PubMed

Related Articles Metabonomics-based analysis of Brachyspira pilosicoli's response to tiamulin reveals metabolic activity despite significant growth inhibition. Anaerobe. 2017 Jun;45:71-77 Authors: Le Roy CI, Passey JL, Woodward MJ, La Ragione RM, Claus SP Abstract Pathogenic anaerobes Brachyspira spp. are responsible for an increasing number of Intestinal Spirochaetosis (IS) cases in livestock against which few approved treatments are available. Tiamulin is used to treat swine dysentery caused by Brachyspira spp. and recently has been used to handle avian intestinal spirochaetosis (AIS). The therapeutic dose used in chickens requires further evaluation since cases of bacterial resistance to tiamulin have been reported. In this study, we evaluated the impact of tiamulin at varying concentrations on the metabolism of B. pilosicoli using a 1H-NMR-based metabonomics approach allowing the capture of the overall bacterial metabolic response to antibiotic treatment. Based on growth curve studies, tiamulin impacted bacterial growth even at very low concentration (0.008 μg/mL) although its metabolic activity was barely affected 72 h post exposure to antibiotic treatment. Only the highest dose of tiamulin tested (0.250 μg/mL) caused a major metabolic shift. Results showed that below this concentration, bacteria could maintain a normal metabolic trajectory despite significant growth inhibition by the antibiotic, which may contribute to disease reemergence post antibiotic treatment. Indeed, we confirmed that B. pilosicoli remained viable even after exposition to the highest antibiotic dose. This paper stresses the need to ensure new evaluation of bacterial viability post bacteriostatic exposure such as tiamulin to guarantee treatment efficacy and decrease antibiotic resistance development. PMID: 28373121 [PubMed - indexed for MEDLINE]

Related Articles Regulating dyslipidemia effect of polysaccharides from Pleurotus ostreatus on fat-emulsion-induced hyperlipidemia rats. Int J Biol Macromol. 2017 Aug;101:107-116 Authors: Zhang Y, Wang Z, Jin G, Yang X, Zhou H Abstract This study was conducted to evaluate the regulating dyslipidemia effect of polysaccharides from Pleurotus ostreatus (POP) on fat-emulsion-induced hyperlipidemia rats. A plasma metabonomics method based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was applied to analyze the holistic mechanism of POP in a hyperlipidemia rat model. Multivariate statistical approaches such as principal component analysis and orthogonal projection to latent structure square-discriminant analysis revealed distinctions among the control, hyperlipidemia model, and POP groups.The results demonstrated that POP had an effect on regulating dyslipidemia. The mechanism of POP on regulating dyslipidemia was partially relevant with correcting the abnormal levels of fifteen potential biomarkers towards their normal levels. These biomarkers were belong to glycerophospholipids, fatty acids, prenol lipids, sphingolipids metabolism. PMID: 28322967 [PubMed - indexed for MEDLINE]

Related Articles Assessing Sertoli Cell Metabolic Activity. Methods Mol Biol. 2018;1748:157-171 Authors: Jarak I, Oliveira PF, Rindone G, Carvalho RA, Galardo MN, Riera MF, Meroni SB, Alves MG Abstract Nuclear magnetic resonance (NMR)-based metabolomics is widely used in the research of metabolic conditions of complex biological systems under various conditions, and its use has been found in the field of male fertility. Here we describe the implementation of total and targeted NMR-based metabolomics in the research on Sertoli cell metabolism. Main principles and techniques of cell medium, cellular extracts, and intact cells are explained, as well as some classical experiments that can give complementary information on the Sertoli cell metabolism. PMID: 29453571 [PubMed - in process]

