PubMed

Related Articles The Natural Products Atlas: An Open Access Knowledge Base for Microbial Natural Products Discovery. ACS Cent Sci. 2019 Nov 27;5(11):1824-1833 Authors: van Santen JA, Jacob G, Singh AL, Aniebok V, Balunas MJ, Bunsko D, Neto FC, Castaño-Espriu L, Chang C, Clark TN, Cleary Little JL, Delgadillo DA, Dorrestein PC, Duncan KR, Egan JM, Galey MM, Haeckl FPJ, Hua A, Hughes AH, Iskakova D, Khadilkar A, Lee JH, Lee S, LeGrow N, Liu DY, Macho JM, McCaughey CS, Medema MH, Neupane RP, O'Donnell TJ, Paula JS, Sanchez LM, Shaikh AF, Soldatou S, Terlouw BR, Tran TA, Valentine M, van der Hooft JJJ, Vo DA, Wang M, Wilson D, Zink KE, Linington RG Abstract Despite rapid evolution in the area of microbial natural products chemistry, there is currently no open access database containing all microbially produced natural product structures. Lack of availability of these data is preventing the implementation of new technologies in natural products science. Specifically, development of new computational strategies for compound characterization and identification are being hampered by the lack of a comprehensive database of known compounds against which to compare experimental data. The creation of an open access, community-maintained database of microbial natural product structures would enable the development of new technologies in natural products discovery and improve the interoperability of existing natural products data resources. However, these data are spread unevenly throughout the historical scientific literature, including both journal articles and international patents. These documents have no standard format, are often not digitized as machine readable text, and are not publicly available. Further, none of these documents have associated structure files (e.g., MOL, InChI, or SMILES), instead containing images of structures. This makes extraction and formatting of relevant natural products data a formidable challenge. Using a combination of manual curation and automated data mining approaches we have created a database of microbial natural products (The Natural Products Atlas, www.npatlas.org) that includes 24 594 compounds and contains referenced data for structure, compound names, source organisms, isolation references, total syntheses, and instances of structural reassignment. This database is accompanied by an interactive web portal that permits searching by structure, substructure, and physical properties. The Web site also provides mechanisms for visualizing natural products chemical space and dashboards for displaying author and discovery timeline data. These interactive tools offer a powerful knowledge base for natural products discovery with a central interface for structure and property-based searching and presents new viewpoints on structural diversity in natural products. The Natural Products Atlas has been developed under FAIR principles (Findable, Accessible, Interoperable, and Reusable) and is integrated with other emerging natural product databases, including the Minimum Information About a Biosynthetic Gene Cluster (MIBiG) repository, and the Global Natural Products Social Molecular Networking (GNPS) platform. It is designed as a community-supported resource to provide a central repository for known natural product structures from microorganisms and is the first comprehensive, open access resource of this type. It is expected that the Natural Products Atlas will enable the development of new natural products discovery modalities and accelerate the process of structural characterization for complex natural products libraries. PMID: 31807684 [PubMed]

Related Articles Metabolomics analysis of the saliva in patients with chronic hepatitis B using nuclear magnetic resonance: a pilot study. Iran J Basic Med Sci. 2019 Sep;22(9):1044-1049 Authors: Gilany K, Mohamadkhani A, Chashmniam S, Shahnazari P, Amini M, Arjmand B, Malekzadeh R, Nobakht Motlagh Ghoochani BF Abstract Objectives: Hepatitis B virus infection causes chronic disease such as cirrhosis and hepatocellular carcinoma. The metabolomics investigations have been demonstrated to be related to pathophysiologic mechanisms in many disorders such as hepatitis B infection. The aim of this study was to investigate the saliva metabolic profile of patients with chronic hepatitis B infection and to identify underlying mechanisms as well as potential biomarkers associated with the disease. Materials and Methods: Saliva from 16 healthy subjects and 20 patients with chronic hepatitis B virus were analyzed by nuclear magnetic resonance (NMR). Then, multivariate statistical analysis was performed to identify discriminative metabolites between two groups. Results: A set of metabolites were detected, including propionic acid, putrescine, acetic acid, succinic acid, tyrosine, lactic acid, butyric acid, pyruvic acid, 4-pyridoxic acid and 4-hydroxybenzoic acid, which in combination with one another could accurately distinguish patients from healthy controls. Our results clearly demonstrated altered metabolites are involved in nine metabolic pathways. Conclusion: Metabolomics has the potential to be considered as a novel clinical tool for hepatitis B diagnosis while contributing to a comprehensive understanding of disease mechanisms. PMID: 31807248 [PubMed]

