PubMed

Related Articles Untargeted metabolomics of strawberry (Fragaria x ananassa 'Camarosa') fruit from plants grown under osmotic stress conditions. J Sci Food Agric. 2019 Aug 15;: Authors: Antunes ACN, Dos Santos Acunha T, Perin EC, Rombaldi CV, Galli V, Chaves FC Abstract BACKGROUND: In order to cope with adverse environmental conditions, plants activate defense mechanisms leading to the accumulation and/or depletion of general and specialized metabolites. In this study, a multiplatform untargeted metabolomics strategy was employed to evaluate metabolic changes in strawberry fruit of cv. Camarosa grown under osmotic stress conditions. Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry data from strawberry grown under two water deficit conditions, irrigated at 95% crop evapotranspiration (ETc) and 85% ETc, and one excess salt condition with a 80 mM NaCl solution were analyzed to determine treatment effects on fruit metabolism. RESULTS: Multivariate principal component analysis, orthogonal projections to latent structures - discriminant analysis, and univariate statistical analyses were applied to the data set. While multivariate analyses showed group separation by treatment, T-test and fold-change revealed twelve metabolites differentially accumulated in strawberries from different treatments, among them phenolic compounds, glycerophospholipids, phytosterols, carbohydrates and an aromatic amino acid. CONCLUSION: Untargeted metabolomic analysis allowed for the annotation of compounds differentially accumulated in strawberry fruit from plants grown under osmotic stresses and non-stressed plants. The metabolic disturbance in plants under stress involved metabolites associated with inhibition of reactive oxygen species and cell wall and membrane lipid biosynthesis, which might serve as osmotic stress biomarkers. This article is protected by copyright. All rights reserved. PMID: 31414485 [PubMed - as supplied by publisher]

Related Articles Enhancing coverage in LC-MS-based untargeted metabolomics by a new sample preparation procedure using mixed-mode solid-phase extraction and two derivatizations. Anal Bioanal Chem. 2019 Aug 14;: Authors: Wu Q, Xu Y, Ji H, Wang Y, Zhang Z, Lu H Abstract It is a challenge to expand the metabolome coverage of liquid chromatography (LC)-electrospray ionization (ESI) mass spectrometry (MS) based untargeted metabolomics analysis. The limited coverage is attributed to the weak signal of hydroxyl and carboxyl groups in ESI-MS and the limited capacity of LC separation for metabolites with a wide range of polarities. Here a new sample preparation procedure is proposed to solve these problems. Mixed-mode (reversed-phase and anion-exchange) solid-phase extraction sorbents were used to separate metabolites into hydrophilic amine, hydrophobic amine/alcohol, and organic acid groups. Then, alcohols and carboxylic acids in separated groups were tagged with pyridine with use of two derivatization systems for signal enhancement. Finally, hydrophilic amines were analyzed by LC-MS with a hydrophilic interaction LC column, and the two hydrophobic compound groups were analyzed by LC-MS with a C18 column. From the results for standard samples, the detection limits of the new method are lower than those of the classic solvent extraction-protein precipitation method by 3.3-70 times for five amino acids and by 65-1141 times for five fatty acids. Moreover, the detection limit of this new method is 125 ng mL-1 for cholesterol, which has no signal with the classic method even at 10 μg mL-1. In seminal plasma samples, 110 more metabolites were identified by this new method than by the traditional solvent extraction-protein precipitation method in positive-mode ESI (new method vs traditional method, 65 vs 22 identified by comparing MS/MS spectra with those of standards, 203 vs 136 identified by searching MS spectra in a published database). Among them, 53 carboxylic acids and 21 alcohols were identified only by the new method, and more hydrophilic amine metabolites, such as amino acids and nucleosides, were identified by the new method than by the classic method. Finally, in application to the study of male infertility, more potential biomarkers of oligoasthenoteratospermic infertility were found with the new method (46 potential biomarkers) than with the classic method (19 potential biomarkers) and previously reported methods (10-30 potential biomarkers). Thus, it is demonstrated that this new sample preparation method expands the detection coverage of LC-MS-based untargeted metabolomics methods and has application potential in biological research. PMID: 31414155 [PubMed - as supplied by publisher]

