PubMed

Related Articles Proteomic and metabolomic study of wax apple (Syzygium samarangense) fruit during ripening process. Electrophoresis. 2018 12;39(23):2954-2964 Authors: Jamil NAM, Rahmad N, Rosli NHM, Al-Obaidi JR Abstract Wax apple is one of the underutilized fruits that is considered a good source of fibers, vitamins, minerals as well as antioxidants. In this study, a comparative analysis of the developments of wax fruit ripening at the proteomic and metabolomic level was reported. 2D electrophoresis coupled with MALDI-TOF/TOF was used to compare the proteome profile from three developmental stages named immature, young, and mature fruits. In general, the protein expression profile and the identified proteins function were discussed for their potential roles in fruit physiological development and ripening processes. The metabolomic investigation was also performed on the same samples using quadrupole LC-MS (LC-QTOF/MS). Roles of some of the differentially expressed proteins and metabolites are discussed in relation to wax apple ripening during the development. This is the first study investigating the changes in the proteins and metabolites in wax apple at different developmental stages. The information obtained from this research will be helpful in developing biomarkers for breeders and help the plant researchers to avoid wax apple cultivation problems such as fruit cracking. PMID: 30074628 [PubMed - indexed for MEDLINE]

Related Articles NMR-based Metabolomic Techniques Identify the Toxicity of Emodin in HepG2 Cells. Sci Rep. 2018 06 20;8(1):9379 Authors: Chen C, Gao J, Wang TS, Guo C, Yan YJ, Mao CY, Gu LW, Yang Y, Li ZF, Liu A Abstract Emodin is a natural anthraquinone derivative that is present in various herbal preparations. The pharmacological effects of emodin include anticancer, hepatoprotective, anti-inflammatory, antioxidant and even antimicrobial activities. However, emodin also has been reported to induce hepatotoxicity, nephrotoxicity, genotoxicity and reproductive toxicity. The mechanism of emodin's adverse effects is complicated and currently not well understood. This study aimed to establish a cell metabonomic method to investigate the toxicity of emodin and explore its potential mechanism and relevant targets. In the present study, metabonomic profiles of cell extracts and cell culture media obtained using the 1H NMR technique were used to assess emodin toxicity in HepG2 cells. Multivariate statistical analyses such as partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to characterize the metabolites that differed between the control and emodin groups. The results indicated that emodin resulted in differences in 33 metabolites, including acetate, arginine, aspartate, creatine, isoleucine, leucine and histidine in the cell extract samples and 23 metabolites, including alanine, formate, glutamate, succinate and isoleucine, in the cell culture media samples. Approximately 8 pathways associated with these metabolites were disrupted in the emodin groups. These results demonstrated the potential for using cell metabonomics approaches to clarify the toxicological effects of emodin, the underlying mechanisms and potential biomarkers. Our findings may help with the development of novel strategies to discover targets for drug toxicity, elucidate the changes in regulatory signal networks and explore its potential mechanism of action. PMID: 29925852 [PubMed - indexed for MEDLINE]

Related Articles Comparative assessment of Graves' disease and main extrathyroidal manifestation, Graves' ophthalmopathy, by non-targeted metabolite profiling of blood and orbital tissue. Sci Rep. 2018 06 18;8(1):9262 Authors: Ji DY, Park SH, Park SJ, Kim KH, Ku CR, Shin DY, Yoon JS, Lee DY, Lee EJ Abstract Graves' disease (GD) is an autoimmune disorder that causes the overproduction of thyroid hormones and consequent cascade of systemic metabolism dysfunction. Moreover, Graves' ophthalmopathy (GO) is the main extrathyroidal manifestation of Graves' disease (GD). The goal of the study was to identify metabolic signatures in association with diagnostic biomarkers of GD without GO and GO, respectively. Ninety metabolites were profiled and analyzed based on a non-targeted primary metabolite profiling from plasma samples of 21 GD patients without GO, 26 subjects with GO, and 32 healthy subjects. Multivariate statistics showed a clear discrimination between healthy controls and disease group (R2Y = 0.518, Q2 = 0.478) and suggested a biomarker panel consisting of 10 metabolites. Among them, most of metabolites showed the positive association with the levels of thyrotropin receptor antibodies. With combination of proline and 1,5-anhydroglucitol, which were identified as GO-specific modulators, the re-constructed biomarker model greatly improved the statistical power and also facilitated simultaneous discrimination among healthy control, GO, and GD without GO groups (AUC = 0.845-0.935). Finally, the comparative analysis of tissue metabolite profiles from GO patients proposed putative metabolic linkage between orbital adipose/connective tissues and the biofluidic consequences, in which fumarate, proline, phenylalanine, and glycerol were coordinately altered with the blood metabolites. PMID: 29915201 [PubMed - indexed for MEDLINE]