Related Articles Next-generation metabolic screening: targeted and untargeted metabolomics for the diagnosis of inborn errors of metabolism in individual patients. J Inherit Metab Dis. 2018 Feb 16;: Authors: Coene KLM, Kluijtmans LAJ, van der Heeft E, Engelke UFH, de Boer S, Hoegen B, Kwast HJT, van de Vorst M, Huigen MCDG, Keularts IMLW, Schreuder MF, van Karnebeek CDM, Wortmann SB, de Vries MC, Janssen MCH, Gilissen C, Engel J, Wevers RA Abstract The implementation of whole-exome sequencing in clinical diagnostics has generated a need for functional evaluation of genetic variants. In the field of inborn errors of metabolism (IEM), a diverse spectrum of targeted biochemical assays is employed to analyze a limited amount of metabolites. We now present a single-platform, high-resolution liquid chromatography quadrupole time of flight (LC-QTOF) method that can be applied for holistic metabolic profiling in plasma of individual IEM-suspected patients. This method, which we termed "next-generation metabolic screening" (NGMS), can detect >10,000 features in each sample. In the NGMS workflow, features identified in patient and control samples are aligned using the "various forms of chromatography mass spectrometry (XCMS)" software package. Subsequently, all features are annotated using the Human Metabolome Database, and statistical testing is performed to identify significantly perturbed metabolite concentrations in a patient sample compared with controls. We propose three main modalities to analyze complex, untargeted metabolomics data. First, a targeted evaluation can be done based on identified genetic variants of uncertain significance in metabolic pathways. Second, we developed a panel of IEM-related metabolites to filter untargeted metabolomics data. Based on this IEM-panel approach, we provided the correct diagnosis for 42 of 46 IEMs. As a last modality, metabolomics data can be analyzed in an untargeted setting, which we term "open the metabolome" analysis. This approach identifies potential novel biomarkers in known IEMs and leads to identification of biomarkers for as yet unknown IEMs. We are convinced that NGMS is the way forward in laboratory diagnostics of IEMs. PMID: 29453510 [PubMed - as supplied by publisher]

Related Articles Integrated Metabolomics and Morphogenesis Reveals Volatile Signaling of the Nematode-Trapping Fungus Arthrobotrys oligospora. Appl Environ Microbiol. 2018 Feb 16;: Authors: Wang BL, Chen YH, He JN, Xue HX, Yan N, Zeng ZJ, Bennett JW, Zhang KQ, Niu XM Abstract The adjustment of metabolic patterns is fundamental to fungal biology and plays vital roles in adaption to diverse ecological challenges. Nematode trapping fungi can switch lifestyles from saprophytic to pathogenic by developing specific trapping devices induced by nematodes to infect their prey as a response to nutrient depletion in nature. However, the chemical identity of the specific fungal metabolites used during the switch remains poorly understood. We hypothesized that these important signal molecules might be volatile in nature. GC-MS was used to carry out comparative analysis of fungal metabolomics during saprophytic and pathogenic lifestyles of the model species Arthrobotrys oligospora Two media commonly used in research on this species, corn meal agar (CMA) and potato dextrose agar (PDA), were chosen in this study. The fungus produced a small group of volatile furanone and pyrone metabolites that were associated with the switch from saprophytic to pathogenic stages. A. oligospora grown on CMA tended to produce more traps and employ attractive furanones to improve utilization of traps, while fungus grown on PDA developed fewer traps and used nematodetoxic furanone metabolites to compensate for insufficient traps. Another volatile pyrone metabolite, maltol, was identified as a morphological regulator for enhancing trap formation. Deletion of gene AOL_s00079g496 in A. oligospora led to increased furanone attractant (2 folds) in mutants and enhanced attractive activity (1.5 fold) of the fungus, while resulted in decreased trap formation. This investigation provides new insights regarding the comprehensive tactics of fungal adaptation to environmental stress, integrating both morphological and metabolomic mechanisms.Importance Nematode-trapping fungi are a unique group of soil-living fungi that can switch from saprophytic to pathogenic lifestyle once in contact with nematodes as a response to nutrient depletion. In this study, we investigated the metabolic response during the switch and the key types of metabolites involved in the interaction between fungi and nematodes. Our findings indicated that A. oligospora develop multiple and flexible metabolic tactics corresponding to different morphological responses to nematodes. A. oligospora can use similar volatile furanone and pyrone metabolites with different ecological functions to help capture nematodes in the fungal switch from saprophytic to pathogenic lifestyles. Furthermore, A. oligospora mutants with increased furanone and pyrone metabolites confirmed the results. This investigation reveals the importance of volatile signaling in the comprehensive tactics used by nematode trapping fungi, integrating both morphological and metabolomic mechanisms. PMID: 29453265 [PubMed - as supplied by publisher]