Related Articles A fluorescent biosensor-based platform for the discovery of immunogenic cancer cell death inducers. Oncoimmunology. 2019;8(8):1606665 Authors: Kepp O, Sauvat A, Leduc M, Forveille S, Liu P, Zhao L, Bezu L, Xie W, Zitvogel L, Kroemer G Abstract Systemic anticancer immunity can be reinstated via the induction of immunogenic cell death (ICD) in malignant cells. Thus, certain classes of cytotoxic compounds, for example, anthracyclines, oxaliplatin and taxanes are endowed with the capacity to act on cancer cells to ignite premortem stress pathways that lead to the surface exposure of calreticulin (CALR) and the cellular release of adenosine triphosphate, annexin A1, high mobility group B1 and type-1 interferons. Altogether, these alterations constitute the hallmarks of ICD. Here we report the design of a discovery pipeline for the identification of novel ICD inducers by means of a phenotypic screening platform. The use of fluorescent biosensors as proxies for the manifestation of ICD hallmarks has enabled the exploration of large collections of chemical compounds by automatized screening routines. Imaging-based assessment and phenotypic selection led to the identification of potential ICD inducers that could be validated further in vitro and in vivo, confirming that bona fide ICD inducers possess the capacity to induce immunological long-term memory and to confer resistance against rechallenge with syngeneic tumors. Machine learning algorithms analyzing the physicochemical properties of ICD inducers can assist in the preselection of compounds with potential ICD-stimulatory properties, further accelerating the screening efforts designed to develop new immunotherapeutic agents. PMID: 31413915 [PubMed]

Related Articles Assessment of the Phenylketonuria (PKU)-Associated Mutation p.R155H Biochemical Manifestations by Mass Spectrometry-Based Blood Metabolite Profiling. Acta Naturae. 2019 Apr-Jun;11(2):42-46 Authors: Baturina OA, Chernonosov AA, Koval VV, Morozov IV Abstract Homozygous siblings with different treatment histories represent an excellent model to study both the phenotypic manifestation of mutations and the efficacy of therapy. We compared phenylketonuria (PKU) manifestations in two different gender siblings who were homozygous carriers of a rare phenylalanine hydroxylase (PAH) mutation, p.R155H, subjected to different treatments. PKU caused by mild mutations may be easily underdiagnosed if the diagnosis is based solely on the phenylalanine (Phe) blood concentration. One of the described patients is an example of this diagnostic error. For reducing diagnostic errors, we suggest the use of more elaborate methods in screening practice, in particular mass spectrometric analysis of blood metabolites, the efficiency of which is demonstrated in the present study. PMID: 31413878 [PubMed]

Related Articles Bortezomib administered prior to temozolomide depletes MGMT, chemosensitizes glioblastoma with unmethylated MGMT promoter and prolongs animal survival. Br J Cancer. 2019 Aug 15;: Authors: Rahman MA, Gras Navarro A, Brekke J, Engelsen A, Bindesbøll C, Sarowar S, Bahador M, Bifulco E, Goplen D, Waha A, Lie SA, Gjertsen BT, Selheim F, Enger PØ, Simonsen A, Chekenya M Abstract BACKGROUND: Resistance to temozolomide (TMZ) is due in part to enhanced DNA repair mediated by high expression of O6-methyl guanine DNA methyltransferase (MGMT) that is often characterised by unmethylated promoter. Here, we investigated pre-treatment of glioblastoma (GBM) cells with the 26S-proteasome inhibitor bortezomib (BTZ) as a strategy to interfere with MGMT expression and thus sensitise them to TMZ. METHODS: Cell lines and patient GBM-derived cells were examined in vitro, and the latter also implanted orthotopically into NOD-SCID C.B.-Igh-1b/lcrTac-Prkdc mice to assess efficacy and tolerability of BTZ and TMZ combination therapy. MGMT promoter methylation was determined using pyrosequencing and PCR, protein signalling utilised western blotting while drug biodistribution was examined by LC-MS/MS. Statistical analysis utilised Analysis of variance and the Kaplan-Meier method. RESULTS: Pre-treatment with BTZ prior to temozolomide killed chemoresistant GBM cells with unmethylated MGMT promoter through MGMT mRNA and protein depletion in vitro without affecting methylation. Chymotryptic activity was abolished, processing of NFkB/p65 to activated forms was reduced and corresponded with low MGMT levels. BTZ crossed the blood-brain barrier, diminished proteasome activity and significantly prolonged animal survival. CONCLUSION: BTZ chemosensitized resistant GBM cells, and the schedule may be amenable for temozolomide refractory patients with unmethylated MGMT promoter. PMID: 31413318 [PubMed - as supplied by publisher]

20 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 2019/08/15PubMed 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.

