PubMed

Related Articles Combined Proteomic and Metabolomic Profiling of the Arabidopsis thaliana vps29 Mutant Reveals Pleiotropic Functions of the Retromer in Seed Development. Int J Mol Sci. 2019 Jan 16;20(2): Authors: Durand TC, Cueff G, Godin B, Valot B, Clément G, Gaude T, Rajjou L Abstract The retromer is a multiprotein complex conserved from yeast to humans, which is involved in intracellular protein trafficking and protein recycling. Selection of cargo proteins transported by the retromer depends on the core retromer subunit composed of the three vacuolar protein sorting (VPS) proteins, namely VPS26, VPS29, and VPS35. To gain a better knowledge of the importance of the plant retromer in protein sorting, we carried out a comparative proteomic and metabolomic analysis of Arabidopsis thaliana seeds from the wild-type and the null-retromer mutant vps29. Here, we report that the retromer mutant displays major alterations in the maturation of seed storage proteins and synthesis of lipid reserves, which are accompanied by severely impaired seed vigor and longevity. We also show that the lack of retromer components is counterbalanced by an increase in proteins involved in intracellular trafficking, notably members of the Ras-related proteins in brain (RAB) family proteins. Our study suggests that loss of the retromer stimulates energy metabolism, affects many metabolic pathways, including that of cell wall biogenesis, and triggers an osmotic stress response, underlining the importance of retromer function in seed biology. PMID: 30654520 [PubMed - in process]

Related Articles 1D "Spikelet" Projections from Heteronuclear 2D NMR Data-Permitting 1D Chemometrics While Preserving 2D Dispersion. Metabolites. 2019 Jan 16;9(1): Authors: Tabatabaei Anaraki M, Bermel W, Dutta Majumdar R, Soong R, Simpson M, Monnette M, Simpson AJ Abstract Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for the non-targeted metabolomics of intact biofluids and even living organisms. However, spectral overlap can limit the information that can be obtained from 1D 1H NMR. For example, magnetic susceptibility broadening in living organisms prevents any metabolic information being extracted from solution-state 1D 1H NMR. Conversely, the additional spectral dispersion afforded by 2D 1H-13C NMR allows a wide range of metabolites to be assigned in-vivo in 13C enriched organisms, as well as a greater depth of information for biofluids in general. As such, 2D 1H-13C NMR is becoming more and more popular for routine metabolic screening of very complex samples. Despite this, there are only a very limited number of statistical software packages that can handle 2D NMR datasets for chemometric analysis. In comparison, a wide range of commercial and free tools are available for analysis of 1D NMR datasets. Overtime, it is likely more software solutions will evolve that can handle 2D NMR directly. In the meantime, this application note offers a simple alternative solution that converts 2D 1H-13C Heteronuclear Single Quantum Correlation (HSQC) data into a 1D "spikelet" format that preserves not only the 2D spectral information, but also the 2D dispersion. The approach allows 2D NMR data to be converted into a standard 1D Bruker format that can be read by software packages that can only handle 1D NMR data. This application note uses data from Daphnia magna (water fleas) in-vivo to demonstrate how to generate and interpret the converted 1D spikelet data from 2D datasets, including the code to perform the conversion on Bruker spectrometers. PMID: 30654443 [PubMed]