Related Articles Altered cellular metabolism in gliomas - an emerging landscape of actionable co-dependency targets. Nat Rev Cancer. 2019 Dec 05;: Authors: Bi J, Chowdhry S, Wu S, Zhang W, Masui K, Mischel PS Abstract Altered cellular metabolism is a hallmark of gliomas. Propelled by a set of recent technological advances, new insights into the molecular mechanisms underlying glioma metabolism are rapidly emerging. In this Review, we focus on the dynamic nature of glioma metabolism and how it is shaped by the interaction between tumour genotype and brain microenvironment. Recent advances integrating metabolomics with genomics are discussed, yielding new insight into the mechanisms that drive glioma pathogenesis. Studies that shed light on interactions between the tumour microenvironment and tumour genotype are highlighted, providing important clues as to how gliomas respond to and adapt to their changing tissue and biochemical contexts. Finally, a road map for the discovery of potential new glioma drug targets is suggested, with the goal of translating these new insights about glioma metabolism into clinical benefits for patients. PMID: 31806884 [PubMed - as supplied by publisher]

Related Articles Lipokine 5-PAHSA is Regulated by Adipose Triglyceride Lipase and Primes Adipocytes for de novo Lipogenesis in Mice. Diabetes. 2019 Dec 05;: Authors: Paluchova V, Oseeva M, Brezinova M, Cajka T, Bardova K, Adamcova K, Zacek P, Brejchova K, Balas L, Chodounska H, Kudova E, Schreiber R, Zechner R, Durand T, Rossmeisl M, Abumrad NA, Kopecky J, Kuda O Abstract Branched esters of palmitic acid and hydroxy-stearic acid (PAHSA) are anti-inflammatory and anti-diabetic lipokines that connect glucose and lipid metabolism. We aimed to characterize involvement of the 5-PAHSA regioisomer in the adaptive metabolic response of white adipose tissue (WAT) to cold exposure (CE) in mice, exploring the crosstalk between glucose utilization and lipid metabolism. CE promoted local production of 5- and 9-PAHSAs in WAT. Metabolic labeling of de novo lipogenesis (DNL) using 2H2O revealed that 5-PAHSA potentiated the effects of CE and stimulated triacylglycerol/fatty acid (TAG/FA) cycling in WAT through impacting lipogenesis and lipolysis. Adipocyte lipolytic products were altered by 5-PAHSA through selective FA re-esterification. The impaired lipolysis in global adipose triglyceride lipase (ATGL) knockout mice reduced free PAHSA levels and uncovered a metabolite reservoir of TAG-bound PAHSAs (TAG-estolides) in WAT. Utilization of 13C isotope tracers and dynamic metabolomics documented that 5-PAHSA primed adipocytes for glucose metabolism in a different way from insulin, promoting DNL, and impeding TAG synthesis. In summary, our data revealed new cellular and physiological mechanisms underlying the beneficial effects of 5-PAHSA, its relation to insulin action in adipocytes, and independently confirmed a PAHSA metabolite reservoir linked to ATGL-mediated lipolysis. PMID: 31806624 [PubMed - as supplied by publisher]