36 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 2019/08/14PubMed 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.

Related Articles Examining the predictive accuracy of metabolomics for small-for-gestational-age babies: a systematic review. BMJ Open. 2019 Aug 10;9(8):e031238 Authors: Leite DFB, Morillon AC, Melo Júnior EF, Souza RT, McCarthy FP, Khashan A, Baker P, Kenny LC, Cecatti JG Abstract INTRODUCTION: To date, there is no robust enough test to predict small-for-gestational-age (SGA) infants, who are at increased lifelong risk of morbidity and mortality. OBJECTIVE: To determine the accuracy of metabolomics in predicting SGA babies and elucidate which metabolites are predictive of this condition. DATA SOURCES: Two independent researchers explored 11 electronic databases and grey literature in February 2018 and November 2018, covering publications from 1998 to 2018. Both researchers performed data extraction and quality assessment independently. A third researcher resolved discrepancies. STUDY ELIGIBILITY CRITERIA: Cohort or nested case-control studies were included which investigated pregnant women and performed metabolomics analysis to evaluate SGA infants. The primary outcome was birth weight <10th centile-as a surrogate for fetal growth restriction-by population-based or customised charts. STUDY APPRAISAL AND SYNTHESIS METHODS: Two independent researchers extracted data on study design, obstetric variables and sampling, metabolomics technique, chemical class of metabolites, and prediction accuracy measures. Authors were contacted to provide additional data when necessary. RESULTS: A total of 9181 references were retrieved. Of these, 273 were duplicate, 8760 were removed by title or abstract, and 133 were excluded by full-text content. Thus, 15 studies were included. Only two studies used the fifth centile as a cut-off, and most reports sampled second-trimester pregnant women. Liquid chromatography coupled to mass spectrometry was the most common metabolomics approach. Untargeted studies in the second trimester provided the largest number of predictive metabolites, using maternal blood or hair. Fatty acids, phosphosphingolipids and amino acids were the most prevalent predictive chemical subclasses. CONCLUSIONS AND IMPLICATIONS: Significant heterogeneity of participant characteristics and methods employed among studies precluded a meta-analysis. Compounds related to lipid metabolism should be validated up to the second trimester in different settings. PROSPERO REGISTRATION NUMBER: CRD42018089985. PMID: 31401613 [PubMed - in process]

Related Articles TDCIPP exposure affects Artemia franciscana growth and osmoregulation. Sci Total Environ. 2019 Jul 19;694:133486 Authors: Morgan MA, Griffith CM, Volz DC, Larive CK Abstract Environmental monitoring has demonstrated widespread occurrence of the flame-retardant tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), raising concerns about the impact on aquatic life. Using 1H NMR and GC-MS metabolomics and 20-day body length experiments, we have determined that exposure to TDCIPP affects Artemia franciscana. The LC50 for a 48 h TDCIPP exposure was determined to be 37.1 ± 1.3 μM. Acute exposure (48 h) to 20.0 μM did not affect A. franciscana body length but did elicit a metabolic change. Chronic exposure to 0.50 μM TDCIPP caused decreased body length in A. franciscana exposed for 20 days and elicited a metabolic response. Principal component analysis revealed variance between acute and chronic exposure along PC1 (36.4%) and between control and TDCIPP along PC2 (17.4%). One-way ANOVA indicated that 19 metabolites were significantly affected by TDCIPP exposure; namely metabolites of the osmolyte class, including betaine, phosphocholine, gadusol, taurine, glycerol and trehalose - metabolites that are essential osmoprotectants in extremophile species. Other pathways that may be perturbed by TDCIPP exposure include one carbon, glycine, serine, threonine, and glycerophospholipid metabolism. PMID: 31401516 [PubMed - as supplied by publisher]

