PubMed

Related Articles MS-based metabolomics revealing Bornean Sinularia sp. extract dysregulated lipids triggering programmed cell death in Hepatocellular carcinoma. Nat Prod Res. 2018 Dec 26;:1-8 Authors: Ling YS, Lim LR, Yong YS, Tamin O, Puah PY Abstract Soft coral, Sinularia sp. had been proven to inherit promising anti-cancer properties against variety of cancer. Current study, Sinularia sp. extract was introduced to Hepatocellular carcinoma (Hep 3B). Cell viability assay indicated the extract exhibit a dose and time dependent cytotoxicity. LC50 exhibited the lowest at 72 h post treatment estimated as 45.3 µg/mL. Morphological alterations including nuclear condensation, cytoplasm shrinkage and deformed cellular shape in treated Hep 3B were observable. Chemometric analysis revealed hydrophobic metabolites were significantly altered. Elevated vitamin D and derivatives tend to up-regulation Ca2+ and ROS subsequently triggering apoptosis. Dysregulated glycerolipids may suggest that they were biotransformed to compensate the needs of phospholipids during cell damage. Perturbation of sphingolipids, ceramide and carbohydrate-conjugated ceramides species increased the release of pro-apoptotic components reside within mitochondria and promote programmed cell death in treated Hep 3B. To conclude, MS-based metabolomics enabled the characterization of Sinularia sp. extract-induced cell death. PMID: 30587039 [PubMed - as supplied by publisher]

Related Articles We Are What We Eat: A Stoichiometric and Ecometabolomic Study of Caterpillars Feeding on Two Pine Subspecies of Pinus sylvestris. Int J Mol Sci. 2018 Dec 24;20(1): Authors: Rivas-Ubach A, Peñuelas J, Hódar JA, Oravec M, Paša-Tolić L, Urban O, Sardans J Abstract Many studies have addressed several plant-insect interaction topics at nutritional, molecular, physiological, and evolutionary levels. However, it is still unknown how flexible the metabolism and the nutritional content of specialist insect herbivores feeding on different closely related plants can be. We performed elemental, stoichiometric, and metabolomics analyses on leaves of two coexisting Pinus sylvestris subspecies and on their main insect herbivore; the caterpillar of the processionary moth (Thaumetopoea pityocampa). Caterpillars feeding on different pine subspecies had distinct overall metabolome structure, accounting for over 10% of the total variability. Although plants and insects have very divergent metabolomes, caterpillars showed certain resemblance to their plant-host metabolome. In addition, few plant-related secondary metabolites were found accumulated in caterpillar tissues which could potentially be used for self-defense. Caterpillars feeding on N and P richer needles had lower N and P tissue concentration and higher C:N and C:P ratios, suggesting that nutrient transfer is not necessarily linear through trophic levels and other plant-metabolic factors could be interfering. This exploratory study showed that little chemical differences between plant food sources can impact the overall metabolome of specialist insect herbivores. Significant nutritional shifts in herbivore tissues could lead to larger changes of the trophic web structure. PMID: 30586850 [PubMed - in process]

Related Articles A Glycolytic Switch is Required for Transdifferentiation to Endothelial Lineage. Circulation. 2018 Sep 28;: Authors: Lai L, Reineke E, Hamilton DJ, Cooke JP Abstract BACKGROUND: Previously we have shown that activation of cell-autonomous innate immune signaling facilitates the trandifferentiation of fibroblasts into induced endothelial cells (iECs), and is required to generate iECs with high fidelity for endothelial lineage. Recent studies indicate that a glycolytic switch plays a role in iPSC generation from somatic cells. METHODS: Seahorse and metabolomics flux assays were used to measure the metabolic changes during transdifferentiation in vitro, and matrigel plug assay was used to assess the effects of glycolysis modulators on transdifferentiation in vivo. RESULTS: The metabolic switch begins rapidly after activation of innate immunity, prior to the expression of markers of endothelial lineage. Inhibiting glycolysis impaired, whereas facilitating glycolysis enhanced, the generation of iECs. The TLR3 agonist PolyI:C increased expression of the mitochondrial citrate transporter Slc25A1, and the nuclear ATP-citrate lyase(ACL), in association with intracellular accumulation of citrate, the precursor for acetyl-CoA. These metabolic changes were coordinated with increased histone acetylation during transdifferentiation. CONCLUSIONS: Innate immune signaling promotes a glycolytic switch that is required for transdifferentiation, both processes being attenuated by ACL knockdown. These data shed light on a novel link between metabolism and epigenetic modulation in transdifferentiation. PMID: 30586707 [PubMed - as supplied by publisher]

