Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

[The role of omics in precision nutrition: strengths and weaknesses].

Fri, 03/08/2018 - 12:19
Related Articles [The role of omics in precision nutrition: strengths and weaknesses]. Nutr Hosp. 2018 Jun 12;35(Spec No4):10-18 Authors: Corella D, Ordovás JM Abstract Precision medicine has taken huge strides forward in recent years. Although there is still no generally accepted single definition, it basically considers the particular characteristics of each person as relevant in order to better adapt therapeutic or preventive measures in a more personalized fashion. Likewise, the concept of precision nutrition has gathered strength, in which the aim is to provide the best dietary recommendations to prevent or treat a disease in accordance with the characteristics of the individual in question. Of special importance among these characteristics are those based on omics. Initially genomics, and now epigenomics, metabolomics, proteomics and transcriptomics are providing us with new information on the different responses to the diet based on genotype, on new early biomarkers of disease, on dietary intake, or on the regulatory effects of diet. However, precision nutrition can go further still to include much more holistic aspects, not focusing on the disease, but on wellbeing and other indicators of positive health. Hence, other omics have been added to those mentioned above that provide us with a more multidimensional analysis. Gastronomy also plays an important role in precision nutrition. Although we are still at the preliminary validation stage of precision nutrition, this field presents huge potential for development. In this context, we shall review the role of omics in precision nutrition as well as their main strengths and weaknesses. PMID: 30070116 [PubMed - in process]

NMR metabolomics study of follicular fluid in women with cancer resorting to fertility preservation.

Fri, 03/08/2018 - 12:19
Related Articles NMR metabolomics study of follicular fluid in women with cancer resorting to fertility preservation. J Assist Reprod Genet. 2018 Aug 01;: Authors: Castiglione Morelli MA, Iuliano A, Schettini SCA, Petruzzi D, Ferri A, Colucci P, Viggiani L, Cuviello F, Ostuni A Abstract PURPOSE: The purpose of this study was to evaluate the possible application of metabolomics to identify follicular fluid changes in cancer patients undergoing fertility preservation. Although metabolomics have been applied already in cancer studies, this is the first application on follicular fluid of cancer patients. METHODS: We selected for the study ten patients with breast cancer and lymphoma who resorted to oocyte cryopreservation to preserve fertility and ten healthy women undergoing in vitro fertilization treatments. Follicular fluid was collected at the time of oocytes retrieval. Metabolomic analysis of follicular fluids was performed by 1H-nuclear magnetic resonance (NMR) spectroscopy in combination with multivariate analysis to interpret the spectral data. Univariate statistical analysis was applied to find correlations between patients' features and metabolites identified by NMR. RESULTS: Partial least squares discriminant analysis allowed to discriminate samples from cancer patients and healthy controls. Univariate statistical analysis found significant correlations between patients' features and metabolites identified by NMR. This finding allowed to identify biomarkers to differentiate both healthy controls from cancer patients and the two different classes of oncological patients. CONCLUSION: The follicular fluids of cancer patients display significant metabolic alterations in comparison to healthy subjects. NMR-based metabolomics could be a valid prognostic tool for identifying and selecting the best cryopreserved oocytes and improving the outcome prediction in cancer women undergoing in vitro fertilization. PMID: 30069850 [PubMed - as supplied by publisher]

Chronic Dysregulation of Cortical and Subcortical Metabolism After Experimental Traumatic Brain Injury.

Fri, 03/08/2018 - 12:19
Related Articles Chronic Dysregulation of Cortical and Subcortical Metabolism After Experimental Traumatic Brain Injury. Mol Neurobiol. 2018 Aug 01;: Authors: McGuire JL, DePasquale EAK, Watanabe M, Anwar F, Ngwenya LB, Atluri G, Romick-Rosendale LE, McCullumsmith RE, Evanson NK Abstract Traumatic brain injury (TBI) is a leading cause of death and long-term disability worldwide. Although chronic disability is common after TBI, effective treatments remain elusive and chronic TBI pathophysiology is not well understood. Early after TBI, brain metabolism is disrupted due to unregulated ion release, mitochondrial damage, and interruption of molecular trafficking. This metabolic disruption causes at least part of the TBI pathology. However, it is not clear how persistent or pervasive metabolic injury is at later stages of injury. Using untargeted 1H-NMR metabolomics, we examined ex vivo hippocampus, striatum, thalamus, frontal cortex, and brainstem tissue in a rat lateral fluid percussion model of chronic brain injury. We found altered tissue concentrations of metabolites in the hippocampus and thalamus consistent with dysregulation of energy metabolism and excitatory neurotransmission. Furthermore, differential correlation analysis provided additional evidence of metabolic dysregulation, most notably in brainstem and frontal cortex, suggesting that metabolic consequences of injury are persistent and widespread. Interestingly, the patterns of network changes were region-specific. The individual metabolic signatures after injury in different structures of the brain at rest may reflect different compensatory mechanisms engaged to meet variable metabolic demands across brain regions. PMID: 30069831 [PubMed - as supplied by publisher]