Related Articles 1H NMR-based metabolomics reveals interactive effects between the carrier solvent methanol and a pharmaceutical mixture in an amphibian developmental bioassay with Limnodynastes peronii. Chemosphere. 2018 Feb 10;199:372-381 Authors: Melvin SD, Jones OAH, Carroll AR, Leusch FDL Abstract Organic carrier solvents are used in aquatic toxicity testing to improve chemical solubility and facilitate the exploration of dose-response relationships. Both water- and solvent-control groups are normally included in these scenarios to ensure that the solvent itself has no effect on the test organism, but this fails to consider possible interactive effects between carrier solvents and contaminants of interest. We explored this topic by exposing Limnodynastes peronii tadpoles to a mixture of common water-soluble pharmaceuticals (diclofenac, metformin and valproic acid) in the presence and absence of the carrier solvent methanol, according to standard developmental bioassay methodology. Nuclear Magnetic Resonance (NMR) spectroscopy was applied as a platform for untargeted metabolomics, to compare broad sub-lethal hepatotoxicity in solvent- and solvent-free exposure scenarios. Considerable interactive effects were identified between the pharmaceutical mixture and a typical dose of methanol (0.003%). Specifically, pronounced differences were observed between the solvent- and solvent-free exposure groups for leucine, acetate, glutamine, citrate, glycogen, tyrosine, arginine, purine nucleotides and an unidentified metabolite at 6.53 ppm. Various other metabolites exhibited similar disparity related to the use of carrier solvent, but the interactions were non-significant. These results raise important questions about the use of carrier solvents for chemical exposures in aquatic ecotoxicology, and particularly for studies interested in sub-lethal mechanistic information and/or biomarker discovery. PMID: 29453063 [PubMed - as supplied by publisher]

Related Articles Evaluation of the anti-hypertensive effect of Tengfu Jiangya tablet by combination of UPLC-Q-exactive-MS-based metabolomics and iTRAQ-based proteomics technology. Biomed Pharmacother. 2018 Feb 13;100:324-334 Authors: Tian Y, Jiang F, Li Y, Jiang H, Chu Y, Zhu L, Guo W Abstract OBJECTIVE: Tengfu Jiangya tablet (TJT) is a traditional Chinese medicine formulation composed of Uncaria rhynchophylla and Semen raphani. It is a hospital preparation that is widely used in clinics for treating hypertension. A previous metabolomics study reported that TJT exerted a protective effect on hypertension by restoring impaired NO production, ameliorating the inflammatory state, and vascular remodeling. A clinical proteomics study also revealed five key target proteins during TJT intervention. This study aimed to integrate proteome and metabolome data sets for a holistic view of the molecular mechanisms of TJT in treating hypertension. METHODS: Serum samples from spontaneously hypertensive rats and Wistar Kyoto rats were analyzed using ultra-high performance liquid chromatography coupled to Q Exactive hybrid quadrupole-Orbitrap mass spectrometry (UPLC-Q-Exactive-MS)-based metabolomics technology and isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics technology. Moreover, we selected two candidate proteins and determined their expression levels in rat serum using an enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 20 potential biomarkers and 14 differential proteins in rat serum were identified. These substances were mainly involved in three biological pathways: the kallikrein-kinin pathway, the lipid metabolism pathway, and the PPARγ signaling pathway. CONCLUSIONS: The results suggested that TJT could effectively treat hypertension, partially by regulating the above three metabolic pathways. The combination of proteomics and metabolomics provided a feasible method to uncover the underlying interventional effect and therapeutic mechanism of TJT on spontaneously hypertensive rats. PMID: 29453042 [PubMed - as supplied by publisher]