Related Articles Layer-by-layer electrochemical biosensors configuring xanthine oxidase and carbon nanotubes/graphene complexes for hypoxanthine and uric acid in human serum solutions. Biosens Bioelectron. 2018 Dec 15;121:265-271 Authors: Si Y, Park JW, Jung S, Hwang GS, Goh E, Lee HJ Abstract A selective biosensing platform for the determination of hypoxanthine (Hx) and uric acid (UA) concentrations in both buffer and human serum sample solutions was developed. The biosensor features the layer-by-layer (LbL) self-assembly of negatively charged xanthine oxidase (XOD) and positively charged poly(diallyldimethyl ammonium chloride) (PDDA) wrapped oxidized multi-walled carbon nanotubes and graphene (CNTs-G) complexes (PDDA-CNTs-G) on screen printed carbon electrode (SPCE) surfaces. Catalytic responses of the XOD modified biosensor with the chosen optimum number of layers for LbL assembly on SPCE towards Hx in buffer solutions were first investigated using both cyclic and square wave voltammetries. The peak current at around 0.08 V (vs. Ag/AgCl) associated with the production of UA increased as a function of the Hx concentration due to the surface selective catalytic reaction of XOD and Hx. A linear dynamic range of 5-50 µM Hx with a detection limit of 4.40 µM was obtained and the sensor was further applied to the analysis of Hx in normal human serum solutions in addition to myocardial infarction (MI) patient serum sample solutions from a local hospital. Since untreated serum solutions contain a certain amount of UA, a XOD free SPCE biosensor consisted of only PDDA-CNTs-G was also employed to evaluate the native concentration of UA in the serum and further assist the determination of Hx concentration when using the developed LbL biosensor. Our sensing results for the real biological fluidic solutions were finally validated by comparing to those using liquid chromatography-mass spectrometry(LC-MS). PMID: 30223102 [PubMed - indexed for MEDLINE]

Related Articles Effects of Qijian mixture on type 2 diabetes assessed by metabonomics, gut microbiota and network pharmacology. Pharmacol Res. 2018 04;130:93-109 Authors: Gao K, Yang R, Zhang J, Wang Z, Jia C, Zhang F, Li S, Wang J, Murtaza G, Xie H, Zhao H, Wang W, Chen J Abstract Qijian mixture, a new traditional Chinese medicine (TCM) formula comprising of Astragalus membranaceus, Ramulus euonymi, Coptis chinensis and Pueraria lobata, was designed to ameliorate the type 2 diabetes (T2D), and its safety and efficacy were evaluated in the research by metabonomics, gut microbiota and system pharmacology. To study the hypoglycemic effect of Qijian mixture, male KKay mice (28-30 g, 8-9 week) and C57/BL6 mice (18-19 g, 8-9 week) were used. Thirty KKay diabetic mice were randomly distributed into 5 groups, abbreviated as Model group (Model), Low Qijian Mixture group (QJM(L)), High Qijian Mixture group (QJM(H)), Chinese Medicine (Gegen Qinlian Decoction) Positive group (GGQL), and Western Medicine (Metformin hydrochloride) Positive group (Metformin). C57/BL6 was considered as the healthy control group (Control). Moreover, a system pharmacology approach was utilized to assess the physiological targets involved in the action of Qijian mixture. There was no adverse drug reaction of Qijian mixture in the acute toxicity study and HE result, and, compared with Model group, Qijian mixture could modulate blood glycemic level safely and effectively. Qijian Mixture was lesser effective than metformin hydrochloride; however, both showed similar hypoglycemic trend. Based on 1H NMR based metabonomics study, the profoundly altered metabolites in Qijian mixture treatment group were identified. Qijian mixture-related 55 proteins and 4 signaling pathways, including galactose metabolism, valine, leucine and isoleucine degradation metabolism, aminoacyl-tRNA biosynthesis metabolism and alanine, aspartate and glutamate metabolism pathways, were explored. The PCoA analysis of gut microbiota revealed that Qijian mixture treatment profoundly enriched bacteroidetes. In addition, the system pharmacology paradigm revealed that Qijian mixture acted through TP53, AKT1 and PPARA proteins. It was concluded that Qijian mixture effectively alleviated T2D, and this effect was linked with the altered features of the metabolite profiles and the gut microbiota. PMID: 29391233 [PubMed - indexed for MEDLINE]

16 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 2019/01/18PubMed 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.

16 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 2019/01/18PubMed 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.