Related Articles Responses in the crucian carp (Carassius auratus) exposed to environmentally relevant concentration of 17α-Ethinylestradiol based on metabolomics. Ecotoxicol Environ Saf. 2019 Aug 08;183:109501 Authors: Zhou X, Li Y, Li H, Yang Z, Zuo C Abstract 17α-ethynylestradiol (EE2), a ubiquitous synthetic endocrine disrupting chemical, was the principal component of contraceptive drugs and one of common hormone medications. The detrimental impact of EE2 on the reproduction of organisms was widely recognized. However, the underlying mechanisms of physiological and metabolome effects of EE2 on freshwater fish are still unclear. This study investigated the toxic effects and related mechanisms of EE2 on freshwater fish crucian carp (Carassius auratus) based on metabolomics. Crucian carp were exposed to EE2 at environmentally relevant concentration for 9 days, 18 days, and 27 days, and the biological responses were explored through analysis of the physiological endpoints, steroid hormones, and metabolome. The physiological endpoints of crucian carp had no distinct change after EE2 exposure. However, metabolomics analysis probed significant deviation based on chemometrics, indicating that the metabolomics approach was more sensitive to the effects of EE2 at environmentally relevant concentration to freshwater fish than the traditional endpoints. The alterations of 24 metabolites in gonad and 16 metabolites in kidney were induced by treatment with EE2, respectively, which suggesting the perturbations in amino acid metabolism, lipid metabolism, energy metabolism, and oxidative stress. Moreover, EE2 exposure could induce the disruption of lipid metabolism and then broke the homeostasis of endogenous steroid hormones. Metabolomics provided a new strategy for the studies on contaminant exposure at a low dose in the short term and gave important information for the toxicology and mechanism of EE2. PMID: 31401330 [PubMed - as supplied by publisher]

Related Articles UPLC-ESI-IT-TOF-MS metabolomic study of the therapeutic effect of Xuefu Zhuyu decoction on rats with traumatic brain injury. J Ethnopharmacol. 2019 Aug 08;:112149 Authors: Fu C, Wu Q, Zhang Z, Xia Z, Ji H, Lu H, Wang Y Abstract It has been widely reported that Xuefu Zhuyu decoction (XFZYD), a traditional Chinese medicine, is effective in the treatment of traumatic brain injury (TBI). However, the mechanism of the therapeutic process is still not fully understood. Metabolomic technique can be used to explore the mechanisms underlying the treatment of TBI with XFZYD. The purpose of this work was to investigate the metabolic characteristics of blood samples from rats with and without XFZYD treatment and the dynamic changes in metabolite profiles on days 1, 3, 7, 14 and 21 after injury (within the severe phase of TBI) based on untargeted UPLC-ESI-IT-TOF-MS analysis. Pattern recognition, clustering analysis and metabolic pathway analysis were used to analyse the metabolomic data of three groups (a sham-operated group, a TBI model, and an XFZYD-treated TBI model). The results showed that XFZYD reversed the abnormalities in the levels of small-molecule metabolites (such as L-acetylcarnitine, L-tryptophan, indoleacrylic acid, γ-aminobutyric acid, hypotaurine, LysoPC(18:1)(11Z), creatine, L-phenylalanine and L-leucine) in TBI rats through six metabolic pathways (including phenylalanine, tyrosine and tryptophan biosynthesis; phenylalanine metabolism; valine, leucine and isoleucine biosynthesis; taurine and hypotaurine metabolism; tryptophan metabolism; and alanine, aspartate and glutamate metabolism) involved in the therapy process. XFZYD regulated the metabolic disorders of endogenous markers by the possible mechanisms of neuroprotection, energy metabolism, inflammatory response and oxidative stress. This study revealed the holistic and dynamic metabolic changes caused by XFZYD in rats with TBI and provided important research methods and approaches for exploring the multiple metabolites and metabolic pathways involved in the therapeutic effect of XFZYD on TBI. PMID: 31401321 [PubMed - as supplied by publisher]