Nanoformulated Antiretroviral Therapy Attenuates Brain Metabolic Oxidative Stress.

Fri, 03/08/2018 - 12:19
Related Articles Nanoformulated Antiretroviral Therapy Attenuates Brain Metabolic Oxidative Stress. Mol Neurobiol. 2018 Aug 01;: Authors: Montenegro-Burke JR, Woldstad CJ, Fang M, Bade AN, McMillan J, Edagwa B, Boska MD, Gendelman HE, Siuzdak G Abstract Antiretroviral therapy (ART) restricts human immunodeficiency virus type one (HIV-1) replication and by so doing, improves the quality and longevity of life for infected people. Nonetheless, treatment can also lead to adverse clinical outcomes such as drug resistance and systemic adverse events. Both could be affected by long-acting slow effective release ART. Indeed, maintenance of sustained plasma drug levels, for weeks or months, after a single high-level dosing, could improve regimen adherence but, at the same time, affect systemic toxicities. Of these, the most troubling are those that affect the central nervous system (CNS). To address this, dolutegravir (Tivicay, DTG), a potent and durable HIV integrase inhibitor used effectively in combination ART was tested. Rodents were administered parenteral 45-mg/kg doses. DTG-associated changes in CNS homeostasis were assessed by measuring brain metabolic activities. After antiretroviral treatment, brain subregions were dissected and screened by mass spectrometry-based metabolomics. Metabolic drug-related dysregulation of energy and oxidative stress were readily observed within the cerebellum and frontal cortex following native drug administrations. Each was associated with alterations in neural homeostasis and depleted canonical oxidation protection pools that included glutathione and ascorbic acid. Surprisingly, the oxidative stress-related metabolites were completely attenuated when DTG was administered as nanoformulations. These data demonstrate the importance of formulation design in control of DTG or perhaps other antiretroviral drug-associated CNS events. PMID: 30069830 [PubMed - as supplied by publisher]

Chronic refined low-fat diet consumption reduces cholecystokinin satiation in rats.

Fri, 03/08/2018 - 12:19
Related Articles Chronic refined low-fat diet consumption reduces cholecystokinin satiation in rats. Eur J Nutr. 2018 Aug 01;: Authors: Guerville M, Hamilton MK, Ronveaux CC, Ellero-Simatos S, Raybould HE, Boudry G Abstract PURPOSE: Reduced ability of cholecystokinin (CCK) to induce satiation contributes to hyperphagia and weight gain in high-fat/high-sucrose (HF/HS) diet-induced obesity, and has been linked to altered gut microbiota. Rodent models of obesity use chow or low-fat (LF) diets as control diets; the latter has been shown to alter gut microbiota and metabolome. We aimed to determine whether LF-diet consumption impacts CCK satiation in rats and if so, whether this is prevented by addition of inulin to LF diet. METHODS: Rats (n = 40) were fed, for 8 weeks, a chow diet (chow) or low-fat (10%) or high-fat/high-sucrose (45 and 17%, respectively) refined diets with either 10% cellulose (LF and HF/HS) or 10% inulin (LF-I and HF/HS-I). Caecal metabolome was assessed by 1H-NMR-based metabolomics. CCK satiation was evaluated by measuring the suppression of food intake after intraperitoneal CCK injection (1 or 3 µg/kg). RESULTS: LF-diet consumption altered the caecal metabolome, reduced caecal weight, and increased IAP activity, compared to chow. CCK-induced inhibition of food intake was abolished in LF diet-fed rats compared to chow-fed rats, while HF/HS diet-fed rats responded only to the highest CCK dose. Inulin substitution ameliorated caecal atrophy, reduced IAP activity, and modulated caecal metabolome, but did not improve CCK-induced satiety in either LF- or HF/HS-fed rats. CONCLUSIONS: CCK signaling is impaired by LF-diet consumption, highlighting that caution must be taken when using LF diet until a more suitable refined control diet is identified. PMID: 30069617 [PubMed - as supplied by publisher]

The Metabolomic Bioenergetic Signature of Opa1-Disrupted Mouse Embryonic Fibroblasts Highlights Aspartate Deficiency.