Related Articles Transient Nutrient Deprivation Promotes Macropinocytosis-Dependent Intracellular Bacterial Community Development. mSphere. 2018 09 12;3(5): Authors: Hardison RL, Heimlich DR, Harrison A, Beatty WL, Rains S, Moseley MA, Thompson JW, Justice SS, Mason KM Abstract Nutrient limitation restricts bacterial growth in privileged sites such as the middle ear. Transient heme-iron restriction of nontypeable Haemophilus influenzae (NTHI), the major causative agent of chronic and recurrent otitis media (OM), promotes new and diverse phenotypes that can influence planktonic, biofilm, and intracellular lifestyles of NTHI. However, the bacterial responses to nutrient restriction that impact intracellular fate and survival of NTHI are unknown. In this work, we provide evidence for the role of transient heme-iron restriction in promoting the formation of intracellular bacterial communities (IBCs) of NTHI both in vitro and in vivo in a preclinical model of OM. We show that transient heme-iron restriction of NTHI results in significantly increased invasion and intracellular populations that escape or evade the endolysosomal pathway for increased intracellular survival. In contrast, NTHI continuously exposed to heme-iron traffics through the endolysosomal pathway for degradation. The use of pharmacological inhibitors revealed that prior heme-iron status does not appear to influence NTHI internalization through endocytic pathways. However, inhibition of macropinocytosis altered the intracellular fate of transiently restricted NTHI for degradation in the endolysosomal pathway. Furthermore, prevention of macropinocytosis significantly reduced the number of IBCs in cultured middle ear epithelial cells, providing evidence for the feasibility of this approach to reduce OM persistence. These results reveal that microenvironmental cues can influence the intracellular fate of NTHI, leading to new mechanisms for survival during disease progression.IMPORTANCE Otitis media is the most common bacterial infection in childhood. Current therapies are limited in the prevention of chronic or recurrent otitis media which leads to increased antibiotic exposure and represents a significant socioeconomic burden. In this study, we delineate the effect of nutritional limitation on the intracellular trafficking pathways used by nontypeable Haemophilus influenzae (NTHI). Moreover, transient limitation of heme-iron led to the development of intracellular bacterial communities that are known to contribute to persistence and recurrence in other diseases. New approaches for therapeutic interventions that reduce the production of intracellular bacterial communities and promote trafficking through the endolysosomal pathway were revealed through the use of pharmacological inhibition of macropinocytosis. This work demonstrates the importance of an intracellular niche for NTHI and provides new approaches for intervention for acute, chronic, and recurring episodes of otitis media. PMID: 30209128 [PubMed - indexed for MEDLINE]

Lipidomic profiling reveals early-stage metabolic dysfunction in overweight or obese humans. Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Dec 23;: Authors: Mousa A, Naderpoor N, Mellett N, Wilson K, Plebanski M, Meikle PJ, de Courten B Abstract BACKGROUND: Advances in mass spectrometry and lipidomics techniques are providing new insights into the role of lipid metabolism in obesity-related diseases. However, human lipidomic studies have been inconsistent, owing to the use of indirect proxy measures of metabolic outcomes and relatively limited coverage of the lipidome. Here, we employed comprehensive lipid profiling and gold-standard metabolic measures to test the hypothesis that distinct lipid signatures in obesity may signify early stages of pathogenesis toward type 2 diabetes. METHODS: Using high-performance liquid chromatography-electrospray tandem mass spectrometry, we profiled >450 lipid species across 26 classes in 65 overweight or obese non-diabetic individuals. Intensive metabolic testing was conducted using direct gold-standard measures of adiposity (% body fat by dual X-ray absorptiometry), insulin sensitivity (hyperinsulinaemic-euglycaemic clamps), and insulin secretion (intravenous glucose tolerance tests), as well as measurement of serum inflammatory cytokines and adipokines (multiplex assays; flow cytometry). Univariable and multivariable linear regression models were computed using Matlab R2011a, and all analyses were corrected for multiple testing using the Benjamini-Hochberg method. RESULTS: We present new evidence showing a strong and independent positive correlation between the lysophosphatidylinositol (LPI) lipid class and insulin secretion in vivo in humans (β [95% CI] = 781.9 [353.3, 1210.4], p = 0.01), supporting the insulinotropic effects of LPI demonstrated in mouse islets. Dihydroceramide, a sphingolipid precursor, was independently and negatively correlated with insulin sensitivity (β [95% CI] = -1.9 [-2.9, -0.9], p = 0.01), indicating a possible upregulation in sphingolipid synthesis in obese individuals. These associations remained significant in multivariable models adjusted for age, sex, and % body fat. The dihexosylceramide class correlated positively with interleukin-10 before and after adjustment for age, sex, and % body fat (p = 0.02), while the phosphatidylethanolamine class and its vinyl ether-linked (plasmalogen) derivatives correlated negatively with % body fat in both univariable and age- and sex-adjusted models (all p < 0.04). CONCLUSIONS: Our data suggest that these lipid classes may signify early pathogenesis toward type 2 diabetes and could serve as novel therapeutic targets or biomarkers for diabetes prevention. PMID: 30586632 [PubMed - as supplied by publisher]

