PubMed

Metabolomics in breast cancer: A decade in review. Cancer Treat Rev. 2018 May 03;67:88-96 Authors: McCartney A, Vignoli A, Biganzoli L, Love R, Tenori L, Luchinat C, Di Leo A Abstract Breast cancer (BC) is a heterogeneous disease which has been characterised and stratified by many platforms such as clinicopathological risk factors, genomic assays, computer generated models, and various "-omic" technologies. Genomic, proteomic and transcriptomic analysis in breast cancer research is well established, and metabolomics, which can be considered a downstream manifestation of the former disciplines, is of growing interest. The past decade has seen significant progress made within the field of clinical metabolomic BC research, with several groups demonstrating results with significant promise in the setting of BC screening and biological characterisation, as well as future potential for prognostic metabolomic biomarkers. PMID: 29775779 [PubMed - as supplied by publisher]

Defining the Osteoarthritis Patient: Back to the Future. Osteoarthritis Cartilage. 2018 May 15;: Authors: Dobson GP, Letson HL, Grant A, McEwen P, Hazratwala K, Wilkinson M, Morris JL Abstract The history of osteoarthritis (OA) is important because it can help broaden our perspective on past and present controversies. The naming of OA, beginning with Heberden's nodes, is itself a fascinating story. According to Albert Hoffa, R. Llewellyn Jones and Archibald Edward Garrod, the name OA was introduced in the mid-19th century by surgeon Richard von Volkmann who distinguished it from rheumatoid arthritis and gout. Others preferred the terms 'chronical rheumatism', 'senile arthritis', 'hypertrophic arthritis' or 'arthritis deformans'. A similar narrative applies to the concept of OA affecting the whole joint vs. the 'wear-and-tear' hypothesis, inflammation and the role of the central nervous system (CNS). In the late 19th and early 20th centuries, the Garrods (father and son) and Hermann Senator argued that OA was a whole joint disease, and that inflammation played a major role in its progression. Garrod Jnr and John Spender also linked OA to a neurogenic lesion 'outside the joint'. The remaining 20th century was no less dynamic, with major advances in basic science, diagnostics, treatments, surgical interventions and technologies. Today, OA is characterized as a multi-disease with inflammation, immune and CNS dysfunction playing central roles in whole joint damage, injury progression, pain and disability. In the current 'omics' era (genomics, proteomics and metabolomics), we owe a great debt to past physicians and surgeons who dared to think 'outside-the-box' to explain and treat OA. Over 130 years later, despite these developments, we still don't fully understand the unravelling complexities of OA, and we still don't have a cure. PMID: 29775734 [PubMed - as supplied by publisher]

Related Articles Metabolomics Analysis of the Toxic Effects of the Production of Lycopene and Its Precursors. Front Microbiol. 2018;9:760 Authors: Miguez AM, McNerney MP, Styczynski MP Abstract Using cells as microbial factories enables highly specific production of chemicals with many advantages over chemical syntheses. A number of exciting new applications of this approach are in the area of precision metabolic engineering, which focuses on improving the specificity of target production. In recent work, we have used precision metabolic engineering to design lycopene-producing Escherichia coli for use as a low-cost diagnostic biosensor. To increase precursor availability and thus the rate of lycopene production, we heterologously expressed the mevalonate pathway. We found that simultaneous induction of these pathways increases lycopene production, but induction of the mevalonate pathway before induction of the lycopene pathway decreases both lycopene production and growth rate. Here, we aim to characterize the metabolic changes the cells may be undergoing during expression of either or both of these heterologous pathways. After establishing an improved method for quenching E. coli for metabolomics analysis, we used two-dimensional gas chromatography coupled to mass spectrometry (GCxGC-MS) to characterize the metabolomic profile of our lycopene-producing strains in growth conditions characteristic of our biosensor application. We found that the metabolic impacts of producing low, non-toxic levels of lycopene are of much smaller magnitude than the typical metabolic changes inherent to batch growth. We then used metabolomics to study differences in metabolism caused by the time of mevalonate pathway induction and the presence of the lycopene biosynthesis genes. We found that overnight induction of the mevalonate pathway was toxic to cells, but that the cells could recover if the lycopene pathway was not also heterologously expressed. The two pathways appeared to have an antagonistic metabolic effect that was clearly reflected in the cells' metabolic profiles. The metabolites homocysteine and homoserine exhibited particularly interesting behaviors and may be linked to the growth inhibition seen when the mevalonate pathway is induced overnight, suggesting potential future work that may be useful in engineering increased lycopene biosynthesis. PMID: 29774011 [PubMed]