Fri, 03/08/2018 - 12:19
Related Articles The Metabolomic Bioenergetic Signature of Opa1-Disrupted Mouse Embryonic Fibroblasts Highlights Aspartate Deficiency. Sci Rep. 2018 Aug 01;8(1):11528 Authors: Bocca C, Kane MS, Veyrat-Durebex C, Chupin S, Alban J, Kouassi Nzoughet J, Le Mao M, Chao de la Barca JM, Amati-Bonneau P, Bonneau D, Procaccio V, Lenaers G, Simard G, Chevrollier A, Reynier P Abstract OPA1 (Optic Atrophy 1) is a multi-isoform dynamin GTPase involved in the regulation of mitochondrial fusion and organization of the cristae structure of the mitochondrial inner membrane. Pathogenic OPA1 variants lead to a large spectrum of disorders associated with visual impairment due to optic nerve neuropathy. The aim of this study was to investigate the metabolomic consequences of complete OPA1 disruption in Opa1-/- mouse embryonic fibroblasts (MEFs) compared to their Opa1+/+ counterparts. Our non-targeted metabolomics approach revealed significant modifications of the concentration of several mitochondrial substrates, i.e. a decrease of aspartate, glutamate and α-ketoglutaric acid, and an increase of asparagine, glutamine and adenosine-5'-monophosphate, all related to aspartate metabolism. The signature further highlighted the altered metabolism of nucleotides and NAD together with deficient mitochondrial bioenergetics, reflected by the decrease of creatine/creatine phosphate and pantothenic acid, and the increase in pyruvate and glutathione. Interestingly, we recently reported significant variations of five of these molecules, including aspartate and glutamate, in the plasma of individuals carrying pathogenic OPA1 variants. Our findings show that the disruption of OPA1 leads to a remodelling of bioenergetic pathways with the central role being played by aspartate and related metabolites. PMID: 30068998 [PubMed - in process]

Celastrol Suppresses Tryptophan Catabolism in Human Colon Cancer Cells as Revealed by Metabolic Profiling and Targeted Metabolite Analysis.

Fri, 03/08/2018 - 12:19
Related Articles Celastrol Suppresses Tryptophan Catabolism in Human Colon Cancer Cells as Revealed by Metabolic Profiling and Targeted Metabolite Analysis. Biol Pharm Bull. 2018;41(8):1243-1250 Authors: Qi Y, Wang R, Zhao L, Lv L, Zhou F, Zhang T, Lu F, Yan H, Duan G Abstract Celastrol is well known for its anti-cancer effects, yet its specific mechanisms against colon cancer are still not fully elucidated. In this study, cytotoxic effect of celastrol against HCT116 colon cancer cells was investigated based on cell viability assay and flow cytometry assay, and the possible mechanism was explored using a strategy combining metabolic profiling and targeted metabolite analysis based on ultra performance liquid chromatography (UPLC)/MS. Celastrol was found to inhibit the growth of colon cancer cells and induce apoptosis. Metabolomics analysis revealed characteristic changes in metabolic profiles of the colon cancer cells, revealing altered levels of amino acids, carnitine, and lipid markers. Most interestingly, with the assistance of targeted metabolite analysis, tryptophan (Trp) level was significantly increased whereas kynurenine (Kyn) level was decreased in colon cancer cells after celastrol treatment, together with markedly declined Kyn/Trp ratios. Western blot analysis revealed that expression of indoleamine 2,3-dioxygenase (IDO), the enzyme catalyzing Trp to generate Kyn, was dramatically inhibited in colon cancer cells after celastrol treatment, with a dose-dependent manner. These results suggest that suppression of IDO expression and tryptophan catabolism may be part of the mechanisms of celastrol in its cytotoxic effect against HCT116 colon cancer cells. This study provided scientific basis for further development of celastrol on treating colon cancer. PMID: 30068874 [PubMed - in process]

Identification of Metabolites Associated with Onset of CAD in Diabetic Patients Using CE-MS Analysis: A Pilot Study.