Peak annotation and verification engine (PAVE) for untargeted LC-MS metabolomics. Anal Chem. 2018 Dec 26;: Authors: Wang L, Xing X, Chen L, Yang L, Su X, Rabitz HA, Lu W, Rabinowitz JD Abstract Untargeted metabolomics can detect more than 10,000 peaks in a single LC-MS run. The correspondence between these peaks and metabolites, however, remains unclear. Here we introduce a Peak Annotation and Verification Engine (PAVE) for systematically annotating untargeted microbial metabolomics data. The workflow involves growing cells in 13C and 15N isotope-labeled media to identify peaks from biological compounds and their carbon and nitrogen atom counts. Improved de-isotoping and de-adducting is enabled by algorithms that integrate positive mode, negative mode and labeling data. To distinguish metabolites and their fragments, PAVE experimentally measures the response of each peak to a weak in-source collision-induced-dissociation voltage, which increases the peak intensity for fragments while decreasing it for their parent ions. The molecular formulae of the putative metabolites are then assigned based on database searching using both m/z and C/N atom counts. Application of this procedure to S. cerevisiae and E. coli revealed that more than 80% peaks do not label, i.e. are environmental contaminants. More than 70% of the biological peaks are isotopic variants, adducts, fragments, or mass spectrometry artifacts yielding ~2,000 apparent metabolites across the two organisms. About 650 match to a known metabolite formula based on m/z and C/N atom counts, with 220 assigned structures based on MS/MS and/or retention time to match to authenticated standards. Thus, PAVE provides an efficient route to systematically annotate LC-MS metabolomics data. PMID: 30586294 [PubMed - as supplied by publisher]

The metabolome as a biomarker of mortality risk in the common marmoset. Am J Primatol. 2018 Dec 26;:e22944 Authors: Hoffman JM, Ross C, Tran V, Promislow DEL, Tardif S, Jones DP Abstract Recently, the common marmoset has been proposed as a non-human primate model of aging. Their short lifespan coupled with pathologies that are similar to humans make them an ideal model to understand the genetic, metabolic, and environmental factors that influence aging and longevity. However, many of the underlying physiological changes that occur with age in the marmoset are unknown. Here, we attempt to determine if individual metabolites are predictive of future death and to recapitulate past metabolomic results after a change in environment (move across the country) was imposed on a colony of marmosets. We first determined that low levels of tryptophan metabolism metabolites were associated with risk of death in a 2-year follow-up in the animals, suggesting these metabolites may be used as future biomarkers of mortality. We also discovered that betaine metabolism and methionine metabolism are associated with aging regardless of environment for the animals, or of metabolomic assay technique. These two metabolic pathways are therefore of particular interest to examine as future targets for health and lifespan extending interventions. Many of the pathways associated with age in our first study of marmoset metabolomics were not found to have significant age effects in our second study, suggesting more work is needed to understand the reproducibility of large scale metabolomic studies in mammalian models. Overall, we were able to show that while several metabolomics markers show promise in understanding health and lifespan relationships with aging, it is possible that choice of technique for assay and reproducibility in these types of studies are still issues that need to be examined further. PMID: 30585652 [PubMed - as supplied by publisher]

