PubMed

Related Articles Plasma metabolites predict both insulin resistance and incident type 2 diabetes: a metabolomics approach within the Prevención con Dieta Mediterránea (PREDIMED) study. Am J Clin Nutr. 2019 Feb 23;: Authors: Papandreou C, Bulló M, Ruiz-Canela M, Dennis C, Deik A, Wang D, Guasch-Ferré M, Yu E, Razquin C, Corella D, Estruch R, Ros E, Fitó M, Fiol M, Liang L, Hernández-Alonso P, Clish CB, Martínez-González MA, Hu FB, Salas-Salvadó J Abstract BACKGROUND: Insulin resistance is a complex metabolic disorder and is often associated with type 2 diabetes (T2D). OBJECTIVES: The aim of this study was to test whether baseline metabolites can additionally improve the prediction of insulin resistance beyond classical risk factors. Furthermore, we examined whether a multimetabolite model predicting insulin resistance in nondiabetics can also predict incident T2D. METHODS: We used a case-cohort study nested within the Prevención con Dieta Mediterránea (PREDIMED) trial in subsets of 700, 500, and 256 participants without T2D at baseline and 1 and 3 y. Fasting plasma metabolites were semiquantitatively profiled with liquid chromatography-tandem mass spectrometry. We assessed associations between metabolite concentrations and the homeostasis model of insulin resistance (HOMA-IR) through the use of elastic net regression analysis. We subsequently examined associations between the baseline HOMA-IR-related multimetabolite model and T2D incidence through the use of weighted Cox proportional hazard models. RESULTS: We identified a set of baseline metabolites associated with HOMA-IR. One-year changes in metabolites were also significantly associated with HOMA-IR. The area under the curve was significantly greater for the model containing the classical risk factors and metabolites together compared with classical risk factors alone at baseline [0.81 (95% CI: 0.79, 0.84) compared with 0.69 (95% CI: 0.66, 0.73)] and during a 1-y period [0.69 (95% CI: 0.66, 0.72) compared with 0.57 (95% CI: 0.53, 0.62)]. The variance in HOMA-IR explained by the combination of metabolites and classical risk factors was also higher in all time periods. The estimated HRs for incident T2D in the multimetabolite score (model 3) predicting high HOMA-IR (median value or higher) or HOMA-IR (continuous) at baseline were 2.00 (95% CI: 1.58, 2.55) and 2.24 (95% CI: 1.72, 2.90), respectively, after adjustment for T2D risk factors. CONCLUSIONS: The multimetabolite model identified in our study notably improved the predictive ability for HOMA-IR beyond classical risk factors and significantly predicted the risk of T2D. PMID: 30796776 [PubMed - as supplied by publisher]

Related Articles GC-QTOFMS with a low-energy electron ionization source for advancing isotopologue analysis in 13C-based metabolic flux analysis. Anal Bioanal Chem. 2019 Feb 22;: Authors: Mairinger T, Sanderson J, Hann S Abstract For the study of different levels of (intra)cellular regulation and condition-dependent insight into metabolic activities, fluxomics experiments based on stable isotope tracer experiments using 13C have become a well-established approach. The experimentally obtained non-naturally distributed 13C labeling patterns of metabolite pools can be measured by mass spectrometric detection with front-end separation and can be consequently incorporated into biochemical network models. Here, despite a tedious derivatization step, gas chromatographic separation of polar metabolites is favorable because of the wide coverage range and high isomer separation efficiency. However, the typically employed electron ionization energy of 70 eV leads to significant fragmentation and consequently only low-abundant ions with an intact carbon backbone. Since these ions are considered a prerequisite for the analysis of the non-naturally distributed labeling patterns and further integration into modeling strategies, a softer ionization technique is needed. In the present work, a novel low energy electron ionization source is optimized for the analysis of primary metabolites and compared with a chemical ionization approach in terms of trueness, precision, and sensitivity. PMID: 30796486 [PubMed - as supplied by publisher]