Related Articles A Multi-Cohort Metabolomics Analysis Discloses Sphingomyelin (32:1) Levels to be Inversely Related to Incident Ischemic Stroke. J Stroke Cerebrovasc Dis. 2019 Dec 02;:104476 Authors: Lind L, Salihovic S, Ganna A, Sundström J, Broeckling CD, Magnusson PK, Pedersen NL, Siegbahn A, Prenni J, Fall T, Ingelsson E, Ärnlöv J Abstract BACKGROUND AND PURPOSE: To search for novel pathophysiological pathways related to ischemic stroke using a metabolomics approach. METHODS: We identified 204 metabolites in plasma by liquid chromatography mass spectrometry in 3 independent population-based samples (TwinGene, Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) and Uppsala Longitudinal Study of Adult Men). TwinGene was used for discovery and the other 2 samples were meta-analyzed as replication. In PIVUS, traditional cardiovascular (CV) risk factors, multiple markers of subclinical CV disease, markers of coagulation/fibrinolysis were measured and analyzed in relation to top metabolites. RESULTS: In TwinGene (177 incident cases, median follow-up 4.3 years), levels of 28 metabolites were associated with incident ischemic stroke at a false discover rate (FDR) of 5%. In the replication (together 194 incident cases, follow-up 10 and 12 years, respectively), only sphingomyelin (32:1) was significantly associated (HR .69 per SD change, 95% CI .57-0.83, P value = .00014; FDR <5%) when adjusted for systolic blood pressure, diabetes, smoking, low density lipoportein (LDL)- and high density lipoprotein (HDL), body mass index (BMI) and atrial fibrillation. In PIVUS, sphingomyelin (32:1) levels were significantly related to both LDL- and HDL-cholesterol in a positive fashion, and to serum triglycerides, BMI and diabetes in a negative fashion. Furthermore, sphingomyelin (32:1) levels were related to vasodilation in the forearm resistance vessels, and inversely to leukocyte count (P < .0069 and .0026, respectively). CONCLUSIONS: An inverse relationship between sphingomyelin (32:1) and incident ischemic stroke was identified, replicated, and characterized. A possible protective role for sphingomyelins in stroke development has to be further investigated in additional experimental and clinical studies. PMID: 31806450 [PubMed - as supplied by publisher]

Related Articles UPLC-MS based urine untargeted metabolomic analyses to differentiate bladder cancer from renal cell carcinoma. BMC Cancer. 2019 Dec 05;19(1):1195 Authors: Wang Z, Liu X, Liu X, Sun H, Guo Z, Zheng G, Zhang Y, Sun W Abstract BACKGROUND: To discover biomarker panels that could distinguish cancers (BC and RCC) from healthy controls (HCs) and bladder cancers (BC) from renal cell carcinoma (RCC), regardless of whether the patients have haematuria. In addition, we also explored the altered metabolomic pathways of BC and RCC. METHODS: In total, 403 participants were enrolled in our study, which included 146 BC patients (77 without haematuria and 69 with haematuria), 115 RCC patients (94 without haematuria and 21 with haematuria) and 142 sex- and age-matched HCs. Their midstream urine samples were collected and analysed by performing UPLC-MS. The statistical methods and pathway analyses were applied to discover potential biomarker panels and altered metabolic pathways. RESULTS: The panel of α-CEHC, β-cortolone, deoxyinosine, flunisolide, 11b,17a,21-trihydroxypreg-nenolone and glycerol tripropanoate could distinguish the patients with cancer from the HCs (the AUC was 0.950) and the external validation also displayed a good predictive ability (the AUC was 0.867). The panel of 4-ethoxymethylphenol, prostaglandin F2b, thromboxane B3, hydroxybutyrylcarnitine, 3-hydroxyphloretin and N'-formylkynurenine could differentiate BC from RCC without haematuria. The AUC was 0.829 in the discovering group and 0.76 in the external validation. The metabolite panel comprising 1-hydroxy-2-oxopropyl tetrahydropterin, 1-acetoxy-2-hydroxy-16-heptadecyn-4-one, 1,2-dehydrosalsolinol and L-tyrosine could significantly discriminate BC from RCC with haematuria (AUC was 0.913). Pathway analyses revealed altered lipid and purine metabolisms between cancer patients and HCs, together with disordered amino acid and purine metabolisms between BC and RCC with haematuria. CONCLUSIONS: UPLC-MS urine metabolomic analyses could not only differentiate cancers from HCs but also discriminate BC from RCC. In addition, pathway analyses demonstrated a deeper metabolic mechanism of BC and RCC. PMID: 31805976 [PubMed - in process]