Related Articles Synthetic microbial consortium with specific roles designated by genetic circuits for cooperative chemical production. Metab Eng. 2019 Aug 08;: Authors: Honjo H, Iwasaki K, Soma Y, Tsuruno K, Hamada H, Hanai T Abstract Synthetic microbial consortia consisting of microorganisms with different synthetic genetic circuits or divided synthetic metabolic pathway components can exert functions that are beyond the capacities of single microorganisms. However, few consortia of microorganisms with different synthetic genetic circuits have been developed. We designed and constructed a synthetic microbial consortium composed of an enzyme-producing strain and a target chemical-producing strain using Escherichia coli for chemical production with efficient saccharification. The enzyme-producing strain harbored a synthetic genetic circuit to produce beta-glucosidase, which converts cellobiose to glucose, destroys itself via the lytic genes, and release the enzyme when the desired cell density is reached. The target chemical-producing strain was programmed by a synthetic genetic circuit to express enzymes in the synthetic metabolic pathway for isopropanol production when the enzyme-producing strain grows until release of the enzyme. Our results demonstrate the benefits of synthetic microbial consortia with distributed tasks for effective chemical production from biomass. PMID: 31401244 [PubMed - as supplied by publisher]

Related Articles Integrated analysis of proteomics and metabolomics reveals the potential sex determination mechanism in Odontobutis potamophila. J Proteomics. 2019 Aug 08;:103482 Authors: Wang T, Zhu W, Zhang H, Wen X, Yin S, Jia Y Abstract Odontobutis potamophila is a valuable species for aquaculture in China, which shows asexually dimorphic growth pattern. In this study, the integrated proteomics and metabolomics were used to analyze the sex determination mechanism. A total of 2781 significantly different regulated proteins were identified by proteomics and 2693 significantly different expressed metabolites were identified by metabolomics. Among them, 2560 proteins and 1701 metabolites were significantly up-regulated in testes, whereas 221 proteins and 992 metabolites were significantly up-regulated in ovaries. Venn diagram analysis showed 513 proteins were differentially regulated at both protein and metabolite levels. Correlation analysis of differentially-regulated proteins and metabolites were identified by Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis. The results showed lipid metabolism plays an important role in sex determination. The metabolites decanoyl-CoA, leukotriene, 3-dehydrosphinganine, and arachidonate were the biomarkers in testes, whereas estrone and taurocholate were the biomarkers in ovaries. Interaction networks of the significant differentially co-regulated proteins and metabolites in the process of lipid metabolism showed arachidonic acid metabolism and steroid hormone biosynthesis were the most important pathways in sex determination. The findings of this study provide valuable information for selective breeding of O. potamophila. SIGNIFICANCE OF THE STUDY: The male O. potamophila grows substantially larger and at a quicker rate than the female. Thus, males have greater economic value than females. However, limited research was done to analyze the sex determination mechanism of O. potamophila, which seriously hindered the development of whole-male O. potamophila breeding. In this study, four key proteins (Ctnnb1, Piwil1, Hsd17b1, and Dnali1), six most important biomarkers (decanoyl-CoA, leukotriene, 3-dehydrosphinganine, arachidonate, estrone, and taurocholate) and two key pathways (arachidonic acid metabolism and steroid hormone biosynthesis) in sex determination of O. potamophila were found by integrated application of iTRAQ and LC-MS techniques. The results give valuable information for molecular breeding of O. potamophila in aquaculture. PMID: 31401171 [PubMed - as supplied by publisher]