Fri, 03/08/2018 - 12:19
Related Articles Identification of Metabolites Associated with Onset of CAD in Diabetic Patients Using CE-MS Analysis: A Pilot Study. J Atheroscler Thromb. 2018 Aug 01;: Authors: Omori K, Katakami N, Yamamoto Y, Ninomiya H, Takahara M, Matsuoka TA, Bamba T, Fukusaki E, Shimomura I Abstract AIM: Coronary artery disease (CAD) is the result of a complex metabolic disorder caused by various environmental and genetic factors. Metabolomics is a potential tool for identifying biomarkers for better risk classification and for understanding the pathophysiological mechanisms of CAD. With this background, we performed a pilot study to identify metabolites associated with the future onset of CAD in patients with type 2 diabetes. METHODS: Sixteen subjects who suffered from CAD event during the observation period and 39 non-CAD subjects who were matched to the CAD subjects for Framingham Coronary Heart Disease Risk Score, diabetes duration, and HbA1c were selected. Capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) was used to perform non-targeted metabolome analysis of serum samples collected in 2005. RESULTS: A total of 104 metabolites were identified. Unsupervised principal component analysis (PCA) did not to reveal two distinct clusters of individuals. However, a significant association with CAD was found for 7 metabolites (pelargonic acid, glucosamine:galactosamine, thymine, 3-hydroxybutyric acid, creatine, 2-aminoisobutyric acid, hypoxanthine) and the levels of all these metabolites were significantly lower in the CAD group compared with the non-CAD group. CONCLUSIONS: We identified 7 metabolites related to long-term future onset of CAD in Japanese patients with diabetes. Further studies with large sample size would be necessary to confirm our findings, and future studies using in vivo or in vitro models would be necessary to elucidate whether direct relationships exist between the detected metabolites and CAD pathophysiology. PMID: 30068816 [PubMed - as supplied by publisher]

Application of "Omics" and Systems Biology to Sarcoidosis Research.

Fri, 03/08/2018 - 12:19
Related Articles Application of "Omics" and Systems Biology to Sarcoidosis Research. Ann Am Thorac Soc. 2017 Dec;14(Supplement_6):S445-S451 Authors: Crouser ED, Fingerlin TE, Yang IV, Maier LA, Nana-Sinkam P, Collman RG, Kaminski N Abstract Sarcoidosis is a complex, polygenic disease of unknown cause with diverse clinical phenotypes, ranging from self-limited, asymptomatic disease to life-altering symptoms and early disease-related mortality. It is unlikely that a single common environmental exposure (e.g., infection, antigen) entirely explains the disease, and numerous genetic mutations are associated with the disease. As such, it is reasonable to assume, as with other phenotypically diverse diseases, that distinct genetic mechanisms and related biological biomarkers will serve to further define sarcoidosis subphenotypes, mechanisms, and possibly etiology, thus guiding personalized care. The fields of "omics" and systems biology research are widely applied to understand polygenic and phenotypically diverse diseases, such as sarcoidosis. "Omics" refers to technologies that allow comprehensive profiling of sets of molecules in an organism. Systems biology applies advanced computational approaches to make sense of the enormous data sets that are typically generated from "omics" platforms. The primary objectives of this article are to review the available "omics" tools, assess the current status of "omics" and systems biology research in the field of sarcoidosis, and consider how this technology could be applied to advance our understanding of the mechanistic underpinnings of disease and to develop novel treatments. PMID: 29053026 [PubMed - indexed for MEDLINE]

The General Explanation Method Using NMR Enables Identification of Metabolite Profiles Specific for Normal and Tumor Cell Lines.

Thu, 02/08/2018 - 14:58
The General Explanation Method Using NMR Enables Identification of Metabolite Profiles Specific for Normal and Tumor Cell Lines. Chembiochem. 2018 Aug 01;: Authors: Pečnik K, Todorović V, Bošnjak M, Čemažar M, Kononenko I, Serša G, Plavec J Abstract Machine learning models in metabolomics, despite their great prediction accuracy, are still not widely adopted due to lack of efficient explanation of their predictions. In this study we propose using the general explanation method to explain machine learning model's predictions in order to gain detailed insights into metabolic differences between biological systems. The method was tested on a dataset of 1H NMR spectra acquired on normal lung and mesothelial cell lines and their tumor counterparts. Initially, the random forests and artificial neural network models were applied to the dataset and achieved excellent prediction accuracy. The models' predictions were explained with the general explanation method which enabled identification of discriminating metabolic concentration differences between individual cell lines and enabled the construction of their specific metabolic concentration profiles. This intuitive and robust method holds great promises for in-depth understanding of the mechanisms that underline phenotypes as well as biomarker discovery in complex diseases. PMID: 30067305 [PubMed - as supplied by publisher]

Interactomics and tick vaccine development: New directions for the control of tick-borne diseases.