Lack of FIBRILLIN6 in Arabidopsis thaliana affects light acclimation and sulfate metabolism. New Phytol. 2019 Oct 09;: Authors: Lee K, Lehmann M, Paul MV, Wang L, Luckner M, Wanner G, Geigenberger P, Leister D, Kleine T Abstract Arabidopsis thaliana contains 13 fibrillins (FBNs), which are all localized to chloroplasts. FBN1 and FBN2 are involved in photoprotection of photosystem II, and FBN4 and FBN5 are thought to be involved in plastoquinone transport and biosynthesis, respectively. The functions of the other FBNs remain largely unknown. To gain insight into the function of FBN6, we performed co-expression and Western analyses, conducted fluorescence and transmission electron microscopy, stained reactive oxygen species (ROS), measured photosynthetic parameters and glutathione levels, and applied transcriptomics and metabolomics. Using co-expression analyses, FBN6 was identified as a photosynthesis-associated gene. FBN6 is localized in thylakoids, envelope and plastoglobules, and its knock-out results in stunted plants. The delayed growth phenotype cannot be attributed to altered basic photosynthesis parameters or a reduced CO2 assimilation rate. Under moderate light stress, primary leaves of fbn6 plants begin to bleach and contain enlarged plastoglobules. RNA-Seq and metabolomics analyses point to an alteration in sulfate reduction in fbn6. Indeed, glutathione content is higher in fbn6, which in turn confers cadmium tolerance of fbn6 seedlings. We conclude that loss of FBN6 leads to perturbation of ROS homeostasis. FBN6 enables plants to cope with moderate light stress and affects cadmium tolerance. PMID: 31596965 [PubMed - as supplied by publisher]

Elevated Endogenous SDHA Drives Pathological Metabolism in Highly Metastatic Uveal Melanoma. Invest Ophthalmol Vis Sci. 2019 Oct 01;60(13):4187-4195 Authors: Chattopadhyay C, Oba J, Roszik J, Marszalek JR, Chen K, Qi Y, Eterovic K, Robertson AG, Burks JK, McCannel TA, Grimm EA, Woodman SE Abstract Purpose: Metastatic uveal melanoma (UM) has a very poor prognosis and no effective therapy. Despite remarkable advances in treatment of cutaneous melanoma, UM remains recalcitrant to chemotherapy, small-molecule kinase inhibitors, and immune-based therapy. Methods: We assessed two sets of oxidative phosphorylation (OxPhos) genes within 9858 tumors across 31 cancer types. An OxPhos inhibitor was used to characterize differential metabolic programming of highly metastatic monosomy 3 (M3) UM. Seahorse analysis and global metabolomics profiling were done to identify metabolic vulnerabilities. Analyses of UM TCGA data set were performed to determine expressions of key OxPhos effectors in M3 and non-M3 UM. We used targeted knockdown of succinate dehydrogenase A (SDHA) to determine the role of SDHA in M3 UM in conferring resistance to OxPhos inhibition. Results: We identified UM to have among the highest median OxPhos levels and showed that M3 UM exhibits a distinct metabolic profile. M3 UM shows markedly low succinate levels and has highly increased levels of SDHA, the enzyme that couples the tricarboxylic acid cycle with OxPhos by oxidizing (lowering) succinate. We showed that SDHA-high M3 UM have elevated expression of key OxPhos molecules, exhibit abundant mitochondrial reserve respiratory capacity, and are resistant to OxPhos antagonism, which can be reversed by SDHA knockdown. Conclusions: Our study has identified a critical metabolic program within poor prognostic M3 UM. In addition to the heightened mitochondrial functional capacity due to elevated SDHA, M3 UM SDHA-high mediate resistance to therapy that is reversible with targeted treatment. PMID: 31596927 [PubMed - in process]