Related Articles Maternal Obesity/Diabetes, Plasma Branched-Chain Amino Acids, and Autism Spectrum Disorder Risk in Urban Low-Income Children: Evidence of Sex Difference. Autism Res. 2019 Aug 09;: Authors: Panjwani AA, Ji Y, Fahey JW, Palmer A, Wang G, Hong X, Zuckerman B, Wang X Abstract Maternal metabolic conditions are known risk factors for child autism spectrum disorder (ASD). Branched-chain amino acids (BCAAs) are also associated with ASD. We examined the joint associations of maternal metabolic conditions and BCAAs on the risk of child ASD and whether the associations differed by child's sex. We analyzed 789 mother-infant pairs, a subset of the Boston Birth Cohort, from a predominantly urban, low-income, minority population. Maternal plasma BCAAs were measured by liquid chromatography-tandem mass spectrometry in samples collected 24-72 hr postpartum. A composite BCAA score was created using factor analysis, and prepregnancy obesity and diabetes (ob/DM) were combined into one variable. Logistic regression was used to explore the role of BCAAs as mediators or cofactors with ob/DM and child's sex on ASD risk. BCAA-ob/DM and BCAA-sex interactions were also examined. Maternal BCAAs alone were not associated with ASD and did not mediate the path between ob/DM and ASD. In the presence of maternal ob/DM, BCAA score was significantly associated with ASD (adjusted OR 2.33, 95% CI 1.18, 4.60). Interactions were present for valine with ob/DM and for valine and isoleucine with male sex on ASD risk. The odds ratio (OR) for risk of ASD was the greatest with all three risk factors combined-male sex, above median BCAA score, and ob/DM (OR 10.79, 95% CI 4.40, 26.42). Similar patterns were found for other developmental disorders, though not as strong as for ASD. Additional studies are warranted to clarify the role of maternal BCAAs, ob/DM, and child's sex in ASD. Autism Res 2019. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study investigated whether maternal obesity/diabetes and maternal circulating branched-chain amino acids (BCAAs) can jointly affect child ASD risk and whether the associations differ by child's sex. We found that the risk of ASD was greater among mothers with obesity/diabetes who also had elevated concentrations of BCAAs and that this risk was even greater for male children. These findings provide new evidence on fetal origins of ASD and sex difference and warrant additional investigation. PMID: 31400063 [PubMed - as supplied by publisher]

Related Articles Fish-oil supplementation in pregnancy, child metabolomics and asthma risk. EBioMedicine. 2019 Aug 06;: Authors: Rago D, Rasmussen MA, Lee-Sarwar KA, Weiss ST, Lasky-Su J, Stokholm J, Bønnelykke K, Chawes BL, Bisgaard H Abstract BACKGROUND: We recently demonstrated that maternal dietary supplementation with fish oil-derived n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) during pregnancy reduces the risk of asthma in the offspring but the mechanisms involved are unknown. METHODS: Here we investigated potential metabolic mechanisms using untargeted liquid chromatography-mass spectrometry-based metabolomics on 577 plasma samples collected at age 6 months in the offspring of mothers participating in the n-3 LCPUFA randomized controlled trial. First, associations between the n-3 LCPUFA supplementation groups and child metabolite levels were investigated using univariate regression models and data-driven partial least square discriminant analyses (PLS-DA). Second, we analyzed the association between the n-3 LCPUFA metabolomic profile and asthma development using Cox-regression. Third, we conducted mediation analyses to investigate whether the protective effect of n-3 LCPUFA on asthma was mediated via the metabolome. FINDINGS: The univariate analyses and the PLS-DA showed that maternal fish oil supplementation affected the child's metabolome, especially with lower levels of the n-6 LCPUFA pathway-related metabolites and saturated and monounsaturated long-chain fatty acids-containing compounds, lower levels of metabolites of the tryptophan pathway, and higher levels of metabolites in the tyrosine and glutamic acid pathway. This fish oil-related metabolic profile at age 6 months was significantly associated with a reduced risk of asthma by age 5 and the metabolic profile explained 24% of the observed asthma-protective effect in the mediation analysis. INTERPRETATION: Several of the observed pathways may be involved in the asthma-protective effect of maternal n-3 LCPUFA supplementation and act as mediators between the intervention and disease development. FUNDING: COPSAC is funded by private and public research funds all listed on www.copsac.com. PMID: 31399385 [PubMed - as supplied by publisher]