Related Articles Metabolic perturbations of post-load hyperglycemia vs. fasting hyperglycemia. Acta Pharmacol Sin. 2018 May 17;: Authors: Lu JY, Peng JH, Ma XJ, Zhang YN, Zhu W, He XX, Ying LW, Bao YQ, Zhou J, Jia WP Abstract There is evidence that post-load/post-meal hyperglycemia is a stronger risk factor for cardiovascular disease than fasting hyperglycemia. The underlying mechanism remains to be elucidated. The current study aimed to compare the metabolic profiles of post-load hyperglycemia and fasting hyperglycemia. All subjects received an oral glucose tolerance test (OGTT) and were stratified into fasting hyperglycemia (FH) or post-load hyperglycemia (PH). Forty-six (FH, n = 23; PH, n = 23) and 40 patients (FH, n = 20; PH, n = 20) were recruited as the exploratory and the validation set, respectively, and underwent metabolic profiling. Eighty-seven subjects including normal controls (NC: n = 36; FH: n = 22; PH: n = 29) were additionally enrolled and assayed with enzyme-linked immunosorbent assay (ELISA). In the exploratory set, 10 metabolites were selected as differential metabolites of PH (vs. FH). Of them, mannose and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) were confirmed in the validation set to be significantly higher in FH than in PH. In the 87 subjects measured with ELISA, FH had numerically higher mannose (466.0 ± 179.3 vs. 390.1 ± 140.2 pg/ml) and AICAR (523.5 ± 164.8 vs. 512.1 ± 186.0 pg/ml) than did PH. In the pooled dataset comprising 173 subjects, mannose was independently associated with FPG (β = 0.151, P = 0.035) and HOMA-IR (β = 0.160, P = 0.026), respectively. The associations of AICAR with biochemical parameters did not reach statistical significance. FH and PH exhibited distinct metabolic profiles. The perturbation of mannose may be involved in the pathophysiologic disturbances in diabetes. PMID: 29773885 [PubMed - as supplied by publisher]

Related Articles When fed foods with similar palatability, healthy adult dogs and cats choose different macronutrient compositions. J Exp Biol. 2018 May 17;: Authors: Hall JA, Vondran JC, Vanchina MA, Jewell DE Abstract Dogs and cats make short-term food choices based on palatability. We hypothesized that if palatability were masked, long-term food choices would be based on physiologic requirements, and circulating metabolite concentrations would reflect those choices. Four experimental foods with similar palatability, but varying in macronutrient composition, were prepared for healthy adult dogs (n=17) and cats (n=27). Food 1 was high protein; Food 2 was high fat; Food 3 was high carbohydrates; and Food 4 was balanced for macronutrients. By choosing any combination of foods, dogs and cats could individually set their macronutrient intake. Plasma metabolomic profiles were determined at baseline and after animals had consumed their food intake of choice for 28 days. Based on food intake calculations over 28 days, dogs on average chose to consume most of their calories from fat (41.1±4.3%) and then carbohydrate (35.8±3.7%), whereas cats on average chose to consume most of their calories from carbohydrate (43.1±4.0%) and then protein (30.3±3.9%; all P<0.001). Age and lean or fat body mass also influenced protein intake. Younger, leaner cats consumed more protein compared with older cats, whereas younger leaner dogs consumed less protein compared with dogs having more fat body mass. Older cats with moderate protein intake had lower circulating docosahexaenoic acid (DHA) concentrations as well as higher concentrations of sulfated microbial catabolic products compared with younger, leaner cats. In summary, when fed foods with similar palatability, dogs and cats consume different macronutrient compositions, and concentrations of circulating metabolites in cats reflect food choices. PMID: 29773684 [PubMed - as supplied by publisher]