Related Articles Urinary metabolic variation analysis during pregnancy and application in Gestational Diabetes Mellitus and spontaneous abortion biomarker discovery. Sci Rep. 2019 Feb 22;9(1):2605 Authors: Liu X, Wang X, Sun H, Guo Z, Liu X, Yuan T, Fu Y, Tang X, Li J, Sun W, Zhao W Abstract Pregnancy is associated with the onset of many adaptation processes that are likely to change over the course of gestation. Understanding normal metabolites' variation with pregnancy progression is crucial for gaining insights of the key nutrients for normal fetal growth, and for comparative research of pregnancy-related complications. This work presents liquid chromatography-mass spectrum-based urine metabolomics study of 50 health pregnant women at three time points during pregnancy. The influence of maternal physiological factors, including age, BMI, parity and gravity to urine metabolome was explored. Additionally, urine metabolomics was applied for early prediction of two pregnancy complications, gestational diabetes mellitus and spontaneous abortion. Our results suggested that during normal pregnancy progression, pathways of steroid hormone biosynthesis and tyrosine metabolism were significantly regulated. BMI is a factor that should be considered during cross-section analysis. Application analysis discovered potential biomarkers for GDM in the first trimester with AUC of 0.89, and potential biomarkers for SA in the first trimester with AUC of 0.90. In conclusion, our study indicated that urine metabolome could reflect variations during pregnancy progression, and has potential value for pregnancy complications early prediction. The clinical trial number for this study is NCT03246295. PMID: 30796299 [PubMed - in process]

Related Articles Application of metabolomics and molecular networking in investigating the chemical profile and antitrypanosomal activity of British bluebells (Hyacinthoides non-scripta). Sci Rep. 2019 Feb 22;9(1):2547 Authors: Raheem DJ, Tawfike AF, Abdelmohsen UR, Edrada-Ebel R, Fitzsimmons-Thoss V Abstract Bulb, leaf, scape and flower samples of British bluebells (Hyacinthoides non-scripta) were collected regularly for one growth period. Methanolic extracts of freeze-dried and ground samples showed antitrypanosomal activity, giving more than 50% inhibition, for 20 out of 41 samples. High-resolution mass spectrometry was used in the dereplication of the methanolic extracts of the different plant parts. The results revealed differences in the chemical profile with bulb samples being distinctly different from all aerial parts. High molecular weight metabolites were more abundant in the flowers, shoots and leaves compared to smaller molecular weight ones in the bulbs. The anti-trypanosomal activity of the extracts was linked to the accumulation of high molecular weight compounds, which were matched with saponin glycosides, while triterpenoids and steroids occurred in the inactive extracts. Dereplication studies were employed to identify the significant metabolites via chemotaxonomic filtration and considering their previously reported bioactivities. Molecular networking was implemented to look for similarities in fragmentation patterns between the isolated saponin glycoside at m/z 1445.64 [M + formic-H]- equivalent to C64H104O33 and the putatively found active metabolite at m/z 1283.58 [M + formic-H]- corresponding to scillanoside L-1. A combination of metabolomics and bioactivity-guided approaches resulted in the isolation of a norlanostane-type saponin glycoside with antitrypanosomal activity of 98.9% inhibition at 20 µM. PMID: 30796274 [PubMed - in process]

Related Articles Function, Detection and Alteration of Acylcarnitine Metabolism in Hepatocellular Carcinoma. Metabolites. 2019 Feb 21;9(2): Authors: Li S, Gao D, Jiang Y Abstract Acylcarnitines play an essential role in regulating the balance of intracellular sugar and lipid metabolism. They serve as carriers to transport activated long-chain fatty acids into mitochondria for β-oxidation as a major source of energy for cell activities. The liver is the most important organ for endogenous carnitine synthesis and metabolism. Hepatocellular carcinoma (HCC), a primary malignancy of the live with poor prognosis, may strongly influence the level of acylcarnitines. In this paper, the function, detection and alteration of acylcarnitine metabolism in HCC were briefly reviewed. An overview was provided to introduce the metabolic roles of acylcarnitines involved in fatty acid β-oxidation. Then different analytical platforms and methodologies were also briefly summarised. The relationship between HCC and acylcarnitine metabolism was described. Many of the studies reported that short, medium and long-chain acylcarnitines were altered in HCC patients. These findings presented current evidence in support of acylcarnitines as new candidate biomarkers for studies on the pathogenesis and development of HCC. Finally we discussed the challenges and perspectives of exploiting acylcarnitine metabolism and its related metabolic pathways as a target for HCC diagnosis and prognosis. PMID: 30795537 [PubMed]