Related Articles Obese Individuals with and without Type 2 Diabetes Show Different Gut Microbial Functional Capacity and Composition. Cell Host Microbe. 2019 Aug 01;: Authors: Thingholm LB, Rühlemann MC, Koch M, Fuqua B, Laucke G, Boehm R, Bang C, Franzosa EA, Hübenthal M, Rahnavard A, Frost F, Lloyd-Price J, Schirmer M, Lusis AJ, Vulpe CD, Lerch MM, Homuth G, Kacprowski T, Schmidt CO, Nöthlings U, Karlsen TH, Lieb W, Laudes M, Franke A, Huttenhower C Abstract Obesity and type 2 diabetes (T2D) are metabolic disorders that are linked to microbiome alterations. However, their co-occurrence poses challenges in disentangling microbial features unique to each condition. We analyzed gut microbiomes of lean non-diabetic (n = 633), obese non-diabetic (n = 494), and obese individuals with T2D (n = 153) from German population and metabolic disease cohorts. Microbial taxonomic and functional profiles were analyzed along with medical histories, serum metabolomics, biometrics, and dietary data. Obesity was associated with alterations in microbiome composition, individual taxa, and functions with notable changes in Akkermansia, Faecalibacterium, Oscillibacter, and Alistipes, as well as in serum metabolites that correlated with gut microbial patterns. However, microbiome associations were modest for T2D, with nominal increases in Escherichia/Shigella. Medications, including antihypertensives and antidiabetics, along with dietary supplements including iron, were significantly associated with microbiome variation. These results differentiate microbial components of these interrelated metabolic diseases and identify dietary and medication exposures to consider in future studies. PMID: 31399369 [PubMed - as supplied by publisher]

Related Articles Untargeted Metabolomics Reveals Molecular Effects of Ketogenic Diet on Healthy and Tumor Xenograft Mouse Models. Int J Mol Sci. 2019 Aug 08;20(16): Authors: Licha D, Vidali S, Aminzadeh-Gohari S, Alka O, Breitkreuz L, Kohlbacher O, Reischl RJ, Feichtinger RG, Kofler B, Huber CG Abstract The application of ketogenic diet (KD) (high fat/low carbohydrate/adequate protein) as an auxiliary cancer therapy is a field of growing attention. KD provides sufficient energy supply for healthy cells, while possibly impairing energy production in highly glycolytic tumor cells. Moreover, KD regulates insulin and tumor related growth factors (like insulin growth factor-1, IGF-1). In order to provide molecular evidence for the proposed additional inhibition of tumor growth when combining chemotherapy with KD, we applied untargeted quantitative metabolome analysis on a spontaneous breast cancer xenograft mouse model, using MDA-MB-468 cells. Healthy mice and mice bearing breast cancer xenografts and receiving cyclophosphamide chemotherapy were compared after treatment with control diet and KD. Metabolomic profiling was performed on plasma samples, applying high-performance liquid chromatography coupled to tandem mass spectrometry. Statistical analysis revealed metabolic fingerprints comprising numerous significantly regulated features in the group of mice bearing breast cancer. This fingerprint disappeared after treatment with KD, resulting in recovery to the metabolic status observed in healthy mice receiving control diet. Moreover, amino acid metabolism as well as fatty acid transport were found to be affected by both the tumor and the applied KD. Our results provide clear evidence of a significant molecular effect of adjuvant KD in the context of tumor growth inhibition and suggest additional mechanisms of tumor suppression beyond the proposed constrain in energy supply of tumor cells. PMID: 31398922 [PubMed - in process]

Related Articles Genome-Wide Identification, Expression Pattern Analysis and Evolution of the Ces/Csl Gene Superfamily in Pineapple (Ananas comosus). Plants (Basel). 2019 Aug 08;8(8): Authors: Cao S, Cheng H, Zhang J, Aslam M, Yan M, Hu A, Lin L, Ojolo SP, Zhao H, Priyadarshani SVGN, Yu Y, Cao G, Qin Y Abstract The cellulose synthase (Ces) and cellulose synthase-like (Csl) gene families belonging to the cellulose synthase gene superfamily, are responsible for the biosynthesis of cellulose and hemicellulose of the plant cell wall, and play critical roles in plant development, growth and evolution. However, the Ces/Csl gene family remains to be characterized in pineapple, a highly valued and delicious tropical fruit. Here, we carried out genome-wide study and identified a total of seven Ces genes and 25 Csl genes in pineapple. Genomic features and phylogeny analysis of Ces/Csl genes were carried out, including phylogenetic tree, chromosomal locations, gene structures, and conserved motifs identification. In addition, we identified 32 pineapple AcoCes/Csl genes with 31 Arabidopsis AtCes/Csl genes as orthologs by the syntenic and phylogenetic approaches. Furthermore, a RNA-seq investigation exhibited the expression profile of several AcoCes/Csl genes in various tissues and multiple developmental stages. Collectively, we provided comprehensive information of the evolution and function of pineapple Ces/Csl gene superfamily, which would be useful for screening out and characterization of the putative genes responsible for tissue development in pineapple. The present study laid the foundation for future functional characterization of Ces/Csl genes in pineapple. PMID: 31398920 [PubMed]