Related Articles Relations of gut liver axis components and gut microbiota in obese children with fatty liver: A pilot study. Clin Res Hepatol Gastroenterol. 2018 May 14;: Authors: Pierri L, Saggese P, Guercio Nuzio S, Troisi J, Di Stasi M, Poeta M, Savastano R, Marchese G, Tarallo R, Massa G, Ciccone V, Ziegenhardt D, Cavallo P, Bergheim I, Weisz A, Vajro P PMID: 29773420 [PubMed - as supplied by publisher]

Related Articles Protective effects of ethanolic peel and pulp extracts of Citrus macroptera fruit against isoproterenol-induced myocardial infarction in rats. Biomed Pharmacother. 2017 Oct;94:256-264 Authors: Paul S, Das S, Tanvir EM, Hossen MS, Saha M, Afroz R, Islam MA, Hossain MS, Gan SH, Ibrahim Khalil M Abstract Increases in the incidence of cardiovascular disease (CVD) have aroused strong interest in identifying antioxidants from natural sources for use in preventive medicine. Citrus macroptera (C. macroptera), commonly known as "Satkara", is an important herbal and medicinal plant reputed for its antioxidant, nutritious and therapeutic uses. The aim of the present study was to investigate the cardio-protective effects of ethanol extracts of C. macroptera peel and pulp against isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Male albino Wistar rats (n=36) were pre-treated with peel and pulp extracts (500mg/kg) for 45days. They received a challenge with ISO (85mg/kg) on the 44th and 45th days. Our findings indicated that subcutaneous injection of ISO induced severe myocardial injuries associated with oxidative stress, as confirmed by elevated lipid peroxidation (LPO) and decreased cellular reduced glutathione (GSH) and anti-peroxidative enzymes, including glutathione peroxidase, glutathione reductase and glutathione-S-transferase, compared with levels observed in control animals. Pre-treatment with C. macroptera peel and pulp extracts prior to ISO administration however, significantly improved many of the investigated biochemical parameters, i.e., cardiac troponin I, cardiac marker enzymes, lipid profile and oxidative stress markers. The fruit peel extract showed stronger cardio-protective effects than the pulp extract. The biochemical findings were further confirmed by histopathological examinations. Overall, the increased endogenous antioxidant enzyme activity against heightened oxidative stress in the myocardium is strongly suggestive of the cardio-protective potential of C. macroptera. PMID: 28763749 [PubMed - indexed for MEDLINE]

Related Articles RIP3 attenuates the pancreatic damage induced by deletion of ATG7. Cell Death Dis. 2017 Jul 13;8(7):e2918 Authors: Zhou X, Xie L, Xia L, Bergmann F, Büchler MW, Kroemer G, Hackert T, Fortunato F Abstract Invalidation of pancreatic autophagy entails pancreatic atrophy, endocrine and exocrine insufficiency and pancreatitis. The aim of this study was to investigate whether depletion of Rip3, which is involved in necroptotic signaling, may attenuate the pancreatic atrophy and pancreatitis resulting from autophagy inhibition. Autophagy and necroptosis signaling were evaluated in mice lacking expression of Rip3 in all organs and Atg7 in the pancreas. Acinar cell death, inflammation and fibrosis were evaluated by using of a compendium of immunofluorescence methods and immunoblots. Mice deficient for pancreatic Atg7 developed acute pancreatitis, which progressed to chronic pancreatitis. This phenotype reduces autophagy, increase apoptosis and necroptosis, inflammation and fibrosis, as well as premature death of the animals. Knockout of Rip3 exacerbated the apoptotic death of acinar cells, increased tissue damage, reduced macrophage infiltration and further accelerated the death of the mice with Atg7-deficient pancreas. The pancreatic degeneration induced by autophagy inhibition was exacerbated by Rip3 deletion. PMID: 28703808 [PubMed - indexed for MEDLINE]