How does homeostasis happen? Integrative physiologic, systems biologic, and evolutionary perspectives. Am J Physiol Regul Integr Comp Physiol. 2019 Jan 16;: Authors: Goldstein DS Abstract Homeostasis is a founding principle of integrative physiology. In current systems biology, however, homeostasis seems almost invisible. Is homeostasis a key goal driving body processes, or is it an emergent mechanistic fact? In this perspective piece I propose that the integrative physiologic and systems biologic viewpoints about homeostasis reflect different epistemologies-different philosophies of knowledge. Integrative physiology is concept-driven. It attempts to explain biological phenomena by continuous formation of theories that experimentation or observation can test. In integrative physiology, "function" refers to goals or purposes. Systems biology is data-driven. It explains biological phenomena in terms of "omics"-genomics, gene expression, epigenomics, proteomics, metabolomics-depicts the data in computer models of complex cascades or networks, and makes predictions from the models. In systems biology "function" refers more to mechanisms than to goals. The integrative physiologist emphasizes homeostasis of internal variables such as pCO2 and blood pressure. The systems biologist views these emphases as teleologic and unparsimonious in that the "regulated variable" (e.g., arterial pCO2 and blood pressure) and the "regulator" (e.g., the "carbistat" and "barostat") are unobservable constructs. The integrative physiologist views systems biologic explanations as not really explanations but descriptions that cannot account for phenomena we humans believe exist although they cannot be observed directly, such as feelings and, ultimately, the conscious mind. This essay reviews the history of the two epistemologies, emphasizing autonomic neuroscience. I predict rapprochement of integrative physiology with systems biology. The resolution will avoid teleological purposiveness, transcend pure mechanism, and incorporate adaptiveness in evolution-"Darwinian medicine." PMID: 30649893 [PubMed - as supplied by publisher]

Atmo-ecometabolomics: a novel atmospheric particle chemical characterization methodology for ecological research. Environ Monit Assess. 2019 Jan 16;191(2):78 Authors: Rivas-Ubach A, Liu Y, Steiner AL, Sardans J, Tfaily MM, Kulkarni G, Kim YM, Bourrianne E, Paša-Tolić L, Peñuelas J, Guenther A Abstract Aerosol particles play important roles in processes controlling the composition of the atmosphere and function of ecosystems. A better understanding of the composition of aerosol particles is beginning to be recognized as critical for ecological research to further comprehend the link between aerosols and ecosystems. While chemical characterization of aerosols has been practiced in the atmospheric science community, detailed methodology tailored to the needs of ecological research does not exist yet. In this study, we describe an efficient methodology (atmo-ecometabolomics), in step-by-step details, from the sampling to the data analyses, to characterize the chemical composition of aerosol particles, namely atmo-metabolome. This method employs mass spectrometry platforms such as liquid and gas chromatography mass spectrometries (MS) and Fourier transform ion cyclotron resonance MS (FT-ICR-MS). For methodology evaluation, we analyzed aerosol particles collected during two different seasons (spring and summer) in a low-biological-activity ecosystem. Additionally, to further validate our methodology, we analyzed aerosol particles collected in a more biologically active ecosystem during the pollination peaks of three different representative tree species. Our statistical results showed that our sampling and extraction methods are suitable for characterizing the atmo-ecometabolomes in these two distinct ecosystems with any of the analytical platforms. Datasets obtained from each mass spectrometry instrument showed overall significant differences of the atmo-ecometabolomes between spring and summer as well as between the three pollination peak periods. Furthermore, we have identified several metabolites that can be attributed to pollen and other plant-related aerosol particles. We additionally provide a basic guide of the potential use ecometabolomic techniques on different mass spectrometry platforms to accurately analyze the atmo-ecometabolomes for ecological studies. Our method represents an advanced novel approach for future studies in the impact of aerosol particle chemical compositions on ecosystem structure and function and biogeochemistry. PMID: 30649631 [PubMed - in process]