42 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 2019/02/23PubMed 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 Comprehensive mass spectrometry-guided plant specialized metabolite phenotyping reveals metabolic diversity in the cosmopolitan plant family Rhamnaceae. Plant J. 2019 Feb 20;: Authors: Kang KB, Ernst M, van der Hooft JJJ, da Silva RR, Park J, Medema MH, Sung SH, Dorrestein PC Abstract Plants produce a myriad of specialized metabolites to overcome their sessile habit and combat biotic as well as abiotic stresses. Evolution has shaped specialized metabolite diversity, which drives many other aspects of plant biodiversity. However, until recently, large-scale studies investigating specialized metabolite diversity in an evolutionary context have been limited by the impossibility to identify chemical structures of hundreds to thousands of compounds in a time-feasible manner. Here, we introduce a workflow for large-scale, semi-automated annotation of specialized metabolites, and apply it for over 1000 metabolites of the cosmopolitan plant family Rhamnaceae. We enhance the putative annotation coverage dramatically, from 2.5% based on spectral library matches alone to 42.6% of total MS/MS molecular features extending annotations from well-known plant compound classes into the dark plant metabolomics matter. To gain insights in substructural diversity within the plant family, we also extract patterns of co-occurring fragments and neutral losses, so-called Mass2Motifs, from the dataset; for example, only the Ziziphoid clade developed the triterpenoid biosynthetic pathway, whereas the Rhamnoid clade predominantly developed diversity in flavonoid glycosides, including 7-O-methyltransferase activity. Our workflow provides the foundations towards the automated, high-throughput chemical identification of massive metabolite spaces, and we expect it to revolutionize our understanding of plant chemoevolutionary mechanisms. This article is protected by copyright. All rights reserved. PMID: 30786088 [PubMed - as supplied by publisher]

Related Articles Metabolomic profiling reveals correlations between spermiogram parameters and the metabolites present in human spermatozoa and seminal plasma. PLoS One. 2019;14(2):e0211679 Authors: Engel KM, Baumann S, Rolle-Kampczyk U, Schiller J, von Bergen M, Grunewald S Abstract In 50% of all infertility cases, the male is subfertile or infertile, however, the underlying mechanisms are often unknown. Even when assisted reproductive procedures such as in vitro fertilization and intracytoplasmic sperm injection are performed, the causes of male factor infertility frequently remain elusive. Since the overall activity of cells is closely linked to their metabolic capacity, we analyzed a panel of 180 metabolites in human sperm and seminal plasma and elucidated their associations with spermiogram parameters. Therefore, metabolites from a group of 20 healthy donors were investigated using a targeted LC-MS/MS approach. The correlation analyses of the amino acids, biogenic amines, acylcarnitines, lysophosphatidylcholines, phosphatidylcholines, sphingomyelins and sugars from sperm and seminal plasma with standard spermiogram parameters revealed that metabolites in sperm are closely related to sperm motility, whereas those in seminal plasma are closely related to sperm concentration and morphology. This study provides essential insights into the metabolome of human sperm and seminal plasma and its associations with sperm functions. This metabolomics technique could be a promising screening tool to detect the factors of male infertility in cases where the cause of infertility is unclear. PMID: 30785892 [PubMed - in process]

Related Articles Pyrophosphate modulates plant stress responses via SUMOylation. Elife. 2019 Feb 20;8: Authors: Patir-Nebioglu MG, Andrés Z, Krebs M, Fink F, Drzewicka K, Stankovic-Valentin N, Segami S, Schuck S, Büttner M, Hell R, Maeshima M, Melchior F, Schumacher K Abstract Pyrophosphate (PPi), a byproduct of macromolecule biosynthesis is maintained at low levels by soluble inorganic pyrophosphatases (sPPase) found in all eukaryotes. In plants, H+-pumping pyrophosphatases (H+-PPase) convert the substantial energy present in PPi into an electrochemical gradient. We show here, that both cold- and heat stress sensitivity of fugu5 mutants lacking the major H+-PPase isoform AVP1 is correlated with reduced SUMOylation. In addition, we show that increased PPi concentrations interfere with SUMOylation in yeast and we provide evidence that SUMO activating E1-enzymes are inhibited by micromolar concentrations of PPi in a non-competitive manner. Taken together, our results do not only provide a mechanistic explanation for the beneficial effects of AVP1 overexpression in plants but they also highlight PPi as an important integrator of metabolism and stress tolerance. PMID: 30785397 [PubMed - in process]