Related Articles Immunological Effects of Epigenetic Modifiers. Cancers (Basel). 2019 Dec 01;11(12): Authors: Bezu L, Chuang AW, Liu P, Kroemer G, Kepp O Abstract Epigenetic alterations are associated with major pathologies including cancer. Epigenetic dysregulation, such as aberrant histone acetylation, altered DNA methylation, or modified chromatin organization, contribute to oncogenesis by inactivating tumor suppressor genes and activating oncogenic pathways. Targeting epigenetic cancer hallmarks can be harnessed as an immunotherapeutic strategy, exemplified by the use of pharmacological inhibitors of DNA methyltransferases (DNMT) and histone deacetylases (HDAC) that can result in the release from the tumor of danger-associated molecular patterns (DAMPs) on one hand and can (re-)activate the expression of tumor-associated antigens on the other hand. This finding suggests that epigenetic modifiers and more specifically the DNA methylation status may change the interaction of chromatin with chaperon proteins including HMGB1, thereby contributing to the antitumor immune response. In this review, we detail how epigenetic modifiers can be used for stimulating therapeutically relevant anticancer immunity when used as stand-alone treatments or in combination with established immunotherapies. PMID: 31805711 [PubMed]

17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/12/06PubMed 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.

17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/12/06PubMed 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.

28 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 2019/12/05PubMed 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.

39 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 2019/12/04PubMed 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 Analysis of brain metabolites by gas chromatography-mass spectrometry reveals the risk-benefit concerns of prednisone in MRL/lpr lupus mice. Inflammopharmacology. 2019 Nov 30;: Authors: Zhou J, Lu F, Li S, Xie M, Lu H, Xie Z, Wu D, Wang S, Wen C, Xu ZH Abstract OBJECTIVE: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a common cause of disability in systemic lupus erythematosus (SLE). This study aims to investigate the metabolic changes in the hypothalamus and frontal cortex in lupus-prone MRL/lpr mice. METHODS: Metabolic changes were analyzed using gas chromatography-mass spectrometry (GC-MS). RESULTS: According to the principal component analysis (PCA), the metabolic profiles were different between the frontal cortex and hypothalamus, but they were comparable between MRL/lpr and MRL/MpJ mice (16 weeks of age). By OPLS-DA, eight cortical and six hypothalamic differential metabolites were identified in MRL/lpr as compared to MRL/MpJ mice. Among these differential metabolites, we found a decrease of N-acetyl-L-aspartate (NAA, a potential marker of neuronal integrity), an increase of pyruvate and a decrease of glutamate in the frontal cortex but not in the hypothalamus. Prednisone treatment (3 mg/kg from 8 weeks of age) relieved the decrease of NAA but further increased the accumulation of pyruvate in the frontal cortex, additionally affected eight enriched pathways in the hypothalamus, and led to significant imbalances between the excitation and inhibition in both the frontal cortex and hypothalamus. CONCLUSION: These results suggest that the frontal cortex may be more preferentially affected than the hypothalamus in SLE. Prednisone disrupted rather than relieved metabolic abnormalities in the brain, especially in the hypothalamus, indicating that the risk-benefit balance of prednisone for SLE or NPSLE remains to be further evaluated. PMID: 31786803 [PubMed - as supplied by publisher]