Related Articles Metabolomic profiling of Campylobacter jejuni with resistance gene ermB by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry and tandem quadrupole mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Feb 10;1079:62-68 Authors: Fu Q, Liu D, Wang Y, Li X, Wang L, Yu F, Shen J, Xia X Abstract The metabolome changes of Campylobacter jejuni with resistant gene ermB remain unclear. Here, we described an untargeted metabolomic workflow based on ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry to investigate the metabolites perturbations mediated by ermB in C. jejuni. After optimization of extractants and chromatographic conditions, the combination of 100% methanol extraction with a 12 min gradient by C18 column was adopted for untargeted metabolomic profiling in reversed phase separation. Meanwhile, 60% methanol extraction followed by a 14 min separation using hydrophilic interaction chromatography column was suitable to complementally expand the metabolite coverage of C. jejuni. Multivariate statistical analysis was performed by means of orthogonal projection to latent structures-discriminant analysis to select metabolic features. The selected features were further confirmed by ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry. A total of thirty-six differential metabolites between the susceptible strain (C. jejuni NCTC 11168) and resistant stain (C. jejuni NCTC 11168 with ermB) were identified. These pivotal metabolites were primarily participated in biological processes as cell signaling, membrane integrity/stability, fuel and energy source/storage and nutrient. The biofilm formation capability of resistant strain was inferior to that of susceptible strain, confirming the influence of ermB on membrane integrity/stability of C. jejuni. Our findings revealed important metabolic regulatory pathways associated with resistant C. jejuni with ermB. PMID: 29453015 [PubMed - as supplied by publisher]

Related Articles Metabolic and Lipidomic Reprogramming in Renal Cell Carcinoma Subtypes Reflects Regions of Tumor Origin. Eur Urol Focus. 2018 Feb 13;: Authors: Schaeffeler E, Büttner F, Reustle A, Klumpp V, Winter S, Rausch S, Fisel P, Hennenlotter J, Kruck S, Stenzl A, Wahrheit J, Sonntag D, Scharpf M, Fend F, Agaimy A, Hartmann A, Bedke J, Schwab M Abstract BACKGROUND: Renal cell carcinoma (RCC) consists of prognostic distinct subtypes derived from different cells of origin (eg, clear cell RCC [ccRCC], papillary RCC [papRCC], and chromophobe RCC [chRCC]). ccRCC is characterized by lipid accumulation and metabolic alterations, whereas data on metabolic alterations in non-ccRCC are limited. OBJECTIVE: We assessed metabolic alterations and the lipid composition of RCC subtypes and ccRCC-derived metastases. Moreover, we elucidated the potential of metabolites/lipids for subtype classification and identification of therapeutic targets. DESIGN, SETTING, AND PARTICIPANTS: Metabolomic/lipidomic profiles were quantified in ccRCC (n=58), chRCC (n=19), papRCC (n=14), corresponding nontumor tissues, and metastases (n=9) through a targeted metabolomic approach. Transcriptome profiling was performed in corresponding samples and compared with expression data of The Cancer Genome Atlas cohorts (patients with ccRCC, n=452; patients with papRCC, n=260; and patients with chRCC, n=59). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: In addition to cluster analyses, metabolomic/transcriptomic data were analyzed to evaluate metabolic differences of ccRCC and chRCC using Welch's t test or paired t test as appropriate. Where indicated, p values were adjusted for multiple testing using Bonferroni or Benjamini-Hochberg correction. RESULTS AND LIMITATIONS: Based on their metabolic profiles, RCC subtypes clustered into two groups separating ccRCC and papRCC from chRCC, which mainly reflected the different cells of origin. ccRCC-derived metastases clustered with primary ccRCCs. In addition to differences in certain lipids (lysophosphatidylcholines and sphingomyelins), the coregulation network of lipids differed between ccRCC and chRCC. Consideration of metabolic gene expression indicated, for example, alterations of the polyamine pathway at metabolite and transcript levels. In vitro treatment of RCC cells with the ornithine-decarboxylase inhibitor difluoromethylornithine resulted in reduced cell viability and mitochondrial activity. Further evaluation of clinical utility was limited by the retrospective study design and cohort size. CONCLUSIONS: In summary, we provide novel insight into the metabolic profiles of ccRCC and non-ccRCC, thereby confirming the different ontogeny of RCC subtypes. Quantification of differentially regulated metabolites/lipids improves classification of RCC with an impact on the identification of novel therapeutic targets. PATIENT SUMMARY: Several subtypes of renal cell carcinoma (RCC) with different metastatic potentials and prognoses exist. In the present study, we provide novel insight into the metabolism of these different subtypes, which improves classification of subtypes and helps identify novel targets for RCC therapy. PMID: 29452772 [PubMed - as supplied by publisher]