Related Articles The effect of vegetable and spice addition on the acrylamide content and antioxidant activity of innovative cereal products. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2019 Feb 20;:1-11 Authors: Jaworska D, Mojska H, Gielecińska I, Najman K, Gondek E, Przybylski W, Krzyczkowska P Abstract The aim of the work was to assess the impact of vegetable and spice addition on the acrylamide content and antioxidant activity of extruded cereal crisps. The foods were based on grain ingredients, such as brown rice, whole grain flour, wheat bran, with different vegetables. Products from one group contained green vegetables, such as broccoli and zucchini; garlic was included as a flavour additive (0.75-1.50%). The second group of crisps consisted of similar cereal ingredients with pumpkin and cinnamon; additionally ginger was included as a flavour additive (0.75-1.50%). The results indicate that the production of a new, innovative product with appropriate nutritional value and acceptable quality is a complex process. The production process significantly changed the nutritional value of the product. The content of acrylamide in zucchini and broccoli crisps was relatively low; ranging from 78 to 86 μg/kg of product. The addition of garlic did not significantly affect the acrylamide content in the final product. For cereal-pumpkin crisps, the acrylamide content was 7 times higher in comparison with zucchini and broccoli products. The acrylamide content in pumpkin and ginger crisps exceeded the benchmark level. The antioxidant activity of the pumpkin product was significantly higher (p < 0.05) than for crisps with green vegetables. PMID: 30785367 [PubMed - as supplied by publisher]

Related Articles Integrated metallomic and metabolomic profiling of plasma and tissues provides deep insights into the protective effect of raw and salt-processed Achyranthes bidentata Blume extract in ovariectomia rats. J Ethnopharmacol. 2019 Feb 19;234:85-95 Authors: Tao Y, Huang S, Yan J, Li W, Cai B Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Achyranthes bidentata Blume (AB) is a well-known traditional Chinese medicine for treating osteoporosis and bone fracture. In the current, researches on pharmacological mechanism of AB mostly focused on molecular pathways, knowledge about its metabolic signatures is largely unclear. This study aims to develop an integrative metabolomics and metallomic approach for deciphering the biochemical basis of anti-osteoporosis effects of raw and salt-processed AB. METHOD: Gas chromatography-mass spectrometry (GC-MS) and inductively coupled plasma mass spectrometry (ICP-MS) were combined for metabolomic and metallomic profiling of rats serum, liver and kidney derived from the sham group, model group, E2, raw and salt-processed AB treated groups. Meanwhile, micro-CT and biomechanical analysis were carried out to ensure the success of the osteoporosis model and to validate the anti-osteoporosis effect of raw and salt-processed AB. Partial least squares discriminant analysis (PLS-DA) was employed to screen potential biomarkers and the MetaboAnalyst and KEGG PATHWAY Database were used to investigate the metabolic pathway. RESULTS: Raw and salt-processed AB protected the rats against osteoporosis, as evidenced by the restoration of the alkaline phosphatase activity, osteocalcin concentration, urine calcium/creatinine ratio and urine phosphorus/creatinine ratio. The combination of PCA and PLS-DA revealed deviations in ninety-four differential biomarkers between raw AB treated group and model group. The identified biomarkers were primarily engaged in the metabolic pathways including galactose metabolism, urea cycle, arginine and proline metabolism, alanine metabolism, lactose degradation, ammonia recycling and glycine and serine metabolism. The levels of these biomarkers showed significant alterations and a tendency to be restored to normal values in raw and salt-processed AB treated osteoporosis rats. Of note, the levels of trace elements, such as Zn, Se, Mn, Cu and Fe, were elevated after raw and salt-processed AB treatment. Finally, a correlation network diagram was constructed to show the biomarkers perturbed by raw and salt-processed AB. CONCLUSION: Our findings indicate that raw and salt-processed AB has positive effects on osteoporosis rats. Meanwhile, metabolomic and metallomic method coupled with metabolites enrichment analysis and pattern recognition serves as a useful tool for revealing the action mechanism of traditional Chinese medicine. PMID: 30784959 [PubMed - as supplied by publisher]