Related Articles Urinary metabolic insights into host-gut microbial interactions in healthy and IBD children. World J Gastroenterol. 2017 May 28;23(20):3643-3654 Authors: Martin FP, Su MM, Xie GX, Guiraud SP, Kussmann M, Godin JP, Jia W, Nydegger A Abstract AIM: To identify metabolic signatures in urine samples from healthy and inflammatory bowel disease (IBD) children. METHODS: We applied liquid chromatography and gas chromatography coupled to targeted mass spectrometry (MS)-based metabolite profiling to identify and quantify bile acids and host-gut microbial metabolites in urine samples collected from 21 pediatric IBD patients monitored three times over one year (baseline, 6 and 12 mo), and 27 age- and gender-matched healthy children. RESULTS: urinary metabolic profiles of IBD children differ significantly from healthy controls. Such metabolic differences encompass central energy metabolism, amino acids, bile acids and gut microbial metabolites. In particular, levels of pyroglutamic acid, glutamic acid, glycine and cysteine, were significantly higher in IBD children in the course of the study. This suggests that glutathione cannot be optimally synthesized and replenished. Whilst alterations of the enterohepatic circulation of bile acids in pediatric IBD patients is known, we show here that non-invasive urinary bile acid profiling can assess those altered hepatic and intestinal barrier dysfunctions. CONCLUSION: The present study shows how non-invasive sampling of urine followed by targeted MS-based metabonomic analysis can elucidate and monitor the metabolic status of children with different GI health/disease status. PMID: 28611517 [PubMed - indexed for MEDLINE]

Related Articles Brain changes detected by functional magnetic resonance imaging and spectroscopy in patients with Crohn's disease. World J Gastroenterol. 2017 May 28;23(20):3607-3614 Authors: Lv K, Fan YH, Xu L, Xu MS Abstract Crohn's disease (CD) is a chronic, non-specific granulomatous inflammatory disorder that commonly affects the small intestine and is a phenotype of inflammatory bowel disease (IBD). CD is prone to relapse, and its incidence displays a persistent increase in developing countries. However, the pathogenesis of CD is poorly understood, with some studies emphasizing the link between CD and the intestinal microbiota. Specifically, studies point to the brain-gut-enteric microbiota axis as a key player in the occurrence and development of CD. Furthermore, investigations have shown white-matter lesions and neurologic deficits in patients with IBD. Based on these findings, brain activity changes in CD patients have been detected by blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI). BOLD-fMRI functions by detecting a local increase in relative blood oxygenation that results from neurotransmitter activity and thus reflects local neuronal firing rates. Therefore, biochemical concentrations of neurotransmitters or metabolites may change in corresponding brain regions of CD patients. To further study this phenomenon, brain changes of CD patients can be detected non-invasively, effectively and accurately by BOLD-fMRI combined with magnetic resonance spectroscopy (MRS). This approach can further shed light on the mechanisms of the occurrence and development of neurological CD. Overall, this paper reviews the current status and prospects on fMRI and MRS for evaluation of patients with CD based on the brain-gut-enteric microbiota axis. PMID: 28611513 [PubMed - indexed for MEDLINE]