Thu, 02/08/2018 - 14:58
Interactomics and tick vaccine development: New directions for the control of tick-borne diseases. Expert Rev Proteomics. 2018 Aug 01;: Authors: Artigas-Jerónimo S, de la Fuente J, Villar M Abstract INTRODUCTION: Ticks are obligate hematophagous arthropod ectoparasites that transmit pathogens responsible for a growing number of tick-borne diseases (TBDs) throughout the world. Vaccines have been shown to be the most efficient, cost-effective and environmentally friendly approach for the control of ticks and the prevention of TBDs. Although at its infancy, interactomics have shown the possibilities that the knowledge of the interactome offers in understanding tick biology and the molecular mechanisms involved in pathogen infection and transmission. Furthermore, interactomics has provided information for the identification of candidate vaccine protective antigens. Areas covered: In this special report we review the different approaches used for the study of protein-protein physical and functional interactions, and summarize the application of interactomics to the characterization of tick biology and tick-host-pathogen interactions, and the possibilities that offers to vaccine development for the control of ticks and TBDs. Expert commentary: The combination of interacting proteins in antigen formulations may increase vaccine efficacy. In the near future, the combination of interactomics with other omics approaches such as transcriptomics, proteomics, metabolomics and regulomics together with intelligent Big Data analytic techniques will improve the high throughput discovery and characterization of vaccine protective antigens for the prevention and control of TBDs. PMID: 30067120 [PubMed - as supplied by publisher]

Mendelian randomisation analysis of clustered causal effects of body mass on cardiometabolic biomarkers.

Thu, 02/08/2018 - 14:58
Mendelian randomisation analysis of clustered causal effects of body mass on cardiometabolic biomarkers. BMC Bioinformatics. 2018 Jul 09;19(Suppl 7):195 Authors: Conde S, Xu X, Guo H, Perola M, Fazia T, Bernardinelli L, Berzuini C Abstract BACKGROUND: Recent advances in data analysis methods based on principles of Mendelian Randomisation, such as Egger regression and the weighted median estimator, add to the researcher's ability to infer cause-effect links from observational data. Now is the time to gauge the potential of these methods within specific areas of biomedical research. In this paper, we choose a study in metabolomics as an illustrative testbed. We apply Mendelian Randomisation methods in the analysis of data from the DILGOM (Dietary, Lifestyle and Genetic determinants of Obesity and Metabolic syndrome) study, in the context of an effort to identify molecular pathways of cardiovascular disease. In particular, our illustrative analysis addresses the question whether body mass, as measured by body mass index (BMI), exerts a causal effect on the concentrations of a collection of 137 cardiometabolic markers with different degrees of atherogenic power, such as the (highly atherogenic) lipoprotein metabolites with very low density (VLDLs) and the (protective) high density lipoprotein metabolites. RESULTS: We found strongest evidence of a positive BMI effect (that is, evidence that an increase in BMI causes an increase in the metabolite concentration) on those metabolites known to represent strong risk factors for coronary artery disease, such as the VLDLs, and evidence of a negative effect on protective biomarkers. CONCLUSIONS: The methods discussed represent a useful scientific tool, although they assume the validity of conditions that are (at best) only partially verifiable. This paper provides a rigorous account of such conditions. The results of our analysis provide a proof-of-concept illustration of the potential usefulness of Mendelian Randomisation in genomic biobank studies aiming to dissect the molecular causes of disease, and to identify candidate pharmacological targets. PMID: 30066639 [PubMed - in process]

Genome-wide researches and applications on Dendrobium.