CluMSID: an R package for similarity-based clustering of tandem mass spectra to aid feature annotation in metabolomics. Bioinformatics. 2019 Jan 12;: Authors: Depke T, Franke R, Brönstrup M Abstract Summary: Compound identification is one of the most eminent challenges in the untargeted analysis of complex mixtures of small molecules by mass spectrometry. Similarity of tandem mass spectra can provide valuable information on putative structural similarities between known and unknown analytes and hence aids feature identification in the bioanalytical sciences. We have developed CluMSID (Clustering of MS² spectra for metabolite identification), an R package that enables researchers to make use of tandem mass spectra and neutral loss pattern similarities as a part of their metabolite annotation workflow. CluMSID offers functions for all analysis steps from import of raw data to data mining by unsupervised multivariate methods along with respective (interactive) visualisations. A detailed tutorial with example data is provided as supplementary information. Availability: CluMSID is available as R package from https://github.com/tdepke/CluMSID/. Supplementary information: Supplementary data are available at Bioinformatics online. PMID: 30649189 [PubMed - as supplied by publisher]

A comprehensive look into the volatile exometabolome of enteroxic and non-enterotoxic Staphylococcus aureus strains. Int J Biochem Cell Biol. 2019 Jan 12;: Authors: Baptista I, Santos M, Rudnitskaya A, Saraiva JA, Almeida A, Rocha SM Abstract Staphylococcal food poisoning is a disease that originates significant health and economic losses and is caused by Staphylococcus aureus strains able to produce enterotoxins. The aim of this work is to go further on the study of the volatile exometabolome of S. aureus using an advanced gas chromatographic technique. Enterotoxic and non-enterotoxic strains were assessed. The volatile exometabolome profile comprised 240 volatiles belonging to ten chemical families. This volatiles were mainly by-products of branched-chain amino acids and methionine degradation, pyruvate metabolism, diacetyl pathway, oxidative stress and carotenoid cleavage. Metabolites released by the first two pathways were produced in higher contents by the enterotoxic strains. This study add further insights to S. aureus volatile exometabolome, and also shows that by applying it, it is possible to distinguish strains of S. aureus by the number of produced enterotoxins, which is especially important from the food safety point of view. PMID: 30648622 [PubMed - as supplied by publisher]

Related Articles Omics based approach for biodiscovery of microbial natural products in antibiotic resistance era. J Genet Eng Biotechnol. 2018 Jun;16(1):1-8 Authors: Chandra Mohana N, Yashavantha Rao HC, Rakshith D, Mithun PR, Nuthan BR, Satish S Abstract The need for a new antibiotic pipeline to confront threat imposed by resistant pathogens has become a major global concern for human health. To confront the challenge there is a need for discovery and development of new class of antibiotics. Nature which is considered treasure trove, there is re-emerged interest in exploring untapped microbial to yield novel molecules, due to their wide array of negative effects associated with synthetic drugs. Natural product researchers have developed many new techniques over the past few years for developing diverse compounds of biopotential. Taking edge in the advancement of genomics, genetic engineering, in silico drug design, surface modification, scaffolds, pharmacophores and target-based approach is necessary. These techniques have been economically sustainable and also proven efficient in natural product discovery. This review will focus on recent advances in diverse discipline approach from integrated Bioinformatics predictions, genetic engineering and medicinal chemistry for the synthesis of natural products vital for the discovery of novel antibiotics having potential application. PMID: 30647697 [PubMed]

