 [PubMed - as supplied by publisher]