Multi-lab EcoFAB study shows highly reproducible physiology and depletion of soil metabolites by a model grass. New Phytol. 2018 Dec 26;: Authors: Sasse J, Kant J, Cole BJ, Klein AP, Arsova B, Schlaepfer P, Gao J, Lewald K, Zhalnina K, Kosina S, Bowen BP, Treen D, Vogel J, Visel A, Watt M, Dangl JL, Northen TR Abstract There is a dynamic reciprocity between plants and their environment: soil physiochemical properties influence plant morphology and metabolism, and root morphology and exudates shape the environment surrounding roots. Here, we investigate the reproducibility of plant trait changes in response to three growth environments. We utilized fabricated ecosystem (EcoFAB) devices to grow the model grass Brachypodium distachyon in three distinct media across four laboratories: phosphate-sufficient and -deficient mineral media allowed to assess the effects of phosphate starvation, and a complex, sterile soil extract represented a more natural environment with yet uncharacterized effects on plant growth and metabolism. Tissue weight and phosphate content, total root length, and root tissue and exudate metabolic profiles were consistent across laboratories and distinct between experimental treatments. Plants grown in soil extract were morphologically and metabolically distinct, with root hairs four times longer compared to other growth conditions. Further, plants depleted half of the investigated metabolites from the soil extract. To interact with their environment, plants not only adapt morphology and release complex metabolite mixtures; they also selectively deplete a range of soil-derived metabolites. The EcoFABs utilized here generated high inter-laboratory reproducibility, demonstrating that their value in standardized investigations of plant traits. This article is protected by copyright. All rights reserved. PMID: 30585637 [PubMed - as supplied by publisher]

Cerebrospinal fluid untargeted metabolomic profiling of aneurysmal subarachnoid hemorrhage: an exploratory study. Br J Neurosurg. 2018 Dec 26;:1-5 Authors: Lu AY, Damisah EC, Winkler EA, Grant RA, Eid T, Bulsara KR Abstract INTRODUCTION: Despite advancements in medical and surgical therapies, clinical outcomes of aneurysmal subarachnoid hemorrhage (aSAH) continue to be poor. Currently, aSAH pathophysiology remains poorly understood. No aSAH biomarkers are commonly used in the clinical setting. This exploratory study used metabolomics profiling to identify global metabolic changes and metabolite predictors of long-term outcome using cerebrospinal fluid (CSF) samples of aSAH patients. METHODS AND METHODS: Gas chromatography time-of-flight mass spectrometry was applied to CSF samples collected from 15 consecutive high-grade aSAH patients (modified Fisher grade 3 or 4). Collected CSF samples were analyzed at two time points (admission and the anticipated vasospasm timeframe). Metabolite levels at both time points were compared and correlated with vasospasm status and Glasgow Outcome Scale (GOS) of patients at 1 year post-aSAH. Significance level was defined as p < 0.05 with false discovery rate correction for multiple comparisons. RESULTS: Of 97 metabolites identified, 16 metabolites, primarily free amino acids, significantly changed between the two time points. These changes were magnified in modified Fisher grade 4 compared with grade 3. Six metabolites (2-hydroxyglutarate, tryptophan, glycine, proline, isoleucine, and alanine) correlated with GOS at 1 year post-aSAH independent of vasospasm status. When predicting patients who had low disability (GOS 5 vs. GOS ≤4), 2-hydroxyglutarate had a sensitivity and specificity of 0.89 and 0.83 respectively. CONCLUSIONS: Our preliminary study suggests that specific metabolite changes occur in the brain during the course of aSAH and that quantification of specific CSF metabolites may be used to predict long-term outcome in patients with aSAH. This is the first study to implicate 2-hydroxyglutarate, a known marker of tissue hypoxia, in aSAH pathogenesis. PMID: 30585503 [PubMed - as supplied by publisher]