Related Articles Ambient fine particulate matter exposure induces cardiac functional injury and metabolite alterations in middle-aged female mice. Environ Pollut. 2019 Jan 30;248:121-132 Authors: Zhang Y, Ji X, Ku T, Li B, Li G, Sang N Abstract Plenty of epidemiological studies have shown that exposure to ambient particulate matter (PM2.5) is linked to cardiovascular diseases (CVDs) in older even in middle-aged populations; however, experimental evidence through intuitive metabolic analysis to confirm the age susceptibility and explain the related molecular mechanism of PM2.5-induced cardiotoxicity is relatively rare. In the present study, C57BL/6 mice (adult (4-month) and middle-aged (10-month)) were given 3 mg/kg PM2.5 every other day by oropharyngeal aspiration for 4 weeks, and then, body and cardiac parameter, containing weight data, cardiac function, ultrastructure, metabolic analysis, and molecular detection were conducted to investigate the PM2.5-induced cardiotoxicity. The results indicated that middle-aged mice were more susceptible to PM2.5, displaying slow cardiac growth, cardiac dysfunction, abnormal mitochondrial structure and function, and cardiac metabolic disorders. The altered metabolites were enriched in carbohydrate metabolism, fatty acid metabolism, amino acid metabolism, nucleotide metabolism and nicotinate and nicotinamide metabolism. In conclusion, we speculated that the cardiac metabolic disorders may be important factors in PM2.5-induced cardiac dysfunction and mitochondrial structure destruction in middle-aged mice, providing a new direction for the study of the association between PM2.5 and CVDs. PMID: 30784831 [PubMed - as supplied by publisher]

Related Articles Integrated application of transcriptomics and metabolomics provides insights into unsynchronized growth in pearl oyster Pinctada fucata martensii. Sci Total Environ. 2019 Feb 15;666:46-56 Authors: Hao R, Du X, Yang C, Deng Y, Zheng Z, Wang Q Abstract Similar to other marine bivalves, Pinctada fucata martensii presents unsynchronized growth, which is one of the problems farmers currently face. However, the underlying mechanisms have not been studied. In the present study, pearl oyster P. f. martensii from cultured stocks were selected to produce a progeny stock. At 180 days, the stock was sorted by size, and fast- and slow-growing individuals were separately sampled. Then, metabolomic and transcriptomic approaches were applied to assess the metabolic and transcript changes between the fast- and slow-growing P. f. martensii groups and understand the mechanism underlying their unsynchronized growth. In the metabolomics assay, 30 metabolites were considered significantly different metabolites (SDMs) between the fast- and slow-growing groups and pathway analysis indicated that these SDMs were involved in 20 pathways, including glutathione metabolism; sulfur metabolism; valine, leucine, and isoleucine biosynthesis; and tryptophan metabolism. The transcriptome analysis of different growth groups showed 168 differentially expressed genes (DEGs) and pathway enrichment analysis indicated that DEGs were involved in extracellular matrix-receptor interaction, pentose phosphate pathway, aromatic compound degradation. Integrated transcriptome and metabolome analyses showed that fast-growing individuals exhibited higher biomineralization activity than the slow-growing group, which consumed more energy than the fast-growing group in response to environmental stress. Fast-growing group also exhibited higher digestion, anabolic ability, and osmotic regulation ability than the slow-growing group. This study is the first work involving the integrated metabolomic and transcriptomic analyses to identify the key pathways to understand the molecular and metabolic mechanisms underlying unsynchronized bivalve growth. PMID: 30784822 [PubMed - as supplied by publisher]