Thu, 02/08/2018 - 14:58
Related Articles Genome-wide researches and applications on Dendrobium. Planta. 2018 Jul 31;: Authors: Zheng SG, Hu YD, Zhao RX, Yan S, Zhang XQ, Zhao TM, Chun Z Abstract MAIN CONCLUSION: This review summarizes current knowledge of chromosome characterization, genetic mapping, genomic sequencing, quality formation, floral transition, propagation, and identification in Dendrobium. The widely distributed Dendrobium has been studied for a long history, due to its important economic values in both medicine and ornamental. In recent years, some species of Dendrobium and other orchids had been reported on genomic sequences, using the next-generation sequencing technology. And the chloroplast genomes of many Dendrobium species were also revealed. The chromosomes of most Dendrobium species belong to mini-chromosomes, and showed 2n = 38. Only a few of genetic studies were reported in Dendrobium. After revealing of genomic sequences, the techniques of transcriptomics, proteomics and metabolomics could be employed on Dendrobium easily. Some other molecular biological techniques, such as gene cloning, gene editing, genetic transformation and molecular marker developing, had also been applied on the basic research of Dendrobium, successively. As medicinal plants, insights into the biosynthesis of some medicinal components were the most important. As ornamental plants, regulation of flower related characteristics was the most important. More, knowledge of growth and development, environmental interaction, evolutionary analysis, breeding of new cultivars, propagation, and identification of species and herbs were also required for commercial usage. All of these studies were improved using genomic sequences and related technologies. To answer some key scientific issues in Dendrobium, quality formation, flowering, self-incompatibility and seed germination would be the focus of future research. And genome related technologies and studies would be helpful. PMID: 30066218 [PubMed - as supplied by publisher]

Metabolic targets of watercress and PEITC in MCF-7 and MCF-10A cells explain differential sensitisation responses to ionising radiation.

Thu, 02/08/2018 - 14:58
Related Articles Metabolic targets of watercress and PEITC in MCF-7 and MCF-10A cells explain differential sensitisation responses to ionising radiation. Eur J Nutr. 2018 Jul 31;: Authors: Giallourou NS, Rowland IR, Rothwell SD, Packham G, Commane DM, Swann JR Abstract PURPOSE: Watercress is a rich source of phytochemicals with anticancer potential, including phenethyl isothiocyanate (PEITC). We examined the potential for watercress extracts and PEITC to increase the DNA damage caused by ionising radiation (IR) in breast cancer cells and to be protective against radiation-induced collateral damage in healthy breast cells. The metabolic events that mediate such responses were explored using metabolic profiling. METHODS: 1H nuclear magnetic resonance spectroscopy-based metabolic profiling was coupled with DNA damage-related assays (cell cycle, Comet assay, viability assays) to profile the comparative effects of watercress and PEITC in MCF-7 breast cancer cells and MCF-10A non-tumorigenic breast cells with and without exposure to IR. RESULTS: Both the watercress extract and PEITC-modulated biosynthetic pathways of lipid and protein synthesis and resulted in changes in cellular bioenergetics. Disruptions to the redox balance occurred with both treatments in the two cell lines, characterised by shifts in the abundance of glutathione. PEITC enhanced the sensitivity of the breast cancer cells to IR increasing the effectiveness of the cancer-killing process. In contrast, watercress-protected non-tumorigenic breast cells from radiation-induced damage. These effects were driven by changes in the cellular content of the antioxidant glutathione following exposure to PEITC and other phytochemicals in watercress. CONCLUSION: These findings support the potential prophylactic impact of watercress during radiotherapy. Extracted compounds from watercress and PEITC differentially modulate cellular metabolism collectively enhancing the therapeutic outcomes of radiotherapy. PMID: 30066177 [PubMed - as supplied by publisher]

Effects of Diacetyl Flavoring Exposure in Mice Metabolism.

Thu, 02/08/2018 - 14:58
Related Articles Effects of Diacetyl Flavoring Exposure in Mice Metabolism. Biomed Res Int. 2018;2018:9875319 Authors: Jedlicka LDL, Silva JDC, Balbino AM, Neto GB, Furtado DZS, da Silva HDT, Cavalcanti FBC, van der Heijden KM, Penatti CAA, Bechara EJH, Assunção NA Abstract Diacetyl is a flavoring that imparts a buttery flavor to foods, but the use or exposure to diacetyl has been related to some diseases. We investigated the effect of oral intake of diacetyl in male and female C57/Bl mice. We performed a target metabolomics assay using ultraperformance liquid chromatography paired with triple quadrupole mass spectrometry (UPLC-MS/MS) for the determination and quantification of plasmatic metabolites. We observed alterations in metabolites present in the urea and tricarboxylic acid (TCA) cycles. Peroxynitrite plasmatic levels were evaluated by a colorimetric method, final activity of superoxide dismutase (SOD) was evaluated by an enzymatic method, and mouse behavior was evaluated. Majority of the assay showed differences between control and treatment groups, as well as between genders. This may indicate the involvement of sex hormones in the regulation of a normal metabolic profile, and the implication of sex differences in metabolite disease response. PMID: 30065948 [PubMed - in process]

Integrating Genes Affecting Coronary Artery Disease in Functional Networks by Multi-OMICs Approach.