Related Articles A pilot study of the effect of phospholipid curcumin on serum metabolomic profile in patients with non-alcoholic fatty liver disease: a randomized, double-blind, placebo-controlled trial. Eur J Clin Nutr. 2019 Jan 15;: Authors: Chashmniam S, Mirhafez SR, Dehabeh M, Hariri M, Azimi Nezhad M, Nobakht M Gh BF Abstract BACKGROUND/OBJECTIVES: Curcumin, a natural polyphenol compound in the spice turmeric, has been found to have potent anti-oxidative and anti-inflammatory activity. Curcumin may treat non-alcoholic fatty liver disease (NAFLD) through its beneficial effects on biomarkers of oxidative stress (OS) and inflammation, which are considered as two feature of this disease. However, the effects of curcumin on NAFLD have been remained poorly understood. This investigation evaluated the effects of administrating curcumin on metabolic status in NAFLD patients. SUBJECTS/METHODS: Fifty-eight NAFLD patients participated in a randomized, double-blind, placebo-controlled parallel design of study. The subjects were allocated randomly into two groups, which either received 250 mg phospholipid curcumin or placebo, one capsule per day for a period of 8 weeks. Fasting blood samples were taken from each subject at the start and end of the study period. Subsequently, metabolomics analysis was performed for serum samples using NMR. RESULTS: Compared with the placebo, supplementing phospholipid curcumin resulted in significant decreases in serum including 3- methyl-2-oxovaleric acid, 3-hydroxyisobutyrate, kynurenine, succinate, citrate, α-ketoglutarate, methylamine, trimethylamine, hippurate, indoxyl sulfate, chenodeoxycholic acid, taurocholic acid, and lithocholic acid. This profile of metabolic biomarkers could distinguish effectively NAFLD subjects who were treated with curcumin and placebo groups, achieving value of 0.99 for an area under receiver operating characteristic curve (AUC). CONCLUSIONS: Characterizing the serum metabolic profile of the patients with NAFLD at the end of the intervention using NMR-based metabolomics method indicated that the targets of curcumin treatment included some amino acids, TCA cycle, bile acids, and gut microbiota. PMID: 30647436 [PubMed - as supplied by publisher]

Related Articles Urinary profiles associated with bacterial metabolites from asymptomatic pregnant women with at term or preterm premature rupture of membranes: a pilot study. J Matern Fetal Neonatal Med. 2019 Jan 15;:1-11 Authors: Barberini L, Palmas F, Fais MF, Mereu R, Noto A, Fattuoni C, Mais V, Chiodo A, Meloni A Abstract OBJECTIVE: Premature rupture of membranes (PROM) and preterm premature rupture of membranes (pPROM) are frequent conditions with a not fully understood multifactorial etiology. It has been suggested that infection may be the leading cause of pPROM. Metabolomics is nowadays recognized as a successful and versatile approach for the investigation of several pathological conditions, including pregnancy related ones. However, collecting samples such as fetal fluids or placenta poses a limit on the clinical application of this strategy. Therefore, the aim of this study was to detect urinary metabolites that could be associated with bacterial infection in PROM and pPROM and to understand its role in these different conditions, using readily available samples such as urines. METHODS: Urine samples were collected from pregnant women who experienced rupture of membranes: 1) at term (≥ 37 weeks) not in labor (NLPROM); 2) at term in labor (LPROM); 3) preterm (< 37 weeks) not in labor (pPROM). Samples were analyzed using a GC-MS platform. Student t-test, Pearson correlation coefficient, principal component analysis (PCA), and partial least squares discriminant analysis (PLS-DA) were applied to observe differences between groups. RESULTS: Results showed that lactic acid, erythritol, and ethanolamine levels were significantly higher in pPROM than in PROM (NLPROM + LPROM considered as one single group). These three metabolites might be associated with bacterial infections, since they derive from bacterial metabolic processes and environments. CONCLUSIONS: This study might be useful to understand the mechanisms underlying the etiology of pPROM and PROM, and urine samples might represent a useful and readily available sample to discriminate preterm high risk women. PMID: 30646777 [PubMed - as supplied by publisher]