Related Articles Systematic metabolic profiling and bioactivity assays for bioconversion of Aceraceae family. PLoS One. 2018;13(6):e0198739 Authors: Park J, Suh DH, Singh D, Lee S, Lee JS, Lee CH Abstract Plants are an important and inexhaustible source of bioactive molecules in food, medicine, agriculture, and industry. In this study, we performed systematic liquid chromatography-mass spectrometry (LC-MS)-based metabolic profiling coupled with antioxidant assays for indigenous plant family extracts. Partial least-squares discriminant analysis of LC-MS datasets for the extracts of 34 plant species belonging to the families Aceraceae, Asteraceae, and Rosaceae showed that these species were clustered according to their respective phylogenies. In particular, seven Aceraceae species were clearly demarcated with higher average antioxidant activities, rationalizing their application for bioconversion studies. On the basis of further evaluation of the interspecies variability of metabolic profiles and antioxidant activities among Aceraceae family plants, we found that Acer tataricum (TA) extracts were clearly distinguished from those of other species, with a higher relative abundance of tannin derivatives. Further, we detected a strong positive correlation between most tannin derivatives and the observed higher antioxidant activities. Following Aspergillus oryzae-mediated fermentative bioconversion of Acer plant extracts, we observed a time-correlated (0-8 days) linear increase in antioxidant phenotypes for all species, with TA having the highest activity. Temporal analysis of the MS data revealed tannin bioconversion mechanisms with a relatively higher abundance of gallic acid (m/z 169) accumulated at the end of 8 days, particularly in TA. Similarly, quercetin precursor (glycoside) metabolites were also transformed to quercetin aglycones (m/z 301) in most Acer plant extracts. The present study underscores the efficacy of fermentative bioconversion strategies aimed at enhancing the quality and availability of bioactive metabolites from plant extracts. PMID: 29879203 [PubMed - indexed for MEDLINE]

Related Articles The SnRK1 Kinase as Central Mediator of Energy Signaling between Different Organelles. Plant Physiol. 2018 02;176(2):1085-1094 Authors: Wurzinger B, Nukarinen E, Nägele T, Weckwerth W, Teige M PMID: 29311271 [PubMed - indexed for MEDLINE]

Related Articles Draft De Novo Genome Sequence of Agapornis roseicollis for Application in Avian Breeding. Anim Biotechnol. 2018;29(4):241-246 Authors: van der Zwan H, van der Westhuizen F, Visser C, van der Sluis R Abstract In aviculture, lovebirds are considered one of the most popular birds to keep. This African parakeet is known for its range of plumage colors and ease to tame. Plumage variation is the most important price-determining trait of these birds, and also the main selection criterion for breeders. Currently, no genetic screening tests for traits of economic importance or to confirm pedigree data are available for any of the nine lovebird species. As a starting point to develop these tests, the de novo genome of Agapornis roseicollis (rosy-faced lovebird) was sequenced, assembled, and annotated. Sequencing was done on the Illumina HiSeq 2000 platform and the assembly was performed using SOAPdenovo v2.04. The genome was found to be 1.1 Gb in size and 16,044 genes were identified and annotated. This compared well with other previously sequenced avian genomes, such as the chicken, zebra finch, and budgerigar. To assess genome completeness, the number of benchmarking universal single-copy orthologs were identified in the genome. This was compared to other previously assembled avian genomes and the results indicated that the genome will be useful in the development of genetic screening tests to aid lovebird breeders in selecting breeding pairs. PMID: 29035135 [PubMed - indexed for MEDLINE]

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Related Articles Chronic exposure of bumblebees to neonicotinoid imidacloprid suppresses the entire mevalonate pathway and fatty acid synthesis. J Proteomics. 2018 Dec 21;: Authors: Erban T, Sopko B, Talacko P, Harant K, Kadlikova K, Halesova T, Riddellova K, Pekas A Abstract Determining the side effects of pesticides on pollinators is an important topic due to the increasing loss of pollinators. We aimed to determine the effects of chronic sublethal exposure of the neonicotinoid pesticide imidacloprid on the bumblebee Bombus terrestris under laboratory conditions. The analytical standard of imidacloprid in sugar solution was used for the treatment. Verification of pesticides using UHPLC-QqQ-MS/MS in the experimental bumblebees showed the presence of only two compounds, imidacloprid and imidacloprid-olefin, which were found in quantities of 0.57 ± 0.22 and 1.95 ± 0.43 ng/g, respectively. Thus, the level of the dangerous metabolite imidacloprid-olefin was 3.4-fold higher than that of imidacloprid. Label-free nanoLC-MS/MS quantitative proteomics of bumblebee heads enabled quantitative comparison of 2883 proteins, and 206 proteins were significantly influenced by the imidacloprid treatment. The next analysis revealed that the highly downregulated markers are members of the terpenoid backbone biosynthesis pathway (KEGG: bter00900) and that imidacloprid treatment suppressed the entire mevalonate pathway, fatty acid synthesis and associated markers. The proteomics results indicate that the consequences of imidacloprid treatment are complex, and the marker changes are associated with metabolic and neurological diseases and olfaction disruption. This study provides important markers and can help to explain the widely held assumptions from biological observations. PMID: 30583045 [PubMed - as supplied by publisher]