Related Articles Evaluation of the chemical consistency of Yin-Chen-Hao-Tang prepared by combined and separated decoction methods using high-performance liquid chromatography quadrupole time-of-flight mass spectrometry coupled with multivariate statistical analysis. J Sep Sci. 2019 Feb 19;: Authors: Tian Q, Liu F, Xu Z, Liu H, Yin H, Sun Z, Chen M, Li Z, Ma L, Huang C Abstract In this study, Yin-Chen-Hao-Tang prepared by two decoction methods, namely, combined decoction (modern decoction method) and separated decoction (traditional decoction method), was analyzed by high-performance liquid chromatography quadrupole time-of-flight mass spectrometry. The acquired datasets containing sample codes, tR -m/z pairs and ion intensities were processed with multivariate statistical analyses, such as principal component analysis and an orthogonal partial least squared discriminant analysis model, to globally compare the chemical differences between the different decoction samples. Then, the chemical differences between the combined and separated decoctions were screened out by S-plots generated from the orthogonal partial least squared discriminant analysis model and compared with chemical information from an established in-house library. The six components that contributed the most to the chemical differences were identified as chlorogenic acid, caffeic acid, geniposide, genipin, scopoletin, and 3,5-dicaffeoylquinic acid. The concentrations of genipin and caffeic acid from the separated decoction were higher than those from the combined decoction, indicating that the separated decoction may present a stronger hepatoprotective effect. However, the results still require further investigation through pharmacological and clinical studies. Our findings not only establish a strategy to evaluate chemical consistency of Yin-Chen-Hao-Tang but also provide the scientific basis for using traditional separated decoction method. This article is protected by copyright. All rights reserved. PMID: 30784184 [PubMed - as supplied by publisher]

Related Articles A comprehensive analysis of WGCNA and serum metabolomics manifests the lung cancer-associated disordered glucose metabolism. J Cell Biochem. 2019 Feb 19;: Authors: Ding M, Li F, Wang B, Chi G, Liu H Abstract Lung cancer is a worldwide disease and highly heterogeneous at a molecular level. In this study, we both performed the pathway enrichment analysis and the transcriptome-based weighted gene coexpression network analysis (WGCNA) so as to find the critical pathways involved in lung cancer. Our analysis results indicated that genes in viability modules (0 < Z-summary < 2) selected by WGCNA were more reliable for identifying crucial pathways, while gene enrichment analysis provided a wide range of pathways with a little emphasis on target pathways for lung cancer. On the basis of genes, which were classified into various modules by WGCNA, we found a significant aberration of glucose metabolism in lung cancer cells, demonstrating that the glucose metabolism has been perturbed, especially the glycolysis pathway. Our study revealed that disordered glucose metabolism might be closely associated with the carcinogenesis of lung cancer based on the integrated analysis of WGCNA and metabolomics, which could be a potential therapeutic target for lung cancer. PMID: 30784104 [PubMed - as supplied by publisher]

Related Articles Metabolomics reveals citric acid secretion in mechanically-stimulated osteocytes is inhibited by high glucose. Sci Rep. 2019 Feb 19;9(1):2295 Authors: Villaseñor A, Aedo-Martín D, Obeso D, Erjavec I, Rodríguez-Coira J, Buendía I, Ardura JA, Barbas C, Gortazar AR Abstract Osteocytes are the main cells of bone tissue and play a crucial role in bone formation and resorption. Recent studies have indicated that Diabetes Mellitus (DM) affects bone mass and potentially causes higher bone fracture risk. Previous work on osteocyte cell cultures has demonstrated that mechanotransduction is impaired after culture under diabetic pre-conditioning with high glucose (HG), specifically osteoclast recruitment and differentiation. The aim of this study was to analyze the extracellular metabolic changes of osteocytes regarding two conditions: pre-conditioning to either basal levels of glucose (B), mannitol (M) or HG cell media, and mechanical stimulation by fluid flow (FF) in contrast to static condition (SC). Secretomes were analyzed using Liquid Chromatography and Capillary Electrophoresis both coupled to Mass Spectrometry (LC-MS and CE-MS, respectively). Results showed the osteocyte profile was very similar under SC, regardless of their pre-conditioning treatment, while, after FF stimulation, secretomes followed different metabolic signatures depending on the pre-conditioning treatment. An important increment of citrate pointed out that osteocytes release citrate outside of the cell to induce osteoblast activation, while HG environment impaired FF effect. This study demonstrates for the first time that osteocytes increase citrate excretion under mechanical stimulation, and that HG environment impaired this effect. PMID: 30783155 [PubMed - in process]