Thu, 02/08/2018 - 14:58
Related Articles Integrating Genes Affecting Coronary Artery Disease in Functional Networks by Multi-OMICs Approach. Front Cardiovasc Med. 2018;5:89 Authors: Vilne B, Schunkert H Abstract Coronary artery disease (CAD) and myocardial infarction (MI) remain among the leading causes of mortality worldwide, urgently demanding a better understanding of disease etiology, and more efficient therapeutic strategies. Genetic predisposition as well as the environment and lifestyle are thought to contribute to disease risk. It is likely that non-linear and complex interactions occur between these multiple factors, involving simultaneous pathological changes in diverse cell types, tissues, and organs, at multiple molecular levels. Recent technological advances have exponentially expanded the breadth of available -omics data, from genome, epigenome, transcriptome, proteome, metabolome to even the microbiome. Integration of multiple layers of information across several -omics domains, i.e., the so-called multi-omics approach, currently holds the promise as a path toward precision medicine. Indeed, a more meaningful interpretation of genotype-phenotype relationships and the development of successful therapeutics tailored to individual patients are urgently needed. In this review, we will summarize recent findings and applications of integrative multi-omics in elucidating the etiology of CAD/MI; with a special focus on established disease susceptibility loci sequentially identified in genome-wide association studies (GWAS) over the last 10 years. Moreover, in addition to the autosomal genome, we will also consider the genetic variation in our "second genome"-the mitochondrial genome. Finally, we will summarize the current challenges in the field and point to future research directions required in order to successfully and effectively apply these approaches for precision medicine. PMID: 30065929 [PubMed]

Biomarkers of food intake for cocoa and liquorice (products): a systematic review.

Thu, 02/08/2018 - 14:58
Related Articles Biomarkers of food intake for cocoa and liquorice (products): a systematic review. Genes Nutr. 2018;13:22 Authors: Michielsen CCJR, Almanza-Aguilera E, Brouwer-Brolsma EM, Urpi-Sarda M, Afman LA Abstract Background: To unravel true links between diet and health, it is important that dietary exposure is accurately measured. Currently, mainly self-reporting methods (e.g. food frequency questionnaires and 24-h recalls) are used to assess food intake in epidemiological studies. However, these traditional instruments are subjective measures and contain well-known biases. Especially, estimating the intake of the group of confectionary products, such as products containing cocoa and liquorice, remains a challenge. The use biomarkers of food intake (BFIs) may provide a more objective measurement. However, an overview of current candidate biomarkers and their validity is missing for both cocoa- and liquorice-containing foods. Objective: The purpose of the current study was to (1) identify currently described candidate BFIs for cocoa (products) and liquorice, (2) to evaluate the validity of these identified candidate BFIs and (3) to address further validation and/or identification work to be done. Methods: This systematic review was based on a comprehensive literature search of three databases (PubMed, Scopus and ISI web of Science), to identify candidate BFIs. Via a second search step in the Human Metabolome Database (HMDB), the Food Database (FooDB) and Phenol-Explorer, the specificity of the candidate BFIs was evaluated, followed by an evaluation of the validity of the specific candidate BFIs, via pre-defined criteria. Results: In total, 37 papers were included for cocoa and 8 papers for liquorice. For cocoa, 164 unique candidate BFIs were obtained, and for liquorice, four were identified in total. Despite the high number of identified BFIs for cocoa, none of the metabolites was specific. Therefore, the validity of these compounds was not further examined. For liquorice intake, 18-glycyrrhetinic acid (18-GA) was found to have the highest assumed validity. Conclusions: For cocoa, specific BFIs were missing, mainly because the individual BFIs were also found in foods having a similar composition, such as tea (polyphenols) or coffee (caffeine). However, a combination of individual BFIs might lead to discriminating profiles between cocoa (products) and foods with a similar composition. Therefore, studies directly comparing the consumption of cocoa to these similar products are needed, enabling efforts to find a unique profile per product. For liquorice, we identified 18-GA as a promising BFI; however, important information on its validity is missing; thus, more research is necessary. Our findings indicate a need for more studies to determine acceptable BFIs for both cocoa and liquorice. PMID: 30065791 [PubMed]

NMR Metabolomics Defining Genetic Variation in Pea Seed Metabolites.