Related Articles State-of-the-Art Extraction Methodologies for Bioactive Compounds from Algal Biome to Meet Bio-Economy Challenges and Opportunities. Molecules. 2018 Nov 12;23(11): Authors: Sosa-Hernández JE, Escobedo-Avellaneda Z, Iqbal HMN, Welti-Chanes J Abstract Over the years, significant research efforts have been made to extract bioactive compounds by applying different methodologies for various applications. For instance, the use of bioactive compounds in several commercial sectors such as biomedical, pharmaceutical, cosmeceutical, nutraceutical and chemical industries, has promoted the need of the most suitable and standardized methods to extract these bioactive constituents in a sophisticated and cost-effective manner. In practice, several conventional extraction methods have numerous limitations, e.g., lower efficacy, high energy cost, low yield, etc., thus urges for new state-of-the-art extraction methodologies. Thus, the optimization along with the integration of efficient pretreatment strategies followed by traditional extraction and purification processes, have been the primary goal of current research and development studies. Among different sources, algal biome has been found as a promising and feasible source to extract a broader spectrum of bioactive compounds with point-of-care application potentialities. As evident from the literature, algal bio-products includes biofuels, lipids, polyunsaturated fatty acids, pigments, enzymes, polysaccharides, and proteins. The recovery of products from algal biomass is a matter of constant development and progress. This review covers recent advancements in the extraction methodologies such as enzyme-assisted extraction (EAE), supercritical-fluid extraction (SFE), microwave-assisted extraction (MAE) and pressurized-liquid extraction (PLF) along with their working mechanism for extracting bioactive compounds from algal-based sources to meet bio-economy challenges and opportunities. A particular focus has been given to design characteristics, performance evaluation, and point-of-care applications of different bioactive compounds of microalgae. The previous and recent studies on the anticancer, antibacterial, and antiviral potentialities of algal-based bioactive compounds have also been discussed with particular reference to the mechanism underlying the effects of these active constituents with the related pathways. Towards the end, the information is also given on the possible research gaps, future perspectives and concluding remarks. PMID: 30424551 [PubMed - indexed for MEDLINE]

Related Articles Annurca Apple Polyphenols Ignite Keratin Production in Hair Follicles by Inhibiting the Pentose Phosphate Pathway and Amino Acid Oxidation. Nutrients. 2018 Oct 02;10(10): Authors: Badolati N, Sommella E, Riccio G, Salviati E, Heintz D, Bottone S, Di Cicco E, Dentice M, Tenore G, Campiglia P, Stornaiuolo M, Novellino E Abstract Patterned hair loss (PHL) affects around 50% of the adult population worldwide. The negative impact that this condition exerts on people's life quality has boosted the appearance of over-the-counter products endowed with hair-promoting activity. Nutraceuticals enriched in polyphenols have been recently shown to promote hair growth and counteract PHL. Malus pumila Miller cv. Annurca is an apple native to Southern Italy presenting one of the highest contents of Procyanidin B2. We have recently shown that oral consumption of Annurca polyphenolic extracts (AAE) stimulates hair growth, hair number, hair weight and keratin content in healthy human subjects. Despite its activity, the analysis of the molecular mechanism behind its hair promoting effect is still partially unclear. In this work we performed an unprecedented metabolite analysis of hair follicles (HFs) in mice topically treated with AAE. The metabolomic profile, based on a high-resolution mass spectrometry approach, revealed that AAE re-programs murine HF metabolism. AAE acts by inhibiting several NADPH dependent reactions. Glutaminolysis, pentose phosphate pathway, glutathione, citrulline and nucleotide synthesis are all halted in vivo by the treatment of HFs with AAE. On the contrary, mitochondrial respiration, β-oxidation and keratin production are stimulated by the treatment with AAE. The metabolic shift induced by AAE spares amino acids from being oxidized, ultimately keeping them available for keratin biosynthesis. PMID: 30279339 [PubMed - indexed for MEDLINE]