Related Articles Hepatic PGC-1α is not essential for fasting-induced cytochrome p450 regulation in mouse liver. Biochem Pharmacol. 2019 Nov 28;:113736 Authors: Thøgersen R, Maag Kristensen C, Algot Olsen M, Christine Bertram H, Pilegaard H, Krøyer Rasmussen M Abstract Fasting has been shown to regulate the expression of the cytochrome p450 (CYP) enzyme system in the liver. However, the exact mechanism behind the fasting-induced regulation of the CYP's remains unknown. In the present study we tested the hypothesis that the peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), which is a key-regulator of energy metabolism, is responsible for the fasting-induced regulation of the CYP's. Lox/lox and liver specific PGC-1α (LKO) mice of both sexes, fasted for 18 hours and the content of the CYP's as well as the hepatic metabolome was assessed. Fasting increased the mRNA content of Cyp2a4, Cyp2e1, Cyp3a11 and Cyp4a10. The fasting-induced response in Cyp4a10 mRNA content was different between lox/lox and LKO mice, while the absence of PGC-1α had no effect on the fasting-induced response for the other Cyp's. Moreover, the fasting-induced response in mRNA content of Sirtinus 1 and Perilipin 2 was different between lox/lox and LKO mice. Only the CYP1A isoform showed a fasting-induced response at the protein level. Absence of hepatic PGC-1α had no effect on the apparent metabolome, where fasting vs fed was the only discriminate in the following multivariate analysis. In conclusion, hepatic PGC-1α is not essential for the fasting-induced regulation of hepatic CYP's. PMID: 31786263 [PubMed - as supplied by publisher]

Related Articles Experimental design for parameter estimation in steady-state linear models of metabolic networks. Math Biosci. 2019 Nov 28;:108291 Authors: Frøysa HG, Skaug HJ, Alendal G Abstract Metabolic networks are typically large, containing many metabolites and reactions. Dynamical models that aim to simulate such networks will consist of a large number of ordinary differential equations, with many kinetic parameters that must be estimated from experimental data. We assume these data to be metabolomics measurements made under steady-state conditions for different input fluxes. Assuming linear kinetics, analytical criteria for parameter identifiability are provided. For normally distributed error terms, we also calculate the Fisher information matrix analytically to be used in the D-optimality criterion. A test network illustrates the developed tool chain for finding an optimal experimental design. The first stage is to verify global or pointwise parameter identifiability, the second stage to find optimal input fluxes, and finally remove redundant measurements. PMID: 31786081 [PubMed - as supplied by publisher]

Related Articles Activation of Kappa Opioid Receptor Regulates the Hypothermic Response to Calorie Restriction and Limits Body Weight Loss. Curr Biol. 2019 Nov 05;: Authors: Cintron-Colon R, Johnson CW, Montenegro-Burke JR, Guijas C, Faulhaber L, Sanchez-Alavez M, Aguirre CA, Shankar K, Singh M, Galmozzi A, Siuzdak G, Saez E, Conti B Abstract Mammals maintain a nearly constant core body temperature (Tb) by balancing heat production and heat dissipation. This comes at a high metabolic cost that is sustainable if adequate calorie intake is maintained. When nutrients are scarce or experimentally reduced such as during calorie restriction (CR), endotherms can reduce energy expenditure by lowering Tb [1-6]. This adaptive response conserves energy, limiting the loss of body weight due to low calorie intake [7-10]. Here we show that this response is regulated by the kappa opioid receptor (KOR). CR is associated with increased hypothalamic levels of the endogenous opioid Leu-enkephalin, which is derived from the KOR agonist precursor dynorphin [11]. Pharmacological inhibition of KOR, but not of the delta or the mu opioid receptor subtypes, fully blocked CR-induced hypothermia and increased weight loss during CR independent of calorie intake. Similar results were seen with DIO mice subjected to CR. In contrast, inhibiting KOR did not change Tb in animals fed ad libitum (AL). Chemogenetic inhibition of KOR neurons in the hypothalamic preoptic area reduced the CR-induced hypothermia, whereas chemogenetic activation of prodynorphin-expressing neurons in the arcuate or the parabrachial nucleus lowered Tb. These data indicate that KOR signaling is a pivotal regulator of energy homeostasis and can affect body weight during dieting by modulating Tb and energy expenditure. PMID: 31786059 [PubMed - as supplied by publisher]