Related Articles Involvement of non melanocytic skin cells in vitiligo. Exp Dermatol. 2018 Dec 24;: Authors: Bastonini E, Bellei B, Filoni A, Kovacs D, Iacovelli P, Picardo M Abstract Despite melanocytes are the key players in vitiligo, a continuous cross-talk between epidermal and dermal cells may strictly affect their functionality, in both lesional and non-lesional skin. Focusing on this interplay, we have reviewed existing literature supporting evidence on cellular and functional alterations of surrounding epidermal keratinocytes, extracellular matrix (ECM) proteins and fibroblasts in the underlying dermal compartment that may contribute to melanocyte disappearance in vitiligo. We have also examined some clinical and therapeutic aspects of the disease to sustain the non-exclusive involvement of melanocytes within vitiligo. As a result, a different and more complex scenario has appeared that may enable to provide better understanding about origins and progress of vitiligo and that should be considered in the evaluation of new treatment approaches. This article is protected by copyright. All rights reserved. PMID: 30582762 [PubMed - as supplied by publisher]

Related Articles Omics in traditional vegetable fermented foods and beverages. Crit Rev Food Sci Nutr. 2018 Dec 22;:1-19 Authors: Rizo J, Guillén D, Farrés A, Díaz-Ruiz G, Sánchez S, Wacher C, Rodríguez-Sanoja R Abstract For a long time, food microbiota has been studied using traditional microbiological techniques. With the arrival of molecular or culture-independent techniques, a strong understanding of microbiota dynamics has been achieved. However, analyzing the functional role of microbial communities is not an easy task. The application of omics sciences to the study of fermented foods would provide the metabolic and functional understanding of the microbial communities and their impact on the fermented product, including the molecules that define its aroma and flavor, as well as its nutritional properties. Until now, most omics studies have focused on commercial fermented products, such as cheese, wine, bread and beer, but traditional fermented foods have been neglected. Therefore, the information that allows to relate the present microbiota in the food and its properties remains limited. In this review, reports on the applications of omics in the study of traditional fermented foods and beverages are reviewed to propose new ways to analyze the fermentation phenomena. PMID: 30582346 [PubMed - as supplied by publisher]

Related Articles Phytochemical characterization of Tabernanthe iboga root bark and its effects on dysfunctional metabolism and cognitive performance in high-fat-fed C57BL/6J mice. J Food Bioact. 2018 Sep;3:111-123 Authors: Bading-Taika B, Akinyeke T, Magana AA, Choi J, Ouanesisouk M, Torres ERS, Lione LA, Maier CS, Bobe G, Raber J, Miranda CL, Stevens JF Abstract Preparations of the root bark of Tabernanthe iboga have long been used in Central and West African traditional medicine to combat fatigue, as a neuro-stimulant in rituals, and for treatment of diabetes. The principal alkaloid of T. iboga, ibogaine, has attracted attention in many countries around the world for providing relief for opioid craving in drug addicts. Using a plant metabolomics approach, we detected five phenolic compounds, including 3-O-caffeoylquinic acid, and 30 alkaloids, seven of which were previously reported from T. iboga root bark. Following a report that iboga extracts contain insulinotropic agents, we aimed to determine the potential alleviating effects of the water extract of iboga root bark on high-fat diet (HFD)-induced hyperglycemia as well as its effects on cognitive function in male C57BL/6J mice. Feeding a HFD to mice for 10 weeks produced manifestations of metabolic syndrome such as increased body weight and increased plasma levels of glucose, triacylglycerols, total cholesterol, LDL-cholesterol, insulin, leptin, and pro-inflammatory mediators (IL-6, MCP-1, ICAM-1), as compared to mice fed a low-fat diet (LFD). Supplementation of HFD with iboga extract at ibogaine doses of 0.83 (low) and 2.07 (high) mg/kg/day did not improve these HFD-induced metabolic effects except for a reduction of plasma MCP-1 in the low dose group, indicative of an anti-inflammatory effect. When the HFD mice were tested in the water maze, the high-dose iboga extract caused hippocampus-dependent impairments in spatial learning and memory, as compared to mice receiving only a HFD. PMID: 30582133 [PubMed]