Related Articles Plasma metabonomics investigation reveals involvement of fatty acid oxidation in hematotoxicity in Chinese benzene-exposed workers with low white blood cell count. Environ Sci Pollut Res Int. 2018 Nov;25(32):32506-32514 Authors: Sun R, Xu K, Zhang Q, Jiang X, Man Z, Yin L, Zhang J, Pu Y Abstract Benzene is an environmental and occupational contaminant. Health hazards associated with occupational benzene exposure is a major public health problem in China. In this study, we analyzed metabolite profiles among plasma samples collected from benzene-exposed workers with low white blood cell count (BLWs) and healthy controls using high-performance liquid chromatography-time-of-flight mass spectrometry. To screen potential benzene hematotoxicity biomarkers and metabolic pathways, principal component analysis was used to examine metabolite profile changes in plasma samples. The alterations in fatty acid oxidation (FAO) pathway were consistent with our previous findings in a mouse model; hence, two key genes were selected and verified in WBC samples. A total of nine identified metabolites were significantly changed in BLWs, which were involved in glutathione metabolism, porphyrin metabolism, lipid metabolism pathway, and FAO metabolism. Furthermore, compared with healthy controls, the mRNA expressions of carnitine acyltransferase (CRAT) and ACADVL were significantly increased in BLWs. Particularly, WBC counts was negatively correlated with the expression of AVADVL in BLWs. These aberrant metabolites could act as potential biomarkers for benzene hematotoxicity. In addition, fatty acid oxidation pathway may play a critical role in the development of hematotoxicity caused by benzene. PMID: 30238259 [PubMed - indexed for MEDLINE]

Related Articles Accessing Bioactive Natural Products from the Human Microbiome. Cell Host Microbe. 2018 06 13;23(6):725-736 Authors: Milshteyn A, Colosimo DA, Brady SF Abstract Natural products have long played a pivotal role in the development of therapeutics for a variety of diseases. Traditionally, soil and marine environments have provided a rich reservoir from which diverse chemical scaffolds could be discovered. Recently, the human microbiome has been recognized as a promising niche from which secondary metabolites with therapeutic potential have begun to be isolated. In this Review, we address how the expansive history of identifying bacterial natural products in other environments is informing the approaches being brought to bear on the study of the human microbiota. We also touch on how these tools can lead to insights about microbe-microbe and host-microbe interactions and help generate biological hypotheses that may lead to developments of new therapeutic modalities. PMID: 29902438 [PubMed - indexed for MEDLINE]

Related Articles Ultra Performance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry-Based Metabonomics Reveal Protective Effect of Terminalia chebula Extract on Ischemic Stroke Rats. Rejuvenation Res. 2018 Dec;21(6):541-552 Authors: Liu W, Mu F, Liu T, Xu H, Chen J, Jia N, Zhang Y, Dou F, Shi L, Li Y, Wen A, Ding Y Abstract Terminalia chebula (TC), a kind of Combretaceae, is a widely used herb in India and East Asia to treat cerebrovascular diseases. However, the potential mechanism of the neuroprotective effects of TC at the metabonomics level is still not clear. The present study focused on the effects of TC on metabonomics in a stroke model. Rats were divided randomly into sham, model, and TC groups. Rats in the TC group were intragastrically administered with TC for 7 days after a middle cerebral artery occlusion (MCAO) operation. The sham and the model groups received vehicle for the same length of time. Subsequently, the neuroprotective effects of TC were examined by evaluation of neurological defects, assessment of infarct volume, and identification of biochemical indicators for antioxidant and anti-inflammatory activities. Further, metabonomics technology was employed to evaluate the endogenous metabolites profiling systematically. Consist with the results of biochemical and histopathological assays, pattern recognition analysis showed a clear separation of the model group and the sham group, indicating the recovery impact of TC on the MCAO rats. Moreover, 12 potential biomarkers were identified in the MCAO model group, involving energy (lactic acid, succinic acid, and fumarate), amino acids (leucine, alanine, and phenylalanine), and glycerophospholipid (PC [16:0/20:4], PC [20:4/20:4], LysoPC [18:0], and LysoPC [16:0]) metabolism, as well as other types of metabolism (arachidonic acid and palmitoylcarnitine). Notably, it was found that metabolite levels of TC group were partially reversed to normal. In conclusion, TC could ameliorate MCAO in rats by affecting energy metabolism (glycolysis and the TCA cycle), amino acid metabolism, glycerophospholipid metabolism, and other types of metabolism. PMID: 29804491 [PubMed - indexed for MEDLINE]