Related Articles Immunosuppression by Mutated Calreticulin Released from Malignant Cells. Mol Cell. 2019 Nov 23;: Authors: Liu P, Zhao L, Loos F, Marty C, Xie W, Martins I, Lachkar S, Qu B, Waeckel-Énée E, Plo I, Vainchenker W, Perez F, Rodriguez D, López-Otin C, van Endert P, Zitvogel L, Kepp O, Kroemer G Abstract Mutations affecting exon 9 of the CALR gene lead to the generation of a C-terminally modified calreticulin (CALR) protein that lacks the KDEL endoplasmic reticulum (ER) retention signal and consequently mislocalizes outside of the ER where it activates the thrombopoietin receptor in a cell-autonomous fashion, thus driving myeloproliferative diseases. Here, we used the retention using selective hooks (RUSH) assay to monitor the trafficking of CALR. We found that exon-9-mutated CALR was released from cells in response to the biotin-mediated detachment from its ER-localized hook, in vitro and in vivo. Cellular CALR release was confirmed in suitable mouse models bearing exon-9-mutated hematopoietic systems or tumors. Extracellular CALR mediated immunomodulatory effects and inhibited the phagocytosis of dying cancer cells by dendritic cells (DC), thereby suppressing antineoplastic immune responses elicited by chemotherapeutic agents or by PD-1 blockade. Altogether, our results demonstrate paracrine immunosuppressive effects for exon-9-mutated CALR. PMID: 31785928 [PubMed - as supplied by publisher]

Related Articles High-throughput non-targeted metabolomics study of the effects of perfluorooctane sulfonate (PFOS) on the metabolic characteristics of A. thaliana leaves. Sci Total Environ. 2019 Nov 23;:135542 Authors: Guo Q, He Z, Liu X, Liu B, Zhang Y Abstract The ecotoxicity of perfluorooctane sulfonate (PFOS) is complex and has been reported in animals (including fish and mice), but the effects of PFOS in plants, especially the toxic mechanisms, have rarely been studied. High-throughput nontargeted metabolomics methods for comprehensive assessment were selected to study changes in metabolic characteristics in Arabidopsis thaliana leaves by exposure to different concentrations of PFOS throughout the growth period (30 days). All the metabolites were analyzed by PCA and OPLS-DA methods, by the cutoff of VIP and p-value, 53 biomarkers were found and significantly regulated, all amino acids except glutamate were inhibited and probably associated with binding to protein, auxin and cytokinin of phytohormones were significantly down-regulated. In response mechanism to oxidative stress from PFOS, the phenylpropanoid pathway were fully activated to form several polyphenols and further enhanced into several flavonoids against the reactive oxygen species (ROS) as the primary defend pathway, in addition, ascorbate, trehalose and nicotinamide also were activated and help decrease the damage from oxidative stress. These results provide insights into the mechanism underlying the phytotoxicity of PFOS. PMID: 31785916 [PubMed - as supplied by publisher]

Related Articles Brain and blood metabolome for Alzheimer's dementia: findings from a targeted metabolomics analysis. Neurobiol Aging. 2019 Nov 05;: Authors: Huo Z, Yu L, Yang J, Zhu Y, Bennett DA, Zhao J Abstract The development of Alzheimer's dementia (AD) accompanies both central and peripheral metabolic disturbance, but the metabolic basis underlying AD and metabolic markers predictive of AD risk remain to be determined. It is also unclear whether the metabolic changes in the peripheral blood and brain are overlapping in relation to AD. The present study addresses these questions by targeted metabolomics in both antemortem blood and postmortem brain samples in 2 community-based longitudinal cohorts of aging and dementia. We found that higher serum levels of 3 acylcarnitines, including decanoylcarnitine (C10), pimelylcarnitine (C7-DC), and tetradecadienylcarnitine (C14:2), significantly predict a lower risk of incident AD (composite hazard ratio = 0.368, 95% CI [0.207, 0.653]) after an average of 4.5-year follow-up, independent of age, sex, and education. In addition, baseline serum levels of ten glycerophospholipids, one amino acid, and 5 acylcarnitines predict the longitudinal change in cognitive functions. Moreover, 28 brain metabolites were associated with AD phenotypes. Of the putative metabolites identified in the serum and brain, 4 metabolites (3 glycerophospholipids [PC aa C30:0, PC ae C34:0, PC ae C36:1] and 1 acylcarnitine [C14:2]) were present in both the postmortem brain and antemortem blood, but only one metabolite (C14:2) was associated with AD in the same direction (i.e., protective). Partial correlation and network analyses suggest a potential tissue-specific regulation of metabolism, although other alternatives exist. Together, we identified significant associations of both central and peripheral metabolites with AD phenotypes, but there seems to be little overlap between the 2 tissues. PMID: 31785839 [PubMed - as supplied by publisher]