Thu, 02/08/2018 - 14:58
Related Articles NMR Metabolomics Defining Genetic Variation in Pea Seed Metabolites. Front Plant Sci. 2018;9:1022 Authors: Ellis N, Hattori C, Cheema J, Donarski J, Charlton A, Dickinson M, Venditti G, Kaló P, Szabó Z, Kiss GB, Domoney C Abstract Nuclear magnetic resonance (NMR) spectroscopy profiling was used to provide an unbiased assessment of changes to the metabolite composition of seeds and to define genetic variation for a range of pea seed metabolites. Mature seeds from recombinant inbred lines, derived from three mapping populations for which there is substantial genetic marker linkage information, were grown in two environments/years and analyzed by non-targeted NMR. Adaptive binning of the NMR metabolite data, followed by analysis of quantitative variation among lines for individual bins, identified the main genomic regions determining this metabolic variability and the variability for selected compounds was investigated. Analysis by t-tests identified a set of bins with highly significant associations to genetic map regions, based on probability (p) values that were appreciably lower than those determined for randomized data. The correlation between bins showing high mean absolute deviation and those showing low p-values for marker association provided an indication of the extent to which the genetics of bin variation might be explained by one or a few loci. Variation in compounds related to aromatic amino acids, branched-chain amino acids, sucrose-derived metabolites, secondary metabolites and some unidentified compounds was associated with one or more genetic loci. The combined analysis shows that there are multiple loci throughout the genome that together impact on the abundance of many compounds through a network of interactions, where individual loci may affect more than one compound and vice versa. This work therefore provides a framework for the genetic analysis of the seed metabolome, and the use of genetic marker data in the breeding and selection of seeds for specific seed quality traits and compounds that have high commercial value. PMID: 30065739 [PubMed]

Health benefits and bioactive compounds of eggplant.

Thu, 02/08/2018 - 14:58
Related Articles Health benefits and bioactive compounds of eggplant. Food Chem. 2018 Dec 01;268:602-610 Authors: Gürbüz N, Uluişik S, Frary A, Frary A, Doğanlar S Abstract Eggplant is a vegetable crop that is grown around the world and can provide significant nutritive benefits thanks to its abundance of vitamins, phenolics and antioxidants. In addition, eggplant has potential pharmaceutical uses that are just now becoming recognized. As compared to other crops in the Solanaceae, few studies have investigated eggplant's metabolic profile. Metabolomics and metabolic profiling are important platforms for assessing the chemical composition of plants and breeders are increasingly concerned about the nutritional and health benefits of crops. In this review, the historical background and classification of eggplant are shortly explained; then the beneficial phytochemicals, antioxidant activity and health effects of eggplant are discussed in detail. PMID: 30064803 [PubMed - in process]

Cell wall and metabolite composition of berries of Vitis vinifera (L.) cv. Thompson Seedless with different firmness.

Thu, 02/08/2018 - 14:58
Related Articles Cell wall and metabolite composition of berries of Vitis vinifera (L.) cv. Thompson Seedless with different firmness. Food Chem. 2018 Dec 01;268:492-497 Authors: Zepeda B, Olmedo P, Ejsmentewicz T, Sepúlveda P, Balic I, Balladares C, Delgado-Rioseco J, Fuentealba C, Moreno AA, Defilippi BG, Meneses C, Pedreschi R, Campos-Vargas R Abstract Firm berries are highly appreciated by table grape consumers. Cell wall composition is one of the main factors influencing the firmness of table grape berries. Nevertheless, the biological factors driving changes in berry firmness remain unclear. In the present work, we evaluated the firmness of berries of Vitis vinifera cv. Thompson Seedless. We selected two orchards displaying contrasting berry firmness and evaluated polar metabolites and cell wall composition. Our results suggest that berries from the soft orchard exhibited a higher accumulation of sugars at veraison whereas berries from the hard orchard accumulated the same sugars at harvest plus a higher amount of glucose monosaccharide at the cell wall. Thus, this study opens new insights about a connection between metabolic and cell wall changes with fruit firmness in a table grape variety, suggesting that it is possible to use metabolomic tools to identify metabolic biomarkers associated with table grape berry firmness. PMID: 30064789 [PubMed - in process]

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