Related Articles The mitochondrial pyruvate carrier mediates high fat diet-induced increases in hepatic TCA cycle capacity. Mol Metab. 2017 11;6(11):1468-1479 Authors: Rauckhorst AJ, Gray LR, Sheldon RD, Fu X, Pewa AD, Feddersen CR, Dupuy AJ, Gibson-Corley KN, Cox JE, Burgess SC, Taylor EB Abstract OBJECTIVE: Excessive hepatic gluconeogenesis is a defining feature of type 2 diabetes (T2D). Most gluconeogenic flux is routed through mitochondria. The mitochondrial pyruvate carrier (MPC) transports pyruvate from the cytosol into the mitochondrial matrix, thereby gating pyruvate-driven gluconeogenesis. Disruption of the hepatocyte MPC attenuates hyperglycemia in mice during high fat diet (HFD)-induced obesity but exerts minimal effects on glycemia in normal chow diet (NCD)-fed conditions. The goal of this investigation was to test whether hepatocyte MPC disruption provides sustained protection from hyperglycemia during long-term HFD and the differential effects of hepatocyte MPC disruption on TCA cycle metabolism in NCD versus HFD conditions. METHOD: We utilized long-term high fat feeding, serial measurements of postabsorptive blood glucose and metabolomic profiling and 13C-lactate/13C-pyruvate tracing to investigate the contribution of the MPC to hyperglycemia and altered hepatic TCA cycle metabolism during HFD-induced obesity. RESULTS: Hepatocyte MPC disruption resulted in long-term attenuation of hyperglycemia induced by HFD. HFD increased hepatic mitochondrial pyruvate utilization and TCA cycle capacity in an MPC-dependent manner. Furthermore, MPC disruption decreased progression of fibrosis and levels of transcript markers of inflammation. CONCLUSIONS: By contributing to chronic hyperglycemia, fibrosis, and TCA cycle expansion, the hepatocyte MPC is a key mediator of the pathophysiology induced in the HFD model of T2D. PMID: 29107293 [PubMed - indexed for MEDLINE]

Related Articles Outer membrane vesicles secreted by pathogenic and nonpathogenic Bacteroides fragilis represent different metabolic activities. Sci Rep. 2017 07 10;7(1):5008 Authors: Zakharzhevskaya NB, Vanyushkina AA, Altukhov IA, Shavarda AL, Butenko IO, Rakitina DV, Nikitina AS, Manolov AI, Egorova AN, Kulikov EE, Vishnyakov IE, Fisunov GY, Govorun VM Abstract Numerous studies are devoted to the intestinal microbiota and intercellular communication maintaining homeostasis. In this regard, vesicles secreted by bacteria represent one of the most popular topics for research. For example, the outer membrane vesicles (OMVs) of Bacteroides fragilis play an important nutritional role with respect to other microorganisms and promote anti-inflammatory effects on immune cells. However, toxigenic B. fragilis (ETBF) contributes to bowel disease, even causing colon cancer. If nontoxigenic B. fragilis (NTBF) vesicles exert a beneficial effect on the intestine, it is likely that ETBF vesicles can be utilized for potential pathogenic implementation. To confirm this possibility, we performed comparative proteomic HPLC-MS/MS analysis of vesicles isolated from ETBF and NTBF. Furthermore, we performed, for the first time, HPLC-MS/MS and GS-MS comparative metabolomic analysis for the vesicles isolated from both strains with subsequent reconstruction of the vesicle metabolic pathways. We utilized fluxomic experiments to validate the reconstructed biochemical reaction activities and finally observed considerable difference in the vesicle proteome and metabolome profiles. Compared with NTBF OMVs, metabolic activity of ETBF OMVs provides their similarity to micro reactors that are likely to be used for long-term persistence and implementing pathogenic potential in the host. PMID: 28694488 [PubMed - indexed for MEDLINE]