Related Articles Metabolic effects of repeated ketamine administration in the rat brain. Biochem Biophys Res Commun. 2019 Nov 27;: Authors: Chen F, Ye Y, Dai X, Zheng Y, Fang S, Liao L Abstract Ketamine is a popular recreational drug used in club and dance music settings. Evidence suggests that chronic or repeated ketamine use could induce neurological and psychological harm, while the mechanisms underlying ketamine's effects on the nervous system are still unclear. The aim of this study was to explore the metabolic changes that occur in the prefrontal cortex (PFC), hippocampus (Hip) and striatum of rats with repeated ketamine exposure and withdrawal intervention and to identify the potential metabolic pathways influenced by ketamine. An untargeted ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS)-based metabolomics method coupled with multivariate and univariate statistical analysis was applied to analyze the metabolic profiles of the PFC, Hip, and striatum and to identify metabolite alterations. The pathway analysis tool in MetaboAnalyst was subsequently applied for pathway predictions. A total of 79, 54 and 58 changed metabolites were identified in the PFC, Hip and striatum, respectively, after repeated ketamine exposure. Pathway analysis indicated that purine metabolism and glycerophospholipid metabolism were the main pathways disturbed by ketamine in all three brain regions. After one week of withdrawal intervention, most changed metabolites in the Hip and striatum had been restored to control levels, while the metabolite alterations in the PFC were persistent. These results revealed that repeated ketamine exposure significantly changed purine metabolism and glycerophospholipid metabolism in the PFC, Hip and striatum, which might be involved in the neurotoxic effects of ketamine. Additionally, this study also identified that the PFC, rather than the Hip or striatum, was more likely to be the target region of the long-term effects of ketamine. PMID: 31785818 [PubMed - as supplied by publisher]

Related Articles Tween 80 induces a carbon flux rerouting in Mycobacterium tuberculosis. J Microbiol Methods. 2019 Nov 27;:105795 Authors: Pietersen RD, du Preez I, Loots DT, van Reenen M, Beukes D, Leisching G, Baker B Abstract As a means to increase the growth rate and reduce aggregation, Tween 80 is routinely added to growth media during mycobacterial culturing. This detergent has, however, been associated with causing alterations to the morphology, pathogenicity and virulence of these bacteria. In an attempt to better understand the underlying mechanism of these alterations, we investigated the effect of Tween 80 on the metabolomes of a M. tuberculosis lab strain (H37Rv) and multidrug-resistant clinical strain (R179), using GC-GCxTOF-MS metabolomics. The metabolite markers identified indicated Tween 80-induced disparities in the central carbon metabolism of both strains, with an upregulation in the glyoxylate cycle, glucogenogenesis and the pentose phosphate pathway. The results also signified an increased production of mycobacterial biosynthetic precursors such as triacylglycerols, proteinogenic amino acids and nucleotide precursors, in the presence of the detergent. Collectively, these metabolome variations mimic the phenotypic changes observed when M. tuberculosis is grown in vivo, in a lipid rich environment. However, in addition to the increased availability of oleic acid as a carbon source from Tween 80, the observed variations, and the morphological changes associated with the detergent, could also be a result of an overall stress response in these bacteria. This study is the first to identify specific metabolome variations related to the addition of Tween 80 to the growth media during M. tuberculosis culturing. The consideration of these results during the method development and data interpretation phases of future metabolomics investigations will improve the quality of the analyses as well as the credibility of potential research outcomes. These results will also assist in the interpretation of research questions specifically aimed at aspects of mycobacterial metabolism, even when using other methodologies such as transcriptomics or fluxomics. PMID: 31785333 [PubMed - as supplied by publisher]