Related Articles Zinc oxide nanoparticles impose metabolic toxicity by de-regulating proteome and metabolome in Saccharomyces cerevisiae. Toxicol Rep. 2019;6:64-73 Authors: Kumar Babele P Abstract As zinc oxide nanoparticles are being increasingly used in various applications, it is important to assess their potential toxic implications. Stress responses and adaptations are primarily controlled by modulation in cellular proteins (enzyme) and concentration of metabolites. To date proteomics or metabolomics applications in nanotoxicity assessment have been applied to a restricted extent. Here we utilized 2DE and 1H NMR based proteomics and metabolomics respectively to delineate the toxicity mechanism of zinc oxide nanoparticles (ZnO-NPs) in budding yeast S. cerevisiae. We found that the physiological and metabolic processes were altered in the S. cerevisiae upon ZnO-NPs exposure. Almost 40% proteins were down-regulated in ZnO-NPs (10 mg L-1) exposed cell as compared to control. Metabolomics and system biology based pathway analysis, revealed that ZnO-NPs repressed a wide range of key metabolites involved in central carbon metabolism, cofactors synthesis, amino acid and fatty acid biosynthesis, purines and pyrimidines, nucleoside and nucleotide biosynthetic pathways. These metabolic changes may be associated with the energy metabolism, antioxidation, DNA and protein damage and membrane stability. We concluded that untargeted proteomic and metabolic approaches provide more complete measurements and suggest probable molecular mechanisms of nanomaterials toxicity. PMID: 30581761 [PubMed]

Related Articles Study of Methanol Extracts from Different Parts of Peganum harmala L. Using 1H-NMR Plant Metabolomics. J Anal Methods Chem. 2018;2018:6532789 Authors: Li Y, He Q, Du S, Guo S, Geng Z, Deng Z Abstract A nuclear magnetic resonance- (NMR-) based metabolomics method was used to identify differential metabolites of methanol extracts obtained from six parts of Peganum harmala L. (P. harmala), namely, the root, stem, leaf, flower, testa, and seed. Two multivariate statistical analysis methods, principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), were combined to clearly distinguish among the P. harmala samples from the six different parts. Eleven differential components were screened by the PLS-DA loading plot, and the relative contents were calculated by univariate analysis of variance. Chemometric results showed significant differences in the metabolites of the different parts of P. harmala. The seeds contained large amounts of harmaline, harmine, and vasicine compared to other organs. The acetic acid, proline, lysine, and sucrose contents of the roots were significantly higher than those of the other parts. In the testa, the vasicine, asparagine, choline, and 4-hydroxyisoleucine contents were clearly dominant. The obtained data revealed the distribution characteristics of the metabolomes of the different P. harmala parts and provided fundamental knowledge for the rational development of its medicinal parts. PMID: 30581649 [PubMed]

Related Articles Independent or integrative processing approach of metabolite datasets from different biospecimens potentially affects metabolic pathway recognition in metabolomics. J Chromatogr A. 2018 Dec 14;: Authors: Zhou L, Xu JD, Zhou SS, Zhu H, Kong M, Shen H, Zou YT, Cong LJ, Xu J, Li SL Abstract In metabolomics studies, metabolic pathway recognition (MPR) is performed by software tools to screen out the significant pathways disturbed by diseases or reinstated by drugs. To achieve MPR, the significantly changed metabolites determined in different biospecimens (e.g. plasma and urine) are analyzed either independently (metabolites from each biospecimen as a dataset) or integratively (metabolites from all biospecimens as a dataset). However, whether the choice of these two processing approaches affects the results of MPR remains unknown. In this study, this issue was addressed by selecting evaluation of the effects of the herbal medicine Rehmanniae Radix (RR) on anemia and adrenal fatigue by UPLC-QTOF-MS/MS-based metabolomics as an example. The significant pathways disturbed by the modeling of anemia and adrenal fatigue and those reinstated by treatments with raw and processed RR were recognized using MetPA software tool (MetaboAnalyst 3.0), and compared by independent and integrative processing of the significantly changed metabolites determined in plasma and urine. The results showed that the two processing approaches could yield different impact values of pathways and thereby recognize different significant pathways. The differences appear to happen more easily when metabolites from different biospecimens shared the same metabolic pathway. Such pathway could be recognized as a significant pathway by integrative processing but could be excluded by independent processing due to the converged and dispersed importance contributions of the involved metabolites to MPR in the two processing approaches. This issue should concern researchers because MPR is crucial not only to understanding metabolomics data but also to guiding subsequent mechanistic research. PMID: 30580960 [PubMed - as supplied by publisher]