Related Articles Investigation of the urinary metabolic variations and the application in bladder cancer biomarker discovery. Int J Cancer. 2018 Feb 16;: Authors: Liu X, Cheng X, Liu X, He L, Zhang W, Wang Y, Sun W, Ji Z Abstract Urine metabolomics have been used to identify biomarkers for clinical diseases. However, inter-individual variations and effect factors need to be further evaluated. In the present study, we explored the urine metabolome in a cohort of 203 health adults, 6 patients with benign bladder lesions, and 53 patients with bladder cancer (BCa) using liquid chromatography coupled with high resolution mass spectrometry. Inter-individual analysis of both healthy controls and bladder cancer patients showed that the urine metabolome was relatively stable. Further analysis indicated that sex and age affect inter-individual variations of urine metabolome. Metabolic pathways such as tryptophan metabolism, the citrate cycle, and pantothenate and CoA biosynthesis were found to be related to sex and age. To eliminate age and sex interference, additional BCa urine metabolomic biomarkers were explored using age and sex-matched urine samples (Test group: 44 health adults vs. 33 patients with BCa). Metabolic profiling of urine could significantly differentiate the cases with cancer from the controls and high-grade from low-grade BCa. A metabolite panel consisting of trans-2-dodecenoylcarnitine, serinyl-valine, feruloyl-2-hydroxyputrescine, and 3-hydroxynonanoyl carnitine were discovered to have good predictive ability for BCa with an area under the curve (AUC) of 0.956 (cross validation: AUC=0.924). A panel of indolylacryloylglycine, N2 -galacturonyl-L-lysine, and aspartyl-glutamate was used to establish a robust model for high and low-grade BCa distinction with AUC of 0.937 (cross validation: AUC=0.891).External sample(26 control vs. 20 BCa) validation verified the acceptable accuracy of these models for BCa detection.This study showed that urinary metabolomics is a useful strategy for differential analysis and biomarker discovery. This article is protected by copyright. All rights reserved. PMID: 29451296 [PubMed - as supplied by publisher]

Related Articles Access to the CNS: Biomarker Strategies for Dopaminergic Treatments. Pharm Res. 2018 Feb 15;35(3):64 Authors: van den Brink WJ, Palic S, Köhler I, de Lange ECM Abstract Despite substantial research carried out over the last decades, it remains difficult to understand the wide range of pharmacological effects of dopaminergic agents. The dopaminergic system is involved in several neurological disorders, such as Parkinson's disease and schizophrenia. This complex system features multiple pathways implicated in emotion and cognition, psychomotor functions and endocrine control through activation of G protein-coupled dopamine receptors. This review focuses on the system-wide effects of dopaminergic agents on the multiple biochemical and endocrine pathways, in particular the biomarkers (i.e., indicators of a pharmacological process) that reflect these effects. Dopaminergic treatments developed over the last decades were found to be associated with numerous biochemical pathways in the brain, including the norepinephrine and the kynurenine pathway. Additionally, they have shown to affect peripheral systems, for example the hypothalamus-pituitary-adrenal (HPA) axis. Dopaminergic agents thus have a complex and broad pharmacological profile, rendering drug development challenging. Considering the complex system-wide pharmacological profile of dopaminergic agents, this review underlines the needs for systems pharmacology studies that include: i) proteomics and metabolomics analysis; ii) longitudinal data evaluation and mathematical modeling; iii) pharmacokinetics-based interpretation of drug effects; iv) simultaneous biomarker evaluation in the brain, the cerebrospinal fluid (CSF) and plasma; and v) specific attention to condition-dependent (e.g., disease) pharmacology. Such approach is considered essential to increase our understanding of central nervous system (CNS) drug effects and substantially improve CNS drug development. PMID: 29450650 [PubMed - in process]

Related Articles Plant Genetics and Molecular Biology: An Introduction. Adv Biochem Eng Biotechnol. 2018 Feb 16;: Authors: Varshney RK, Pandey MK, Chitikineni A Abstract The rapidly evolving technologies can serve as a potential growth engine in agriculture as many of these technologies have revolutionized several industries in the recent past. The tremendous advancements in biotechnology methods, cost-effective sequencing technology, refinement of genomic tools, and standardization of modern genomics-assisted breeding methods hold great promise in taking the global agriculture to the next level through development of improved climate-smart seeds. These technologies can dramatically increase our capacity to understand the molecular basis of traits and utilize the available resources for accelerated development of stable high-yielding, nutritious, input-use efficient, and climate-smart crop varieties. This book aimed to document the monumental advances witnessed during the last decade in multiple fields of plant biotechnology such as genetics, structural and functional genomics, trait and gene discovery, transcriptomics, proteomics, metabolomics, epigenomics, nanotechnology, and analytical tools. This book will serve to update the scientific community, academicians, and other stakeholders in global agriculture on the rapid progress in various areas of agricultural biotechnology. This chapter provides a summary of the book, "Plant Genetics and Molecular Biology." Graphical Abstract. PMID: 29450572 [PubMed - as supplied by publisher]