"Photobiomics": Can Light, Including Photobiomodulation, Alter the Microbiome? Photobiomodul Photomed Laser Surg. 2019 Oct 09;: Authors: Liebert A, Bicknell B, Johnstone DM, Gordon LC, Kiat H, Hamblin MR Abstract Objective: The objective of this review is to consider the dual effects of microbiome and photobiomodulation (PBM) on human health and to suggest a relationship between these two as a novel mechanism. Background: PBM describes the use of low levels of visible or near-infrared (NIR) light to heal and stimulate tissue, and to relieve pain and inflammation. In recent years, PBM has been applied to the head as an investigative approach to treat diverse brain diseases such as stroke, traumatic brain injury (TBI), Alzheimer's and Parkinson's diseases, and psychiatric disorders. Also, in recent years, increasing attention has been paid to the total microbial population that colonizes the human body, chiefly in the gut and the mouth, called the microbiome. It is known that the composition and health of the gut microbiome affects many diseases related to metabolism, obesity, cardiovascular disorders, autoimmunity, and even brain disorders. Materials and methods: A literature search was conducted for published reports on the effect of light on the microbiome. Results: Recent work by our research group has demonstrated that PBM (red and NIR light) delivered to the abdomen in mice, can alter the gut microbiome in a potentially beneficial way. This has also now been demonstrated in human subjects. Conclusions: In consideration of the known effects of PBM on metabolomics, and the now demonstrated effects of PBM on the microbiome, as well as other effects of light on the microbiome, including modulating circadian rhythms, the present perspective introduces a new term "photobiomics" and looks forward to the application of PBM to influence the microbiome in humans. Some mechanisms by which this phenomenon might occur are considered. PMID: 31596658 [PubMed - as supplied by publisher]

Recent advances in our understanding of the mechanisms of lung alveolarization and bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol. 2019 Oct 09;: Authors: Lignelli E, Palumbo F, Myti D, Morty RE Abstract Bronchopulmonary dysplasia (BPD) is the most common cause of morbidity and mortality in preterm infants. A key histopathological feature of BPD is stunted late lung development, where the process of alveolarization -the generation of alveolar gas exchange units- is impeded, through mechanisms that remain largely unclear. As such, there is interest in the clarification both of the pathomechanisms at play in affected lungs, and the mechanisms of de novo alveoli generation in healthy, developing lungs. A better understanding of normal and pathological alveolarization might reveal opportunities for improved medical management of affected infants. Furthermore, disturbances to the alveolar architecture are a key histopathological feature of several adult chronic lung diseases, including emphysema and fibrosis; and it is envisaged that knowledge about the mechanisms of alveologenesis might facilitate regeneration of healthy lung parenchyma in affected patients. To this end, recent efforts have interrogated clinical data, developed new -and refined existing- in vivo and in vitro models of BPD, have applied new microscopic and radiographic approaches, and have developed advanced cell‑culture approaches, including organoid generation. Advances have also been made in the development of other methodologies, including single-cell analysis, metabolomics, lipidomics, and proteomics; as well as the generation and use of complex mouse genetics tools. The objective of this review is to present advances made in our understanding of the mechanisms of lung alveolarization and BPD over the period 01 January 2017 - 30 June 2019, a period that spans the 50th anniversary of the original clinical description of BPD in preterm infants. PMID: 31596603 [PubMed - as supplied by publisher]

MetumpX - A Metabolomics Support Package for Untargeted Mass Spectrometry. Bioinformatics. 2019 Oct 09;: Authors: Wajid B, Iqbal H, Jamil M, Rafique H, Anwar F Abstract MOTIVATION: Metabolomics is a data analysis and interpretation field aiming to study functions of small molecules within the organism. Consequently Metabolomics requires researchers in life sciences to be comfortable in downloading, installing and scripting of software that are mostly not user friendly and lack basic GUIs. As the researchers struggle with these skills, there is a dire need to develop software packages that can automatically install software pipelines truely speeding up the learning curve to build software workstations. Therefore this paper aims to provide MetumpX, a software package that eases in their installation of 103 software by automatically resolving their individual dependencies and also allowing the users to choose which software works best for them. RESULTS: MetumpX is a Ubuntu based software package that facilitate easy download and installation of about 103 tools spread across the standard metabolomics pipeline. As far as the authors know MetumpX is the only solution of this kind where the focus lies on automating development of software workstations. AVAILABILITY: https://github.com/hasaniqbal777/MetumpX-bin. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID: 31596440 [PubMed - as supplied by publisher]

33 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 2019/10/09PubMed 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.