Related Articles Metabolic profiling identification of metabolites formed in Mediterranean mussels (Mytilus galloprovincialis) after diclofenac exposure. Sci Total Environ. 2017 Apr 01;583:257-268 Authors: Bonnefille B, Arpin-Pont L, Gomez E, Fenet H, Courant F Abstract Despite the growing concern on the presence of pharmaceutically active compounds in the environment, few studies have been conducted on their metabolism in marine organisms. In this study, a non-targeted strategy based on the generation of chemical profiles generated by liquid chromatography combined with high resolution mass spectrometry was used to highlight metabolite production by the Mediterranean mussel (Mytilus galloprovincialis) after diclofenac exposure. This method allowed revealing the production of 13 metabolites in mussel tissues. Three of them were phase I metabolites, including 4'-hydroxy-diclofenac and 5-hydroxy-diclofenac. The remaining 10 were phase II metabolites, including sulfate and amino acids conjugates. Among all of the metabolites highlighted, 5 were reported for the first time in an aquatic organism exposed to diclofenac. PMID: 28108094 [PubMed - indexed for MEDLINE]

Related Articles Differential integrative omic analysis for mechanism insights and biomarker discovery of abnormal Savda syndrome and its unique Munziq prescription. Sci Rep. 2016 06 14;6:27831 Authors: Guo X, Bakri I, Abudula A, Arken K, Mijit M, Mamtimin B, Upur H Abstract Research has shown that many cancers have acommon pathophysiological origin and often present with similar symptoms. In terms of Traditional Uighur Medicine (TUM) Hilit (body fluid) theory, abnormal Savda syndrome (ASS) formed by abnormal Hilit is the common phenotype of complex diseases and in particular tumours. Abnormal Savda Munziq (ASMq), one representative of TUM, has been effective in the treatment of cancer since ancient times. Despite the physiopathology of ASS, the relationship between causative factors and the molecular mechanism of ASMq are not fully understood. The current study expanded upon earlier work by integrating traditional diagnostic approaches with others utilizing systems biology technology for the analysis of proteomic (iTRAQ) and metabolomic ((1)H-NMR) profiles of Uighur Medicine target organ lesion (liver) tumours. The candidate proteins were analyzed by enrichment analysis of the biological process and biomarker filters. Subsequently, 3Omics web-based tools were used to determine the relationships between proteins and appropriate metabolites. ELISA assay and IHC methods were used to verify the proteomic result; the protein von Willebrand factor (vWF) may be the "therapeutic window" of ASMq and biomarkers of ASS. This study is likely to be of great significance for the standardization and modernization of TUM. PMID: 27296761 [PubMed - indexed for MEDLINE]

Related Articles [¹H-NMR-based metabonomics on chemical component groups with toxicity alleviation effect to Realgar in Niuhuang Jiedu tablet]. Zhongguo Zhong Yao Za Zhi. 2016 Jun;41(12):2228-2234 Authors: Xu WF, Pei YH Abstract To study the chemical component groups with toxicity alleviation effect to Realgar in Niuhuang Jiedu tablet based on ¹H-NMR metabonomics. Twenty-four male Wistar rats were divided into four groups： control group, R group (treated with Realgar), RRSPG group (treated with Realgar, the root and rhizoma of Rheum palmatum, the root of Scutellaria baicalensis, the root of Platycodon grandiflorum and the root and rhizoma of Glycyrrhiza uralensis) and RC group (treated with total anthraquinones from the root and rhizoma of R. palmatum, total flavonoids from the root of S. baicalensis, total saponins from the root of P. grandiflorum, total flavonoids and saponins from the root and rhizoma of G. uralensis). Based on ¹H-NMR spectra of urine and serum from rats, PLS-DA was performed to identify different metabolic profiles.The metabolic profiles of R group were different from that of control group, while the metabolic profiles of RC group were almost similar to control group.Total anthraquinones from the root and rhizoma of R. palmatum, total flavonoids from the root of S. baicalensis, total saponins from the root of P. grandiflorum, total flavonoids and saponins from the root and rhizoma of G. uralensis regulated energy, choline and amino acid metabolism and gut flora disorder affected by realgar's toxicity. PMID: 28901065 [PubMed - indexed for MEDLINE]