Related Articles The flavonoid 4,4'-dimethoxychalcone promotes autophagy-dependent longevity across species. Nat Commun. 2019 Feb 19;10(1):651 Authors: Carmona-Gutierrez D, Zimmermann A, Kainz K, Pietrocola F, Chen G, Maglioni S, Schiavi A, Nah J, Mertel S, Beuschel CB, Castoldi F, Sica V, Trausinger G, Raml R, Sommer C, Schroeder S, Hofer SJ, Bauer MA, Pendl T, Tadic J, Dammbrueck C, Hu Z, Ruckenstuhl C, Eisenberg T, Durand S, Bossut N, Aprahamian F, Abdellatif M, Sedej S, Enot DP, Wolinski H, Dengjel J, Kepp O, Magnes C, Sinner F, Pieber TR, Sadoshima J, Ventura N, Sigrist SJ, Kroemer G, Madeo F Abstract Ageing constitutes the most important risk factor for all major chronic ailments, including malignant, cardiovascular and neurodegenerative diseases. However, behavioural and pharmacological interventions with feasible potential to promote health upon ageing remain rare. Here we report the identification of the flavonoid 4,4'-dimethoxychalcone (DMC) as a natural compound with anti-ageing properties. External DMC administration extends the lifespan of yeast, worms and flies, decelerates senescence of human cell cultures, and protects mice from prolonged myocardial ischaemia. Concomitantly, DMC induces autophagy, which is essential for its cytoprotective effects from yeast to mice. This pro-autophagic response induces a conserved systemic change in metabolism, operates independently of TORC1 signalling and depends on specific GATA transcription factors. Notably, we identify DMC in the plant Angelica keiskei koidzumi, to which longevity- and health-promoting effects are ascribed in Asian traditional medicine. In summary, we have identified and mechanistically characterised the conserved longevity-promoting effects of a natural anti-ageing drug. PMID: 30783116 [PubMed - in process]

Related Articles Health Outcomes, Pathogenesis and Epidemiology of Severe Acute Malnutrition (HOPE-SAM): rationale and methods of a longitudinal observational study. BMJ Open. 2019 Feb 01;9(1):e023077 Authors: Bwakura-Dangarembizi M, Amadi B, Bourke CD, Robertson RC, Mwapenya B, Chandwe K, Kapoma C, Chifunda K, Majo F, Ngosa D, Chakara P, Chulu N, Masimba F, Mapurisa I, Besa E, Mutasa K, Mwakamui S, Runodamoto T, Humphrey JH, Ntozini R, Wells JCK, Manges AR, Swann JR, Walker AS, Nathoo KJ, Kelly P, Prendergast AJ, HOPE-SAM study team Abstract INTRODUCTION: Mortality among children hospitalised for complicated severe acute malnutrition (SAM) remains high despite the implementation of WHO guidelines, particularly in settings of high HIV prevalence. Children continue to be at high risk of morbidity, mortality and relapse after discharge from hospital although long-term outcomes are not well documented. Better understanding the pathogenesis of SAM and the factors associated with poor outcomes may inform new therapeutic interventions. METHODS AND ANALYSIS: The Health Outcomes, Pathogenesis and Epidemiology of Severe Acute Malnutrition (HOPE-SAM) study is a longitudinal observational cohort that aims to evaluate the short-term and long-term clinical outcomes of HIV-positive and HIV-negative children with complicated SAM, and to identify the risk factors at admission and discharge from hospital that independently predict poor outcomes. Children aged 0-59 months hospitalised for SAM are being enrolled at three tertiary hospitals in Harare, Zimbabwe and Lusaka, Zambia. Longitudinal mortality, morbidity and nutritional data are being collected at admission, discharge and for 48 weeks post discharge. Nested laboratory substudies are exploring the role of enteropathy, gut microbiota, metabolomics and cellular immune function in the pathogenesis of SAM using stool, urine and blood collected from participants and from well-nourished controls. ETHICS AND DISSEMINATION: The study is approved by the local and international institutional review boards in the participating countries (the Joint Research Ethics Committee of the University of Zimbabwe, Medical Research Council of Zimbabwe and University of Zambia Biomedical Research Ethics Committee) and the study sponsor (Queen Mary University of London). Caregivers provide written informed consent for each participant. Findings will be disseminated through peer-reviewed journals, conference presentations and to caregivers at face-to-face meetings. PMID: 30782694 [PubMed - in process]