22 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 2019/10/08PubMed 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.

22 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 2019/10/08PubMed 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.

Metabolism of fatty acids and bile acids in plasma is associated with overactive bladder in males: potential biomarkers and targets for novel treatments in a metabolomics analysis. Int Urol Nephrol. 2019 Oct 05;: Authors: Mitsui T, Kira S, Ihara T, Sawada N, Nakagomi H, Miyamoto T, Shimura H, Tsuchiya S, Kanda M, Takeda M Abstract OBJECTIVES: The present study was conducted to identify metabolites using a metabolomics approach and investigate the relationship between these metabolites and urgency as a major symptom of overactive bladder (OAB). PATIENTS AND METHODS: In 47 male participants without any apparent neurological disease, OAB was defined as an urgency score on the International Prostate Symptom Score of 2 and higher (OAB group, n = 26), while patients with a score of 1 or 0 were placed in a control group (n = 21). A comprehensive study on plasma metabolites was conducted, and metabolites were compared between the OAB and control groups. RESULTS: Age was significantly higher in the OAB group, while prostate volume did not differ between the groups. A 24-h bladder diary revealed that nocturnal urine volume, 24-h micturition frequency, nocturnal micturition frequency, and the nocturnal index were significantly higher in the OAB group, whereas maximum voided volume was significantly lower in this group. The metabolomics analysis identified 79 metabolites from the plasma of participants. The multivariate analysis showed that increases in the fatty acids (22:1), erucic acid and palmitoleic acid, and a decrease in cholic acid correlated with incidence of male OAB. A decrease in acylcarnitine (18:2)-3 and an increase in cis-11-eicosenoic acid also appeared to be associated with OAB in males. CONCLUSIONS: OAB in males may occur through the abnormal metabolism of fatty acids and bile acids. Further studies on these pathways will contribute to the detection of new biomarkers and development of potential targets for novel treatments. PMID: 31587188 [PubMed - as supplied by publisher]

An LCMS-based untargeted metabolomics protocol for cochlear perilymph: highlighting metabolic effects of hydrogen gas on the inner ear of noise exposed Guinea pigs. Metabolomics. 2019 Oct 05;15(10):138 Authors: Pirttilä K, Videhult Pierre P, Haglöf J, Engskog M, Hedeland M, Laurell G, Arvidsson T, Pettersson C Abstract INTRODUCTION: Noise-induced hearing loss (NIHL) is an increasing problem in society and accounts for a third of all cases of acquired hearing loss. NIHL is caused by formation of reactive oxygen species (ROS) in the cochlea causing oxidative stress. Hydrogen gas (H2) can alleviate the damage caused by oxidative stress and can be easily administered through inhalation. OBJECTIVES: To present a protocol for untargeted metabolomics of guinea pig perilymph and investigate the effect of H2 administration on the perilymph metabolome of noise exposed guinea pigs. METHODS: The left ear of guinea pigs were exposed to hazardous impulse noise only (Noise, n = 10), noise and H2 (Noise + H2, n = 10), only H2 (H2, n = 4), or untreated (Control, n = 2). Scala tympani perilymph was sampled from the cochlea of both ears. The polar component of the perilymph metabolome was analyzed using a HILIC-UHPLC-Q-TOF-MS-based untargeted metabolomics protocol. Multivariate data analysis (MVDA) was performed separately for the exposed- and unexposed ear. RESULTS: MVDA allowed separation of groups Noise and Noise + H2 in both the exposed and unexposed ear and yielded 15 metabolites with differentiating relative abundances. Seven were found in both exposed and unexposed ear data and included two osmoprotectants. Eight metabolites were unique to the unexposed ear and included a number of short-chain acylcarnitines. CONCLUSIONS: A HILIC-UHPLC-Q-TOF-MS-based protocol for untargeted metabolomics of perilymph is presented and shown to be fit-for-purpose. We found a clear difference in the perilymph metabolome of noise exposed guinea pigs with and without H2 treatment. PMID: 31587113 [PubMed - in process]