Related Articles LCM-seq reveals the crucial role of LsSOC1 in heat-promoted bolting of lettuce (Lactuca sativa L.). Plant J. 2018 May 17;: Authors: Chen Z, Zhao W, Ge D, Han Y, Ning K, Luo C, Wang S, Liu R, Zhang X, Wang Q Abstract Lettuce (Lactuca sativa L.) is one of the most economically important vegetables. The floral transition in lettuce is accelerated under high temperatures, which can significantly decrease yields. However, the molecular mechanism underlying the floral tranition in lettuce is poorly known. Using laser capture microdissection coupled with RNA sequencing, we isolated shoot apical meristem cells from the bolting-sensitive lettuce line S39 at four critical stages of development. Subsequently, we screened specifically for the flowering-related gene LsSOC1 during the floral transition through comparative transcriptomic analysis. Molecular biology, developmental biology, and biochemical tools were combined to investigate the biological function of LsSOC1 in lettuce. LsSOC1 knockdown by RNA interference resulted in a significant delay in the timing of bolting and insensitivity to high temperature, which indicated that LsSOC1 functions as an activator during heat-promoted bolting in lettuce. We determined that two heat-shock transcription factors, HsfA1e and HsfA4c, bound to the promoter of LsSOC1 to confirm that LsSOC1 played an important role in heat-promoted bolting. This study indicates that LsSOC1 plays a crucial role in the heat-promoted bolting process in lettuce. Further investigation of LsSOC1 may be useful for clarification of the bolting mechanism in lettuce. This article is protected by copyright. All rights reserved. PMID: 29772090 [PubMed - as supplied by publisher]

Related Articles Detection of novel metabolite for roxadustat doping by global metabolomics. J Biochem. 2018 Jun 01;163(6):e1 Authors: Saigusa D, Suzuki N, Matsumoto Y, Umeda K, Tomioka Y, Koshiba S, Yamamoto M PMID: 29771375 [PubMed - in process]

Related Articles The influence of juicing on the appearance of blueberry metabolites 2 h after consumption: a metabolite profiling approach. Br J Nutr. 2018 Jun;119(11):1233-1244 Authors: Langer S, Kennel A, Lodge JK Abstract The consumption of berries has been linked to decreased risk of degenerative disease. Berries are regularly processed into juices. It is largely unknown how the juicing process affects the bioavailability of metabolites. As metabolomics has shown to be a valuable nutritional tool to study global metabolite differences, the aim of this study was to investigate the effect of juicing on the relative appearance of blueberry metabolites in humans using metabolomics. Nine healthy subjects consumed 250 g of fresh blueberries either as the whole fruit or after juicing, and provided blood and urine samples before and 2 h after intake in a cross-over design. Samples underwent metabolite profiling using LCMS, and data were mined with multivariate analysis. Overall, <12 % of all ions detected were significantly influenced by blueberry treatment (P<0·05). Partial least-squared discriminant analysis models of post-treatment samples revealed good discrimination. In urinary samples, whole blueberry treatment resulted in 108 ions that were significantly higher compared with juiced treatment (positive and negative mode combined), whereas only eight were significantly higher after juiced treatment. Examples of putative annotations included metabolites of ferulic and caffeic acids, several phenolic metabolites conjugated to sulphate, glycoside or glucuronide and fatty acyl derivatives, which were of higher intensity after whole blueberry treatment. In conclusion, consumption of whole blueberries resulted in a higher range of phenolic and other metabolites in plasma and urine samples 2 h after consumption. Both whole and juiced blueberries resulted in very similar metabolite profiles at 2 h, although this was the only time point measured. PMID: 29770756 [PubMed - in process]