Related Articles Identifying novel treeline biomarkers in lake sediments using an untargeted screening approach. Sci Total Environ. 2019 Jul 30;694:133684 Authors: Saleem A, Bell MA, Kimpe LE, Korosi JB, Arnason JT, Blais JM Abstract Paleolimnology uses sedimentary biomarkers as proxies to reconstruct long-term changes in environmental conditions from lake sediment cores. This work describes an untargeted metabolomics-based approach and uniquely applies it to the field of paleolimnology to identify novel sediment biomarkers to track long-term patterns in treeline dynamics. We identified new potential biomarkers across the Canadian northern Arctic, non-alpine, treeline using high-resolution accurate mass spectrometry, and pattern recognition analysis. This method was applied to 120 sediment core extracts from 14 boreal, 25 forest-tundra, and 21 tundra lakes to assess long-term fluctuations in treeline position. High resolution accurate mass spectrometry resolved many compounds from complex mixtures with low mass accuracy errors. This generated a large dataset that required metabolomics styled statistical analyses to identify potential biomarkers. In total, 29 potential biomarkers discriminated between boreal and tundra lakes. Tetrapyrrole-type phorbides and squalene derivatives dominated in boreal regions, while biohopane-type lipids were in the tundra regions. Tetrapyrroles were in both surface and subsurface sediments of boreal lakes indicating these compounds can survive long-term burial in sediments. At the ecozone level, tetrapyrroles were more abundant in boreal Taiga Shield, and Taiga Plains. Boreal plant extracts belonging to Pinaceae and Ericaceae also contained tetrapyrroles. Squalene derivatives demonstrated long-term preservation, but wider distribution than tetrapyrroles. Hopanoids were present in tundra and forest-tundra lake regions, specifically the Low Arctic and Taiga Shield, and were absent in all boreal lake sediments. Herein, we describe a method that can systematically identify new paleolimnological biomarkers. Novel biomarkers would facilitate multi-proxy paleolimnological studies and potentially lead to more accurate paleoenvironmental reconstructions. PMID: 31398651 [PubMed - as supplied by publisher]

Related Articles Maternal-to-zygotic transition as a potential target for niclosamide during early embryogenesis. Toxicol Appl Pharmacol. 2019 Aug 06;:114699 Authors: Vliet SMF, Dasgupta S, Sparks NRL, Kirkwood JS, Vollaro A, Hur M, Zur Nieden NI, Volz DC Abstract Niclosamide is an antihelminthic drug used worldwide for the treatment of tapeworm infections. Recent drug repurposing screens have highlighted the broad bioactivity of niclosamide across diverse mechanisms of action. As a result, niclosamide is being evaluated for a range of alternative drug-repurposing applications, including the treatment of cancer, bacterial infections, and Zika virus. As new applications of niclosamide will require non-oral delivery routes that may lead to exposure in utero, it is important to understand the mechanism of niclosamide toxicity during early stages of embryonic development. Previously, we showed that niclosamide induces a concentration-dependent delay in epiboly progression in the absence of effects on oxidative phosphorylation - a well-established target for niclosamide. Therefore, the overall objective of this study was to further examine the mechanism of niclosamide-induced epiboly delay during zebrafish embryogenesis. Based on this study, we found that (1) niclosamide exposure during early zebrafish embryogenesis resulted in a decrease in yolk sac integrity with a concomitant decrease in the presence of yolk sac actin networks and increase in cell size; (2) within whole embryos, niclosamide exposure did not alter non-polar metabolites and lipids, but significantly altered amino acids specific to aminoacyl-tRNA biosynthesis; (3) niclosamide significantly altered transcripts related to translation, transcription, and mRNA processing pathways; and (4) niclosamide did not significantly alter levels of rRNA and tRNA. Overall, our findings suggest that niclosamide may be causing a systemic delay in embryonic development by disrupting the translation of maternally-supplied mRNAs, an effect that may be mediated through disruption of aminoacyl-tRNA biosynthesis. PMID: 31398420 [PubMed - as supplied by publisher]