Related Articles Effects of dietary fat on gut microbiota and faecal metabolites, and their relationship with cardiometabolic risk factors: a 6-month randomised controlled-feeding trial. Gut. 2019 Feb 19;: Authors: Wan Y, Wang F, Yuan J, Li J, Jiang D, Zhang J, Li H, Wang R, Tang J, Huang T, Zheng J, Sinclair AJ, Mann J, Li D Abstract OBJECTIVE: To investigate whether diets differing in fat content alter the gut microbiota and faecal metabolomic profiles, and to determine their relationship with cardiometabolic risk factors in healthy adults whose diet is in a transition from a traditional low-fat diet to a diet high in fat and reduced in carbohydrate. METHODS: In a 6-month randomised controlled-feeding trial, 217 healthy young adults (aged 18-35 years; body mass index <28 kg/m2; 52% women) who completed the whole trial were included. All the foods were provided during the intervention period. The three isocaloric diets were: a lower-fat diet (fat 20% energy), a moderate-fat diet (fat 30% energy) and a higher-fat diet (fat 40% energy). The effects of the dietary interventions on the gut microbiota, faecal metabolomics and plasma inflammatory factors were investigated. RESULTS: The lower-fat diet was associated with increased α-diversity assessed by the Shannon index (p=0.03), increased abundance of Blautia (p=0.007) and Faecalibacterium (p=0.04), whereas the higher-fat diet was associated with increased Alistipes (p=0.04), Bacteroides (p<0.001) and decreased Faecalibacterium (p=0.04). The concentration of total short-chain fatty acids was significantly decreased in the higher-fat diet group in comparison with the other groups (p<0.001). The cometabolites p-cresol and indole, known to be associated with host metabolic disorders, were decreased in the lower-fat diet group. In addition, the higher-fat diet was associated with faecal enrichment in arachidonic acid and the lipopolysaccharide biosynthesis pathway as well as elevated plasma proinflammatory factors after the intervention. CONCLUSION: Higher-fat consumption by healthy young adults whose diet is in a state of nutrition transition appeared to be associated with unfavourable changes in gut microbiota, faecal metabolomic profiles and plasma proinflammatory factors, which might confer adverse consequences for long-term health outcomes. TRIAL REGISTRATION NUMBER: NCT02355795; Results. PMID: 30782617 [PubMed - as supplied by publisher]

Related Articles A Comprehensive LC-QTOF-MS Metabolic Phenotyping Strategy: Application to Alkaptonuria. Clin Chem. 2019 Feb 19;: Authors: Norman BP, Davison AS, Ross GA, Milan AM, Hughes AT, Sutherland H, Jarvis JC, Roberts NB, Gallagher JA, Ranganath LR Abstract BACKGROUND: Identification of unknown chemical entities is a major challenge in metabolomics. To address this challenge, we developed a comprehensive targeted profiling strategy, combining 3 complementary liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) techniques and in-house accurate mass retention time (AMRT) databases established from commercial standards. This strategy was used to evaluate the effect of nitisinone on the urinary metabolome of patients and mice with alkaptonuria (AKU). Because hypertyrosinemia is a known consequence of nitisinone therapy, we investigated the wider metabolic consequences beyond hypertyrosinemia. METHODS: A total of 619 standards (molecular weight, 45-1354 Da) covering a range of primary metabolic pathways were analyzed using 3 liquid chromatography methods-2 reversed phase and 1 normal phase-coupled to QTOF-MS. Separate AMRT databases were generated for the 3 methods, comprising chemical name, formula, theoretical accurate mass, and measured retention time. Databases were used to identify chemical entities acquired from nontargeted analysis of AKU urine: match window theoretical accurate mass ±10 ppm and retention time ±0.3 min. RESULTS: Application of the AMRT databases to data acquired from analysis of urine from 25 patients with AKU (pretreatment and after 3, 12, and 24 months on nitisinone) and 18 HGD -/- mice (pretreatment and after 1 week on nitisinone) revealed 31 previously unreported statistically significant changes in metabolite patterns and abundance, indicating alterations to tyrosine, tryptophan, and purine metabolism after nitisinone administration. CONCLUSIONS: The comprehensive targeted profiling strategy described here has the potential of enabling discovery of novel pathways associated with pathogenesis and management of AKU. PMID: 30782595 [PubMed - as supplied by publisher]