Diverse therapeutic efficacies and more diverse mechanisms of nicotinamide. Metabolomics. 2019 Oct 05;15(10):137 Authors: Song SB, Park JS, Chung GJ, Lee IH, Hwang ES Abstract BACKGROUND: Nicotinamide (NAM) is a form of vitamin B3 that, when administered at near-gram doses, has been shown or suggested to be therapeutically effective against many diseases and conditions. The target conditions are incredibly diverse ranging from skin disorders such as bullous pemphigoid to schizophrenia and depression and even AIDS. Similar diversity is expected for the underlying mechanisms. In a large portion of the conditions, NAM conversion to nicotinamide adenine dinucleotide (NAD+) may be a major factor in its efficacy. The augmentation of cellular NAD+ level not only modulates mitochondrial production of ATP and superoxide, but also activates many enzymes. Activated sirtuin proteins, a family of NAD+-dependent deacetylases, play important roles in many of NAM's effects such as an increase in mitochondrial quality and cell viability countering neuronal damages and metabolic diseases. Meanwhile, certain observed effects are mediated by NAM itself. However, our understanding on the mechanisms of NAM's effects is limited to those involving certain key proteins and may even be inaccurate in some proposed cases. AIM OF REVIEW: This review details the conditions that NAM has been shown to or is expected to effectively treat in humans and animals and evaluates the proposed underlying molecular mechanisms, with the intention of promoting wider, safe therapeutic application of NAM. KEY SCIENTIFIC CONCEPTS OF REVIEW: NAM, by itself or through altering metabolic balance of NAD+ and tryptophan, modulates mitochondrial function and activities of many molecules and thereby positively affects cell viability and metabolic functions. And, NAM administration appears to be quite safe with limited possibility of side effects which are related to NAM's metabolites. PMID: 31587111 [PubMed - in process]

Metabolomics: a search for biomarkers of visceral fat and liver fat content. Metabolomics. 2019 Oct 05;15(10):139 Authors: Boone S, Mook-Kanamori D, Rosendaal F, den Heijer M, Lamb H, de Roos A, le Cessie S, Willems van Dijk K, de Mutsert R Abstract INTODUCTION: Excess visceral and liver fat are known risk factors for cardiometabolic disorders. Metabolomics might allow for easier quantification of these ectopic fat depots, instead of using invasive and costly tools such as MRI or approximations such as waist circumference. OBJECTIVE: We explored the potential use of plasma metabolites as biomarkers of visceral adipose tissue (VAT) and hepatic triglyceride content (HTGC). METHODS: We performed a cross-sectional analysis of a subset of the Netherlands Epidemiology of Obesity study. Plasma metabolite profiles were determined using the Biocrates AbsoluteIDQ p150 kit in 176 individuals with normal fasting plasma glucose. VAT was assessed with magnetic resonance imaging and HTGC with proton-MR spectroscopy. We used linear regression to investigate the associations of 190 metabolite variables with VAT and HTGC. RESULTS: After adjustment for age, sex, total body fat, currently used approximations of visceral and liver fat, and multiple testing, three metabolite ratios were associated with VAT. The strongest association was the lysophosphatidylcholines to total phosphatidylcholines (PCs) ratio [- 14.1 (95% CI - 21.7; - 6.6) cm2 VAT per SD of metabolite concentration]. Four individual metabolites were associated with HTGC, especially the diacyl PCs of which C32:1 was the strongest at a 1.31 (95% CI 1.14; 1.51) fold increased HTGC per SD of metabolite concentration. CONCLUSION: Metabolomics may be a useful tool to identify biomarkers of visceral fat and liver fat content that have added diagnostic value over current approximations. Replication studies are required to validate the diagnostic value of these metabolites. PMID: 31587110 [PubMed - in process]