Related Articles GC-MS analysis of the ruminal metabolome response to thiamine supplementation during high grain feeding in dairy cows. Metabolomics. 2018;14(5):67 Authors: Xue F, Pan X, Jiang L, Guo Y, Xiong B Abstract Introduction: Thiamine is known to attenuate high-concentrate diet induced subacute ruminal acidosis (SARA) in dairy cows, however, the underlying mechanisms remain unclear. Objectives: The major objective of this study was to investigate the metabolic mechanisms of thiamine supplementation on high-concentrate diet induced SARA. Methods: Six multiparous, rumen-fistulated Holstein cows were used in a replicated 3 × 3 Latin square design. The treatments included a control diet (CON; 20% starch, dry matter basis), a SARA-inducing diet (SAID; 33.2% starch, dry matter basis) and SARA-inducing diet supplemented with 180 mg of thiamine/kg of dry matter intake (SAID + T). On d21 of each period, ruminal fluid samples were collected at 3 h post feeding, and GC/MS was used to analyze rumen fluid samples. Results: PCA and OPLS-DA analysis demonstrated that the ruminal metabolite profile were different in three treatments. Compared with CON treatment, SAID feeding significantly decreased rumen pH, acetate, succinic acid, increased propionate, pyruvate, lactate, glycine and biogenic amines including spermidine and putrescine. Thiamine supplementation significantly decreased rumen content of propionate, pyruvate, lactate, glycine and spermidine; increase rumen pH, acetate and some medium-chain fatty acids. The enrichment analysis of different metabolites indicated that thiamine supplementation mainly affected carbohydrates, amino acids, pyruvate and thiamine metabolism compared with SAID treatment. Conclusions: These findings revealed that thiamine supplementation could attenuate high-concentrate diet induced SARA by increasing pyruvate formate-lyase activity to promote pyruvate to generate acetyl-CoA and inhibit lactate generation. Besides, thiamine reduced biogenic amines to alleviate ruminal epithelial inflammatory response. PMID: 29770108 [PubMed]

Related Articles Metabolomic profile of systemic sclerosis patients. Sci Rep. 2018 May 16;8(1):7626 Authors: Murgia F, Svegliati S, Poddighe S, Lussu M, Manzin A, Spadoni T, Fischetti C, Gabrielli A, Atzori L Abstract Systemic sclerosis (SSc) is an autoimmune disease of unknown aetiology characterized by vascular lesions, immunological alterations and diffuse fibrosis of the skin and internal organs. Since recent evidence suggests that there is a link between metabolomics and immune mediated disease, serum metabolic profile of SSc patients and healthy controls was investigated by 1H-NMR and GC-MS techniques. The results indicated a lower level of aspartate, alanine, choline, glutamate, and glutarate in SSc patients compared with healthy controls. Moreover, comparing patients affected by limited SSc (lcSSc) and diffuse SSc (dcSSc), 6 discriminant metabolites were identified. The multivariate analysis performed using all the metabolites significantly different revealed glycolysis, gluconeogenesis, energetic pathways, glutamate metabolism, degradation of ketone bodies and pyruvate metabolism as the most important networks. Aspartate, alanine and citrate yielded a high area under receiver-operating characteristic (ROC) curves (AUC of 0.81; CI 0.726-0.93) for discriminating SSc patients from controls, whereas ROC curve generated with acetate, fructose, glutamate, glutamine, glycerol and glutarate (AUC of 0.84; CI 0.7-0.98) discriminated between lcSSc and dcSSc. These results indicated that serum NMR-based metabolomics profiling method is sensitive and specific enough to distinguish SSc from healthy controls and provided a feasible diagnostic tool for the diagnosis and classification of the disease. PMID: 29769578 [PubMed - in process]