Related Articles Calycosin Orchestrates Osteogenesis of Danggui Buxue Tang in Cultured Osteoblasts: Evaluating the Mechanism of Action by Omics and Chemical Knock-out Methodologies. Front Pharmacol. 2018;9:36 Authors: Gong AGW, Duan R, Wang HY, Dong TTX, Tsim KWK Abstract Danggui Buxue Tang (DBT), an ancient Chinese herbal decoction commonly used to mitigate menopausal osteoporosis, contains two herbs: Astragali Radix (AR) and Angelicae Sinensis Radix (ASR). The exact efficacy of individual chemical(s) within DBT, or in any herbal mixture, is hard to be revealed. Calycosin and ferulic acid have been reported to be the predominant chemicals found within DBT, and its roles in regulating osteoblastic differentiation have been proposed here. To probe the roles of calycosin and ferulic acid, these chemicals were specifically depleted from the DBT extracts. Here, calycosin-depleted DBT (DBTΔcal) and ferulic acid-depleted DBT (DBTΔfa), generated by semi-preparative HPLC, were coupled with RNA-seq and metabolomics analyses to reveal the synergistic functions of individual chemicals within a complex herbal mixture. The expressions of osteogenic differentiation markers were significantly increased under the treatments of DBT and DBTΔfa. The DBT-induced genes were markedly reduced in the absent of calycosin, i.e., DBTΔcal. In cultured osteoblasts, the DBT-activated Wnt/β-catenin and MAPK/Erk and signaling pathways were greatly affected when calycosin was depleted. By metabolomics analysis in DBT-treated osteoblasts, the profile of metabolites triggered by DBTΔcal showed distinction to that of DBT and/or DBTΔfa. Thus, our findings indicated that calycosin, rather than ferulic acid, could be an indispensable chemical in DBT to orchestrate multi-components of DBT in achieving maximal osteogenic properties. PMID: 29449812 [PubMed]

Related Articles Changes in grape polyphenols (V. vinifera L.) as a consequence of post-harvest withering by high-resolution mass spectrometry: Raboso Piave versus Corvina. J Mass Spectrom. 2016 Sep;51(9):750-60 Authors: Rosso MD, Soligo S, Panighel A, Carraro R, Vedova AD, Maoz I, Tomasi D, Flamini R Abstract Grape dehydration is an oenological process used for the production of high-quality reinforced and sweet wines. Corvina and Raboso Piave are two red grape varieties used for production of high-quality Italian wines, such as Recioto, Amarone di Valpolicella and Raboso Passito. Changes of polyphenolic composition of the grapes as a consequence of the withering were studied by ultra-high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC/QTOF); for identification of compounds a homemade HR-MS database of grape and wine metabolites, was used. Concomitant with trans-resveratrol and viniferins, relevant increases of other stilbenes (piceatannol, resveratrol trimers and tetramers) and antioxidant compounds (quercetin, syringetin and tamarixetin) were observed. These compounds are part of the induced metabolism occurring during the withering process and in general improve the nutraceutical properties of grapes and wines. On the other hand, longer processes showed to decrease flavan-3-ols and glycoside flavonols. Constant increase of E/Z ε-viniferin ratio was observed in all samples, and this parameter can be used to monitor the process. Copyright © 2016 John Wiley & Sons, Ltd. PMID: 27491020 [PubMed - indexed for MEDLINE]