Related Articles Botanical metabolite ions extraction from full electrospray ionization mass spectrometry using high-dimensional penalized regression. Metabolomics. 2019 Oct 04;15(10):136 Authors: Rostandy B, Gao X Abstract INTRODUCTION: Mass spectrometric data analysis of complex biological mixtures can be a challenge due to its vast datasets. There is lack of data treatment pipelines to analyze chemical signals versus noise. These tasks, so far, have been up to the discretion of the analysts. OBJECTIVES: The aim of this work is to demonstrate an analytical workflow that would enhance the confidence in metabolomics before answering biological questions by serial dilution of botanical complex mixture and high-dimensional data analysis. Furthermore, we would like to provide an alternative approach to a univariate p-value cutoff from t-test for blank subtraction procedure between negative control and biological samples. METHODS: A serial dilution of complex mixture analysis under electrospray ionization was proposed to study firsthand chemical complexity of metabolomics. Advanced statistical models using high-dimensional penalized regression were employed to study both the concentration and ion intensity relationship and the ion-ion relationship per second of retention time sub dataset. The multivariate analysis was carried out with a tool built in-house, so called metabolite ions extraction and visualization, which was implemented in R environment. RESULTS: A test case of the medicinal plant goldenseal (Hydrastis canandensis L.), showed an increase in metabolome coverage of features deemed as "important" by a multivariate analysis compared to features deemed as "significant" by a univariate t-test. For an illustration, the data analysis workflow suggested an unexpected putative compound, 20-hydroxyecdysone. This suggestion was confirmed with MS/MS acquisition and literature search. CONCLUSION: The multivariate analytical workflow selects "true" metabolite ions signals and provides an alternative approach to a univariate p-value cutoff from t-test, thus enhancing the data analysis process of metabolomics. PMID: 31586238 [PubMed - in process]

Related Articles In vivo efficacy of mutant IDH1 inhibitor HMS-101 and structural resolution of distinct binding site. Leukemia. 2019 Oct 04;: Authors: Chaturvedi A, Goparaju R, Gupta C, Weder J, Klünemann T, Araujo Cruz MM, Kloos A, Goerlich K, Schottmann R, Othman B, Struys EA, Bähre H, Grote-Koska D, Brand K, Ganser A, Preller M, Heuser M Abstract Mutations in isocitrate dehydrogenase 1 (IDH1) are found in 6% of AML patients. Mutant IDH produces R-2-hydroxyglutarate (R-2HG), which induces histone- and DNA-hypermethylation through the inhibition of epigenetic regulators, thus linking metabolism to tumorigenesis. Here we report the biochemical characterization, in vivo antileukemic effects, structural binding, and molecular mechanism of the inhibitor HMS-101, which inhibits the enzymatic activity of mutant IDH1 (IDH1mut). Treatment of IDH1mut primary AML cells reduced 2-hydroxyglutarate levels (2HG) and induced myeloid differentiation in vitro. Co-crystallization of HMS-101 and mutant IDH1 revealed that HMS-101 binds to the active site of IDH1mut in close proximity to the regulatory segment of the enzyme in contrast to other IDH1 inhibitors. HMS-101 also suppressed 2HG production, induced cellular differentiation and prolonged survival in a syngeneic mutant IDH1 mouse model and a patient-derived human AML xenograft model in vivo. Cells treated with HMS-101 showed a marked upregulation of the differentiation-associated transcription factors CEBPA and PU.1, and a decrease in cell cycle regulator cyclin A2. In addition, the compound attenuated histone hypermethylation. Together, HMS-101 is a unique inhibitor that binds to the active site of IDH1mut directly and is active in IDH1mut preclinical models. PMID: 31586149 [PubMed - as supplied by publisher]