Related Articles PBDEs Altered Gut Microbiome and Bile Acid Homeostasis in Male C57BL/6 Mice. Drug Metab Dispos. 2018 May 16;: Authors: Li CY, Dempsey JL, Wang D, Lee S, Weigel KM, Fei Q, Bhatt DK, Prasad B, Raftery D, Gu H, Cui JY Abstract Polybrominated diphenyl ethers (PBDEs) are persistent environmental contaminants with well-characterized toxicities in host organs. Gut microbiome is increasingly recognized as an important regulator of xenobiotic biotransformation; however, little is known about its interactions with PBDEs. Primary bile acids (BAs) are metabolized by the gut microbiome into more lipophilic secondary BAs that may be absorbed and interact with certain host receptors. The goal of this study was to test our hypothesis that PBDEs cause dysbiosis and aberrant regulation of BA homeostasis. Nine-week-old male C57BL/6 conventional (CV) and germ-free (GF) mice were orally gavaged with corn oil (10 mg/kg), BDE-47 (100 μmol/kg), or BDE-99 (100 μmol/kg) once daily for 4-days (n=3-5/group). Gut microbiome was characterized using 16S rRNA sequencing of the large intestinal content in CV mice. Both BDE-47 and BDE-99 profoundly decreased the alpha diversity of gut microbiome and differentially regulated 45 bacterial species. Both PBDE congeners increased Akkermansia muciniphila and Erysipelotrichacea Allobaculum spp., which have been reported to have anti-inflammatory and anti-obesity functions. Targeted metabolomics of 56 BAs was conducted in serum, liver, and small and large intestinal content of CV and GF mice. BDE-99 increased many unconjugated BAs in multiple bio-compartments in a gut microbiota-dependent manner. This correlated with an increase in microbial 7α-dehydroxylation enzymes for secondary BA synthesis and increased expression of host intestinal transporters for BA absorption. Targeted proteomics showed that PBDEs down-regulated host BA-synthesizing enzymes and transporters in livers of CV but not GF mice. In conclusion, there is a novel interaction between PBDEs and the endogenous BA-signaling through modifying the "gut-liver axis". PMID: 29769268 [PubMed - as supplied by publisher]

Related Articles Inhibition of UDP-glucuronosyltransferases (UGTs) by phthalate monoesters. Chemosphere. 2018 Apr;197:7-13 Authors: Du Z, Cao YF, Li SN, Hu CM, Fu ZW, Huang CT, Sun XY, Liu YZ, Yang K, Fang ZZ Abstract Phthalate monoesters are important metabolites of phthalate esters (PAEs) which have been extensively utilized in industry. This study aims to investigate the inhibition of phthalate monoesters on the activity of various isoforms of UDP-glucuronosyltransferases (UGTs), trying to elucidate the toxicity mechanism of environmental endocrine disruptors from the new perspectives. In vitro recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was employed to evaluate 8 kinds of phthalate monoesters on 11 sorts of main human UGT isoforms. 100 μM phthalate monoesters exhibited negligible inhibition towards the activity of UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A10, UGT2B4, UGT2B7, UGT2B15 and UGT2B17. The activity of UGT1A7 was strongly inhibited by monoethylhexyl phthalate (MEHP), but slightly inhibited by all the other phthalate monoesters. UGT1A9 was broadly inhibited by monobenzyl phthalate (MBZP), monocyclohexyl phthalate (MCHP), MEHP, monohexyl phthalate (MHP) and monooctyl phthalate (MOP), respectively. MEHP exhibited competitive inhibition towards UGT1A7, and MBZP, MCHP, MEHP, MHP and MOP showed competitive inhibition towards UGT1A9. The inhibition kinetic parameters (Ki) were calculated to be 11.25 μM for MEHP-UGT1A7, and 2.13, 0.09, 1.17, 7.47, 0.16 μM for MBZP-UGT1A9, MCHP-UGT1A9, MEHP-UGT1A9, MHP-UGT1A9, MOP-UGT1A9, respectively. Molecular docking indicated that both hydrogen bonds formation and hydrophobic interactions significantly contributed to the interaction between phthalate monoesters and UGT isoforms. All these information will be beneficial for understanding the adverse effects of PAEs. PMID: 29328989 [PubMed - indexed for MEDLINE]