Related Articles Metabolomic study of wild and cultivated caper (Capparis spinosa L.) from different areas of Sardinia and their comparative evaluation. J Mass Spectrom. 2016 Sep;51(9):716-28 Authors: Maldini M, Foddai M, Natella F, Addis R, Chessa M, Petretto GL, Tuberoso CI, Pintore G Abstract Capparis spinosa L. (Capparidaceae), also known as caper, is widely known for its very aromatic flower buds (capers),that are largely employed as a flavouring in cooking. Capparis species are regarded as a potential source of important bioactive compounds, in fact, due to their botanical relationship with Brassica species; they contain glucosinolates, secondary plant metabolites, that have been studied for their potential anticarcinogenic properties. In addition, the presence of other numerous beneficial compounds such as polyphenols, alkaloids, lipids, vitamins and minerals have been reported. The aim of this study was to individuate and determinate the principal bioactive compounds occurring in different part (leaves, buds and flowers) of wild and cultivated C. spinosa collected from different area of Sardinia (Italy). Ultra-high performance liquid chromatography-triple quadrupole/linear ion trap tandem mass spectrometry methods were used for identification and simultaneous determination of 27 bioactive molecules. Analysis of different samples revealed qualitative and quantitative differences in the content of flavonoids, glucosinolates, anthocyanins and phenolic acids. In particular, glucocapparin resulted the most abundant with values ranging from 112 to 364 mg/100 g Fresh Weight (FW); followed by rutin with highest value of 126 mg/100 g FW, 4-hydroxyglucobrassicin with highest value of 42 mg/100 g FW and isorhamnetin 3-O-rutinoside with highest value of 24 mg/100 g FW. Based on this metabolomic targeted approach, quantitative results were treated by principal component analysis to explore and visualise correlation and discrimination among collections of C. spinosa samples. Copyright © 2016 John Wiley & Sons, Ltd. PMID: 27489055 [PubMed - indexed for MEDLINE]

6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid attenuates colon carcinogenesis via blockade of IL-6 mediated signals. Biomed Pharmacother. 2018 Feb 12;100:282-295 Authors: Mishra P, Raj V, Bhadauria AS, Singh AK, Rai A, Kumar P, Keshari AK, De A, Samanta A, Kumar U, Kumar D, Maity B, Nath S, Prakash A, Ansari KM, Saha S Abstract In this study, we investigated the in vivo antiproliferative activity of 6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid (M1) in dimethylhydrazine (DMH) induced colorectal carcinoma (CRC) using albino Wistar rats. M1 was administered to DMH induced CRC rats at 10 and 25 mg/kg doses for 15 days. Various physiological, oxidative parameters, histopathology, ELISA, gene and protein expression studies were conducted to evaluate the anti-CRC potential of M1. The histopathology and biochemical tests indicated the protective action of M1 in DMH-induced colon cancer. ELISA confirms that M1 reduced the increased concentration of IL-6 more prominently than those of IL-2 and COX-2. Gene expression analysis revealed that M1 attenuated the increased mRNA over-expression of IL-6, JAK2 and STAT3. The result obtained from quantitative western blot analysis demonstrated that the CRC condition was produced by the IL-6 induced activation/phosphorylation of JAK2 and STAT3 and further down-regulated with M1 treatment. This evidence was supported well with the application of data-based mathematical modeling. Applying the fitted model, we predicted the quantitative behavior of STAT3 populations not accessible to experimental measurement. Later, 1H NMR based serum metabolic profiling was carried out using rat sera to investigate the impact of M1 on CRC-induced metabolic alterations. M1 showed its ability to restore the perturbed metabolites in CRC condition. Altogether, our study provided the first time evidence that M1 exhibits anti-CRC potential through the blockade of IL-6/JAK2/STAT3 oncogenic signaling. PMID: 29448205 [PubMed - as supplied by publisher]