Related Articles Evidence from 3-month-old infants shows that a combination of postnatal feeding and exposures in utero shape lipid metabolism. Sci Rep. 2019 Oct 04;9(1):14321 Authors: Furse S, Snowden SG, Olga L, Prentice P, Ong KK, Hughes IA, Acerini CL, Dunger DB, Koulman A Abstract We tested the hypothesis that both postnatal feeding and conditions in utero affect lipid metabolism in infants. Infants who experienced restrictive growth conditions in utero and others exposed to maternal hyperglycaemia were compared to a control group with respect to feeding mode. Dried blood spots were collected from a pilot subset of infant participants of the Cambridge Baby Growth Study at 3mo. Groups: (a) a normal gestation (control, n = 40), (b) small for gestational age (SGA, n = 34) and (c) whose mothers developed hyperglycaemia (n = 59). These groups were further stratified by feeding mode; breastfed, formula-fed or received a mixed intake. Their phospholipid, glyceride and sterol fractions were profiled using direct infusion mass spectrometry. Statistical tests were used to identify molecular species that indicated differences in lipid metabolism. The abundance of several phospholipids identified by multivariate analysis, PC(34:1), PC(34:2) and PC-O(34:1), was 30-100% higher across all experimental groups. SM(39:1) was around half as abundant in in utero groups among breastfed infants only. The evidence from this pilot study shows that phospholipid metabolism is modulated by both conditions in utero and postnatal feeding in a cohort of 133 Caucasian infants, three months post partum. PMID: 31586083 [PubMed - in process]

Related Articles Decreased ω6/ω3 PUFA ratio attenuates ethanol-induced alterations in intestinal homeostasis, microbiota and liver injury. J Lipid Res. 2019 Oct 04;: Authors: Warner DR, Warner JB, Hardesty JE, Song YL, King TN, Kang JX, Chen CY, Xie S, Yuan F, Prodhan MAI, Ma X, Zhang X, Rouchka EC, Maddipati KR, Whitlock J, Li EC, Wang GP, McClain CJ, Kirpich IA Abstract Ethanol-induced alterations in intestinal homeostasis lead to multi-system pathologies, including liver injury.  w6-PUFAs exert pro-inflammatory activity, while ω3-PUFAs promote anti-inflammatory activity that is mediated, in part, through specialized pro-resolving mediators (e.g. RvD1).  We tested the hypothesis that a decrease in ω6/ω3 PUFA ratio would attenuate ethanol-mediated alterations in the gut-liver axis.  fat-1 mice, which endogenously increase w3-PUFA levels, were protected against ethanol-mediated down-regulation of intestinal tight junction proteins in organoid cultures and in vivo.  Ethanol and LPS-induced expression of INF-g, Il-6, and Cxcl1 was attenuated in fat-1 and WT RvD1-treated mice. RNA-seq of ileum tissue revealed up-regulation of several genes involved in cell proliferation and stem cell renewal, and anti-microbial defense (including Alpi and Leap2) in fat-1 vs WT mice fed ethanol.  fat-1 mice were also resistant to ethanol-mediated down-regulation of genes important for xenobiotic/bile acid detoxification.  Further, gut microbiome and plasma metabolomics revealed several changes in fat-1 vs. WT mice that may contribute to a reduced inflammatory response.  Finally, these data correlated with a significant reduction in liver injury.  Our study suggests that w3-PUFA enrichment or treatment with resolvins can attenuate the disruption in alcohol-induced intestinal homeostasis caused by ethanol consumption and systemic inflammation with a concomitant reduction in liver injury. PMID: 31586017 [PubMed - as supplied by publisher]

Related Articles The systems medicine of neonatal abstinence syndrome. Front Biosci (Landmark Ed). 2020 Jan 01;25:736-759 Authors: Stone WL, Wood DL, Justice NA, Shah DS, Olsen ME, Bharti D Abstract This review will focus on a systems medicine approach to neonatal abstinence syndrome (NAS). Systems medicine utilizes information gained from the application of "omics" technology and bioinformatics (1). The omic approaches we will emphasize include genomics, epigenomics, proteomics, and metabolomics. The goals of systems medicine are to provide clinically relevant and objective insights into disease diagnosis, prognosis, and stratification as well as pharmacological strategies and evidence-based individualized clinical guidance. Despite the increasing incidence of NAS and its societal and economic costs, there has been only a very modest emphasis on utilizing a systems medicine approach, and this has been primarily in the areas of genomics and epigenomics. As detailed below, proteomics and metabolomics hold great promise in advancing our knowledge of NAS and its treatment. Metabolomics, in particular, can provide a quantitative assessment of the exposome, which is a comprehensive picture of both internal and external environmental factors affecting health. PMID: 31585915 [PubMed - in process]