Metabolomics facilitates the discrimination of the specific anti-cancer effects of free- and polymer-conjugated doxorubicin in breast cancer models. Biomaterials. 2018 Feb 08;162:144-153 Authors: Armiñán A, Palomino-Schätzlein M, Deladriere C, Arroyo-Crespo JJ, Vicente-Ruiz S, Vicent MJ, Pineda-Lucena A Abstract Metabolomics is becoming a relevant tool for understanding the molecular mechanisms involved in the response to new drug delivery systems. The applicability of this experimental approach to cell cultures and animal models makes metabolomics a useful tool for establishing direct connections between in vitro and in vivo data, thus providing a reliable platform for the characterization of chemotherapeutic agents. Herein, we used metabolomic profiles based on nuclear magnetic resonance (NMR) spectroscopy to evaluate the biochemical pathways involved in the response to a chemotherapeutic anthracycline drug (Doxorubicin, Dox) and an N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-conjugated form (HPMA-Dox) in an in vitro cell culture model and an in vivo orthotopic breast cancer model. We also used protein expression and flow cytometry studies to obtain a better coverage of the biochemical alterations associated with the administration of these compounds. The overall analysis revealed that polymer conjugation leads to increased apoptosis, reduced glycolysis, and reduced levels of phospholipids when compared to the free chemotherapeutic drug. Our results represent a first step in the application of integrated in vitro and in vivo metabolomic studies to the evaluation of drug delivery systems. PMID: 29448142 [PubMed - as supplied by publisher]

Advances in analytical tools for high throughput strain engineering. Curr Opin Biotechnol. 2018 Feb 12;54:33-40 Authors: Marcellin E, Nielsen LK Abstract The emergence of inexpensive, base-perfect genome editing is revolutionising biology. Modern industrial biotechnology exploits the advances in genome editing in combination with automation, analytics and data integration to build high-throughput automated strain engineering pipelines also known as biofoundries. Biofoundries replace the slow and inconsistent artisanal processes used to build microbial cell factories with an automated design-build-test cycle, considerably reducing the time needed to deliver commercially viable strains. Testing and hence learning remains relatively shallow, but recent advances in analytical chemistry promise to increase the depth of characterization possible. Analytics combined with models of cellular physiology in automated systems biology pipelines should enable deeper learning and hence a steeper pitch of the learning cycle. This review explores the progress, advances and remaining bottlenecks of analytical tools for high throughput strain engineering. PMID: 29448095 [PubMed - as supplied by publisher]

Salicin-7-sulfate: A new salicinoid from willow and implications for herbal medicine. Fitoterapia. 2018 Feb 12;: Authors: Noleto-Dias C, Ward JL, Bellisai A, Lomax C, Beale MH Abstract Willow (Salix sp.) is a historically well-known herbal medicine that provided the lead compound (salicin) for the discovery of aspirin, one of the most successful plant derived drugs in human medicine. During a metabolomics screen of 86 Salix species contained in the UK National Willow Collection, we have discovered, isolated and fully characterised a new natural salicinoid - salicin-7-sulfate. This molecule may have important human pharmacological actions that need to be considered in determining the efficacy and safety of willow herbal medicines. PMID: 29447984 [PubMed - as supplied by publisher]

Related Articles Fc-Glycosylation in Human IgG1 and IgG3 Is Similar for Both Total and Anti-Red-Blood Cell Anti-K Antibodies. Front Immunol. 2018;9:129 Authors: Sonneveld ME, Koeleman CAM, Plomp HR, Wuhrer M, van der Schoot CE, Vidarsson G Abstract After albumin, immunoglobulin G (IgG) are the most abundant proteins in human serum, with IgG1 and IgG3 being the most abundant subclasses directed against protein antigens. The quality of the IgG-Fc-glycosylation has important functional consequences, which have been found to be skewed toward low fucosylation in some antigen-specific immune responses. This increases the affinity to IgG1-Fc-receptor (FcγR)IIIa/b and thereby directly affects downstream effector functions and disease severity. To date, antigen-specific IgG-glycosylation have not been analyzed for IgG3. Here, we analyzed 30 pregnant women with anti-K alloantibodies from a prospective screening cohort and compared the type of Fc-tail glycosylation of total serum- and antigen-specific IgG1 and IgG3 using mass spectrometry. Total serum IgG1 and IgG3 Fc-glycoprofiles were highly similar. Fc glycosylation of antigen-specific IgG varied greatly between individuals, but correlated significantly with each other for IgG1 and IgG3, except for bisection. However, although the magnitude of changes in fucosylation and galactosylation were similar for both subclasses, this was not the case for sialylation levels, which were significantly higher for both total and anti-K IgG3. We found that the combination of relative IgG1 and IgG3 Fc-glycosylation levels did not improve the prediction of anti-K mediated disease over IgG1 alone. In conclusion, Fc-glycosylation profiles of serum- and antigen-specific IgG1 and IgG3 are highly similar. PMID: 29445378 [PubMed]